Atopic diseases in pediatric population: prematurity and small for gestational age

Atopic diseases in pediatric population: prematurity and small for gestational age | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Atopic diseases in pediatric population: prematurity and small for gestational age Yi-Yu Su, Chi-Jen Chen, Mei-Huei Chen, Ching-Chun Lin, Wu-Shiun Hsieh, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4337052/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The aim of our study was to conduct a national-wide longitudinal follow-up investigation to elucidate the association between prematurity, small for gestational age (SGA), and later development of atopic diseases in pediatric population. Research data was obtained from Taiwan’s National Health Insurance Research Database (NHIRD). Our cohort included infants born between 1 January 2004 and 31 December 2019 with exclusion of death during follow-up period and multiple births. Children born prematurely or SGA were identified as study cases and those born term and appropriate for gestational age (AGA) as controls. Data was then analyzed and adjusted for covariates. A total of 1,758,460 infants comprising 914,713 male and 843,747 female were included in the study. Prematurity was associated with atopic rhinitis (AR) (HR, 1.03, male and HR, 1.03, female), asthma (HR, 1.19, male and HR, 1.17, female) and protective against atopic dermatitis (AD) (HR, 0.94, male and HR, 0.95, female) in both male and female AGA groups. SGA were not associated with atopic diseases in term infants. Further investigations are required to clarify the underlying mechanisms and establish the causal relationship of the issue. Health sciences/Medical research/Epidemiology Biological sciences/Immunology/Immunological disorders/Inflammatory diseases/Asthma Biological sciences/Immunology/Immunological disorders/Inflammatory diseases/Atopic dermatitis Biological sciences/Immunology/Immunological disorders/Inflammatory diseases/Allergy Health sciences/Risk factors Biological sciences/Developmental biology/Intrauterine growth Atopic diseases prematurity small for gestational age asthma allergic rhinitis atopic dermatitis Figures Figure 1 Figure 2 Introduction Atopic diseases including atopic dermatitis (AD), asthma, allergic rhinitis (AR), and food allergy are important chronic diseases in pediatric population with increasing incidence in recent years. Despite their lifelong impacts to the patients and causing massive economic burden to the healthcare system, prevent strategies and treatable causes of the disease entity remain uncertain 1 . Studying the exposures of atopic diseases especially in young age or even prenatally, when immune system was developing, has been crucial to understand their etiology and thus forming strategy to prevent or treat them 2 . Research in recent decades revealed that atopic diseases may occur in a time-based order, from AD and food allergy in infancy to development of asthma and AR in childhood. The phenomenon is defined as the “atopic march” and probably owing to a group of atopic diseases that have common genetic and environmental risk factors, sharing similar immune responses 3 . While the underlying mechanisms of atopic march remain incompletely understood, common risk factors are evident across various atopic diseases. Prematurity and small for gestational age (SGA) are both critical factors stressed by the “developmental origins of health and disease” (DOHaD) hypothesis, indicating that early developmental exposures and fetal growth may influence the risks of developing chronic illnesses, including atopic diseases, in later life 4 . Studies revealed that premature or SGA infants had peculiar atopic march presentations comparing to their term or appropriate for gestational age (AGA) counterparts. For example, prematurity was found to pose higher risks in developing asthma but protective against AD 5–7 while SGA may affect asthma risks in limited stratifications 8,9 . The aim of our study was to conduct a national-wide longitudinal follow-up investigation to elucidate the association between prematurity, SGA, and development of atopic diseases in pediatric population. Methods Research data was obtained from Taiwan’s NHIRD, which collects the medical records of almost 23 million Taiwanese population since 1996 till now and covers around 99.9 percent of population in Taiwan 10 . The Health and Welfare Data Center (HWDC) of Taiwan’s Ministry of Health and Welfare (MOHW) further merged the NHIRD and other health-related databases since 2015 establishing the Taiwan Maternal and Child Health Database (TMCHD) 11 , providing reliable and accurate links between mothers and children. Diagnosis in the NHIRD were coded by International Classification of Diseases (ICD) in both Ninth Revision Clinical Modification (ICD-9-CM) and Tenth Revision Clinical Modification (ICD-10-CM) format. Asthma (ICD-9: 493, ICD-10: J45), atopic dermatitis (ICD-9: 691.8, ICD-10: L20), allergic rhinitis (ICD-9: 477, ICD-10: J30), and food allergy (ICD-9: 693.1, 995.6, ICD-10: Z91.01) are categorized by their respective ICD codes. Our cohort included infants born between 1 January 2004 and 31 December 2019 with exclusion of death during follow-up period and multiple births. Children born prematurely or SGA were identified as study cases and those born term and AGA as controls. Diagnosis of prematurity is generally defined as a birth that occurs at a gestational age before 37 weeks and SGA indicating birth weight below the 10 th percentile for specific gestational age, judged by each healthcare provider. Children were reviewed to confirm the diagnosis of atopic diseases including AD, asthma, AR, and food allergy with the primary outcome being each atopic disease documented in at least three outpatient visits or one admission. Data was then analyzed and adjusted for covariates including age, gender, pregnancy related variables, prematurity complications, socioeconomic status, and urbanization level. We defined the socioeconomic status measured by monthly insurance salary and urbanization level of the residential area and as confounders. The urbanization level, which includes four categories, was determined based on factors such as population density, education level, percentage of elderly residents, percentage of agricultural workers, and medical resource intensity, with level I representing the highest and level IV the lowest urbanization 12 . This study adhered to strict confidentiality guidelines, in accordance with regulations regarding personal electronic data protection, and was approved by the ethics review board. The data were analyzed anonymously and the need to obtain informed consent was waived by research Ethics Committee, National Health Research Institutes (No: EC1120508-E). All experiments were performed in accordance with relevant guidelines and regulations mentioned. We employed the Kaplan-Meier method to estimate the cumulative incidence of diseases (AD, asthma, AR, and food allergy) separately and used the log-rank test to compare the differences in disease risks among different groups. Additionally, we used Cox proportional hazards models to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs). All statistical analyses were conducted using SAS statistical software (version 9.4; SAS Institute, Cary, NC). Results