Adherence to World Health Organisation guidelines for treatment of early onset neonatal sepsis in low-income settings; a cohort study in Nepal

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Wrammert This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-19505/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Sep, 2020 Read the published version in BMC Infectious Diseases → Version 2 posted 9 You are reading this latest preprint version Show more versions Abstract Background Neonatal sepsis is one of the major causes of death during the first month of life and early empirical treatment with injectable antibiotics is a life-saving intervention. Adherence to World Health Organisation guidelines on first line antibiotics is crucial to mitigate the risks of increased antimicrobial resistance. The aim of this paper was to evaluate if treatment of early onset neonatal sepsis in a low-income facility setting observe current guidelines and if compliance is influenced by contextual factors. Methods This cohort study used data on antimicrobial treatment of neonatal sepsis onset within 72 hours of life from 12 regional hospitals participating in a scale-up trial of a neonatal resuscitation quality improvement package intervention in Nepal. Infants treated according to guidelines were compared with those receiving other antimicrobials. A multiple logistic regression analysis adjusted for the intervention and time trend was applied. Results 1,564 infants with a preliminary diagnosis of early onset sepsis were included. A majority (74.9%) were treated according to guidelines and adherence was increasing over time. Infants born at larger facilities (adjusted Odds Ratio 5.6), those that were inborn (adjusted Odds Ratio 1.97) or belonging to a family of dis-advantaged caste (adjusted Odds Ratio 2.15) had higher odds for treatment according to guidelines. A clinical presentation of lethargy or tachypnoea was associated with adherence to guidelines. Conclusion Adherence to guidelines for antibiotic treatment of early neonatal sepsis was moderately high in this low-income setting. Odds for observing guidelines increased with facility size, for inborn infants and if the family belonged to a dis-advantaged caste. Cefotaxime was a common alternative choice when guidelines were not followed, highly relevant for the risk of increased antimicrobial resistance. Infectious Diseases Pediatrics Neonatal Sepsis Guideline Adherence Drug Resistance Microbial Socioeconomic Factors Figures Figure 1 Figure 2 Background The reduction of neonatal mortality globally continues and road maps like the Every Newborn Action Plan sets ambitious targets and milestones for 2030. Still, deaths during the first month of life continue to increase its proportion of total child mortality before five years of age (1). Invasive newborn infection is one of the major causes of death during the first month of life, especially in high mortality settings (2). As quality of care and universal health coverage improves world-wide, the availability of injectable antibiotics for infants with sepsis is improving (3). Empirical treatment of infants presenting with clinical signs of sepsis is a life-saving intervention, but the antimicrobial resistance (AMR) that follow, especially as a result of broad-spectrum antibiotic use, is threatening future progress (4, 5). It has been estimated that almost one third of the annual 690 000 neonatal deaths from sepsis are associated with AMR (6). Early onset sepsis (EOS) is defined as bacteraemia in the newborn occurring in the first 72 hours of life (7). Mainly caused by vertical infection from mother to infant, the proportion of EOS compared to late onset sepsis (LOS) has been rapidly decreasing in high-income countries (HIC) because of better Group B Streptococci control during pregnancy (8). The other common EOS pathogen in HIC is Escherichia Coli, also commonly infecting vertically from the mother. Studies on pathogen prevalence in low- and middle-income countries (LMIC) are few, but there is some evidence to suggest that Klebsiella species and Staphylococcus Aureus are more common, indicating horizontal infection (7). The higher number of potential pathogens in LMIC has led to an increased use of broader spectrum antibiotics for EOS, predominantly in south Asia (6). Although the panorama of pathogens differs between contexts, there has been no reason to change the World Health Organisation (WHO) guidelines for treatment of neonatal sepsis in health facilities. First choice is still Ampicillin or Benzylpenicillin for 7-10 days with 2 doses of Gentamicin (7). Also, in an effort to address the burden of AMR, the 20 th edition of the WHO Model List of Essential Medicines released in 2017 included three groups of antibiotics (9). ACCESS (affordable and safe antibiotics that should be widely available), WATCH (antibiotics with higher resistance potential recommended as first choice only for a few specific indications or as second choice), and RESERVE (antibiotics that should be restricted for use in specific patients when all other alternatives have failed). The only injectable first choices for EOS in the ACCESS group are Ampicillin and Benzylpenicillin together with Gentamicin as adjuvant. Apart from the time point of onset before 72 hours of age, there is no homogenic definition of EOS in the literature (10). Blood culture has been used as a golden standard to confirm sepsis but such laboratory evidence is seldom available in LMIC and risks of falsely negative cases has been described (11). Outside HIC settings, clinicians are generally left to depend only on clinical presentation to detect EOS cases in order to make decisions on empirical antibiotic treatment. WHO has listed symptoms that should be seen as red flags for neonatal sepsis; difficult to feed, lethargy, fast breathing, grunting, sub-costal recessions, fever, hypothermia and central cyanosis. All of those signs could however be present also without an infection, making the case definition difficult (12). The aim of this paper is to evaluate to what extent treatment of early neonatal sepsis in a low-income facility setting adhere to WHO guidelines and if compliance is influenced by contextual factors or clinical case presentation. Methods Data for this observational cohort study was collected during a large scale-up trial of a neonatal resuscitation quality improvement package in Nepal (13). The Nepal Perinatal Quality Improvement Project (NePeriQIP) was performed in 12 public second level delivery facilities during 18 months in 2017 and 2018. Data collection for the study presented in this paper stopped when the NePeriQIP ended. The registered trial (ISRCTN30829654) had a stepped-wedge cluster randomized controlled design with a quality improvement intervention targeting quality of care for neonatal resuscitation. The included facilities were of low-volume (>1,000 deliveries a year), medium-volume (>3,000 deliveries a year), and high-volume (>8,000 deliveries a year). One facility from each size group formed one out of totally four wedges (clusters). All facilities provided normal and assisted vaginal delivery along with caesarean section services. Labor units were led by nurse-midwives. For infants with complications, the large and medium sized facilities provided specialised sick newborn care units staffed by pediatricians while small size facilities cared for sick infants at the regular pediatric unit led by medical doctors. The intervention did not contain any education on management of neonatal sepsis. However, all facilities had implemented the Comprehensive newborn care training package for level II hospital care introduced by Department of health services in Nepal that conform with WHO guidelines for treatment of neonatal sepsis before the start of the study (14). For this study, infants referred for sick newborn care before 72 hours of age with a primary diagnosis of neonatal sepsis, early onset sepsis, pneumonia or acute respiratory infection were included. Antibiotics administered were registered and collected along with data on maternal and infant characteristics. EOS infants treated with Ampicillin or Benzylpenicillin were included in the guideline group and infants treated with all other antibiotics were included in the non-guideline group. Gentamicin was considered an adjuvant treatment used in both groups and thus did not affect the group designation. No follow-up after discharge was performed. An independent data collection team was established at each facility. Data collection was done in paper format and a central research office checked the forms for completeness. A standard operating protocol was applied for data management and quality assurance was done on a quarterly basis. General, maternal and infant factors were compared for the two groups using Chi-square and Fisher exact tests for categorical variables and student t-tests for continuous variables. Time trend in adherence to guidelines was analysed with linear regression using study month as an independent variable. Odds ratios for significant general characteristics and clinical signs were calculated using univariate logistic regression. A final multiple logistic regression model included all previously significant variables. All logistic regressions were adjusted for time trend and the NePeriQIP intervention. Missing data was excluded from analysis. Stata/IC 16.0 (StataCorp, TX, USA) was used for analysis. Statistical significance was set at p -values <0.05 and confidence intervals (CI) were reported at 95%. Results During the study period, 8,888 infants were referred for sick newborn care at the 12 facilities. A majority (70.3%) received injectable antibiotics during care, whereas a little more than one third received a primary diagnosis of sepsis upon admission. Of the sepsis cases, almost half were referred before 72 hours of age. Of those EOS cases (n=1564), 74.9% (n=1,172) were treated according to WHO guidelines and 22.6% (n=354) were not. For 2.4% (n=38) there was no information on antibiotics available (Figure 1). The proportion of EOS cases treated according to WHO guidelines varied over time with an increasing trend ( p =0.03) during the study (Figure 2). In the group of patients not treated according to guidelines, Cefotaxime (90%) was the most common antibiotic used, followed by Amikacin (6%), Cloxacillin (2%) and others (2%). Blood culture was only collected in less than 1% of the cases and no results from the cultures were available in the data. Table 1: General, maternal and infant factors for infants with early onset sepsis during the NePeriQIP 1 trial, by antibiotic treatment group; Guideline (n=1172) and Non-Guideline (n=354) Background characteristic Guideline n (valid %) Non-guideline n (valid %) p -value General factors Size of hospital Large (n=998) 870 (87.2) 128 (12.8) <0.01 Medium (n=467) 261 (55.9) 206 (44.1) Small (n=61) 41 (66.2) 20 (32.8) NePeriQIP trial 1 Baseline (n=467) 326 (69.8) 141 (30.2) <0.01 Intervention (n=970) 769 (79.3) 201 (20.7) Born at home 62 (6.5) 20 (6.1) 0.81 Inborn infants 719 (82.3) 211 (66.7) <0.01 Maternal factors Maternal age in years, mean (SD) 24.5 (4.8) 24.8 (0.27) 0.27 Disadvantaged caste 2 276 (23.6) 58 (16.4) <0.01 Caesarean section (elective & emergency) 47 (4.3) 21 (6.1) 0.16 Infant factors Admission weight, mean (SD) 2820 (612) 2841 (636) 0.58 Gestational age, mean (SD) 38.5 (2.7) 38.9 (2.9) 0.06 Apgar 5 min < 7 53 (8.8) 16 (7.7) 0.64 Outcome (death or referral to higher centre) 96 (8.4) 39 (11.3) 0.10 Missing data: Intervention (n=89); Born at home (n=242); Inborn (n=336); Caesarean section (n=89); Admission weight (n=31); Gestational age (n=616); Apgar 5 min (n=716); Outcome (n=39) 1 Nepal Perinatal Quality Improvement Project 2 Dalit and Muslim Guideline and non-guideline groups were compared regarding background characteristics. Facility size, the NePeriQIP intervention, inborn infants and belonging to a dis-advantaged caste were associated with treatment according to WHO guidelines. The rate of caesarean section was low in the EOS cohort but did not differ between groups. Death or referral to a higher centre was approximately 10% in the cohort but not different between treatment groups. (Table 1). For clinical signs, lethargy, tachypnoea, grunting, fever, cyanosis and breastfeeding infants were associated with treatment group (Table 2). Table 2: Clinical presentation at the newborn unit for infants with early onset sepsis, by antibiotic treatment group; Guideline (n=1172) and Non-Guideline (n=354) Characteristics of cases Guideline n (valid %) Non-guideline n (valid %) p -value Lethargy 167 (19.2) 39 (12.3) 60 breaths per minute) 357 (31.7) 61 (17.9) <0.01 Seizures 41 (4.6) 9 (2.8) 0.18 Grunting 134 (14.8) 13 (4.2) 38 degrees Celsius) 494 (44.4) 120 (35.5) <0.01 Hypothermia (<35.5 degrees Celsius) 9 (0.9) 4 (1.2) 0.75 1 Severe chest indrawing 27 (3.1) 3 (1.0) 0.06 1 Central cyanosis 31 (3.5) 3 (0.9) 0.02 1 Severe jaundice (palms and soles yellow) 14 (1.66) 4 (1.26) 0.79 1 Fisher exact test For variables associated with treatment according to guidelines, crude odds ratios were calculated and adjusted for time trend and the NePeriQIP intervention. There were higher odds of receiving treatment according to guidelines when born at a large facility and lower odds if born at a medium size facility. Infants belonging to a family of dis-advantaged caste or if the infant was inborn had higher odds of guideline treatment. For clinical signs, odds of treatment according to guidelines were higher if the infant presented with lethargy, tachypnoea, grunting or fever (Table 3). Table 3: Crude and adjusted odds for treatment of early neonatal sepsis according to World Health Organisation guidelines Background characteristic cOR (95% CI) aOR 1 (95% CI) p -value Large volume hospital 5.08 (3.95—6.55) 5.03 (3.85—6.60) <0.01 Medium volume hospital 0.21 (0.16—0.26) 0.21 (0.16—0.28) <0.01 Small volume hospital 0.61 (0.35—1.05) 0.70 (0.40—1.23) 0.22 Disadvantaged caste 2 1.57 (1.15—2.15) 1.67 (1.21—2.30) <0.01 Inborn infant 2.31 (1.73—3.09) 2.24 (1.66—3.03) 60 breaths per minute) 2.12 (1.57—2.89) 1.86 (1.34—2.60) <0.01 Grunting 3.99 (2.22—7.16) 3.38 (1.87—6.10) 38 degrees Celsius) 1.45 (1.13—1.87) 1.42 (1.09—1.85) 0.01 Central cyanosis 3.79 (1.15—12.47) 3.32 (1.00—11.02) 0.05 Abbreviations: cOR, crude odds ratios; aOR, adjusted odds ratios; CI, confidence interval 1 Adjusted for time trend and Nepal Perinatal Quality Improvement Project 2 Dalit and Muslim The final model was a multiple logistic regression including all previously significant variables adjusted for time trend and intervention (Table 4). Infants with EOS born at large facilities had more than five-fold higher odds (aOR 5.6, 95% CI 3.75—8.36) of receiving treatment according to guidelines. Odds also increased if the infant was inborn (1.97, 95% CI 1.33—2.93) or if belonging to a family of dis-advantaged caste (aOR 2.15, 95% CI 1.40—3.29). Among clinical signs, odds for receiving treatment according to guidelines was higher if the infant presented with lethargy (aOR 3.22, 95% CI 1.93-5.38) or tachypnoea (aOR 1.96, 95% CI 1.21—3.17). Table 4: Multiple logistic regression of background characteristics and clinical signs with odds for treatment of early neonatal sepsis according to World Health Organisation guidelines Variable Adjusted odds ratio 1 (95% CI) p -value Large hospital (small and medium as reference) 5.60 (3.75—8.36) <0.01 Disadvantaged caste (Dalit and Muslim) 2.15 (1.40—3.29) <0.01 Inborn (infant not referred from other facility) 1.97 (1.33—2.93) <0.01 Lethargy (decreased level of consciousness) 3.22 (1.93—5.38) 60 breaths per minute) 1.96 (1.21—3.17) <0.01 Grunting 1.24 (0.53—2.91) 0.63 Fever (temperature over 38 degrees Celsius) 0.70 (0.48—1.04) 0.08 1 Adjusted for time trend and Nepal Perinatal Quality Improvement Project Discussion In this study of almost 9000 infants admitted to sick newborn care units at twelve regional delivery facilities in Nepal we found a high utilisation of antibacterial treatment. More than two thirds of all infants at the units received injectable antibiotics, suggesting a high rate of prophylactical application in addition to treatment of suspected sepsis. This high prevalence is in line with previous data and probably associated with the high rate of nosocomial infection in this and comparable contexts (7). In a web-based survey among hospitalized children and neonates from eight countries in Asia, it was found that 88% of patients received at least one parenteral antibiotic (15). This potential overuse of antibiotics is however global. In HIC it has been estimated that up to 50% of all antimicrobial prescriptions in neonatal intensive care units (NICU) are inappropriate (16). Focusing on infants with EOS, we have demonstrated that almost three quarters were treated according to WHO guidelines using first line Ampicillin or Benzylpenicillin with or without Gentamicin. This moderately high adherence to guidelines was rising during the study period, indicating an increased awareness of the national protocol for newborn care but also of the risks from AMR among the clinicians working at the facilities. In Nepal, AMR has previously been somehow neglected because of other pressing public health priorities (17). As a response, the Ministry of Health and Population in 2014 issued guidelines for national antibiotic treatment in the healthcare sector (18). This could have gradually affected knowledge of AMR in Nepal and explain the change in treatment according to guidelines over the course of the study. Larger facilities had better adherence to guidelines. There is no data on antibiotic prescription variation over health facilities in Nepal, but we know from research in HIC that the behaviour of physicians can vary a lot in, and between, countries when it comes to utilisation and prescription of antibiotics to children (19). Delivery volume can also be expected to correlate with the size of the faculty or other leadership entities that influence, and enforce, local guidelines. A study of 127 NICU:s in the US reported that community units had higher variation in antibiotic use rate than regional ones, although the burden of proven infection was similar (20). This greater variation of use suggests that the choice of antibiotics could be related to the behaviour of a prescribing physician rather than to guidelines, especially in smaller units. For infants not treated with first-line antimicrobials, Cefotaxime was most commonly used. For some time, it has been known that Cefotaxime and other third generation cephalosporins are particularly strong drivers of AMR. Already in 2000, a study performed in a Netherland NICU found an 18-fold higher rate of colonisation with strains resistant to empiric therapy when infants were treated with Cefotaxime compared to the alternative regimen of Benzylpenicillin (21). Also, there is evidence that resistance to Cefotaxime is alarmingly high in south Asian contexts (22). Cefotaxime is also more expensive. The cost for treatment of a 5 kg neonate during a 7 days course is up to five times higher than recommended first line antibiotics for neonatal sepsis (7). In our study including 1564 infants with EOS, blood culture was available only in 15 cases. This supports the conclusion that the moderately frequent use of Cefotaxime is also empirical and not guided by microbial findings. There was a trend of higher mortality or referral to a higher centre in the group not treated according to guidelines in our data. The data on mortality in our study should be interpreted with caution as it only includes in-hospital deaths. We had no information on neonatal deaths after discharge as there was no follow-up performed. However, this finding may be explained by physician’s choice to use broader antibiotics for more severe clinical cases. This strategy is not supported by evidence, in a recent study from the US, mortality was higher in infants empirically treated with Cefotaxime even after adjusting for confounding factors (23). Given the resistance pattern, the potential of increased AMR, the risk of worse outcomes and also cost, empirical use of Cefotaxime should be discouraged and its use restricted to cases guided by blood culture or in patients were first-line treatment fails (9). Dis-advantaged caste was associated with the choice of antibiotics for EOS cases. It is worrisome