The invisible enemy: a systematic review and meta-analysis of maternal smokeless tobacco use as a risk factor for low birth weight

The invisible enemy: a systematic review and meta-analysis of maternal smokeless tobacco use as a risk factor for low birth weight | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The invisible enemy: a systematic review and meta-analysis of maternal smokeless tobacco use as a risk factor for low birth weight Akanksha Mahajan, Bhawna Gupta This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3800566/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Smokeless tobacco use is a growing public health concern, with potential adverse implications for foetal outcomes if consumed during pregnancy. Birth weight is an important predictive measure for health outcomes of a child throughout their lifespan, from infancy through to adulthood. Although the association between maternal smoking and reduction in birth weight of infants has been studied extensively, it is unclear whether smokeless tobacco has similar effects. Hence, this review was conducted to determine whether an association exists between maternal smokeless tobacco consumption during pregnancy and birth weight of infants. Aims and Methods Systematic literature search was performed in Medline (via PubMed), Embase, Scopus, and CINAHL with no restrictions on language or time until January 2023. All observational studies (case control, cohort and cross sectional) that examined the relationship between maternal smokeless tobacco use and low birth weight of infants were eligible for inclusion. The methodological quality of included studies was assessed using the Newcastle Ottawa Scale. Results Thirty-one studies were eligible for the review, including twenty-seven cohort studies, two case-control and two cross-sectional studies. These studies examined various forms of smokeless tobacco use including khat, betel/areca nut, mishri, snuff, iqmik and pituri. A statistically significant association between use of smokeless tobacco and low birth weight was reported in thirteen studies. An additional eleven studies reported a statistically significant reduction in mean birth weight in maternal smokeless tobacco users. Meta-analysis using a random effects model showed that there was a statistically significant association (OR = 1.91 [1.38, 2.65], P < 0.00001); between maternal smokeless tobacco use during pregnancy and low birth weight. Subgroup analysis found a significant association between maternal mishri consumption during pregnancy and low birth weight (OR = 10.98 [2.03, 59.34], P < 0.05), but not betel nut, betel quid or khat. Conclusions This review found that there is a significant association between maternal smokeless tobacco use and low birth weight of infants, as well as reduction in mean birth weight independent of confounding variables. It is suggested that maternal use of smokeless tobacco should receive specific attention as a part of routine prenatal care. Implications The results of this study highlight the need for further preventive public health campaigns to create awareness about the detrimental effects of smokeless tobacco on foetal outcomes patient education by healthcare workers in the primary care setting will aid in promoting smokeless tobacco cessation prior to pregnancy. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The prevalence of low birth weight infants in a population is an important indicator of complex public health issues including long term maternal malnutrition, ill health and poor antenatal health care. Of the 19.8 million low birthweight babies born in 2020, over 40% were born in South Asia. ( 1 ) Low birth weight is defined as per the World Health Organisation (WHO) International Classification of Diseases (ICD): a birth weight less than 2500 grams (ICD P07.1 birth weight < 2,500g [1,000–2,499 g]). ( 2 ) It is not only a predictor of neonatal mortality and morbidity, but also increases the risk of stunted growth, diminished cognitive development and chronic disease later in life. ( 3 – 5 ) Moreover, it is a primary outcome indicator in the core set of indicators for the Global Nutrition Monitoring Framework; and more than 90% of countries are off track to meet the 2030 low birth weight target as set by UNICEF. ( 3 ) Although cigarette smoking is the most common form of tobacco use globally, smokeless tobacco is consumed by over 300 million people worldwide and is a growing public health concern. Geographically, > 85% of the smokeless tobacco-related burden was in South and Southeast Asia, and in 2017, an estimated 2.5 million disability adjusted life years (DALYs) and 90,791 lives were lost worldwide due to cancers that can be attributed to smokeless tobacco. ( 6 ) Smokeless tobacco products can be found in many forms in different regions around the world, which vary in their preparation, method of use and components. In developed countries, common forms of consumption include snuff (finely ground dry or moist tobacco inhaled nasally) in Sweden, chewing tobacco (dried tobacco leaves) in the United States of America and pituri (chewed smokeless tobacco) amongst indigenous Australian populations. However, in developing countries, tobacco is usually chewed with other ingredients, such as betel (areca) nut, betel leaf, and lime ( 7 ). Other forms of smokeless tobacco in developing countries include mishri which is roasted ground tobacco and gutkha which is a mixture of tobacco with slaked lime, areca nut, acacia plant extract and spices. While smokeless tobacco does not expose users to the toxins produced through burning tobacco and paper, there is increasing evidence to demonstrate that tobacco components such as nicotine are toxicogenic and may increase risk of negative maternal-foetal outcomes if consumed during pregnancy. ( 8 ) Nicotine present in smokeless tobacco products can be absorbed in two forms: protonated and unprotonated; and it has been shown that unprotonated/free nicotine, the amount of which is affected by the pH of the tobacco product, can effectively cross cell membranes. ( 9 ) Metabolism of nicotine in the human body gives rise to tobacco specific N-nitrosomines (TSNAs) which have been classified as a Group 1 carcinogen. ( 10 ) Moreover, nicotine can impair retinoic acid signalling and cell differentiation, and induce a stress reaction or pro-inflammatory response that inhibits the agonistic action of retinoic acid, which is important for embryonic development. ( 8 ) Along with nicotine, there are up to 50 other harmful compounds found in tobacco which may impair foetal development by inducing both oxidative and endoplasmic reticulum stress responses in placental trophoblastic cells. ( 9 ) The use of smokeless tobacco is very common amongst women as it easily available, socially culturally and ceremonially accepted along with the misconception that it is relatively less harmful as compared to smoking. ( 11 ) Some forms of smokeless tobacco such as betel nut are chewed into a mass (known as a quid) and retained behind the lip in the buccal space for extended durations. Previous studies have shown that smokeless tobacco use may be associated with higher levels of nicotine entering the systemic circulation via this route as compared to smoking, resulting in more potent harmful effects. ( 12 ) Although there have been observational studies which investigate smokeless tobacco use and its implications on pregnancy and birth outcomes, the evidence is limited and findings vary. ( 13 ) It is necessary to synthesise this information to facilitate evidence-based practice when advising women about the risks of smokeless tobacco use. This systematically review aims to investigate the currently available evidence on the association between maternal smokeless tobacco and low birth weight infants, and to assess and summarise the main features, methodological quality and results of the included studies. Methods This study is registered at the International Register of Prospective Systematic Reviews (PROSPERO) under the CRD number 42022381144. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ( 14 ) Eligibility Criteria All observational studies (case-control, cohort and cross-sectional) that examined the relationship between maternal smokeless tobacco use and low birth weight of infants were included. Females in any healthcare setting were considered. Smokeless tobacco of at least one form such as snuff, betel nut, gutka,, mishri, pituri and khat, with or without additives, used in any amount or frequency, during or at some time during pregnancy was considered. Concurrent use of smoking tobacco was excluded from this review. Search methods The literature search was conducted from December 2022 to January 2023 using the following electronic databases: Medline (via PubMed), Embase, Scopus, CINAHL. An additional file shows the search strategy, including search terms and Boolean operators used, in more detail (see Additional file 1). There were no date or language restrictions applied. Reference lists from the selected studies and grey literature were also hand searched, and authors were contacted for unpublished studies. Duplicate studies were excluded using Endnote X9. Subsequently, two reviewers (AM and BG) independently reviewed the titles and abstracts of studies. Any disagreements were settled by consensus between the authors. The full texts of all remaining studies were obtained and evaluated using predetermined inclusion and exclusion criteria. Data extraction A standardised data sheet was prepared and used to extract the following data from the studies: title, first author’s name, year of publication, country of the study, time frame of study, study design, sample characteristics (sample size, number of cases/exposed and controls/unexposed), definition of smokeless tobacco and low birth weight, duration of follow up in cohort studies, adjustment for confounding, and the estimated risk with confidence intervals. The authors (AM and BG) independently performed the data extraction and resolved any doubts through consensus. Quality assessment The methodological quality of included studies was assessed using the validated Newcastle-Ottawa Scale. This scale uses a ‘star system’ and includes eight items clustered into three broad domains: the selection of the study groups; comparability of the groups; and the ascertainment of the outcome of interest. ( 15 ) Data synthesis Each study was individually analysed to find quantitative measures of effect for the exposure and outcome, such as odds ratios and relative risk. The odds ratio was calculated by the authors (AM and BG) when these were not included in the published study, but adequate data was provided for calculation. All statistical analyses, including meta-analysis of studies examining the association between low birth weight, were performed using Review Manager (RevMan) version 5.3. ( 16 ) Data from studies with the same outcome (low birth weight defined as < 2500grams) was pooled using forest plots. The effects measure used was odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data. A random effects model for heterogeneity was employed which generates results that generalize to a range of populations and study designs, with a p value less than 0.05 considered as significant. Heterogeneity between studies was evaluated for each analysis using Cochran’s Q statistic (measure of weighted square deviations), with N-1 degrees of freedom (where N is the number of studies), between studies variance (T2), and ratio of the true heterogeneity to total observed variation ( I 2 ). By calculating I 2 values, an I 2 less than 25% was deemed to have low heterogeneity, 25–75% to have medium heterogeneity, and greater than 75% to have high heterogeneity. The effect size of each study was demonstrated by generating forest plots. The data points for the random effects meta-analysis were made up of the logarithms of the effect sizes and their corresponding standard errors. Subgroup analysis was performed based on the type of smokeless tobacco consumed by study participants during pregnancy (betel nut, khat, mishri, betel quid). Publication bias was assessed through visual inspection of the symmetry of funnel plots, which were constructed by plotting the logarithmically transformed ORs against the standard error of the associated log OR. Since the confounding variables used in the multivariate regression model varied significantly between studies, unadjusted effect estimates were used in the meta-analysis, which were calculated using RevMan. Results The search yielded a total of 292 studies (176 from EMBASE, 62 from PUBMED, 51 from Scopus and 3 from CINAHL). After duplicates were removed and the title and abstract of studies were reviewed; 