Demographic Characteristics and Comorbidities A total of 1,758,460 infants comprising 914,713 male and 843,747 female were included in the study from 2004 to 2019 after excluding death during follow-up period and multiple births. Sexual dimorphism was observed in growth, metabolism, and development of atopic diseases for both term and preterm infants 13,14 . As a result, the analyses were conducted for both sexes separately. Infants in each sex were separated to four groups by birth gestational age and birth weight. Variables in term SGA, preterm AGA, and preterm SGA groups were then compared with the term AGA group as control. Characteristics of the cohort were demonstrated in table I and II. Being the controls, the mean gestational age at delivery of term AGA infants were 38.6 ± 1 weeks in male and 38.7 ± 1.1 weeks in female. Term SGA infants were born at 38.8 ± 1 weeks in male and 38.9 ± 1 weeks in female, which were comparable with the controls. The mean gestational age at delivery of preterm AGA infants were 34.8 ± 2 weeks in male and 34.8 ± 2.1 in female, while preterm SGA infants were born at 34.6 ± 2 weeks in male and 34.5 ± 2.1 weeks in female. As expected, term AGA infants had highest birth weight, which were 3192.9 ± 272.8 g in male and 3091.1 ± 265.4 g in female. In contrast, preterm SGA infants had lowest birth weight, being 1851.5 ± 404 g in male and 1734.2 ± 401.1 g in female. Mean maternal age during delivery were similar in each group, yet mothers of preterm infants had higher incidence of pregnancy related comorbidities comparing to term AGA infants, including gestational hypertension, gestational diabetes mellitus, premature rupture of membranes, and preeclampsia. The differences were most obvious in preterm SGA infants of both sexes, especially in incidence of maternal preeclampsia, which were 12.73% in male and 15.95% in female infants comparing to their term AGA controls (0.18% in male and 0.2% in female infants). Great differences were also observed in the incidence of maternal gestational hypertension, which were 10.12% in male and 12.23% in female preterm SGA infants comparing to the controls (0.46% in male and 0.48% in female infants). Although term SGA infants also had higher incidence of maternal preeclampsia and gestational hypertension comparing to the controls, the variations were lesser of both sexes and not apparent in other pregnancy related comorbidities. The cesarean section rate was higher in premature infants, especially in those born SGA. Chronic lung disease, cerebral palsy, hydrocephalus, and necrotizing enterocolitis were accounted for complications of prematurity. The incidences were highest in preterm SGA infants (5.39% in male and 5% in female infants), followed by preterm AGA infants (3.1% in male and 2.89% in female infants), term SGA infants (0.58% in male and 0.45% in female infants), and were lowest in term AGA controls (0.29% in male and 0.2% in female infants). Premature and SGA infants were found living in higher urbanized area and had generally lower socioeconomic status comparing to the controls. Atopic diseases Table III and IV demonstrated the incidence, confidence interval (CI), crude and adjusted hazard ratio (HR) of atopic diseases in the study groups. The incidence of asthma, AR, and AD was higher in males than females in our cohort, highlighting a sexual disparity. Prematurity was associated with AR (HR, 1.03, 95% CI, 1.01–1.04, male and HR, 1.03, 95% CI, 1.02–1.05, female), asthma (HR, 1.19, 95% CI, 1.17–1.21, male and HR, 1.17, 95% CI, 1.15–1.20, female) and protective against AD (HR, 0.94, 95% CI, 0.92–0.97, male and HR, 0.95, 95% CI, 0.93–0.98, female) in both male and female AGA groups. Consistent findings were noted in preterm SGA groups of both sexes, including asthma (HR, 1.17, 95% CI, 1.13–1.22, male and HR, 1.21, 95% CI, 1.16–1.28, female), AR (HR, 1.07, 95% CI, 1.03–1.10, male and HR, 1.06, 95% CI, 1.02–1.11, female), and AD (HR, 0.92, 95% CI, 0.86–0.98, male and HR, 0.95, 95% CI, 0.88–1.03, female). SGA was not associated with development of atopic diseases in term infants. Although not reaching statistical significance, being SGA slightly increased the risk of AR in premature infants compared to preterm AGA infants. Neither prematurity nor SGA were found associated with food allergy diagnosis in later life. Cumulative incidence curve Figure I and II revealed the cumulative incidence of each atopic disease in different groups. The diagnosis of AD mostly established before two years of age when the highest slope of the cumulative curve identified in the cohort. The incidence of AD remained higher in term AGA controls than the other three groups throughout the study period. As for asthma, the diagnosis age were mainly around two to five years old in the cohort, with slope of the cumulative curve decreased rapidly afterward. The incidence of asthma was apparently higher in preterm children than term throughout the study period, with increasing differences over time especially after five years old. Despite the effect of SGA was limited, the cumulative incidence of asthma was highest in preterm SGA group, followed by preterm AGA, term SGA, and term AGA controls in study period. Diagnosis age of AR was like asthma which was around two to five years old. Similarly, cumulative incidence of AR was higher in preterm children than term AGA controls, with preterm SGA group being affected more than preterm AGA group. Term SGA children had the highest food allergy cumulative rate among both sexes, but limited cases may affect representativeness. Discussion In our study, prematurity was positively related to the future development of asthma and AR in the pediatric population, while being protective against the development of AD. These results are consistent with findings from other nationwide databases or reviews on asthma and AD, with a stronger correlation observed as gestational age decreases 6,15–17 . Although beyond the scope of this study, the possible etiology of prematurity-associated asthma is multifactorial. Factors may include the underdevelopment of the airway, antibiotic use, increased risks for viral respiratory infections, decreased breastfeeding, and altered microbiota 18 . On the other hand, the cause for the association of prematurity with a lower risk of AD was proposed to be the increased permeability of their immature skin, early antigen exposure in the neonatal intensive care unit (NICU), and altered skin microbiota 17 . Adversely, the association between prematurity and the development of AR is controversial in relation to previous studies. Some studies describe that prematurity is associated with AR development in certain gestational ages during childhood but becomes protective in young adults 19,20 . While it is possible that AR was only associated with prematurity in certain population, we speculated that the inconsistency in observations were due to follow-up period. The development of atopic diseases takes years to complete, and differences become visible after antigen exposure as these children grow up. However, the effects may not last into adulthood due to medical interventions and the complexity of other exposures. Studies revealed that asthma and AR share symptoms and etiology with histologic evidence. Even for those AR patients without asthma, eosinophilic