that odds for treatment according guidelines was higher in this group despite that the data was from government funded, free-of-charge, facilities. In LMIC, it is common that additional, more advanced, or better quality of care, is offered at government facilities if families pay extra (24). There is also evidence to support that patient sociodemographic status can affect decisions on antibiotic treatment taken by healthcare staff (25). The result in this study indicates that out-of-pocket expenditure could lead to a higher use of broader spectrum antibiotics perceived as better or safer, resulting in higher AMR pressure without evidence for better outcomes. Inborn infants also had higher odds for treatment according to guidelines, suggesting that referred infants were to a higher extent treated with second line antibiotics such as Cefotaxime. Physicians might be more vigilant towards infants referred from other facilities but for first-line empirical treatment of EOS within 72 hours after birth, out-born infants should receive the same antibiotic regimen as inborn peers. There has been attempts to stratify infants in HIC settings into risk groups according to clinical signs combined with maternal risk factors. The intention has been to guide the choice between empirical treatment or a wait and observe approach to reduce the total utilisation of antimicrobials (26). Several clinical red flags for EOS were associated with antibiotic choice in the crude logistic regression. The final model found that patients with lethargy and tachypnoea had higher odds for adherence to WHO guidelines. A plausible explanation could be that when physicians encounter a case that clinically presents as sepsis, they observe guidelines to a higher extent (12). Consequently, in more ambiguous cases, a broader second line treatment such as Cefotaxime is chosen. As we have argued above, this is not supported by evidence for EOS cases. This study has some weaknesses. Firstly, in the Nepali protocol used for second level government facilities, Cefotaxime is recommended for meningitis in newborn infants. In our data, few infants (n=3) were reported as meningitis cases and they were not included in the cohort. This low incidence however suggest that meningitis cases have instead received a sepsis diagnose. This could potentially underestimate the rate of treatment according to protocol in our study. Secondly, there could be a reporting bias, as there was missing data on antibiotic treatment and those cases were excluded from the study. Thirdly, the data only included the initial assessment and antibiotic choice. We could not distinguish between infants initially treated with first-line antibiotics were other antibiotics were added later because of blood culture reports or patient deterioration. Finally, there could also be some cases where Cefotaxime was used as an adjuvant to Ampicillin or Benzylpenicillin, as suggested by some guidelines used outside Nepal (7). This is however unlikely, as Gentamicin according to the data was widely available in all facilities over the course of the study. The data in this study was collected from 12 delivery facilities across Nepal. Facilities differed in size, geographical location, number of staffs, and experience of the medical staff. The cohort was relatively large with more than 1500 EOS cases over a period of 18 months. No other data than background characteristics and clinical presentation and management was collected. This is often the case in low-income situated settings, where lab data or other diagnostics are usually not available, at least outside the tertiary settings. The facts above allow for possible generalisation of the results to other comparable settings. In low-income countries, it is common to use recommendations by WHO in national clinical protocols. However, protocols may be subject to national traditions and adherence to antimicrobial recommendations depend on many other factors as discussed above. Therefore, although factors found influencing the choice of antibiotic treatment has an external validity, our results of a moderately high adherence to WHO recommendations in this setting should be used with caution for other low-income countries. Conclusion Adherence to World Health Organisation guidelines for antibiotic treatment of early neonatal sepsis was moderately high and improving over time in this low-income situated sick newborn care setting. Inborn infants, infants from families with low socio-economic status and delivered at high-volume facilities were more likely to be treated according to guidelines. Clinical case presentation influenced antibiotic choice in this study but as EOS treatment is empirical and not initially guided by blood culture, first choice should always follow guidelines. Cefotaxime was common in infants not treated according to guidelines, but it should be restricted to confirmed sensitive cases or as second line treatment. Raised awareness of risks from antimicrobial resistance and interventions to increase adherence to guidelines is needed, especially in facilities with lower delivery volume. List Of Abbreviations AMR Antimicrobial resistance aOR Adjusted odds ratio CI Confidence interval EOS Early onset sepsis HIC High-income country LMIC Low- and middle-income country LOS Late onset sepsis NePeriQIP Nepal perinatal quality improvement project NICU Neonatal intensive care unit OR Odds ratio WHO World health organisation Declarations Ethics approval and consent to participate All mothers gave written consent before participating in the study. Ethical clearance was obtained from Nepal health research council (ref 26-2017). Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Swedish Research Council funded the implementation and data collection of the study. Swedish Society of Medicine and Gillbergska Foundation funded the analysis and interpretation of data. Authors’ contributions AKC and JW conceptualised the study. AKC, OB and PP implemented the study and supported data collection. BE and JW analysed the data and drafted the manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable References Dickson KE, Simen-Kapeu A, Kinney MV, Huicho L, Vesel L, Lackritz E, et al. Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries. Lancet. 2014;384(9941):438-54. Lawn JE, Blencowe H, Oza S, You D, Lee AC, Waiswa P, et al. Every Newborn: progress, priorities, and potential beyond survival. Lancet. 2014;384(9938):189-205. Bloom G, Merrett GB, Wilkinson A, Lin V, Paulin S. Antimicrobial resistance and universal health coverage. BMJ Glob Health. 2017;2(4):e000518. Pokharel S, Raut S, Adhikari B. Tackling antimicrobial resistance in low-income and middle-income countries. 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Stratification of risk of early-onset sepsis in newborns >/= 34 weeks' gestation. Pediatrics. 2014;133(1):30-6. Supplementary Files CONSORTChecklist.doc STROBEchecklist.doc Cite Share Download PDF Status: Published Journal Publication published 10 Sep, 2020 Read the published version in BMC Infectious Diseases → Version 2 posted Editorial decision: Accept 19 Aug, 2020 Reviewer # 2 agreed at journal 09 Aug, 2020 Review # 2 received at journal 09 Aug, 2020 Reviewers invited by journal 06 Aug, 2020 Reviewer # 1 agreed at journal 06 Aug, 2020 Review # 1 received at journal 06 Aug, 2020 Editor assigned by journal 05 Aug, 2020 Submission checks completed at journal 04 Aug, 2020 Editor invited by journal 04 Aug, 2020 You are reading this latest preprint version Show more versions 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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Wrammert","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYBACxgYeFL6NgYEEaVoS0ghrYWBA1XKYsBbm9t6DnwsYDufzTzud+Ljyx3ljc+kGNmkehjo5nA7rOZcsPYPhsOWM27mbDc8k3DaznHMApOWwMU4tM3IMgApuGzDczt0m2ZBw28bgRgJIy4HEBtxajH+DtMjfzt3+syHhHExLXT0eLWZgWwyAtjA2JBwwg2phTsDtlzNm1jwG/w0MgX6RbEhLNrackdhsOcfgsCEuWwzbe4xv81SkGcjdzt34scHGznC7RPLBG28q6uRx2QIxywDV5gZ0ERSA06xRMApGwSgYBXAAAOR1UbsxpC9BAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-9430-7681","institution":"Uppsala Universitet","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"J.","middleName":"","lastName":"Wrammert","suffix":""}],"badges":[],"createdAt":"2020-03-26 10:18:18","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-19505/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-19505/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-020-05361-4","type":"published","date":"2020-09-10T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1915852,"identity":"8fb5bc1f-199f-4c6a-b0f6-f4c3cb6f9cfd","added_by":"auto","created_at":"2020-08-13 17:04:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34153,"visible":true,"origin":"","legend":"Infants in the Nepal Perinatal Quality Improvement Project included for the study on treatment of early onset sepsis (EOS)","description":"","filename":"1.PNG","url":"https://assets-eu.researchsquare.com/files/rs-19505/v2/1.PNG"},{"id":1915853,"identity":"6389e903-4438-4568-802d-7735b333978a","added_by":"auto","created_at":"2020-08-13 17:04:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":19456,"visible":true,"origin":"","legend":"Proportion of infants with early onset sepsis treated according to WHO (World \nHealth Organisation) guidelines over the full study period (18 months)\n","description":"","filename":"2.PNG","url":"https://assets-eu.researchsquare.com/files/rs-19505/v2/2.PNG"},{"id":13574768,"identity":"d59d1135-8e31-41b0-94bf-4536209b84e8","added_by":"auto","created_at":"2021-09-17 04:00:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":371192,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-19505/v2/99bfdffa-5821-4804-a2f1-ac11e1d91c7a.pdf"},{"id":1915855,"identity":"483960af-cc7d-4c3e-98e8-5b53ada22baa","added_by":"auto","created_at":"2020-08-13 17:04:21","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":221184,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORTChecklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-19505/v2/CONSORTChecklist.doc"},{"id":1915856,"identity":"488184ce-8a6f-4c27-aa1b-d04eb3c88e1d","added_by":"auto","created_at":"2020-08-13 17:04:21","extension":"doc","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":87040,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEchecklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-19505/v2/STROBEchecklist.doc"}],"financialInterests":"","formattedTitle":"Adherence to World Health Organisation guidelines for treatment of early onset neonatal sepsis in low-income settings; a cohort study in Nepal","fulltext":[{"header":"Background","content":"\u003cp\u003eThe reduction of neonatal mortality globally continues and road maps like the Every Newborn Action Plan sets ambitious targets and milestones for 2030. Still, deaths during the first month of life continue to increase its proportion of total child mortality before five years of age (1). Invasive newborn infection is one of the major causes of death during the first month of life, especially in high mortality settings (2). As quality of care and universal health coverage improves world-wide, the availability of injectable antibiotics for infants with sepsis is improving (3). Empirical treatment of infants presenting with clinical signs of sepsis is a life-saving intervention, but the antimicrobial resistance (AMR) that follow, especially as a result of broad-spectrum antibiotic use, is threatening future progress (4, 5). It has been estimated that almost one third of the annual 690\u0026nbsp;000 neonatal deaths from sepsis are associated with AMR (6).