42 studies were considered potentially eligible for this review and assessed as full-texts based on predetermined inclusion and exclusion criteria. There were 11 articles excluded from this review, and 31 articles included, further details of which are shown in Fig. 1 . Characteristics of included studies The characteristics of the 31 studies included in this review such as location, sample size, definitions of outcome, type of smokeless tobacco, and quantitative measures of outcome are shown in Table 1 . There were eighteen studies from Asia (ten from India, three from Yemen, two from Taiwan, one each from Pakistan, Thailand and Indonesia), six studies from Europe (five from Sweden and one from Sweden and Norway), four studies from Oceania (two from Papua New Guinea, one from Palau and one from Australia), two studies from Africa (one from Ethiopia and one from South Africa), and one study from the United States of America. This review included a total sample size of 3,338,826 pregnant women. The largest study was from Sweden with a sample size of 1,070,013 women ( 17 ), while the smallest study was from Australia with a sample size of 50 pregnant women. ( 18 ) The predominant form of smokeless tobacco used in Ethiopian and Yemen studies was khat; whereas in other countries from Asia and Oceania it was betel/areca nut; and in India it was mishri. Snuff was used by both the European and South African subjects, while iqmik and pituri was used by subjects in the study from USA and Australia respectively. None of the studies reported a quantified measure of exposure, and most did not quantify frequency of smokeless tobacco use. Table 1 Quality assessment of included studies as per the Newcastle-Ottawa Scale (referred to in line 252) Overall (maximum 9) Selection Comparability Outcome Representativeness Selection of non-exposed cohort Ascertainment of exposure Demonstration that outcome of interest was not present at start of study Assessment Duration of follow up (adequate follow up minimum 9 months for outcome to occur) Adequacy of follow up (> 80%) (Ghani et al, 1987) 7 1 1 1 1 0 1 1 1 (Ali et al, 2021) 9 1 1 1 1 2 1 1 1 (Baba et al, 2012) 9 1 1 1 1 2 1 1 1 (Berger et al, 2016) 9 1 1 1 1 2 1 1 1 (Chue et al, 2012) 6 0 1 1 1 0 1 1 1 (Charlette et al, 2022) 8 1 1 1 1 1 1 1 1 (de Costa and Griew, 1982) 8 1 1 1 1 1 1 1 1 (Demelash et al, 2015) 8 1 1 1 1 1 1 1 1 (England et al, 2012) 9 1 1 1 1 2 1 1 1 (England et al, 2003) 9 1 1 1 1 2 1 1 1 (Eriksson et al, 1991) 6 1 1 0 1 0 1 1 1 (Ganganahalli et al, 2017) 9 1 1 1 1 2 1 1 1 (Gupta and Subramoney, 2004) 9 1 1 1 1 2 1 1 1 (Idris et al, 2020) 8 1 1 1 1 1 1 1 1 (Juarez and Merlo, 2013) 9 1 1 1 1 2 1 1 1 (Kreyburg et al, 2019) 8 1 1 0 1 2 1 1 1 (Krishna, 1978) 7 1 1 1 1 0 1 1 1 (Krishnamurthy and Joshi, 1993) 6 1 1 1 1 0 0 1 1 (Madley-Dowd et al, 2021) 9 1 1 1 1 2 1 1 1 (Mallick, 2021) 9 1 1 1 1 2 1 1 1 (Ome-Kaius et al, 2015) 6 1 1 0 1 1 1 1 0 (Pratinidhi et al, 2010) 7 1 1 1 1 0 1 1 1 (Pratinidhi et al, 2014) 9 1 1 1 1 2 1 1 1 (Ratsch et al, 2021) 7 0 1 1 1 1 1 1 1 (Rygh et al, 2019) 9 1 1 1 1 2 1 1 1 (Senn et al, 2009) 8 1 1 1 1 1 1 1 1 (Steyn et al, 2006) 9 1 1 1 1 2 1 1 1 (Sulistiyani et al, 2019) 6 1 1 1 1 0 1 1 0 (Verma et al, 1983) 9 1 1 1 1 2 1 1 1 (Wang and Lee, 2012) 9 1 1 1 1 2 1 1 1 (Yang et al, 2008) 9 1 1 1 1 2 1 1 1 Table 1 Quality assessment of included studies as per the Newcastle-Ottawa Scale (referred to in line 252 of manuscript) Overall (maximum 9) Selection Comparability Outcome Representativeness Selection of non-exposed cohort Ascertainment of exposure Demonstration that outcome of interest was not present at start of study Assessment Duration of follow up (adequate follow up minimum 9 months for outcome to occur) Adequacy of follow up (> 80%) (Ghani et al, 1987) 7 1 1 1 1 0 1 1 1 (Ali et al, 2021) 9 1 1 1 1 2 1 1 1 (Baba et al, 2012) 9 1 1 1 1 2 1 1 1 (Berger et al, 2016) 9 1 1 1 1 2 1 1 1 (Chue et al, 2012) 6 0 1 1 1 0 1 1 1 (Charlette et al, 2022) 8 1 1 1 1 1 1 1 1 (de Costa and Griew, 1982) 8 1 1 1 1 1 1 1 1 (Demelash et al, 2015) 8 1 1 1 1 1 1 1 1 (England et al, 2012) 9 1 1 1 1 2 1 1 1 (England et al, 2003) 9 1 1 1 1 2 1 1 1 (Eriksson et al, 1991) 6 1 1 0 1 0 1 1 1 (Ganganahalli et al, 2017) 9 1 1 1 1 2 1 1 1 (Gupta and Subramoney, 2004) 9 1 1 1 1 2 1 1 1 (Idris et al, 2020) 8 1 1 1 1 1 1 1 1 (Juarez and Merlo, 2013) 9 1 1 1 1 2 1 1 1 (Kreyburg et al, 2019) 8 1 1 0 1 2 1 1 1 (Krishna, 1978) 7 1 1 1 1 0 1 1 1 (Krishnamurthy and Joshi, 1993) 6 1 1 1 1 0 0 1 1 (Madley-Dowd et al, 2021) 9 1 1 1 1 2 1 1 1 (Mallick, 2021) 9 1 1 1 1 2 1 1 1 (Ome-Kaius et al, 2015) 6 1 1 0 1 1 1 1 0 (Pratinidhi et al, 2010) 7 1 1 1 1 0 1 1 1 (Pratinidhi et al, 2014) 9 1 1 1 1 2 1 1 1 (Ratsch et al, 2021) 7 0 1 1 1 1 1 1 1 (Rygh et al, 2019) 9 1 1 1 1 2 1 1 1 (Senn et al, 2009) 8 1 1 1 1 1 1 1 1 (Steyn et al, 2006) 9 1 1 1 1 2 1 1 1 (Sulistiyani et al, 2019) 6 1 1 1 1 0 1 1 0 (Verma et al, 1983) 9 1 1 1 1 2 1 1 1 (Wang and Lee, 2012) 9 1 1 1 1 2 1 1 1 (Yang et al, 2008) 9 1 1 1 1 2 1 1 1 Quality assessment There was high variation in the methodological quality of included studies as summarised in Table 2 . Self-reported data regarding the use of smokeless tobacco during pregnancy was collected via interviews and hospital records in all the included studies. Consequently, there a high risk of recall bias and performance bias in these studies since none of the studies reported any biochemical/objective measurements that were performed to ascertain tobacco use. Moreover, statistical adjustments for confounding factors were not made in fifteen of the included studies. ( 17 , 19 – 34 ) Table 2 Characteristics of studies which explored the association between maternal smokeless tobacco use during pregnancy and birth weight (referred to in line 270) Reference Region Time frame Study design Definition of birth weight outcome Smokeless tobacco type Definition of exposure Sample population Number of exposed Number of non-exposed Odds ratio and 95% CI for low birth weight (Abdul Ghani et al, 1987) Yemen Arab Republic 1984 cohort Mean birth weight (g) khat self-reported khat use 1181 414 295 - (Ali et al, 2021) Pakistan 2013–2019 cohort Low birth weight ( 2 standard deviations below the mean weight for gestational age) snuff used snuff 3 months before pregnancy 945371 23,514 663649 1.26 (1.09–1.46) (Berger et al, 2016) Palau 2007–2013 cohort Low birth weight (< 2500g) betel nut self reported at least 1 use of chewing betel nut with tobacco during pregnancy 1629 893 278 2.4 (1.0–6.0) (Charlette et al, 2022) India 2021 cohort Low birth weight (< 2500g) unspecified smokeless tobacco use during pregnancy 463 23 440 2.58 (1.1–6.06) (Chue et al, 2012) Thailand 1997–2006 cohort Low birth weight (< 2500g) betel nut self reported areca nut use during pregnancy 9264 4963 2722 0.9091 (0.7694–1.0742) (de Costa and Griew, 1982) Papua New Guinea 1981 cohort Low birth weight (< 2500g) betel nut self reported history of betel consumption throughout pregnancy 800 400 400 1.4227 (0.418–2.4042) (Demelash et al, 2015) Ethiopia 2013 case control Low birth weight (< 2500g) khat self reported khat chewing during pregnancy 387 129 cases 258 controls 6.4 (2.42–17.10) (England et al, 2012) USA 1997–2005 cohort Low birth weight ( 2 standard deviations below the mean weight for gestational age) snuff snuff use during pregnancy 27762 789 11495 1.25 (0.72–2.17) (Eriksson et al, 1991) Yemen Arab Republic 1991 cohort Low birth weight (< 2500g) khat khat chewing during pregnancy 1141 142 382 1.3302 (0.8495 to 2.0831) (Ganganahalli et al, 2017) India 2011 cohort Low birth weight (< 2500g) mishri used mishri during pregnancy- self reported and case records 210 105 105 - (Gupta and Subramoney, 2004) India 2002 cohort Low birth weight (< 2500g) unspecified used a smokeless tobacco product at least once a day for the past six months 1217 206 768 - (Idris et al, 2020) Yemen 2016 case control Low birth weight (< 2500g) khat khat chewing during pregnancy 252 83 43 1.76 (1.06–2.92) (Juarez and Merlo, 2013) Sweden 2002–2010 cohort Mean birthweight (g) snuff Swedish snus use during pregnancy 938932 8339 591690 - (Kreyberg et al, 2019) Norway and Sweden 2014–2016 cohort Mean birthweight (g) snuff self reported snus use 2697 150 2046 - (Krishna, 1978) India 1971–1972 cohort Mean birthweight (g) unspecified keeping a wad of locally grown and cured tobacco in the mouth for 8 to 10 hours per day during pregnancy 1148 209 1168 - (Krishnamurthy and Joshi, 1993) India 1993 cohort Low birth weight (< 2500g) unspecified self reported maternal use of tobacco, mostly mishri, during pregnancy 178 42 41 3.2(1.5–6.9) (Madley-Dowd et al, 2021) Sweden 1999–2010 cohort small for gestational age (birthweight > two standard deviations below the mean weight for gestational age according to the gender-specific Swedish fetal growth curves) snuff self reported snus use at any time during pregnancy 1181264 14665 1E + 06 1.05(0.94–1.17) (Mallick, 2021) India 2015–2016 cohort Low birth weight (< 2500g) unspecified maternal tobacco chewing 81869 3629 53953 1.163 (1.058–1.227] (Ome-Kaius et al, 2015) Papua New Guinea 2009–2013 cohort Low birth weight (< 2500g) betel nut self reported areca nut chewing during pregnancy 2700 1459 310 0.94 (0.65–1.38) (Pratinidhi et al, 2010) India 2003–2005 cohort Low birth weight (< 2500g) mishri self reported mishri use during pregnancy 705 218 487 2.4026 (1.5206–3.7963) (Pratinidhi et al, 2014) India 2011 cohort Low birth weight (< 2500g) mishri self reported mishri use during pregnancy 2150 258 258 67.9016 (37.3926-123.3033) (Ratsch et al, 2021) Australia 2021 cohort Mean birthweight (g) pituri self reported pituri use during pregnancy 73 19 31 1.75 (0.3152–9.7161) (Rygh et al, 2019) Norway 2012–2017 cohort Mean birthweight (g) snuff self reported snus use during the third trimester of pregnancy 102011 201 9213 - (Senn et al, 2009) India 2007–2008 cross sectional Low birth weight (< 2500g) betel nut betel nut chewing during pregnancy 310 292 18 1.9 (0.4–17) (Steyn et al, 2006) South Africa 1990 cohort Mean birthweight (g) snuff self reported snuff use during pregnancy 1593 120 1376 - (Sulistiyani et al, 2019) Indonesia 2018 cross sectional Low birth weight (< 2500g) unspecified smokeless tobacco use during pregnancy 99 18 81 - (Verma et al, 1983) India 1978–1979 cohort Mean birthweight (g) unspecified tobacco chewing during pregnancy, minimum 150 mg/day 140 70 70 - (Wang and Lee, 2012) Taiwan 2005 cohort Low birth weight (< 2500g) betel nut betel quid chewing during pregnancy 24200 19 8413 0.368 (0.048–2.841) (Yang et al, 2008) Taiwan 2003–2004 cohort Low birth weight (< 2500g) betel nut self reported betel quid chewing during pregnancy 1264 464 800 2.40 (1.21–4.80) Effects of exposure Thirty-one studies included in this review were clinically and methodologically diverse. There were twenty-seven cohort studies, two case-control and two cross-sectional studies included in this systematic review. Crude odds ratios were presented in only eleven ( 17 , 23 , 25 – 27 , 30 , 31 , 33 – 37 ) of the included studies, and could be calculated by the authors using the data published for a further six studies. ( 18 , 22 , 38 – 41 ) Relative risk was presented in two of the included studies. ( 19 , 26 ) A statistically significant association between use of smokeless tobacco and low birth weight was reported in twelve of the studies. ( 20 , 21 , 23 , 26 , 27 , 30 , 33 – 35 , 40 – 42 ) All of these studies defined low birth weight as < 2500 grams. The highest odds ratio [67.9016 (37.3926-123.3033)] was reported in the study conducted in 2014 by Pratinidhi et al. ( 41 ) Meanwhile, the lowest odds ratio [0.368 (0.048–2.841)] was reported by Wang and Lee, although their results were not statistically significant. ( 37 ) A statistically significant reduction in mean birth weight was reported in maternal smokeless tobacco users in a further eleven studies. ( 20 , 22 , 26 , 33 , 36 , 38 , 40 , 41 , 43 – 45 ) On the contrary, four studies reported that there was no statistically significant difference in birth weight in infants born to mothers who used smokeless tobacco during pregnancy. ( 18 , 24 , 29 , 32 ) Out of all the studies included in this review, seven studies reported on snuff users ( 17 , 20 , 25 , 28 , 29 , 32 , 44 ), seven reported on betel nut users ( 21 , 22 , 31 , 33 , 36 – 38 ), four reported on khat users ( 23 , 27 , 39 , 43 ), three on mishri ( 40 – 42 ), one reported on gutka ( 19 ), iqmik ( 24 ) and pituri ( 18 ) users respectively, and seven did not specify the type of smokeless tobacco used by participants ( 26 , 30 , 34 , 35 , 45 – 47 ). Two studies on khat ( 23 , 27 ), two on mishri ( 40 , 41 ), one on snuff ( 20 ), one on betel quid ( 33 ) and none on areca nut, betel nut, pituri, iqmik or gutka