infiltration could be identified in bronchial mucosa 21 . The ”one airway, one disease” concept underscores the similarity between the two conditions, supporting our results and emphasizing the need for simultaneous evaluation and treatment 22 . In our study, SGA was not associated with the development of atopic diseases in term infants of both sexes. Weak association found between SGA and AR in preterm infants, lacking statistical significance. Several studies have reported the association between fetal growth restriction and atopic diseases. For example, a cohort study based on national registers in Denmark, Sweden, and Finland found that SGA was associated with a slightly increased risk of hospitalization for asthma in term infants 8 . Additionally, a cohort survey in the UK revealed prenatal faltering of linear growth prior to the onset of atopic eczema in infancy 23 . It is worth noting that these correlations were modest despite a large sample size and conflicting with other research 24 . Fetal growth alterations can manifest in a wide variety of forms for SGA infants, ranging from asymmetrical intrauterine growth restriction (IUGR), which is often caused by extrinsic exposure such as placental insufficiency, to symmetrical IUGR, driven by intrinsic factors such as early intrauterine infections, aneuploidy, and the risk of preterm birth. SGA alone may not adequately describe the developmental exposures. Furthermore, IUGR fetuses tend to be born prematurely, often before the condition of SGA can be identified at birth 25 . Maternal complications, including preeclampsia and gestational hypertension, can also contribute to fetal growth alterations 26,27 . Concurrently, both conditions were related to the future development of atopic diseases in their offspring 28,29 . Mothers of SGA infants in our cohort had a higher incidence of preeclampsia and gestational hypertension, especially among those of preterm infants, which may significantly impact our results despite statistical adjustment. Finally, mothers with atopic disorders are prone to have SGA or preterm babies, which are themselves risk factors for the future development of atopic diseases in their children 30 . Thus, we speculate that the findings were caused by weak correlations between SGA and the development of atopic diseases, a dilution effect of preterm birth prior to fetal growth restriction, and other factors correlating with fetal growth that are more related to the development of atopic diseases. Our study has several strengths. It is the first nationwide cohort study depicting atopic risks for preterm and SGA infants in Taiwan, and the results have higher confidence levels due to the large number of participants covered by the NHI. The provided data is suitable for further study on atopic diseases in preterm and SGA infants as a reference, aiding in the development of prevention or screening strategies. Based on the high coverage rate of NHI in Taiwan and multiple linked health-related databases, including the TMCHD, the association between perinatal exposures and other immune-related disorders could be further explored. The limitations of the current study mainly lie in the nature of the database. Several confounding factors could not be fully adjusted due to unavailable information such as the severity of SGA and maternal atopic diseases. Second, data acquired did not consider the moving and time-activity patterns of the participants. Exposure of the children and mothers to environmental factors such as air pollution, which is closely linked to atopic diseases, was only partially reflected in the urbanization level of birth locations. Third, although we managed to include the entire pediatric period, the optimal follow-up length remained unknown. It takes years for prenatal or perinatal exposure to show an association with chronic disorders like atopic diseases. Yet, as the follow-up period increases, the association would be theoretically diluted by other exposures, which is impossible to be fully calculated. In summary, our study suggests that prematurity increases the risk of asthma and AR but reduces the likelihood of AD in Taiwanese children. Integrated prevention and screening strategies are crucial for this population. While SGA shows no association with atopic diseases in full-term infants, it may modestly increase the risk of AR in premature infants. Exploring alternative fetal growth indicators like the Ponderal Index could provide deeper insights. Further research is needed to elucidate underlying mechanisms and establish causal relationships. Declarations Additional Information This research received support from National Health Research Institutes (PH-112-SP-17 and EM-113-GP-03), Taiwan. The institutes did not influence the study’s design, data gathering and interpretation, publishing decision, or manuscript drafting. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contribution Y.Y.S. and P.C.C. conceptualized the study. Y.Y.S., C.J.C., and P.C.C. developed the methodology. Y.Y.S. and C.J.C. conducted the investigation. C.J.C. performed the formal analysis. Y.Y.S. drafted the initial manuscript. M.H.C., C.C.L., W.S.H., H.C., C.M.C., H.C.L. and P.C.C.reviewed and edited the manuscript. P.C.C. supervised the project. P.C.C. acquired funding for the study. Acknowledgement We thank the Health and Welfare Data Science Center, Ministry of Health and Welfare (HWDC, MOHW) for supplying the data. Data Availability The data that support the findings of this study are available from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of National Health Research Institutes. The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request. References Pierau, M., Arra, A. & Brunner-Weinzierl, M. C. Preventing Atopic Diseases During Childhood - Early Exposure Matters. Front Immunol 12 , 617731, doi:10.3389/fimmu.2021.617731 (2021). Alkotob, S. S. et al. Advances and novel developments in environmental influences on the development of atopic diseases. Allergy 75 , 3077-3086, doi:10.1111/all.14624 (2020). 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Tables Table I Characteristics of male infants Characteristics Term AGA Term SGA Preterm AGA Preterm SGA n 764369 81599 61104 7641 Birth gestational age (weeks) 38.6 (1) 38.8 (1) 34.8 (2) 34.6 (2) Birth body weight (grams) 3192.9 (272.8) 2602.2 (206.5) 2524.1 (462.1) 1851.5 (404) Pregnancy related variables Maternal age 30.1 (4.7) 29.3 (5) 30.4 (5.2) 30.7 (5.3) Diabetes 5771 (0.76%) 516 (0.63%) 995 (1.63%) 169 (2.21%) Hypertension 3546 (0.46%) 1006 (1.23%) 1093 (1.79%) 773 (10.12%) Premature rupture of membranes 8698 (1.14%) 897 (1.1%) 4679 (7.66%) 587 (7.68%) Preeclampsia or eclampsia 1353 (0.18%) 535 (0.66%) 862 (1.41%) 973 (12.73%) Cesarean section 251752 (32.94%) 22491 (27.56%) 25348 (41.48%) 4205 (55.03%) Prematurity complications † All 2222 (0.29%) 474 (0.58%) 1897 (3.1%) 412 (5.39%) Other variables Urbanization level I (highest) 218909 (28.64%) 21930 (26.88%) 16389 (26.82%) 2092 (27.38%) II 251231 (32.87%) 26653 (32.66%) 19953 (32.65%) 2342 (30.65%) III 144135 (18.86%) 15549 (19.06%) 11672 (19.1%) 1496 (19.58%) IV (lowest) 150094 (19.64%) 17467 (21.41%) 13090 (21.42%) 1711 (22.39%) Socioeconomic status =25001 349123 (45.67%) 33995 (41.66%) 25717 (42.09%) 3255 (42.60%) † Prematurity complications encompassed chronic lung