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEarly onset sepsis (EOS) is defined as bacteraemia in the newborn occurring in the first 72 hours of life (7). Mainly caused by vertical infection from mother to infant, the proportion of EOS compared to late onset sepsis (LOS) has been rapidly decreasing in high-income countries (HIC) because of better Group B Streptococci control during pregnancy (8). The other common EOS pathogen in HIC is Escherichia Coli, also commonly infecting vertically from the mother. Studies on pathogen prevalence in low- and middle-income countries (LMIC) are few, but there is some evidence to suggest that Klebsiella species and Staphylococcus Aureus are more common, indicating horizontal infection (7). The higher number of potential pathogens in LMIC has led to an increased use of broader spectrum antibiotics for EOS, predominantly in south Asia (6).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough the panorama of pathogens differs between contexts, there has been no reason to change the World Health Organisation (WHO) guidelines for treatment of neonatal sepsis in health facilities. First choice is still Ampicillin or Benzylpenicillin for 7-10 days with 2 doses of Gentamicin (7). Also, in an effort to address the burden of AMR, the 20\u003csup\u003eth\u003c/sup\u003e edition of the \u003cem\u003eWHO Model List of Essential Medicines \u003c/em\u003ereleased in 2017 included three groups of antibiotics (9). ACCESS (affordable and safe antibiotics that should be widely available), WATCH (antibiotics with higher resistance potential recommended as first choice only for a few specific indications or as second choice), and RESERVE (antibiotics that should be restricted for use in specific patients when all other alternatives have failed). The only injectable first choices for EOS in the ACCESS group are Ampicillin and Benzylpenicillin together with Gentamicin as adjuvant.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eApart from the time point of onset before 72 hours of age, there is no homogenic definition of EOS in the literature (10). Blood culture has been used as a golden standard to confirm sepsis but such laboratory evidence is seldom available in LMIC and risks of falsely negative cases has been described (11). Outside HIC settings, clinicians are generally left to depend only on clinical presentation to detect EOS cases in order to make decisions on empirical antibiotic treatment. WHO has listed symptoms that should be seen as red flags for neonatal sepsis; difficult to feed, lethargy, fast breathing, grunting, sub-costal recessions, fever, hypothermia and central cyanosis. All of those signs could however be present also without an infection, making the case definition difficult (12).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe aim of this paper is to evaluate to what extent treatment of early neonatal sepsis in a low-income facility setting adhere to WHO guidelines and if compliance is influenced by contextual factors or clinical case presentation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eData for this observational cohort study was collected during a large scale-up trial of a neonatal resuscitation quality improvement package in Nepal (13). The Nepal Perinatal Quality Improvement Project (NePeriQIP) was performed in 12 public second level delivery facilities during 18 months in 2017 and 2018. Data collection for the study presented in this paper stopped when the NePeriQIP ended. The registered trial (ISRCTN30829654) had a stepped-wedge cluster randomized controlled design with a quality improvement intervention targeting quality of care for neonatal resuscitation. The included facilities were of low-volume (\u0026gt;1,000 deliveries a year), medium-volume (\u0026gt;3,000 deliveries a year), and high-volume (\u0026gt;8,000 deliveries a year). One facility from each size group formed one out of totally four wedges (clusters). All facilities provided normal and assisted vaginal delivery along with caesarean section services. Labor units were led by nurse-midwives. For infants with complications, the large and medium sized facilities provided specialised sick newborn care units staffed by pediatricians while small size facilities cared for sick infants at the regular pediatric unit led by medical doctors. The intervention did not contain any education on management of neonatal sepsis. However, all facilities had implemented the \u003cem\u003eComprehensive newborn care training package\u003c/em\u003e \u003cem\u003efor level II hospital care \u003c/em\u003eintroduced by \u003cem\u003eDepartment of health services in\u003c/em\u003e \u003cem\u003eNepal\u003c/em\u003e that conform with WHO guidelines for treatment of neonatal sepsis before the start of the study (14).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor this study, infants referred for sick newborn care before 72 hours of age with a primary diagnosis of neonatal sepsis, early onset sepsis, pneumonia or acute respiratory infection were included. Antibiotics administered were registered and collected along with data on maternal and infant characteristics. EOS infants treated with Ampicillin or Benzylpenicillin were included in the guideline group and infants treated with all other antibiotics were included in the non-guideline group. Gentamicin was considered an adjuvant treatment used in both groups and thus did not affect the group designation. No follow-up after discharge was performed. An independent data collection team was established at each facility. Data collection was done in paper format and a central research office checked the forms for completeness. A standard operating protocol was applied for data management and quality assurance was done on a quarterly basis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGeneral, maternal and infant factors were compared for the two groups using Chi-square and Fisher exact tests for categorical variables and student t-tests for continuous variables. Time trend in adherence to guidelines was analysed with linear regression using study month as an independent variable. Odds ratios for significant general characteristics and clinical signs were calculated using univariate logistic regression. A final multiple logistic regression model included all previously significant variables. All logistic regressions were adjusted for time trend and the NePeriQIP intervention. Missing data was excluded from analysis. Stata/IC 16.0 (StataCorp, TX, USA) was used for analysis. Statistical significance was set at \u003cem\u003ep\u003c/em\u003e-values \u0026lt;0.05 and confidence intervals (CI) were reported at 95%.\u003c/p\u003e"},{"header":"Results","content":"\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eDuring the study period, 8,888 infants were referred for sick newborn care at the 12 facilities. A majority (70.3%) received injectable antibiotics during care, whereas a little more than one third received a primary diagnosis of sepsis upon admission. Of the sepsis cases, almost half were referred before 72 hours of age. Of those EOS cases (n=1564), 74.9% (n=1,172) were treated according to WHO guidelines and 22.6% (n=354) were not. For 2.4% (n=38) there was no information on antibiotics available (Figure 1). The proportion of EOS cases treated according to WHO guidelines varied over time with an increasing trend (\u003cem\u003ep\u003c/em\u003e=0.03) during the study (Figure 2). In the group of patients not treated according to guidelines, Cefotaxime (90%) was the most common antibiotic used, followed by Amikacin (6%), Cloxacillin (2%) and others (2%). Blood culture was only collected in less than 1% of the cases and no results from the cultures were available in the data. \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTable 1: General, maternal and infant factors for infants with early onset sepsis during the NePeriQIP\u003csup\u003e1\u003c/sup\u003e trial, by antibiotic treatment group; Guideline (n=1172) and Non-Guideline (n=354)\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 6.1in; border-collapse: collapse; border: none;\" width=\"586\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eBackground characteristic\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGuideline \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003en (valid %)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eNon-guideline \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003en (valid %)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ep\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e-value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 6.1in; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"5\" width=\"586\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 65.