reported a statistically significant association between maternal smokeless tobacco use and low birth weight. One study on khat ( 43 ), three on snuff ( 25 , 28 , 44 ), one on mishri ( 42 ), two on betel nut ( 33 , 36 ) and none on iqmik or pituri reported a significant reduction in mean birthweight in infants born to mothers who used smokeless tobacco during pregnancy. Meta analysis Seventeen studies involving 732689 participants were included in the meta-analysis, which is shown in Fig. 2 . ( 20 – 23 , 27 , 30 , 31 , 33 – 42 ) Other studies from this review were not included due to the provision of insufficient data for meta-analysis to be performed. The probability of low birth weight infants was greater in those women who consumed smokeless tobacco during pregnancy as compared to those who did not consume any tobacco products during pregnancy. The overall pooled estimate under the random effects model showed that there was a statistically significant association (OR = 1.91 [1.38, 2.65], P < 0.0001);) between maternal smokeless tobacco use during pregnancy and low birth weight. Smokeless tobacco users were almost twice as likely to have low birth weight infants as compared to non tobacco users. The test for heterogeneity produced Tau square of 0.37, I 2 = 95%, test for overall effect z = 3.91, (P < 0.0001)). This demonstrates a high level of heterogeneity between studies. The highest risk estimates observed were (OR = 67.90 [37.39, 123.30]), in a study conducted in India, which evaluated the effects of maternal mishri consumption during pregnancy on birth weight. ( 41 ) However, the wide CIs suggest that this effect estimate may be due to factors such as the small sample size of the study which decrease its reliability. Subgroup analysis was performed for five studies for betel nut ( 21 , 22 , 31 , 36 , 38 ), two studies for betel quid ( 33 , 37 ), three studies for khat ( 23 , 27 , 39 ), and four studies for mishri users, as shown in Fig. 3 . ( 35 , 40 – 42 ) Subgroup analysis could not be performed for snuff users. ( 17 , 20 , 25 , 28 , 29 , 32 , 44 ) This is because only one study provided sufficient data on snuff use and low birth weight to be included in the meta analysis. ( 20 ) The results of the subgroup analysis varied based on type of smokeless tobacco. Our analysis found nearly eleven times greater probability of low birth weight in infants of mothers who consumed mishri during pregnancy (OR = 10.98 [2.03, 59.34], P 0.05), betel quid (OR = 1.51 [0.47, 4.89], P > 0.05) or khat (OR = 1.04 [0.49, 2.21], P < 0.001) users. Although subgroup analysis for khat users showed that P < 0.001, the results are not statistically significant. This is likely due to inadequate pooled sample size of the included studies and the influence of confounding factors. Most of the studies are aggregated towards the centre of the funnel plot (see Fig. 4 and Fig. 5 ), which is symmetrical on visual inspection, indicating that there was no publication bias in this meta analysis. Discussion In this meta-analysis, we aimed to quantify the effect of maternal smokeless tobacco use during pregnancy on low birth weight of infants and our review suggests that there is a significant association between the same. These results may not present the true picture and may be underestimated due to the existence of many potential confounding factors such as the maternal age, socio-economic background, other substance abuse, malnutrition, genetics, preterm birth, environmental factors like housing, and lack of access to adequate health care services. Additionally, countries which do not have the birthweight in national data sources have missing or incomplete information on newborns’ birthweight. This review found that there is a significant association between maternal smokeless tobacco use and low birth weight of infants, as well as reduction in mean birth weight. These findings are in agreement with the previous review conducted by England et al in 2010 who found that smokeless tobacco use in pregnant women was associated with a significant reduction in birth weight in both low income and high-income countries. ( 48 , 49 ) Although there are few published studies on the prevalence of smokeless tobacco use in pregnant women, data suggests that use in these populations is generally higher in low income countries and in vulnerable communities within high income countries. ( 48 , 49 ) For instance, traditional forms of smokeless tobacco are used by Indigenous populations such as use of pituri in Australia ( 18 , 50 ) and iqmik in the USA ( 24 ). There is evidence that pituri has nicotine content as high as 11mg/g and the addition of highly alkaline wood ash raises its pH. ( 51 , 52 ) However, there is little research on these forms of smokeless tobacco and minority populations are also often under-represented in research studies, leading to a double-edged sword placing these populations at increased risk of poor maternal and foetal outcomes as a result of a lack of evidence based medical practice. There are many pathways through which nicotine consumed via smokeless tobacco during pregnancy may influence birth weight of infants. Nicotine in the bloodstream produces both generic reproductive and pregnancy-specific biphasic responses, transitioning from initial simulation to depression in a dose-dependent and cumulative manner. ( 53 ). Moreover, nicotine can transit from the systemic circulation into the placenta, and this has been evidenced through studies which found higher nicotine ratios in the umbilical venous and arterial cord bloods than in maternal serum ( 54 ) as well as nicotinic acetylcholine receptor (nAChR) binding in the developing and immature foetus. ( 55 ) This suggests that nicotine may exert its effects through both maternal and foetal biochemical pathways. There are varying levels of nicotine in different smokeless tobacco products, which suggests that some may pose greater risk. Studies have found that chewing tobacco products contained about 3.4 to 39.7mg/g of nicotine, while snuff products contained 4.7 to 24.8mg/g. ( 56 ) Studies conducted in India report a 100-200gm reduction in birth weight and an excess of preterm deliveries among Indian women who chewed tobacco during their pregnancy as compared to non tobacco users.( 57 , 58 ) Moreover, studies reported that Indian women who used mishri during their pregnancy had nearly three times greater risk of getting low birth weight babies ( 35 , 59 ). Khat leaves are chewed for their euphoric and stimulant properties. The mechanism behind the effect of khat on birth-weight is not known. However, one of the active substances in khat, d-norpseudoephedrine, has been shown to adversely affect the placental blood circulation, particularly if it is already impaired Khat also has an anorectic effect, which could lead to reduction in food intake by the pregnant woman and thus contribute to low birth weight ( 60 , 61 ). Maternal betel and areca nut chewing may exert its harmful effects through similar mechanisms. Animal models have shown that prenatal areca nut chewing has embryotoxic and teratogenic effects ( 62 ). Meanwhile a human study found that it is associated with focal inflammatory changes in the placental amniochorial membranes as well as decreased median diameter of blood vessels supplying placental villi on both the maternal and foetal surfaces ( 63 ). Our findings have wider clinical and public health implications. Public health campaigns to promote awareness about the negative effects of smokeless tobacco in women of childbearing age and education of both males and females by healthcare workers in the primary care setting will aid in promoting smokeless tobacco cessation prior to pregnancy. There is evidence to suggest that various forms of smokeless tobacco cessation programs including behavioural interventions, quit lines and pharmacotherapy such as varenicline and nicotine lozenges are cost-effective and highly efficacious in aiding patients to quit smoking. ( 64 ) Online support groups within a community can be set up to express solidarity and conviviality. Doctors, midwives and nurses can expedite early tobacco use cessation, and educate patients about the potential harms to the foetus. It may also be beneficial to provide additional monitoring in the form of ultrasounds and/or antenatal clinic appointments to mothers who use smokeless tobacco to detect infants who may be small for gestational age and at risk of low birth weight. Such infants may also need to be monitored more closely after birth, which poses an added cost to the healthcare system which is already burdened in many countries where smokeless tobacco use has high prevalence, particularly in South Asia. Limitations Though most of the studies were of fair quality (see Table 2 ), they differed in frequency, duration, different mixtures and administration practices of smokeless tobacco use. Different types of smokeless tobacco may contain varying levels of nicotine and additives, adding to the heterogeneity of the data studied. In fact, some forms of smokeless tobacco included in this review pose unknown and apparently higher risk because they are not actually even tobacco, or the tobacco content is a minor ingredient in what is primarily betel nut, slaked lime, ash or other plant matter or spices. ( 65 ) Self-reported data regarding the use of smokeless tobacco during pregnancy was collected via interviews and hospital records in all the included studies. Consequently, there a high risk of recall bias and performance bias in these studies since none of the studies reported any biochemical/objective measurements that were performed to ascertain tobacco use. Moreover, statistical adjustments for confounding factors were not made in fourteen ( 18 , 35 – 45 , 47 , 57 ) of the included studies. Moreover, most of the studies did not evaluate and exclude participants who consumed both smoking and smokeless tobacco, which may be a confounding factor. Only sixteen ( 17 , 19 – 33 ) studies included in this review adjusted for confounding factors which are a significant consideration affecting the reliability of these results given that it is established that many biopsychosocial factors can influence birth weight. Smokeless tobacco use in some of the included studies was concurrent with cigarette smoking and other risk factors, hence it is challenging to ascertain whether differences in birth weight are attributable to the smokeless tobacco use itself. This review highlights the need for further research to investigate the association between various forms of maternal smokeless tobacco use and low birth weight infants. None of the studies reported a quantified measure of exposure, most did not quantify frequency of smokeless tobacco use, and there are no studies which compare the effects of different forms of smokeless tobacco use. Consequently, a dose response relationship cannot be evaluated. Further research and quality observational studies are needed to strengthen this evidence base. It would be beneficial to include objective, quantitative measures of maternal tobacco consumption such as maternal and neonatal urinary and blood cotinine levels in further studies to better evaluate this association and establish the presence of dose response relationship. ( 66 ) Conclusion The adverse effects of smokeless tobacco found in this review highlights the need for policies which focus on primary prevention of smokeless tobacco use. Pregnant women should be provided with intensive education, counselling and resources regarding quitting or cutting down smokeless tobacco use to improve both maternal and child health outcomes. However, this is a challenging matter due to the addictive nature of tobacco. Declarations Ethics approval and consent to participate: Not applicable Consent for publication: Not applicable Availability of data and materials: This is a systematic review and meta-analysis, and hence only draws upon secondary data collected from other studies, with no primary data included. The author Akanksha Mahajan should be contacted at the email address [email protected] if someone wants to request the data from this study. Competing interests: The authors do not have any conflict of interest. Funding: No funding was obtained to facilitate this research. Authors' contributions: A.M. contributed to conception and design. A.M. and B.G. contributed to data acquisition in the data extraction form. A.M. conducted the statistical analysis. A.M. and B.G. contributed to interpretation of results. A.M. and B.G. wrote the main manuscript text and prepared Tables 1-3. A.M. and B.G. critically reviewed the manuscript for important intellectual content. A.M. and B.G. read and approved the final manuscript. References UNICEF-WHO. Low birthweight estimates 2023 [ WHO. ICD-10: International statistical classification of diseases and related health problems - World Health Organization 2004 [Available from: http://apps.who.int/classifications/icd10/browse/2010/en. Department of Nutrition for Health and Development WHO. Global nutrition targets 2025: low birth weight policy brief. Geneva, Switzerland; 2014. Risnes KR, Vatten LJ, Baker JL, Jameson K, Sovio U, Kajantie E, et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis. International Journal of Epidemiology. 