disease, cerebral palsy, hydrocephalus, and necrotizing enterocolitis Table II Characteristics of female infants Characteristics Term AGA Term SGA Preterm AGA Preterm SGA n 712395 78864 46731 5757 Birth gestational age (weeks) 38.7 (1.1) 38.9 (1) 34.8 (2.1) 34.5 (2.1) Birth body weight (grams) 3091.1 (265.4) 2524.8 (199) 2424.5 (468) 1734.2 (401.1) Pregnancy related variables Maternal age 30.1 (4.7) 29.3 (4.9) 30.4 (5.2) 30.9 (5.3) Diabetes 4925 (0.69%) 446 (0.57%) 812 (1.74%) 120 (2.08%) Hypertension 3441 (0.48%) 884 (1.12%) 1147 (2.45%) 704 (12.23%) Premature rupture of membranes 7873 (1.11%) 805 (1.02%) 3740 (8%) 354 (6.15%) Preeclampsia or eclampsia 1391 (0.2%) 575 (0.73%) 915 (1.96%) 918 (15.95%) Cesarean section 226426 (31.78%) 20723 (26.28%) 20152 (43.12%) 3482 (60.48%) Prematurity complications † All 1478 (0.2%) 356 (0.45%) 1350 (2.89%) 288 (5%) Other variables Urbanization level I (highest) 204526 (28.71%) 21414 (27.15%) 12635 (27.04%) 1570 (27.27%) II 234141 (32.87%) 25716 (32.61%) 15060 (32.23%) 1834 (31.86%) III 134177 (18.83%) 14921 (18.92%) 8947 (19.15%) 1073 (18.64%) IV (lowest) 139551 (19.59%) 16813 (21.32%) 10089 (21.59%) 1280 (22.23%) Socioeconomic status =25001 326426 (45.82%) 32940 (41.77%) 19377 (41.46%) 2429 (42.19%) † Prematurity complications encompassed chronic lung disease, cerebral palsy, hydrocephalus, and necrotizing enterocolitis Table III Allergic diseases in male infants across each group Incidence (per 10 5 ) 95%CI Crude HR 95%CI Adjusted HR † 95%CI Asthma Term AGA 3287.8 3274.4 to 3301.1 1.00 - 1.00 - Term SGA 3274 3233.3 to 3314.7 0.99 0.98 to 1.01 1.01 0.99 to 1.02 Preterm AGA 3947.7 3894.9 to 4000.5 1.20 1.18 to 1.22 1.19 1.17 to 1.21 Preterm SGA 3994.2 3843 to 4145.5 1.20 1.15 to 1.24 1.16 1.12 to 1.21 Atopic dermatitis Term AGA 1251.8 1244.1 to 1259.5 1.00 - 1.00 - Term SGA 1180.9 1158 to 1203.8 0.95 0.93 to 0.96 0.98 0.96 to 1.00 Preterm AGA 1173.4 1147.1 to 1199.8 0.94 0.92 to 0.96 0.94 0.92 to 0.97 Preterm SGA 1159.7 1085.3 to 1234.2 0.92 0.86 to 0.98 0.92 0.86 to 0.98 Allergic rhinitis Term AGA 5971.9 5952.7 to 5991.1 1.00 - 1.00 - Term SGA 5780.3 5722.9 to 5837.7 0.97 0.96 to 0.98 0.99 0.98 to 1.00 Preterm AGA 6144.3 6075 to 6213.5 1.03 1.02 to 1.04 1.03 1.01 to 1.04 Preterm SGA 6492.7 6289 to 6696.4 1.08 1.05 to 1.12 1.06 1.02 to 1.09 Food allergy Term AGA 5.9 5.4 to 6.4 1.00 - 1.00 - Term SGA 7.2 5.5 to 8.9 1.21 0.94 to 1.56 1.18 0.91 to 1.51 Preterm AGA 5.7 4 to 7.5 0.98 0.71 to 1.34 0.94 0.68 to 1.30 Preterm SGA 6.8 1.4 to 12.3 1.15 0.51 to 2.56 0.95 0.41 to 2.21 † Adjusted for age, gender, pregnancy related variables, prematurity complications and other variables mentioned in Table I Table IV Allergic diseases in female infants across each group Incidence (per 10 5 ) 95%CI Crude HR 95%CI Adjusted HR † 95%CI Asthma Term AGA 2466.2 2454.5 to 2477.8 1.00 - 1.00 - Term SGA 2485.6 2450.4 to 2520.7 1.01 0.99 to 1.02 1.02 1.00 to 1.03 Preterm AGA 2938.9 2888.5 to 2989.4 1.19 1.17 to 1.21 1.17 1.15 to 1.20 Preterm SGA 3134.4 2984.4 to 3284.4 1.25 1.19 to 1.31 1.20 1.14 to 1.26 Atopic dermatitis Term AGA 1101 1093.6 to 1108.5 1.00 - 1.00 - Term SGA 1051.4 1029.6 to 1073.3 0.96 0.94 to 0.98 0.99 0.96 to 1.01 Preterm AGA 1042.2 1014 to 1070.4 0.95 0.92 to 0.98 0.95 0.93 to 0.98 Preterm SGA 1084.3 1001.4 to 1167.2 0.98 0.90 to 1.05 0.95 0.88 to 1.03 Allergic rhinitis Term AGA 4577.2 4560.4 to 4594 1.00 - 1.00 - Term SGA 4510.1 4460.2 to 4560 0.98 0.97 to 1.00 1.00 0.99 to 1.02 Preterm AGA 4751.4 4684.3 to 4818.6 1.04 1.03 to 1.06 1.03 1.02 to 1.05 Preterm SGA 5006.1 4807.7 to 5204.5 1.09 1.05 to 1.13 1.05 1.01 to 1.09 Food allergy Term AGA 4.5 4 to 4.9 1.00 - 1.00 - Term SGA 6.1 4.5 to 7.7 1.37 1.04 to 1.82 1.33 1.01 to 1.77 Preterm AGA 5.7 3.7 to 7.7 1.28 0.89 to 1.85 1.10 0.75 to 1.61 Preterm SGA 4.5 0.9 to 13.3 1.01 0.32 to 3.15 0.73 0.22 to 2.36 † Adjusted for age, gender, pregnancy related variables, prematurity complications and other variables mentioned in Table I Additional Declarations No competing interests reported. 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Chen","email":"","orcid":"","institution":"Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chi-Jen","middleName":"","lastName":"Chen","suffix":""},{"id":299744548,"identity":"6f4eeb7a-36f7-4104-97e7-35bb6954ca4a","order_by":2,"name":"Mei-Huei Chen","email":"","orcid":"","institution":"Institute of Population Health Sciences, National Health Research Institutes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mei-Huei","middleName":"","lastName":"Chen","suffix":""},{"id":299744551,"identity":"842e0d36-6b5c-4614-b8c5-b7ac5908da51","order_by":3,"name":"Ching-Chun Lin","email":"","orcid":"","institution":"Institute of Environmental and Occupational Health Sciences, National Taiwan University, College of Public 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08:44:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4337052/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4337052/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56277222,"identity":"2f509db2-c925-4a00-9249-85ce1ed27899","added_by":"auto","created_at":"2024-05-10 20:18:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":779595,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of each atopic disease in male infants\u003c/p\u003e","description":"","filename":"FigureI.png","url":"https://assets-eu.researchsquare.com/files/rs-4337052/v1/e70a92858f4f7a1a76601961.png"},{"id":56277223,"identity":"4c606e13-aef3-4f74-8106-890dca999ba5","added_by":"auto","created_at":"2024-05-10 20:18:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":752139,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of each atopic disease in female infants\u003c/p\u003e","description":"","filename":"FigureII.png","url":"https://assets-eu.researchsquare.com/files/rs-4337052/v1/fcc7d5f0c42220a1b6a9fc08.png"},{"id":61836350,"identity":"45c21efb-913e-410f-9ec2-11ab552c423d","added_by":"auto","created_at":"2024-08-06 05:48:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1730589,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4337052/v1/fe2d54fa-61ae-41dc-ad99-757ed2b66a0c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Atopic diseases in pediatric population: prematurity and small for gestational age","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtopic diseases including atopic dermatitis (AD), asthma, allergic rhinitis (AR), and food allergy are important chronic diseases in pediatric population with increasing incidence in recent years. Despite their lifelong impacts to the patients and causing massive economic burden to the healthcare system, prevent strategies and treatable causes of the disease entity remain uncertain\u003csup\u003e1\u003c/sup\u003e. Studying the exposures of atopic diseases especially in young age or even prenatally, when immune system was developing, has been crucial to understand their etiology and thus forming strategy to prevent or treat them\u003csup\u003e2\u003c/sup\u003e. Research in recent decades revealed that atopic diseases may occur in a time-based order, from AD and food allergy in infancy to development of asthma and AR in childhood. The phenomenon is defined as the \u0026ldquo;atopic march\u0026rdquo; and probably owing to a group of atopic diseases that have common genetic and environmental risk factors, sharing similar immune responses \u003csup\u003e3\u003c/sup\u003e. While the underlying mechanisms of atopic march remain incompletely understood, common risk factors are evident across various atopic diseases.