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; 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line-height: 200%;\"\u003e206 (44.1)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 113.4pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"151\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eSmall (n=61)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e41 (66.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e20 (32.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 120.25pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" rowspan=\"2\" width=\"160\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eNePeriQIP trial\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 113.4pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"151\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eBaseline (n=467)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e326 (69.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e141 (30.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" rowspan=\"2\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 113.4pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"151\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eIntervention (n=970)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e769 (79.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e201 (20.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eBorn at home\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e62 (6.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e20 (6.1)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.81\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eInborn infants\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e719 (82.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e211 (66.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 6.1in; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"5\" width=\"586\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eMaternal factors\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eMaternal age in years, mean (SD)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e24.5 (4.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e24.8 (0.27)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.27\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eDisadvantaged caste\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e276 (23.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e58 (16.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eCaesarean section (elective \u0026amp; emergency)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e47 (4.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e21 (6.1)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.16\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 6.1in; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"5\" width=\"586\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eInfant factors\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eAdmission weight, mean (SD)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2820 (612)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2841 (636)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.58\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGestational age, mean (SD)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e38.5 (2.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e38.9 (2.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eApgar 5 min \u0026lt; 7\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e53 (8.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e16 (7.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.64\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eOutcome (death or referral to higher centre)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.9pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"95\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e96 (8.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e39 (11.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.6pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.10\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003eMissing data: Intervention (n=89); Born at home (n=242); Inborn (n=336); Caesarean section (n=89); Admission weight (n=31); Gestational age (n=616); Apgar 5 min (n=716); Outcome (n=39)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e Nepal Perinatal Quality Improvement Project\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e Dalit and Muslim\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGuideline and non-guideline groups were compared regarding background characteristics. Facility size, the NePeriQIP intervention, inborn infants and belonging to a dis-advantaged caste were associated with treatment according to WHO guidelines. The rate of caesarean section was low in the EOS cohort but did not differ between groups. Death or referral to a higher centre was approximately 10% in the cohort but not different between treatment groups. (Table 1). For clinical signs, lethargy, tachypnoea, grunting, fever, cyanosis and breastfeeding infants were associated with treatment group (Table 2). \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTable 2: Clinical presentation at the newborn unit for infants with early onset sepsis, by antibiotic treatment group; Guideline (n=1172) and Non-Guideline (n=354)\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 446.3pt; border-collapse: collapse; border: none;\" width=\"595\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eCharacteristics of cases\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGuideline \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003en (valid %)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eNon-guideline\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003en (valid %)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ep\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e-value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eLethargy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e167 (19.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e39 (12.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTachypnoea (\u0026gt;60 breaths per minute)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e357 (31.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e61 (17.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eSeizures\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e41 (4.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e9 (2.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.18\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGrunting\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e134 (14.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e13 (4.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eApnoea\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e19 (2.1)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2 (0.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.13\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eFever (\u0026gt;38 degrees Celsius)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e494 (44.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e120 (35.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eHypothermia (\u0026lt;35.5 degrees Celsius)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e9 (0.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e4 (1.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.75\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eSevere chest indrawing\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e27 (3.1)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3 (1.0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.06\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eCentral cyanosis\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e31 (3.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3 (0.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.02\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 233.65pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"312\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eSevere jaundice (palms and soles yellow)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"113\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e14 (1.66)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 77.95pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"104\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e4 (1.26)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.79\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e1 \u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003eFisher exact test\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eFor variables associated with treatment according to guidelines, crude odds ratios were calculated and adjusted for time trend and the NePeriQIP intervention. There were higher odds of receiving treatment according to guidelines when born at a large facility and lower odds if born at a medium size facility. Infants belonging to a family of dis-advantaged caste or if the infant was inborn had higher odds of guideline treatment. For clinical signs, odds of treatment according to guidelines were higher if the infant presented with lethargy, tachypnoea, grunting or fever (Table 3).