2011;40(3):647-61. de Onis M, Onyango AW, Borghi E, Garza C, Yang H. 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Steyn K, De Wet T, Saloojee Y, Nel H, Yach D. The influence of maternal cigarette smoking, snuff use and passive smoking on pregnancy outcomes: The Birth to Ten Study. Paediatric and Perinatal Epidemiology. 2006;20(2):90-9. Yang M-S, Lee C-H, Chang S-J, Chung T-C, Tsai E-M, Ko AM-J, et al. The effect of maternal betel quid exposure during pregnancy on adverse birth outcomes among aborigines in Taiwan. Drug and alcohol dependence. 2008;95(1-2):134-9. Charlette L, Barik S, Malakar A. Incidence and determinants of low birth weight in a tertiary hospital at South Andaman: a prospective study. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2022;12:206. Krishnamurthy S, Joshi S. Gender differences and low birth weight with maternal smokeless tobacco use in pregnancy. Journal of Tropical Pediatrics. 1993;39(4):253-4. Senn M, Baiwog F, Winmai J, Mueller I, Rogerson S, Senn N. Betel nut chewing during pregnancy, Madang province, Papua New Guinea. Drug and Alcohol Dependence. 2009;105(1-2):126-31. Wang S-C, Lee M-C. Effects of age, ethnicity and health behaviours on the prevalence of adverse birth outcomes in Taiwan. Journal of biosocial science. 2012;44(5):513-24. de Costa C, Griew AR. Effects of betel chewing on pregnancy outcome. The Australian & New Zealand journal of obstetrics & gynaecology. 1982;22(1):22-4. Eriksson M, Ghani NA, Kristiansson B. Khat-chewing during pregnancy-effect upon the off-spring and some characteristics of the chewers. East African medical journal. 1991;68(2):106-11. Pratinidhi A, Gandham S, Shrotri A, Patil A, Pardeshi S. Use of 'Mishri' A smokeless form of tobacco during pregnancy and its perinatal outcome. Indian Journal of Community Medicine. 2010;35(1):14-8. Pratinidhi A, Ganganahalli P, Kakade SV. Untoward obstetric outcome among smokeless tobacco (ST - Mishri) users in western Maharashtra. Bangladesh Journal of Medical Science. 2014;13(4):401-5. Ganganahalli P, Pratinidhi A, Patil J, Kakade SV. Correlation of cotinine levels with use of smokeless tobacco (Mishri) among pregnant women and anthropometry of newborn. Journal of Clinical and Diagnostic Research. 2017;11(3):LC16-LC9. Abdul Ghani N, Eriksson M, Kristiansson B, Qirbi A. The influence of khat-chewing on birth-weight in full-term infants. Social science & medicine (1982). 1987;24(7):625-7. Rygh E, Gallefoss F, Grøtvedt L. Trends in maternal use of snus and smoking tobacco in pregnancy. A register study in southern Norway. BMC Pregnancy and Childbirth. 2019;19(1). Verma RC, Chansoriya M, Kaul KK. Effect of tobacco chewing by mothers on fetal outcome. Indian pediatrics. 1983;20(2):105-11. Krishna K. Tobacco chewing in pregnancy. British Journal of Obstetrics and Gynaecology. 1978;85(10):726-8. Sulistiyani S, Darmawati AT, Setiani O. Correlation between local-specific traditions of women agricultural workers and the Incidence of low birth weight in South Metro Sub-District, Metro City, Lampung Province, Indonesia. Annals of Tropical Medicine and Public Health. 2019;22(11). England LJ, Kim SY, Tomar SL, Ray CS, Gupta PC, Eissenberg T, et al. Non-cigarette tobacco use among women and adverse pregnancy outcomes. Acta Obstetricia et Gynecologica Scandinavica. 2010;89(4):454-64. Ratsch A, Bogossian F, Burmeister EA, Ryu B, Steadman KJ. Higher blood nicotine concentrations following smokeless tobacco (pituri) and cigarette use linked to adverse pregnancy outcomes for Central Australian Aboriginal pregnancies. BMC Public Health. 2022;22(1):2157. Fleming J, Watson C, McDonald D, Alexander K. Drug use patterns in Northern Territory Aboriginal communities 1986-1987. Drug Alcohol Rev. 1991;10(4):367-80. Moghbel N, Ryu B, Cabot PJ, Steadman KJ. In vitro cytotoxicity of Nicotiana gossei leaves, used in the Australian Aboriginal smokeless tobacco known as pituri or mingkulpa. Toxicology Letters. 2016;254:45-51. Moghbel N, Ryu B, Ratsch A, Steadman KJ. Nicotine alkaloid levels, and nicotine to nornicotine conversion, in Australian Nicotiana species used as chewing tobacco. Heliyon. 2017;3(11). Mello NK. Hormones, nicotine, and cocaine: clinical studies. Horm Behav. 2010;58(1):57-71. Luck W, Nau H. Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers. The Journal of pediatrics. 1985;107(5):816-20. Jacob N, Golmard J-L, Berlin I. Fetal exposure to tobacco: nicotine and cotinine concentration in amniotic fluid and maternal saliva. The Journal of Maternal-Fetal & Neonatal Medicine. 2017;30(2):233-9. Djordjevic MV, Doran KA. Nicotine content and delivery across tobacco products. Handb Exp Pharmacol. 2009(192):61-82. Krishna K. Tobacco chewing in pregnancy. Br J Obstet Gynaecol. 1978;85(10):726-8. Gupta PC, Subramoney S. Smokeless tobacco use, birth weight, and gestational age: population based, prospective cohort study of 1217 women in Mumbai, India. Bmj. 2004;328(7455):1538. Pratinidhi A, Gandham S, Shrotri A, Patil A, Pardeshi S. Use of 'Mishri' A Smokeless form of Tobacco During Pregnancy and its Perinatal Outcome. Indian J Community Med. 2010;35(1):14-8. Abdul Ghani N, Eriksson M, Kristiansson B, Qirbi A. The influence of khat-chewing on birth-weight in full-term infants. Soc Sci Med. 1987;24(7):625-7. Khawaja M, Al-Nsour M, Saad G. Khat (Catha edulis) chewing during pregnancy in Yemen: findings from a national population survey. Matern Child Health J. 2008;12(3):308-12. Sinha A, Rao AR. Embryotoxicity of betel nuts in mice. Toxicology. 1985;37(3-4):315-26. García-Algar O, Vall O, Alameda F, Puig C, Pellegrini M, Pacifici R, et al. Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes. Arch Dis Child Fetal Neonatal Ed. 2005;90(3):F276-7. Nethan ST, Sinha DN, Chandan K, Mehrotra R. Smokeless tobacco cessation interventions: A systematic review. Indian J Med Res. 2018;148(4):396-410. Glover M, Phillips CV. Potential effects of using non-combustible tobacco and nicotine products during pregnancy: a systematic review. Harm Reduction Journal. 2020;17(1):16. Benowitz NL, Dains KM, Dempsey D, Yu L, Jacob P, III. Estimation of Nicotine Dose after Low-level Exposure Using Plasma and Urine Nicotine Metabolites. Cancer Epidemiology, Biomarkers & Prevention. 2010;19(5):1160-6. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1Searchstrategy.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3800566","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264695115,"identity":"ff3deea2-e7e7-4f6c-ae63-e5d39108f2ea","order_by":0,"name":"Akanksha 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3","display":"","copyAsset":false,"role":"figure","size":802664,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analyses of the effect of maternal smokeless tobacco consumption compared with no tobacco consumption during pregnancy on risk of low birth weight in offspring\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3800566/v1/fecbdcaa404cb13ede499e50.png"},{"id":49128219,"identity":"dda43178-4029-4d6d-93e3-ad802ac98d17","added_by":"auto","created_at":"2024-01-03 15:05:32","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":68009,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFunnel plot of all studies included in this meta 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07:11:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2567072,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3800566/v1/dff2f85b-f0d4-4512-8b1a-01fc0a929cbd.pdf"},{"id":49128222,"identity":"aeefe941-303c-4e66-a2ab-e7d9d1e2cf2f","added_by":"auto","created_at":"2024-01-03 15:05:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13864,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1Searchstrategy.docx","url":"https://assets-eu.researchsquare.com/files/rs-3800566/v1/0c7f697e0e3eba150fbb10d3.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The invisible enemy: a systematic review and meta-analysis of maternal smokeless tobacco use as a risk factor for low birth weight","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe prevalence of low birth weight infants in a population is an important indicator of complex public health issues including long term maternal malnutrition, ill health and poor antenatal health care. Of the 19.8\u0026nbsp;million low birthweight babies born in 2020, over 40% were born in South Asia. (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e) Low birth weight is defined as per the World Health Organisation (WHO) International Classification of Diseases (ICD): a birth weight less than 2500 grams (ICD P07.1 birth weight\u0026thinsp;\u0026lt;\u0026thinsp;2,500g [1,000\u0026ndash;2,499 g]). (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e) It is not only a predictor of neonatal mortality and morbidity, but also increases the risk of stunted growth, diminished cognitive development and chronic disease later in life. (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e) Moreover, it is a primary outcome indicator in the core set of indicators for the Global Nutrition Monitoring Framework; and more than 90% of countries are off track to meet the 2030 low birth weight target as set by UNICEF. (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eAlthough cigarette smoking is the most common form of tobacco use globally, smokeless tobacco is consumed by over 300\u0026nbsp;million people worldwide and is a growing public health concern. Geographically, \u0026gt; 85% of the smokeless tobacco-related burden was in South and Southeast Asia, and in 2017, an estimated 2.5\u0026nbsp;million disability adjusted life years (DALYs) and 90,791 lives were lost worldwide due to cancers that can be attributed to smokeless tobacco. (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e) Smokeless tobacco products can be found in many forms in different regions around the world, which vary in their preparation, method of use and components. In developed countries, common forms of consumption include snuff (finely ground dry or moist tobacco inhaled nasally) in Sweden, chewing tobacco (dried tobacco leaves) in the United States of America and pituri (chewed smokeless tobacco) amongst indigenous Australian populations. However, in developing countries, tobacco is usually chewed with other ingredients, such as betel (areca) nut, betel leaf, and lime (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e). Other forms of smokeless tobacco in developing countries include mishri which is roasted ground tobacco and gutkha which is a mixture of tobacco with slaked lime, areca nut, acacia plant extract and spices.\u003c/p\u003e\n\u003cp\u003eWhile smokeless tobacco does not expose users to the toxins produced through burning tobacco and paper, there is increasing evidence to demonstrate that tobacco components such as nicotine are toxicogenic and may increase risk of negative maternal-foetal outcomes if consumed during pregnancy. (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e) Nicotine present in smokeless tobacco products can be absorbed in two forms: protonated and unprotonated; and it has been shown that unprotonated/free nicotine, the amount of which is affected by the pH of the tobacco product, can effectively cross cell membranes. (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e) Metabolism of nicotine in the human body gives rise to tobacco specific N-nitrosomines (TSNAs) which have been classified as a Group 1 carcinogen. (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e) Moreover, nicotine can impair retinoic acid signalling and cell differentiation, and induce a stress reaction or pro-inflammatory response that inhibits the agonistic action of retinoic acid, which is important for embryonic development. (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e) Along with nicotine, there are up to 50 other harmful compounds found in tobacco which may impair foetal development by inducing both oxidative and endoplasmic reticulum stress responses in placental trophoblastic cells. (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eThe use of smokeless tobacco is very common amongst women as it easily available, socially culturally and ceremonially accepted along with the misconception that it is relatively less harmful as compared to smoking. (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e) Some forms of smokeless tobacco such as betel nut are chewed into a mass (known as a quid) and retained behind the lip in the buccal space for extended durations. Previous studies have shown that smokeless tobacco use may be associated with higher levels of nicotine entering the systemic circulation via this route as compared to smoking, resulting in more potent harmful effects. (\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eAlthough there have been observational studies which investigate smokeless tobacco use and its implications on pregnancy and birth outcomes, the evidence is limited and findings vary. (\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e) It is necessary to synthesise this information to facilitate evidence-based practice when advising women about the risks of smokeless tobacco use. This systematically review aims to investigate the currently available evidence on the association between maternal smokeless tobacco and low birth weight infants, and to assess and summarise the main features, methodological quality and results of the included studies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study is registered at the International Register of Prospective Systematic Reviews (PROSPERO) under the CRD number 42022381144. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eEligibility Criteria\u003c/p\u003e\n\u003cp\u003eAll observational studies (case-control, cohort and cross-sectional) that examined the relationship between maternal smokeless tobacco use and low birth weight of infants were included. Females in any healthcare setting were considered. Smokeless tobacco of at least one form such as snuff, betel nut, gutka,, mishri, pituri and khat, with or without additives, used in any amount or frequency, during or at some time during pregnancy was considered. Concurrent use of smoking tobacco was excluded from this review.\u003c/p\u003e\n\u003cp\u003eSearch methods\u003c/p\u003e\n\u003cp\u003eThe literature search was conducted from December 2022 to January 2023 using the following electronic databases: Medline (via PubMed), Embase, Scopus, CINAHL. An additional file shows the search strategy, including search terms and Boolean operators used, in more detail (see Additional file 1). There were no date or language restrictions applied. Reference lists from the selected studies and grey literature were also hand searched, and authors were contacted for unpublished studies.\u003c/p\u003e\n\u003cp\u003eDuplicate studies were excluded using Endnote X9. Subsequently, two reviewers (AM and BG) independently reviewed the titles and abstracts of studies. Any disagreements were settled by consensus between the authors. The full texts of all remaining studies were obtained and evaluated using predetermined inclusion and exclusion criteria.\u003c/p\u003e\n\u003cp\u003eData extraction\u003c/p\u003e\n\u003cp\u003eA standardised data sheet was prepared and used to extract the following data from the studies: title, first author\u0026rsquo;s name, year of publication, country of the study, time frame of study, study design, sample characteristics (sample size, number of cases/exposed and controls/unexposed), definition of smokeless tobacco and low birth weight, duration of follow up in cohort studies, adjustment for confounding, and the estimated risk with confidence intervals. The authors (AM and BG) independently performed the data extraction and resolved any doubts through consensus.\u003c/p\u003e\n\u003cp\u003eQuality assessment\u003c/p\u003e\n\u003cp\u003eThe methodological quality of included studies was assessed using the validated Newcastle-Ottawa Scale. This scale uses a \u0026lsquo;star system\u0026rsquo; and includes eight items clustered into three broad domains: the selection of the study groups; comparability of the groups; and the ascertainment of the outcome of interest. (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eData synthesis\u003c/p\u003e\n\u003cp\u003eEach study was individually analysed to find quantitative measures of effect for the exposure and outcome, such as odds ratios and relative risk. The odds ratio was calculated by the authors (AM and BG) when these were not included in the published study, but adequate data was provided for calculation. All statistical analyses, including meta-analysis of studies examining the association between low birth weight, were performed using Review Manager (RevMan) version 5.3. (\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e) Data from studies with the same outcome (low birth weight defined as \u0026lt;\u0026thinsp;2500grams) was pooled using forest plots. The effects measure used was odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data. A random effects model for heterogeneity was employed which generates results that generalize to a range of populations and study designs, with a p value less than 0.05 considered as significant. Heterogeneity between studies was evaluated for each analysis using Cochran\u0026rsquo;s Q statistic (measure of weighted square deviations), with N-1 degrees of freedom (where N is the number of studies), between studies variance (T2), and ratio of the true heterogeneity to total observed variation (\u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e). By calculating \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e values, an \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e less than 25% was deemed to have low heterogeneity, 25\u0026ndash;75% to have medium heterogeneity, and greater than 75% to have high heterogeneity. The effect size of each study was demonstrated by generating forest plots. The data points for the random effects meta-analysis were made up of the logarithms of the effect sizes and their corresponding standard errors. Subgroup analysis was performed based on the type of smokeless tobacco consumed by study participants during pregnancy (betel nut, khat, mishri, betel quid). Publication bias was assessed through visual inspection of the symmetry of funnel plots, which were constructed by plotting the logarithmically transformed ORs against the standard error of the associated log OR. Since the confounding variables used in the multivariate regression model varied significantly between studies, unadjusted effect estimates were used in the meta-analysis, which were calculated using RevMan.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe search yielded a total of 292 studies (176 from EMBASE, 62 from PUBMED, 51 from Scopus and 3 from CINAHL). After duplicates were removed and the title and abstract of studies were reviewed; 42 studies were considered potentially eligible for this review and assessed as full-texts based on predetermined inclusion and exclusion criteria. There were 11 articles excluded from this review, and 31 articles included, further details of which are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCharacteristics of included studies\u003c/p\u003e \u003cp\u003eThe characteristics of the 31 studies included in this review such as location, sample size, definitions of outcome, type of smokeless tobacco, and quantitative measures of outcome are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were eighteen studies from Asia (ten from India, three from Yemen, two from Taiwan, one each from Pakistan, Thailand and Indonesia), six studies from Europe (five from Sweden and one from Sweden and Norway), four studies from Oceania (two from Papua New Guinea, one from Palau and one from Australia), two studies from Africa (one from Ethiopia and one from South Africa), and one study from the United States of America. This review included a total sample size of 3,338,826 pregnant women. The largest study was from Sweden with a sample size of 1,070,013 women (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), while the smallest study was from Australia with a sample size of 50 pregnant women. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) The predominant form of smokeless tobacco used in Ethiopian and Yemen studies was khat; whereas in other countries from Asia and Oceania it was betel/areca nut; and in India it was mishri. Snuff was used by both the European and South African subjects, while iqmik and pituri was used by subjects in the study from USA and Australia respectively. None of the studies reported a quantified measure of exposure, and most did not quantify frequency of smokeless tobacco use.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuality assessment of included studies as per the Newcastle-Ottawa Scale (referred to in line 252)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (maximum 9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eSelection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eComparability\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRepresentativeness\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelection of non-exposed cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAscertainment of exposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDemonstration that outcome of interest was not present at start of study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAssessment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDuration of follow up (adequate follow up minimum 9 months for outcome to occur)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eAdequacy of follow up (\u0026gt;\u0026thinsp;80%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ghani et al, 1987)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ali et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Baba et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Berger et al, 2016)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Chue et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Charlette et al, 2022)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(de Costa and Griew, 1982)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Demelash et al, 2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(England et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(England et al, 2003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Eriksson et al, 1991)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ganganahalli et al, 2017)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Gupta and Subramoney, 2004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Idris et al, 2020)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Juarez and Merlo, 2013)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Kreyburg et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Krishna, 1978)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Krishnamurthy and Joshi, 1993)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Madley-Dowd et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Mallick, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ome-Kaius et al, 2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Pratinidhi et al, 2010)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Pratinidhi et al, 2014)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ratsch et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Rygh et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Senn et al, 2009)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Steyn et al, 2006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Sulistiyani et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Verma et al, 1983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Wang and Lee, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Yang et al, 2008)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuality assessment of included studies as per the Newcastle-Ottawa Scale (referred to in line 252 of manuscript)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (maximum 9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eSelection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eComparability\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRepresentativeness\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelection of non-exposed cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAscertainment of exposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDemonstration that outcome of interest was not present at start of study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAssessment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDuration of follow up (adequate follow up minimum 9 months for outcome to occur)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eAdequacy of follow up (\u0026gt;\u0026thinsp;80%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ghani et al, 1987)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ali et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Baba