\u003c/p\u003e \u003cp\u003ePrematurity and small for gestational age (SGA) are both critical factors stressed by the \u0026ldquo;developmental origins of health and disease\u0026rdquo; (DOHaD) hypothesis, indicating that early developmental exposures and fetal growth may influence the risks of developing chronic illnesses, including atopic diseases, in later life\u003csup\u003e4\u003c/sup\u003e. Studies revealed that premature or SGA infants had peculiar atopic march presentations comparing to their term or appropriate for gestational age (AGA) counterparts. For example, prematurity was found to pose higher risks in developing asthma but protective against AD\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e while SGA may affect asthma risks in limited stratifications\u003csup\u003e8,9\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe aim of our study was to conduct a national-wide longitudinal follow-up investigation to elucidate the association between prematurity, SGA, and development of atopic diseases in pediatric population.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eResearch data was obtained from Taiwan\u0026rsquo;s NHIRD, which collects the medical records of almost 23\u0026nbsp;million Taiwanese population since 1996 till now and covers around 99.9 percent of population in Taiwan\u003csup\u003e10\u003c/sup\u003e. The Health and Welfare Data Center (HWDC) of Taiwan\u0026rsquo;s Ministry of Health and Welfare (MOHW) further merged the NHIRD and other health-related databases since 2015 establishing the Taiwan Maternal and Child Health Database (TMCHD)\u003csup\u003e11\u003c/sup\u003e, providing reliable and accurate links between mothers and children. Diagnosis in the NHIRD were coded by International Classification of Diseases (ICD) in both Ninth Revision Clinical Modification (ICD-9-CM) and Tenth Revision Clinical Modification (ICD-10-CM) format. Asthma (ICD-9: 493, ICD-10: J45), atopic dermatitis (ICD-9: 691.8, ICD-10: L20), allergic rhinitis (ICD-9: 477, ICD-10: J30), and food allergy (ICD-9: 693.1, 995.6, ICD-10: Z91.01) are categorized by their respective ICD codes.\u003c/p\u003e \u003cp\u003eOur cohort included infants born between 1 January 2004 and 31 December 2019 with exclusion of death during follow-up period and multiple births. Children born prematurely or SGA were identified as study cases and those born term and AGA as controls. Diagnosis of prematurity is generally defined as a birth that occurs at a gestational age before 37 weeks and SGA indicating birth weight below the 10\u003csub\u003eth\u003c/sub\u003e percentile for specific gestational age, judged by each healthcare provider. Children were reviewed to confirm the diagnosis of atopic diseases including AD, asthma, AR, and food allergy with the primary outcome being each atopic disease documented in at least three outpatient visits or one admission. Data was then analyzed and adjusted for covariates including age, gender, pregnancy related variables, prematurity complications, socioeconomic status, and urbanization level. We defined the socioeconomic status measured by monthly insurance salary and urbanization level of the residential area and as confounders. The urbanization level, which includes four categories, was determined based on factors such as population density, education level, percentage of elderly residents, percentage of agricultural workers, and medical resource intensity, with level I representing the highest and level IV the lowest urbanization\u003csup\u003e12\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e This study adhered to strict confidentiality guidelines, in accordance with regulations regarding personal electronic data protection, and was approved by the ethics review board. The data were analyzed anonymously and the need to obtain informed consent was waived by research Ethics Committee, National Health Research Institutes (No: EC1120508-E). All experiments were performed in accordance with relevant guidelines and regulations mentioned.\u003c/p\u003e \u003cp\u003eWe employed the Kaplan-Meier method to estimate the cumulative incidence of diseases (AD, asthma, AR, and food allergy) separately and used the log-rank test to compare the differences in disease risks among different groups. Additionally, we used Cox proportional hazards models to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs). All statistical analyses were conducted using SAS statistical software (version 9.4; SAS Institute, Cary, NC).\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDemographic Characteristics and Comorbidities\u003c/h2\u003e \u003cp\u003eA total of 1,758,460 infants comprising 914,713 male and 843,747 female were included in the study from 2004 to 2019 after excluding death during follow-up period and multiple births. Sexual dimorphism was observed in growth, metabolism, and development of atopic diseases for both term and preterm infants\u003csup\u003e13,14\u003c/sup\u003e. As a result, the analyses were conducted for both sexes separately. Infants in each sex were separated to four groups by birth gestational age and birth weight. Variables in term SGA, preterm AGA, and preterm SGA groups were then compared with the term AGA group as control.\u003c/p\u003e \u003cp\u003eCharacteristics of the cohort were demonstrated in table I and II. Being the controls, the mean gestational age at delivery of term AGA infants were 38.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1 weeks in male and 38.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 weeks in female. Term SGA infants were born at 38.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1 weeks in male and 38.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1 weeks in female, which were comparable with the controls. The mean gestational age at delivery of preterm AGA infants were 34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2 weeks in male and 34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 in female, while preterm SGA infants were born at 34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2 weeks in male and 34.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 weeks in female. As expected, term AGA infants had highest birth weight, which were 3192.9\u0026thinsp;\u0026plusmn;\u0026thinsp;272.8 g in male and 3091.1\u0026thinsp;\u0026plusmn;\u0026thinsp;265.4 g in female. In contrast, preterm SGA infants had lowest birth weight, being 1851.5\u0026thinsp;\u0026plusmn;\u0026thinsp;404 g in male and 1734.2\u0026thinsp;\u0026plusmn;\u0026thinsp;401.1 g in female.\u003c/p\u003e \u003cp\u003eMean maternal age during delivery were similar in each group, yet mothers of preterm infants had higher incidence of pregnancy related comorbidities comparing to term AGA infants, including gestational hypertension, gestational diabetes mellitus, premature rupture of membranes, and preeclampsia. The differences were most obvious in preterm SGA infants of both sexes, especially in incidence of maternal preeclampsia, which were 12.73% in male and 15.95% in female infants comparing to their term AGA controls (0.18% in male and 0.2% in female infants). Great differences were also observed in the incidence of maternal gestational hypertension, which were 10.12% in male and 12.23% in female preterm SGA infants comparing to the controls (0.46% in male and 0.48% in female infants). Although term SGA infants also had higher incidence of maternal preeclampsia and gestational hypertension comparing to the controls, the variations were lesser of both sexes and not apparent in other pregnancy related comorbidities. The cesarean section rate was higher in premature infants, especially in those born SGA.