\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTable 3: Crude and adjusted odds for treatment of early neonatal sepsis according to World Health Organisation guidelines\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 453.35pt; border-collapse: collapse; border: none;\" width=\"604\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eBackground characteristic\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ecOR (95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eaOR\u003csup\u003e1 \u003c/sup\u003e(95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ep\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e-value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eLarge volume hospital\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e5.08 (3.95\u0026mdash;6.55)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e5.03 (3.85\u0026mdash;6.60)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eMedium volume hospital\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.21 (0.16\u0026mdash;0.26)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.21 (0.16\u0026mdash;0.28)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eSmall volume hospital\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.61 (0.35\u0026mdash;1.05)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.70 (0.40\u0026mdash;1.23)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.22\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eDisadvantaged caste\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.57 (1.15\u0026mdash;2.15)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.67 (1.21\u0026mdash;2.30)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eInborn infant\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2.31 (1.73\u0026mdash;3.09)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2.24 (1.66\u0026mdash;3.03)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eClinical presentation\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ecOR (95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eaOR\u003csup\u003e1\u003c/sup\u003e (95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ep\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e-value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eLethargy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.69 (1.16\u0026mdash;2.46)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.60 (1.09\u0026mdash;2.36)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.02\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTachypnoea (\u0026gt;60 breaths per minute)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2.12 (1.57\u0026mdash;2.89)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.86 (1.34\u0026mdash;2.60)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGrunting\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3.99 (2.22\u0026mdash;7.16)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3.38 (1.87\u0026mdash;6.10)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eFever (\u0026gt;38 degrees Celsius)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.45 (1.13\u0026mdash;1.87)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.42 (1.09\u0026mdash;1.85)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 198.2pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"264\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eCentral cyanosis\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3.79 (1.15\u0026mdash;12.47)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3.32 (1.00\u0026mdash;11.02)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.7pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003eAbbreviations: cOR, crude odds ratios; aOR, adjusted odds ratios; CI, confidence interval\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e1 \u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003eAdjusted for time trend and Nepal Perinatal Quality Improvement Project\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 200%;\"\u003e Dalit and Muslim\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eThe final model was a multiple logistic regression including all previously significant variables adjusted for time trend and intervention (Table 4). Infants with EOS born at large facilities had more than five-fold higher odds (aOR 5.6, 95% CI 3.75\u0026mdash;8.36) of receiving treatment according to guidelines. Odds also increased if the infant was inborn (1.97, 95% CI 1.33\u0026mdash;2.93) or if belonging to a family of dis-advantaged caste (aOR 2.15, 95% CI 1.40\u0026mdash;3.29). Among clinical signs, odds for receiving treatment according to guidelines was higher if the infant presented with lethargy (aOR 3.22, 95% CI 1.93-5.38) or tachypnoea (aOR 1.96, 95% CI 1.21\u0026mdash;3.17).\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTable 4: Multiple logistic regression of background characteristics and clinical signs with odds for treatment of early neonatal sepsis according to World Health Organisation guidelines\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eVariable\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eAdjusted odds ratio\u003csup\u003e1\u003c/sup\u003e (95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003ep\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e-value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eLarge hospital (small and medium as reference)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e5.60 (3.75\u0026mdash;8.36)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eDisadvantaged caste (Dalit and Muslim)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e2.15 (1.40\u0026mdash;3.29)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eInborn (infant not referred from other facility)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.97 (1.33\u0026mdash;2.93)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eLethargy (decreased level of consciousness)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e3.22 (1.93\u0026mdash;5.38)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eTachypnoea (\u0026gt;60 breaths per minute)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.96 (1.21\u0026mdash;3.17)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e\u0026lt;0.01\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eGrunting\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e1.24 (0.53\u0026mdash;2.91)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.63\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 247.85pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"330\"\u003e\n\u003cp style=\"line-height: 200%;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003eFever (temperature over 38 degrees Celsius)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 148.8pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"198\"\u003e\n\u003cp style=\"line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.70 (0.48\u0026mdash;1.04)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 49.65pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"66\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; tab-stops: 141.0pt;\"\u003e\u003cspan style=\"font-size: 11.0pt; line-height: 200%;\"\u003e0.08\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; font-family: 'Calibri',sans-serif;\"\u003e1 \u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 10.0pt; font-family: 'Calibri',sans-serif;\"\u003eAdjusted for time trend and Nepal Perinatal Quality Improvement Project\u003c/span\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study of almost 9000 infants admitted to sick newborn care units at twelve regional delivery facilities in Nepal we found a high utilisation of antibacterial treatment. More than two thirds of all infants at the units received injectable antibiotics, suggesting a high rate of prophylactical application in addition to treatment of suspected sepsis. This high prevalence is in line with previous data and probably associated with the high rate of nosocomial infection in this and comparable contexts (7). In a web-based survey among hospitalized children and neonates from eight countries in Asia, it was found that 88% of patients received at least one parenteral antibiotic (15). This potential overuse of antibiotics is however global. In HIC it has been estimated that up to 50% of all antimicrobial prescriptions in neonatal intensive care units (NICU) are inappropriate (16).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFocusing on infants with EOS, we have demonstrated that almost three quarters were treated according to WHO guidelines using first line Ampicillin or Benzylpenicillin with or without Gentamicin. This moderately high adherence to guidelines was rising during the study period, indicating an increased awareness of the national protocol for newborn care but also of the risks from AMR among the clinicians working at the facilities. In Nepal, AMR has previously been somehow neglected because of other pressing public health priorities (17). As a response, the Ministry of Health and Population in 2014 issued guidelines for national antibiotic treatment in the healthcare sector (18). This could have gradually affected knowledge of AMR in Nepal and explain the change in treatment according to guidelines over the course of the study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLarger facilities had better adherence to guidelines. There is no data on antibiotic prescription variation over health facilities in Nepal, but we know from research in HIC that the behaviour of physicians can vary a lot in, and between, countries when it comes to utilisation and prescription of antibiotics to children (19). Delivery volume can also be expected to correlate with the size of the faculty or other leadership entities that influence, and enforce, local guidelines. A study of 127 NICU:s in the US reported that community units had higher variation in antibiotic use rate than regional ones, although the burden of proven infection was similar (20). This greater variation of use suggests that the choice of antibiotics could be related to the behaviour of a prescribing physician rather than to guidelines, especially in smaller units.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor infants not treated with first-line antimicrobials, Cefotaxime was most commonly used. For some time, it has been known that Cefotaxime and other third generation cephalosporins are particularly strong drivers of AMR. Already in 2000, a study performed in a Netherland NICU found an 18-fold higher rate of colonisation with strains resistant to empiric therapy when infants were treated with Cefotaxime compared to the alternative regimen of Benzylpenicillin (21). Also, there is evidence that resistance to Cefotaxime is alarmingly high in south Asian contexts (22). Cefotaxime is also more expensive. The cost for treatment of a 5 kg neonate during a 7 days course is up to five times higher than recommended first line antibiotics for neonatal sepsis (7). In our study including 1564 infants with EOS, blood culture was available only in 15 cases. This supports the conclusion that the moderately frequent use of Cefotaxime is also empirical and not guided by microbial findings. There was a trend of higher mortality or referral to a higher centre in the group not treated according to guidelines in our data. The data on mortality in our study should be interpreted with caution as it only includes in-hospital deaths. We had no information on neonatal deaths after discharge as there was no follow-up performed. However, this finding may be explained by physician\u0026rsquo;s choice to use broader antibiotics for more severe clinical cases. This strategy is not supported by evidence, in a recent study from the US, mortality was higher in infants empirically treated with Cefotaxime even after adjusting for confounding factors (23). Given the resistance pattern, the potential of increased AMR, the risk of worse outcomes and also cost, empirical use of Cefotaxime should be discouraged and its use restricted to cases guided by blood culture or in patients were first-line treatment fails (9).