et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Berger et al, 2016)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Chue et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Charlette et al, 2022)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(de Costa and Griew, 1982)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Demelash et al, 2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(England et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(England et al, 2003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Eriksson et al, 1991)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ganganahalli et al, 2017)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Gupta and Subramoney, 2004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Idris et al, 2020)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Juarez and Merlo, 2013)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Kreyburg et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Krishna, 1978)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Krishnamurthy and Joshi, 1993)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Madley-Dowd et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Mallick, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ome-Kaius et al, 2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Pratinidhi et al, 2010)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Pratinidhi et al, 2014)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ratsch et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Rygh et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Senn et al, 2009)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Steyn et al, 2006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Sulistiyani et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Verma et al, 1983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Wang and Lee, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Yang et al, 2008)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eQuality assessment\u003c/p\u003e \u003cp\u003eThere was high variation in the methodological quality of included studies as summarised in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Self-reported data regarding the use of smokeless tobacco during pregnancy was collected via interviews and hospital records in all the included studies. Consequently, there a high risk of recall bias and performance bias in these studies since none of the studies reported any biochemical/objective measurements that were performed to ascertain tobacco use. Moreover, statistical adjustments for confounding factors were not made in fifteen of the included studies. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of studies which explored the association between maternal smokeless tobacco use during pregnancy and birth weight (referred to in line 270)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRegion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime frame\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy design\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDefinition of birth weight outcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSmokeless tobacco type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDefinition of exposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSample population\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNumber of exposed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNumber of non-exposed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eOdds ratio and 95% CI for low birth weight\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Abdul Ghani et al, 1987)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYemen Arab Republic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birth weight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ekhat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself-reported khat use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ali et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePakistan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2013\u0026ndash;2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003egutkha\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003egutkha\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Baba et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1999\u0026ndash;2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esmall for gestational age (birthweight\u0026thinsp;\u0026gt;\u0026thinsp;2 standard deviations below the mean weight for gestational age)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eused snuff 3 months before pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e945371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e23,514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e663649\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.26 (1.09\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Berger et al, 2016)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePalau\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2007\u0026ndash;2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported at least 1 use of chewing betel nut with tobacco during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e893\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e278\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.4 (1.0\u0026ndash;6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Charlette et al, 2022)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003esmokeless tobacco use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e463\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.58 (1.1\u0026ndash;6.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Chue et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThailand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1997\u0026ndash;2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported areca nut use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e9264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4963\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2722\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9091 (0.7694\u0026ndash;1.0742)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(de Costa and Griew, 1982)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePapua New Guinea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported history of betel consumption throughout pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.4227 (0.418\u0026ndash;2.4042)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Demelash et al, 2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEthiopia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecase control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ekhat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported khat chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e129 cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e258 controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6.4 (2.42\u0026ndash;17.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(England et al, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1997\u0026ndash;2005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eiqmik\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eiqmik or commercial chew consumption, based on data extracted from clinic records\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e4725\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e247\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(England et al, 2003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1999\u0026ndash;2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esmall for gestational age (birthweight\u0026thinsp;\u0026gt;\u0026thinsp;2 standard deviations below the mean weight for gestational age)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003esnuff use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e27762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11495\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.25 (0.72\u0026ndash;2.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Eriksson et al, 1991)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYemen Arab Republic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ekhat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ekhat chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e382\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.3302 (0.8495 to 2.0831)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ganganahalli et al, 2017)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emishri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eused mishri during pregnancy- self reported and case records\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Gupta and Subramoney, 2004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eused a smokeless tobacco product at least once a day for the past six months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e768\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Idris et al, 2020)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYemen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecase control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ekhat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ekhat chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e252\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.76 (1.06\u0026ndash;2.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Juarez and Merlo, 2013)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2002\u0026ndash;2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSwedish snus use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e938932\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e591690\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Kreyberg et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorway and Sweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2014\u0026ndash;2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported snus use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Krishna, 1978)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1971\u0026ndash;1972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ekeeping a wad of locally grown and cured tobacco in the mouth for 8 to 10 hours per day during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Krishnamurthy and Joshi, 1993)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported maternal use of tobacco, mostly mishri, during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3.2(1.5\u0026ndash;6.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Madley-Dowd et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1999\u0026ndash;2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esmall for gestational age (birthweight\u0026thinsp;\u0026gt;\u0026thinsp;two standard deviations below the mean weight for gestational age according to the gender-specific Swedish fetal growth curves)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported snus use at any time during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1181264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14665\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1E\u0026thinsp;+\u0026thinsp;06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.05(0.94\u0026ndash;1.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Mallick, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2015\u0026ndash;2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ematernal tobacco chewing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e81869\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e53953\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.163 (1.058\u0026ndash;1.227]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ome-Kaius et al, 2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePapua New Guinea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2009\u0026ndash;2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported areca nut chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1459\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.94 (0.65\u0026ndash;1.