\u003c/p\u003e \u003cp\u003eChronic lung disease, cerebral palsy, hydrocephalus, and necrotizing enterocolitis were accounted for complications of prematurity. The incidences were highest in preterm SGA infants (5.39% in male and 5% in female infants), followed by preterm AGA infants (3.1% in male and 2.89% in female infants), term SGA infants (0.58% in male and 0.45% in female infants), and were lowest in term AGA controls (0.29% in male and 0.2% in female infants). Premature and SGA infants were found living in higher urbanized area and had generally lower socioeconomic status comparing to the controls.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAtopic diseases\u003c/h2\u003e \u003cp\u003eTable III and IV demonstrated the incidence, confidence interval (CI), crude and adjusted hazard ratio (HR) of atopic diseases in the study groups. The incidence of asthma, AR, and AD was higher in males than females in our cohort, highlighting a sexual disparity.\u003c/p\u003e \u003cp\u003ePrematurity was associated with AR (HR, 1.03, 95% CI, 1.01\u0026ndash;1.04, male and HR, 1.03, 95% CI, 1.02\u0026ndash;1.05, female), asthma (HR, 1.19, 95% CI, 1.17\u0026ndash;1.21, male and HR, 1.17, 95% CI, 1.15\u0026ndash;1.20, female) and protective against AD (HR, 0.94, 95% CI, 0.92\u0026ndash;0.97, male and HR, 0.95, 95% CI, 0.93\u0026ndash;0.98, female) in both male and female AGA groups. Consistent findings were noted in preterm SGA groups of both sexes, including asthma (HR, 1.17, 95% CI, 1.13\u0026ndash;1.22, male and HR, 1.21, 95% CI, 1.16\u0026ndash;1.28, female), AR (HR, 1.07, 95% CI, 1.03\u0026ndash;1.10, male and HR, 1.06, 95% CI, 1.02\u0026ndash;1.11, female), and AD (HR, 0.92, 95% CI, 0.86\u0026ndash;0.98, male and HR, 0.95, 95% CI, 0.88\u0026ndash;1.03, female). SGA was not associated with development of atopic diseases in term infants. Although not reaching statistical significance, being SGA slightly increased the risk of AR in premature infants compared to preterm AGA infants. Neither prematurity nor SGA were found associated with food allergy diagnosis in later life.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCumulative incidence curve\u003c/h2\u003e \u003cp\u003eFigure I and II revealed the cumulative incidence of each atopic disease in different groups. The diagnosis of AD mostly established before two years of age when the highest slope of the cumulative curve identified in the cohort. The incidence of AD remained higher in term AGA controls than the other three groups throughout the study period. As for asthma, the diagnosis age were mainly around two to five years old in the cohort, with slope of the cumulative curve decreased rapidly afterward. The incidence of asthma was apparently higher in preterm children than term throughout the study period, with increasing differences over time especially after five years old. Despite the effect of SGA was limited, the cumulative incidence of asthma was highest in preterm SGA group, followed by preterm AGA, term SGA, and term AGA controls in study period. Diagnosis age of AR was like asthma which was around two to five years old. Similarly, cumulative incidence of AR was higher in preterm children than term AGA controls, with preterm SGA group being affected more than preterm AGA group. Term SGA children had the highest food allergy cumulative rate among both sexes, but limited cases may affect representativeness.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, prematurity was positively related to the future development of asthma and AR in the pediatric population, while being protective against the development of AD. These results are consistent with findings from other nationwide databases or reviews on asthma and AD, with a stronger correlation observed as gestational age decreases\u003csup\u003e6,15\u0026ndash;17\u003c/sup\u003e. Although beyond the scope of this study, the possible etiology of prematurity-associated asthma is multifactorial. Factors may include the underdevelopment of the airway, antibiotic use, increased risks for viral respiratory infections, decreased breastfeeding, and altered microbiota\u003csup\u003e18\u003c/sup\u003e. On the other hand, the cause for the association of prematurity with a lower risk of AD was proposed to be the increased permeability of their immature skin, early antigen exposure in the neonatal intensive care unit (NICU), and altered skin microbiota\u003csup\u003e17\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAdversely, the association between prematurity and the development of AR is controversial in relation to previous studies. Some studies describe that prematurity is associated with AR development in certain gestational ages during childhood but becomes protective in young adults\u003csup\u003e19,20\u003c/sup\u003e. While it is possible that AR was only associated with prematurity in certain population, we speculated that the inconsistency in observations were due to follow-up period. The development of atopic diseases takes years to complete, and differences become visible after antigen exposure as these children grow up. However, the effects may not last into adulthood due to medical interventions and the complexity of other exposures. Studies revealed that asthma and AR share symptoms and etiology with histologic evidence. Even for those AR patients without asthma, eosinophilic infiltration could be identified in bronchial mucosa\u003csup\u003e21\u003c/sup\u003e. The \u0026rdquo;one airway, one disease\u0026rdquo; concept underscores the similarity between the two conditions, supporting our results and emphasizing the need for simultaneous evaluation and treatment\u003csup\u003e22\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our study, SGA was not associated with the development of atopic diseases in term infants of both sexes. Weak association found between SGA and AR in preterm infants, lacking statistical significance. Several studies have reported the association between fetal growth restriction and atopic diseases. For example, a cohort study based on national registers in Denmark, Sweden, and Finland found that SGA was associated with a slightly increased risk of hospitalization for asthma in term infants\u003csup\u003e8\u003c/sup\u003e. Additionally, a cohort survey in the UK revealed prenatal faltering of linear growth prior to the onset of atopic eczema in infancy\u003csup\u003e23\u003c/sup\u003e. It is worth noting that these correlations were modest despite a large sample size and conflicting with other research\u003csup\u003e24\u003c/sup\u003e. Fetal growth alterations can manifest in a wide variety of forms for SGA infants, ranging from asymmetrical intrauterine growth restriction (IUGR), which is often caused by extrinsic exposure such as placental insufficiency, to symmetrical IUGR, driven by intrinsic factors