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDis-advantaged caste was associated with the choice of antibiotics for EOS cases. It is worrisome that odds for treatment according guidelines was higher in this group despite that the data was from government funded, free-of-charge, facilities. In LMIC, it is common that additional, more advanced, or better quality of care, is offered at government facilities if families pay extra (24). There is also evidence to support that patient sociodemographic status can affect decisions on antibiotic treatment taken by healthcare staff (25). The result in this study indicates that out-of-pocket expenditure could lead to a higher use of broader spectrum antibiotics perceived as better or safer, resulting in higher AMR pressure without evidence for better outcomes. Inborn infants also had higher odds for treatment according to guidelines, suggesting that referred infants were to a higher extent treated with second line antibiotics such as Cefotaxime. Physicians might be more vigilant towards infants referred from other facilities but for first-line empirical treatment of EOS within 72 hours after birth, out-born infants should receive the same antibiotic regimen as inborn peers.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere has been attempts to stratify infants in HIC settings into risk groups according to clinical signs combined with maternal risk factors. The intention has been to guide the choice between empirical treatment or a wait and observe approach to reduce the total utilisation of antimicrobials (26). Several clinical red flags for EOS were associated with antibiotic choice in the crude logistic regression. The final model found that patients with lethargy and tachypnoea had higher odds for adherence to WHO guidelines. A plausible explanation could be that when physicians encounter a case that clinically presents as sepsis, they observe guidelines to a higher extent (12). Consequently, in more ambiguous cases, a broader second line treatment such as Cefotaxime is chosen. As we have argued above, this is not supported by evidence for EOS cases.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has some weaknesses. Firstly, in the Nepali protocol used for second level government facilities, Cefotaxime is recommended for meningitis in newborn infants. In our data, few infants (n=3) were reported as meningitis cases and they were not included in the cohort. This low incidence however suggest that meningitis cases have instead received a sepsis diagnose. This could potentially underestimate the rate of treatment according to protocol in our study. Secondly, there could be a reporting bias, as there was missing data on antibiotic treatment and those cases were excluded from the study. Thirdly, the data only included the initial assessment and antibiotic choice. We could not distinguish between infants initially treated with first-line antibiotics were other antibiotics were added later because of blood culture reports or patient deterioration. Finally, there could also be some cases where Cefotaxime was used as an adjuvant to Ampicillin or Benzylpenicillin, as suggested by some guidelines used outside Nepal (7). This is however unlikely, as Gentamicin according to the data was widely available in all facilities over the course of the study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data in this study was collected from 12 delivery facilities across Nepal. Facilities differed in size, geographical location, number of staffs, and experience of the medical staff. The cohort was relatively large with more than 1500 EOS cases over a period of 18 months. No other data than background characteristics and clinical presentation and management was collected. This is often the case in low-income situated settings, where lab data or other diagnostics are usually not available, at least outside the tertiary settings. The facts above allow for possible generalisation of the results to other comparable settings. In low-income countries, it is common to use recommendations by WHO in national clinical protocols. However, protocols may be subject to national traditions and adherence to antimicrobial recommendations depend on many other factors as discussed above. Therefore, although factors found influencing the choice of antibiotic treatment has an external validity, our results of a moderately high adherence to WHO recommendations in this setting should be used with caution for other low-income countries.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAdherence to World Health Organisation guidelines for antibiotic treatment of early neonatal sepsis was moderately high and improving over time in this low-income situated sick newborn care setting. Inborn infants, infants from families with low socio-economic status and delivered at high-volume facilities were more likely to be treated according to guidelines. Clinical case presentation influenced antibiotic choice in this study but as EOS treatment is empirical and not initially guided by blood culture, first choice should always follow guidelines. Cefotaxime was common in infants not treated according to guidelines, but it should be restricted to confirmed sensitive cases or as second line treatment. Raised awareness of risks from antimicrobial resistance and interventions to increase adherence to guidelines is needed, especially in facilities with lower delivery volume.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eAMR \u0026nbsp;\u0026nbsp; Antimicrobial resistance\u003c/p\u003e\n\u003cp\u003eaOR \u0026nbsp;\u0026nbsp;\u0026nbsp; Adjusted odds ratio\u003c/p\u003e\n\u003cp\u003eCI\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Confidence interval\u003c/p\u003e\n\u003cp\u003eEOS\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Early onset sepsis\u003c/p\u003e\n\u003cp\u003eHIC \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; High-income country\u003c/p\u003e\n\u003cp\u003eLMIC\u0026nbsp;\u0026nbsp;\u0026nbsp; Low- and middle-income country\u003c/p\u003e\n\u003cp\u003eLOS\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Late onset sepsis\u003c/p\u003e\n\u003cp\u003eNePeriQIP \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Nepal perinatal quality improvement project\u003c/p\u003e\n\u003cp\u003eNICU\u0026nbsp;\u0026nbsp;\u0026nbsp; Neonatal intensive care unit\u003c/p\u003e\n\u003cp\u003eOR\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Odds ratio\u003c/p\u003e\n\u003cp\u003eWHO\u0026nbsp;\u0026nbsp; World health organisation\u003c/p\u003e"},{"header":"Declarations ","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll mothers gave written consent before participating in the study. Ethical clearance was obtained from Nepal health research council (ref 26-2017).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSwedish Research Council funded the implementation and data collection of the study. Swedish Society of Medicine and Gillbergska Foundation funded the analysis and interpretation of data.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAKC and JW conceptualised the study. AKC, OB and PP implemented the study and supported data collection. BE and JW analysed the data and drafted the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References ","content":"\u003col\u003e\n\u003cli\u003eDickson KE, Simen-Kapeu A, Kinney MV, Huicho L, Vesel L, Lackritz E, et al. Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries. Lancet. 2014;384(9941):438-54.\u003c/li\u003e\n\u003cli\u003eLawn JE, Blencowe H, Oza S, You D, Lee AC, Waiswa P, et al. Every Newborn: progress, priorities, and potential beyond survival. Lancet. 2014;384(9938):189-205.\u003c/li\u003e\n\u003cli\u003eBloom G, Merrett GB, Wilkinson A, Lin V, Paulin S. Antimicrobial resistance and universal health coverage. BMJ Glob Health. 2017;2(4):e000518.\u003c/li\u003e\n\u003cli\u003ePokharel S, Raut S, Adhikari B. Tackling antimicrobial resistance in low-income and middle-income countries. BMJ Glob Health. 2019;4(6):e002104.\u003c/li\u003e\n\u003cli\u003eHay SI, Rao PC, Dolecek C, Day NPJ, Stergachis A, Lopez AD, et al. Measuring and mapping the global burden of antimicrobial resistance. BMC Med. 2018;16(1):78.\u003c/li\u003e\n\u003cli\u003eLi G, Bielicki JA, Ahmed A, Islam MS, Berezin EN, Gallacci CB, et al. Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network. Arch Dis Child. 2019.\u003c/li\u003e\n\u003cli\u003eFuchs A, Bielicki J, Mathur S, Sharland M, Van Den Anker JN. Reviewing the WHO guidelines for antibiotic use for sepsis in neonates and children. Paediatr Int Child H. 2018;38:S3-S15.\u003c/li\u003e\n\u003cli\u003eSimonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21-47.\u003c/li\u003e\n\u003cli\u003e20th Essential Medicines List: World Health Organisation; 2017 [Available from: \u003ca href=\"https://www.who.int/medicines/publications/essentialmedicines/20th_EML2017.pdf?ua=1\"\u003ehttps://www.who.int/medicines/publications/essentialmedicines/20th_EML2017.pdf?ua=1\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eWynn JL. Defining neonatal sepsis. Curr Opin Pediatr. 2016;28(2):135-40.\u003c/li\u003e\n\u003cli\u003eIroh Tam PY, Bendel CM. Diagnostics for neonatal sepsis: current approaches and future directions. Pediatr Res. 2017;82(4):574-83.