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Pratinidhi et al, 2010)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2003\u0026ndash;2005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emishri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported mishri use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e705\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.4026 (1.5206\u0026ndash;3.7963)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Pratinidhi et al, 2014)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emishri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported mishri use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e67.9016 (37.3926-123.3033)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Ratsch et al, 2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epituri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported pituri use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.75 (0.3152\u0026ndash;9.7161)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Rygh et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorway\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2012\u0026ndash;2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported snus use during the third trimester of pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e102011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Senn et al, 2009)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2007\u0026ndash;2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecross sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ebetel nut chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.9 (0.4\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Steyn et al, 2006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSouth Africa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esnuff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported snuff use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1593\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Sulistiyani et al, 2019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndonesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecross sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003esmokeless tobacco use during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Verma et al, 1983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1978\u0026ndash;1979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean birthweight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eunspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003etobacco chewing during pregnancy, minimum 150 mg/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Wang and Lee, 2012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTaiwan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ebetel quid chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e24200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.368 (0.048\u0026ndash;2.841)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Yang et al, 2008)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTaiwan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2003\u0026ndash;2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow birth weight (\u0026lt;\u0026thinsp;2500g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ebetel nut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eself reported betel quid chewing during pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e464\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.40 (1.21\u0026ndash;4.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEffects of exposure\u003c/p\u003e \u003cp\u003eThirty-one studies included in this review were clinically and methodologically diverse. There were twenty-seven cohort studies, two case-control and two cross-sectional studies\u003c/p\u003e \u003cp\u003eincluded in this systematic review. Crude odds ratios were presented in only eleven (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34 CR35 CR36\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) of the included studies, and could be calculated by the authors using the data published for a further six studies. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan additionalcitationids=\"CR39 CR40\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) Relative risk was presented in two of the included studies. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) A statistically significant association between use of smokeless tobacco and low birth weight was reported in twelve of the studies. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) All of these studies defined low birth weight as \u0026lt;\u0026thinsp;2500 grams. The highest odds ratio [67.9016 (37.3926-123.3033)] was reported in the study conducted in 2014 by Pratinidhi et al. (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) Meanwhile, the lowest odds ratio [0.368 (0.048\u0026ndash;2.841)] was reported by Wang and Lee, although their results were not statistically significant. (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eA statistically significant reduction in mean birth weight was reported in maternal smokeless tobacco users in a further eleven studies. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e) On the contrary, four studies reported that there was no statistically significant difference in birth weight in infants born to mothers who used smokeless tobacco during pregnancy. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOut of all the studies included in this review, seven studies reported on snuff users (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), seven reported on betel nut users (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e), four reported on khat users (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e), three on mishri (\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e), one reported on gutka (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), iqmik (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) and pituri (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) users respectively, and seven did not specify the type of smokeless tobacco used by participants (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTwo studies on khat (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), two on mishri (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), one on snuff (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), one on betel quid (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) and none on areca nut, betel nut, pituri, iqmik or gutka reported a statistically significant association between maternal smokeless tobacco use and low birth weight. One study on khat (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e), three on snuff (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), one on mishri (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e), two on betel nut (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) and none on iqmik or pituri reported a significant reduction in mean birthweight in infants born to mothers who used smokeless tobacco during pregnancy.\u003c/p\u003e \u003cp\u003eMeta analysis\u003c/p\u003e \u003cp\u003eSeventeen studies involving 732689 participants were included in the meta-analysis, which is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. (\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) Other studies from this review were not included due to the provision of insufficient data for meta-analysis to be performed. The probability of low birth weight infants was greater in those women who consumed smokeless tobacco during pregnancy as compared to those who did not consume any tobacco products during pregnancy. The overall pooled estimate under the random effects model showed that there was a statistically significant association (OR\u0026thinsp;=\u0026thinsp;1.91 [1.38, 2.65], P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001);) between maternal smokeless tobacco use during pregnancy and low birth weight. Smokeless tobacco users were almost twice as likely to have low birth weight infants as compared to non tobacco users. The test for heterogeneity produced Tau square of 0.37, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;95%, test for overall effect z\u0026thinsp;=\u0026thinsp;3.91, (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)). This demonstrates a high level of heterogeneity between studies. The highest risk estimates observed were (OR\u0026thinsp;=\u0026thinsp;67.90 [37.39, 123.30]), in a study conducted in India, which evaluated the effects of maternal mishri consumption during pregnancy on birth weight. (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) However, the wide CIs suggest that this effect estimate may be due to factors such as the small sample size of the study which decrease its reliability.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSubgroup analysis was performed for five studies for betel nut (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e), two studies for betel quid (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), three studies for khat (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), and four studies for mishri users, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) Subgroup analysis could not be performed for snuff users. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e) This is because only one study provided sufficient data on snuff use and low birth weight to be included in the meta analysis. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) The results of the subgroup analysis varied based on type of smokeless tobacco. Our analysis found nearly eleven times greater probability of low birth weight in infants of mothers who consumed mishri during pregnancy (OR\u0026thinsp;=\u0026thinsp;10.98 [2.03, 59.34], P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, no statistically significant association with low birth weight was found for betel nut (OR\u0026thinsp;=\u0026thinsp;1.02 [0.84, 1.25], P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), betel quid (OR\u0026thinsp;=\u0026thinsp;1.51 [0.47, 4.89], P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) or khat (OR\u0026thinsp;=\u0026thinsp;1.04 [0.49, 2.21], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) users. Although subgroup analysis for khat users showed that P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, the results are not statistically significant. This is likely due to inadequate pooled sample size of the included studies and the influence of confounding factors.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMost of the studies are aggregated towards the centre of the funnel plot (see Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), which is symmetrical on visual inspection, indicating that there was no publication bias in this meta analysis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this meta-analysis, we aimed to quantify the effect of maternal smokeless tobacco use during pregnancy on low birth weight of infants and our review suggests that there is a significant association between the same. These results may not present the true picture and may be underestimated due to the existence of many potential confounding factors such as the maternal age, socio-economic background, other substance abuse, malnutrition, genetics, preterm birth, environmental factors like housing, and lack of access to adequate health care services. Additionally, countries which do not have the birthweight in national data sources have missing or incomplete information on newborns\u0026rsquo; birthweight.\u003c/p\u003e \u003cp\u003eThis review found that there is a significant association between maternal smokeless tobacco use and low birth weight of infants, as well as reduction in mean birth weight. These findings are in agreement with the previous review conducted by England et al in 2010 who found that smokeless tobacco use in pregnant women was associated with a significant reduction in birth weight in both low income and high-income countries. (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough there are few published studies on the prevalence of smokeless tobacco use in pregnant women, data suggests that use in these populations is generally higher in low income countries and in vulnerable communities within high income countries. (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e) For instance, traditional forms of smokeless tobacco are used by Indigenous populations such as use of pituri in Australia (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e) and iqmik in the USA (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). There is evidence that pituri has nicotine content as high as 11mg/g and the addition of highly alkaline wood ash raises its pH. (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e) However, there is little research on these forms of smokeless tobacco and minority populations are also often under-represented in research studies, leading to a double-edged sword placing these populations at increased risk of poor maternal and foetal outcomes as a result of a lack of evidence based medical practice.