such as early intrauterine infections, aneuploidy, and the risk of preterm birth. SGA alone may not adequately describe the developmental exposures. Furthermore, IUGR fetuses tend to be born prematurely, often before the condition of SGA can be identified at birth\u003csup\u003e25\u003c/sup\u003e. Maternal complications, including preeclampsia and gestational hypertension, can also contribute to fetal growth alterations\u003csup\u003e26,27\u003c/sup\u003e. Concurrently, both conditions were related to the future development of atopic diseases in their offspring\u003csup\u003e28,29\u003c/sup\u003e. Mothers of SGA infants in our cohort had a higher incidence of preeclampsia and gestational hypertension, especially among those of preterm infants, which may significantly impact our results despite statistical adjustment. Finally, mothers with atopic disorders are prone to have SGA or preterm babies, which are themselves risk factors for the future development of atopic diseases in their children\u003csup\u003e30\u003c/sup\u003e. Thus, we speculate that the findings were caused by weak correlations between SGA and the development of atopic diseases, a dilution effect of preterm birth prior to fetal growth restriction, and other factors correlating with fetal growth that are more related to the development of atopic diseases.\u003c/p\u003e \u003cp\u003eOur study has several strengths. It is the first nationwide cohort study depicting atopic risks for preterm and SGA infants in Taiwan, and the results have higher confidence levels due to the large number of participants covered by the NHI. The provided data is suitable for further study on atopic diseases in preterm and SGA infants as a reference, aiding in the development of prevention or screening strategies. Based on the high coverage rate of NHI in Taiwan and multiple linked health-related databases, including the TMCHD, the association between perinatal exposures and other immune-related disorders could be further explored.\u003c/p\u003e \u003cp\u003eThe limitations of the current study mainly lie in the nature of the database. Several confounding factors could not be fully adjusted due to unavailable information such as the severity of SGA and maternal atopic diseases. Second, data acquired did not consider the moving and time-activity patterns of the participants. Exposure of the children and mothers to environmental factors such as air pollution, which is closely linked to atopic diseases, was only partially reflected in the urbanization level of birth locations. Third, although we managed to include the entire pediatric period, the optimal follow-up length remained unknown. It takes years for prenatal or perinatal exposure to show an association with chronic disorders like atopic diseases. Yet, as the follow-up period increases, the association would be theoretically diluted by other exposures, which is impossible to be fully calculated.\u003c/p\u003e \u003cp\u003eIn summary, our study suggests that prematurity increases the risk of asthma and AR but reduces the likelihood of AD in Taiwanese children. Integrated prevention and screening strategies are crucial for this population. While SGA shows no association with atopic diseases in full-term infants, it may modestly increase the risk of AR in premature infants. Exploring alternative fetal growth indicators like the Ponderal Index could provide deeper insights. Further research is needed to elucidate underlying mechanisms and establish causal relationships.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAdditional Information\u003c/h2\u003e \u003cp\u003eThis research received support from National Health Research Institutes (PH-112-SP-17 and EM-113-GP-03), Taiwan. The institutes did not influence the study\u0026rsquo;s design, data gathering and interpretation, publishing decision, or manuscript drafting. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e \u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eY.Y.S. and P.C.C. conceptualized the study. Y.Y.S., C.J.C., and P.C.C. developed the methodology. Y.Y.S. and C.J.C. conducted the investigation. C.J.C. performed the formal analysis. Y.Y.S. drafted the initial manuscript. M.H.C., C.C.L., W.S.H., H.C., C.M.C., H.C.L. and P.C.C.reviewed and edited the manuscript. P.C.C. supervised the project. P.C.C. acquired funding for the study.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank the Health and Welfare Data Science Center, Ministry of Health and Welfare (HWDC, MOHW) for supplying the data.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of National Health Research Institutes. The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePierau, M., Arra, A. \u0026amp; Brunner-Weinzierl, M. C. Preventing Atopic Diseases During Childhood - Early Exposure Matters. \u003cem\u003eFront Immunol\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 617731, doi:10.3389/fimmu.2021.617731 (2021).\u003c/li\u003e\n\u003cli\u003eAlkotob, S. S.\u003cem\u003e et al.\u003c/em\u003e Advances and novel developments in environmental influences on the development of atopic diseases. \u003cem\u003eAllergy\u003c/em\u003e \u003cstrong\u003e75\u003c/strong\u003e, 3077-3086, doi:10.1111/all.14624 (2020).\u003c/li\u003e\n\u003cli\u003eTsuge, M., Ikeda, M., Matsumoto, N., Yorifuji, T. \u0026amp; Tsukahara, H. 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Preeclampsia Associates with Asthma, Allergy, and Eczema in Childhood. \u003cem\u003eAm J Respir Crit Care Med\u003c/em\u003e \u003cstrong\u003e195\u003c/strong\u003e, 614-621, doi:10.1164/rccm.201604-0806OC (2017).\u003c/li\u003e\n\u003cli\u003eSaito, M.\u003cem\u003e et al.\u003c/em\u003e Having small-for-gestational-age infants was associated with maternal allergic features in the JECS birth cohort. \u003cem\u003eAllergy\u003c/em\u003e \u003cstrong\u003e73\u003c/strong\u003e, 1908-1911, doi:10.1111/all.13490 (2018).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable I Characteristics of male infants\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e764369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81599\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7641\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth gestational age (weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.6 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.8 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.8 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.6 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth body weight (grams)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3192.9 (272.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2602.2 (206.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2524.1 (462.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1851.5 (404)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePregnancy related variables\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.1 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.3 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.4 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.7 (5.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5771 (0.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e516 (0.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e995 (1.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e169 (2.21%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3546 (0.