\u003c/li\u003e\n\u003cli\u003evan Herk W, Stocker M, van Rossum AM. Recognising early onset neonatal sepsis: an essential step in appropriate antimicrobial use. J Infect. 2016;72 Suppl:S77-82.\u003c/li\u003e\n\u003cli\u003eKc A, Ewald U, Basnet O, Gurung A, Pyakuryal SN, Jha BK, et al. Effect of a scaled-up neonatal resuscitation quality improvement package on intrapartum-related mortality in Nepal: A stepped-wedge cluster randomized controlled trial. PLoS Med. 2019;16(9):e1002900.\u003c/li\u003e\n\u003cli\u003eComprehensive newborn care training package for level II hospital care. In: services Doh, editor. Nepal: Ministry of health; 2019.\u003c/li\u003e\n\u003cli\u003eVersporten A, Bielicki J, Drapier N, Sharland M, Goossens H, group Ap. The Worldwide Antibiotic Resistance and Prescribing in European Children (ARPEC) point prevalence survey: developing hospital-quality indicators of antibiotic prescribing for children. J Antimicrob Chemother. 2016;71(4):1106-17.\u003c/li\u003e\n\u003cli\u003eHo T, Buus-Frank ME, Edwards EM, Morrow KA, Ferrelli K, Srinivasan A, et al. Adherence of Newborn-Specific Antibiotic Stewardship Programs to CDC Recommendations. Pediatrics. 2018;142(6).\u003c/li\u003e\n\u003cli\u003eBasnyat B, Pokharel P, Dixit S, Giri S. Antibiotic Use, Its Resistance in Nepal and Recommendations for Action: A Situation Analysis. J Nepal Health Res Counc. 2015;13(30):102-11.\u003c/li\u003e\n\u003cli\u003eAcharya KP, Wilson RT. Antimicrobial Resistance in Nepal. Front Med (Lausanne). 2019;6:105.\u003c/li\u003e\n\u003cli\u003eAmadeo B, Zarb P, Muller A, Drapier N, Vankerckhoven V, Rogues AM, et al. European Surveillance of Antibiotic Consumption (ESAC) point prevalence survey 2008: paediatric antimicrobial prescribing in 32 hospitals of 21 European countries. J Antimicrob Chemother. 2010;65(10):2247-52.\u003c/li\u003e\n\u003cli\u003eSchulman J, Dimand RJ, Lee HC, Duenas GV, Bennett MV, Gould JB. Neonatal intensive care unit antibiotic use. Pediatrics. 2015;135(5):826-33.\u003c/li\u003e\n\u003cli\u003ede Man P, Verhoeven BA, Verbrugh HA, Vos MC, van den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet. 2000;355(9208):973-8.\u003c/li\u003e\n\u003cli\u003eWaheed M, Laeeq A, Maqbool S. The etiology of neonatal sepsis and patterns of antibiotic resistance. J Coll Physicians Surg Pak. 2003;13(8):449-52.\u003c/li\u003e\n\u003cli\u003eWagstaff JS, Durrant RJ, Newman MG, Eason R, Ward RM, Sherwin CMT, et al. Antibiotic Treatment of Suspected and Confirmed Neonatal Sepsis Within 28 Days of Birth: A Retrospective Analysis. Front Pharmacol. 2019;10:1191.\u003c/li\u003e\n\u003cli\u003eBoerma T, Eozenou P, Evans D, Evans T, Kieny MP, Wagstaff A. Monitoring progress towards universal health coverage at country and global levels. PLoS Med. 2014;11(9):e1001731.\u003c/li\u003e\n\u003cli\u003eTeixeira Rodrigues A, Roque F, Falcao A, Figueiras A, Herdeiro MT. Understanding physician antibiotic prescribing behaviour: a systematic review of qualitative studies. Int J Antimicrob Agents. 2013;41(3):203-12.\u003c/li\u003e\n\u003cli\u003eEscobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, et al. Stratification of risk of early-onset sepsis in newborns \u0026gt;/= 34 weeks' gestation. Pediatrics. 2014;133(1):30-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neonatal Sepsis, Guideline Adherence, Drug Resistance, Microbial, Socioeconomic Factors","lastPublishedDoi":"10.21203/rs.3.rs-19505/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-19505/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background\n\nNeonatal sepsis is one of the major causes of death during the first month of life and early empirical treatment with injectable antibiotics is a life-saving intervention. Adherence to World Health Organisation guidelines on first line antibiotics is crucial to mitigate the risks of increased antimicrobial resistance. The aim of this paper was to evaluate if treatment of early onset neonatal sepsis in a low-income facility setting observe current guidelines and if compliance is influenced by contextual factors.\n\nMethods\n\nThis cohort study used data on antimicrobial treatment of neonatal sepsis onset within 72 hours of life from 12 regional hospitals participating in a scale-up trial of a neonatal resuscitation quality improvement package intervention in Nepal. Infants treated according to guidelines were compared with those receiving other antimicrobials. A multiple logistic regression analysis adjusted for the intervention and time trend was applied.\n\nResults\n\n1,564 infants with a preliminary diagnosis of early onset sepsis were included. A majority (74.9%) were treated according to guidelines and adherence was increasing over time. Infants born at larger facilities (adjusted Odds Ratio 5.6), those that were inborn (adjusted Odds Ratio 1.97) or belonging to a family of dis-advantaged caste (adjusted Odds Ratio 2.15) had higher odds for treatment according to guidelines. A clinical presentation of lethargy or tachypnoea was associated with adherence to guidelines.\n\nConclusion\n\nAdherence to guidelines for antibiotic treatment of early neonatal sepsis was moderately high in this low-income setting. Odds for observing guidelines increased with facility size, for inborn infants and if the family belonged to a dis-advantaged caste. Cefotaxime was a common alternative choice when guidelines were not followed, highly relevant for the risk of increased antimicrobial resistance.","manuscriptTitle":"Adherence to World Health Organisation guidelines for treatment of early onset neonatal sepsis in low-income settings; a cohort study in Nepal","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-08-13 17:04:20","doi":"10.21203/rs.3.rs-19505/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-08-19T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-09T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-09T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nThe authors have clarified the queries satisfactorily and also now included these details in the manuscript.\nI have no further comments to offer.\nMay be accepted.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewersInvited","content":"","date":"2020-08-06T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-06T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-06T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nthank you for the clarifications. I think this is now clear and am happy to recommend publication* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorAssigned","content":"","date":"2020-08-05T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-04T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-04T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-04-01 16:23:40","doi":"10.21203/rs.3.rs-19505/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-07-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-11T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\n\nThe study is interesting and focuses on EOS in a South Asian setting from where limited data is available.\nHowever there are some concerns which need to be addressed.\nAlthough blood culture would not be available for all the participants,some effort to provide evidence of the aetiology at least in a subset of patients is required. This will help to understand the profile of the organisms causing sepis and the resistance pattern to the recommended WHO antibiotics.\nApart form blood culture, a minimum laboratory information including differential count/CRP etc could be made available to support the clinical diagnosis of sepsis.\nAnother important issue is the outcome which would indirectly help to assess the adherence to and effectiveness of the antibiotics used.\n\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-05-08T12:00:00+00:00","index":4,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-05T12:00:00+00:00","index":3,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nThis is a generally well-done, thorough observational study. I recommend publication without further questions.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Unable to assess**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorInvitedReview","content":"","date":"2020-04-09T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThank you for asking me to review this work. It is potentially important but at present the methodology is not sufficiently well explained for me to understand exactly what is being shown.\nIt is unclear to the reader whether the NePeriQip study included any interventions in this area - i.e was there a focus on education around management of potential EOS?\nThis is key to understanding both what was done and what the results mean, and I cannot really comment further until this is clarified\n\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Unable to assess**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-04-09T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-04-07T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-04-06T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-04-06T12:00:00+00:00","index":1,"fulltext":""},{"type":"submitted","content":"","date":"2020-03-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-03-29T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-28T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6d8a4479-8dee-421d-b9a5-5b638ef62606","owner":[],"postedDate":"August 13th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":292662,"name":"Infectious Diseases"},{"id":292663,"name":"Pediatrics"}],"tags":[],"updatedAt":"2020-09-13T15:02:31+00:00","versionOfRecord":{"articleIdentity":"rs-19505","link":"https://doi.org/10.1186/s12879-020-05361-4","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2020-09-10 12:00:00","publishedOnDateReadable":"September 10th, 2020"},"versionCreatedAt":"2020-08-13 17:04:20","video":"","vorDoi":"10.1186/s12879-020-05361-4","vorDoiUrl":"https://doi.org/10.1186/s12879-020-05361-4","workflowStages":[]},"version":"v2","identity":"rs-19505","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-19505","identity":"rs-19505","version":["v2"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}