\u003c/p\u003e \u003cp\u003eThere are many pathways through which nicotine consumed via smokeless tobacco during pregnancy may influence birth weight of infants. Nicotine in the bloodstream produces both generic reproductive and pregnancy-specific biphasic responses, transitioning from initial simulation to depression in a dose-dependent and cumulative manner. (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e). Moreover, nicotine can transit from the systemic circulation into the placenta, and this has been evidenced through studies which found higher nicotine ratios in the umbilical venous and arterial cord bloods than in maternal serum (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e) as well as nicotinic acetylcholine receptor (nAChR) binding in the developing and immature foetus. (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e) This suggests that nicotine may exert its effects through both maternal and foetal biochemical pathways. There are varying levels of nicotine in different smokeless tobacco products, which suggests that some may pose greater risk. Studies have found that chewing tobacco products contained about 3.4 to 39.7mg/g of nicotine, while snuff products contained 4.7 to 24.8mg/g. (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eStudies conducted in India report a 100-200gm reduction in birth weight and an excess of preterm deliveries among Indian women who chewed tobacco during their pregnancy as compared to non tobacco users.(\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e) Moreover, studies reported that Indian women who used mishri during their pregnancy had nearly three times greater risk of getting low birth weight babies (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eKhat leaves are chewed for their euphoric and stimulant properties. The mechanism behind the effect of khat on birth-weight is not known. However, one of the active substances in khat, d-norpseudoephedrine, has been shown to adversely affect the placental blood circulation, particularly if it is already impaired Khat also has an anorectic effect, which could lead to reduction in food intake by the pregnant woman and thus contribute to low birth weight (\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMaternal betel and areca nut chewing may exert its harmful effects through similar mechanisms. Animal models have shown that prenatal areca nut chewing has embryotoxic and teratogenic effects (\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e). Meanwhile a human study found that it is associated with focal inflammatory changes in the placental amniochorial membranes as well as decreased median diameter of blood vessels supplying placental villi on both the maternal and foetal surfaces (\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur findings have wider clinical and public health implications. Public health campaigns to promote awareness about the negative effects of smokeless tobacco in women of childbearing age and education of both males and females by healthcare workers in the primary care setting will aid in promoting smokeless tobacco cessation prior to pregnancy. There is evidence to suggest that various forms of smokeless tobacco cessation programs including behavioural interventions, quit lines and pharmacotherapy such as varenicline and nicotine lozenges are cost-effective and highly efficacious in aiding patients to quit smoking. (\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e) Online support groups within a community can be set up to express solidarity and conviviality. Doctors, midwives and nurses can expedite early tobacco use cessation, and educate patients about the potential harms to the foetus. It may also be beneficial to provide additional monitoring in the form of ultrasounds and/or antenatal clinic appointments to mothers who use smokeless tobacco to detect infants who may be small for gestational age and at risk of low birth weight. Such infants may also need to be monitored more closely after birth, which poses an added cost to the healthcare system which is already burdened in many countries where smokeless tobacco use has high prevalence, particularly in South Asia.\u003c/p\u003e \u003cp\u003eLimitations\u003c/p\u003e \u003cp\u003eThough most of the studies were of fair quality (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e), they differed in frequency, duration, different mixtures and administration practices of smokeless tobacco use. Different types of smokeless tobacco may contain varying levels of nicotine and additives, adding to the heterogeneity of the data studied. In fact, some forms of smokeless tobacco included in this review pose unknown and apparently higher risk because they are not actually even tobacco, or the tobacco content is a minor ingredient in what is primarily betel nut, slaked lime, ash or other plant matter or spices. (\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSelf-reported data regarding the use of smokeless tobacco during pregnancy was collected via interviews and hospital records in all the included studies. Consequently, there a high risk of recall bias and performance bias in these studies since none of the studies reported any biochemical/objective measurements that were performed to ascertain tobacco use. Moreover, statistical adjustments for confounding factors were not made in fourteen (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e) of the included studies.\u003c/p\u003e \u003cp\u003eMoreover, most of the studies did not evaluate and exclude participants who consumed both smoking and smokeless tobacco, which may be a confounding factor. Only sixteen (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) studies included in this review adjusted for confounding factors which are a significant consideration affecting the reliability of these results given that it is established that many biopsychosocial factors can influence birth weight. Smokeless tobacco use in some of the included studies was concurrent with cigarette smoking and other risk factors, hence it is challenging to ascertain whether differences in birth weight are attributable to the smokeless tobacco use itself.\u003c/p\u003e \u003cp\u003eThis review highlights the need for further research to investigate the association between various forms of maternal smokeless tobacco use and low birth weight infants. None of the studies reported a quantified measure of exposure, most did not quantify frequency of smokeless tobacco use, and there are no studies which compare the effects of different forms of smokeless tobacco use. Consequently, a dose response relationship cannot be evaluated. Further research and quality observational studies are needed to strengthen this evidence base. It would be beneficial to include objective, quantitative measures of maternal tobacco consumption such as maternal and neonatal urinary and blood cotinine levels in further studies to better evaluate this association and establish the presence of dose response relationship. (\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e)\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe adverse effects of smokeless tobacco found in this review highlights the need for policies which focus on primary prevention of smokeless tobacco use. Pregnant women should be provided with intensive education, counselling and resources regarding quitting or cutting down smokeless tobacco use to improve both maternal and child health outcomes. However, this is a challenging matter due to the addictive nature of tobacco.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u0026nbsp;Not applicable\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u0026nbsp;Not applicable \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u0026nbsp;This is a systematic review and meta-analysis, and hence only draws upon secondary data collected from other studies, with no primary data included. The author Akanksha Mahajan should be contacted at the email address [email protected] if someone wants to request the data from this study.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u0026nbsp;The authors do not have any conflict of interest.\u003c/p\u003e\n\u003cp\u003eFunding:\u0026nbsp;No funding was obtained to facilitate this research.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions: A.M. contributed to conception and design. A.M. and B.G. contributed to data acquisition in the data extraction form. A.M. conducted the statistical analysis. A.M. and B.G. contributed to interpretation of results. A.M. and B.G. wrote the main manuscript text and prepared Tables 1-3. A.M. and B.G. critically reviewed the manuscript for important intellectual content. A.M. and B.G. read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUNICEF-WHO. Low birthweight estimates 2023 [\u003c/li\u003e\n\u003cli\u003eWHO. 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Cancer Epidemiology, Biomarkers \u0026amp; Prevention. 2010;19(5):1160-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3800566/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3800566/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eSmokeless tobacco use is a growing public health concern, with potential adverse implications for foetal outcomes if consumed during pregnancy. Birth weight is an important predictive measure for health outcomes of a child throughout their lifespan, from infancy through to adulthood. Although the association between maternal smoking and reduction in birth weight of infants has been studied extensively, it is unclear whether smokeless tobacco has similar effects. Hence, this review was conducted to determine whether an association exists between maternal smokeless tobacco consumption during pregnancy and birth weight of infants.\u003c/p\u003e\u003ch2\u003eAims and Methods\u003c/h2\u003e \u003cp\u003eSystematic literature search was performed in Medline (via PubMed), Embase, Scopus, and CINAHL with no restrictions on language or time until January 2023. All observational studies (case control, cohort and cross sectional) that examined the relationship between maternal smokeless tobacco use and low birth weight of infants were eligible for inclusion. The methodological quality of included studies was assessed using the Newcastle Ottawa Scale.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThirty-one studies were eligible for the review, including twenty-seven cohort studies, two case-control and two cross-sectional studies. These studies examined various forms of smokeless tobacco use including khat, betel/areca nut, mishri, snuff, iqmik and pituri. A statistically significant association between use of smokeless tobacco and low birth weight was reported in thirteen studies. An additional eleven studies reported a statistically significant reduction in mean birth weight in maternal smokeless tobacco users. Meta-analysis using a random effects model showed that there was a statistically significant association (OR\u0026thinsp;=\u0026thinsp;1.91 [1.38, 2.65], P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001); between maternal smokeless tobacco use during pregnancy and low birth weight. Subgroup analysis found a significant association between maternal mishri consumption during pregnancy and low birth weight (OR\u0026thinsp;=\u0026thinsp;10.98 [2.03, 59.34], P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but not betel nut, betel quid or khat.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis review found that there is a significant association between maternal smokeless tobacco use and low birth weight of infants, as well as reduction in mean birth weight independent of confounding variables. It is suggested that maternal use of smokeless tobacco should receive specific attention as a part of routine prenatal care.\u003c/p\u003e\u003ch2\u003eImplications\u003c/h2\u003e \u003cp\u003eThe results of this study highlight the need for further preventive public health campaigns to create awareness about the detrimental effects of smokeless tobacco on foetal outcomes patient education by healthcare workers in the primary care setting will aid in promoting smokeless tobacco cessation prior to pregnancy.\u003c/p\u003e","manuscriptTitle":"The invisible enemy: a systematic review and meta-analysis of maternal smokeless tobacco use as a risk factor for low birth weight","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 15:05:28","doi":"10.21203/rs.3.rs-3800566/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"03da96d5-d697-4c5f-b6df-2d59a8e1534d","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-02T07:03:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 15:05:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3800566","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3800566","identity":"rs-3800566","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}