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1006 (1.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1093 (1.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e773 (10.12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremature rupture of membranes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8698 (1.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e897 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4679 (7.66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e587 (7.68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreeclampsia or eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1353 (0.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e535 (0.66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e862 (1.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e973 (12.73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e251752 (32.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22491 (27.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25348 (41.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4205 (55.03%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePrematurity complications\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2222 (0.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e474 (0.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1897 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e412 (5.39%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eOther variables\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrbanization level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI (highest)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218909 (28.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21930 (26.88%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16389 (26.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2092 (27.38%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e251231 (32.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26653 (32.66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19953 (32.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2342 (30.65%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144135 (18.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15549 (19.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11672 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1496 (19.58%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV (lowest)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150094 (19.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17467 (21.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13090 (21.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1711 (22.39%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocioeconomic status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;15840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95779 (12.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13270 (16.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9746 (15.95%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1346 (17.62%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15841\u0026ndash;25000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e319467 (41.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34334 (42.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25641 (41.96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3040 (39.79%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=25001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e349123 (45.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33995 (41.66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25717 (42.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3255 (42.60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026dagger; Prematurity complications encompassed chronic lung disease, cerebral palsy, hydrocephalus, and necrotizing enterocolitis\u003c/p\u003e \u003cp\u003eTable II Characteristics of female infants\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e712395\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78864\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46731\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5757\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth gestational age (weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.7 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.9 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.8 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.5 (2.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth body weight (grams)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3091.1 (265.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2524.8 (199)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2424.5 (468)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1734.2 (401.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePregnancy related variables\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.1 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.3 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.4 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.9 (5.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4925 (0.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e446 (0.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e812 (1.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120 (2.08%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3441 (0.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e884 (1.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1147 (2.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e704 (12.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremature rupture of membranes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7873 (1.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e805 (1.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3740 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e354 (6.15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreeclampsia or eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1391 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e575 (0.73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e915 (1.96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e918 (15.95%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e226426 (31.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20723 (26.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20152 (43.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3482 (60.48%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePrematurity complications\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1478 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e356 (0.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1350 (2.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e288 (5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eOther variables\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrbanization level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI (highest)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e204526 (28.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21414 (27.15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12635 (27.04%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1570 (27.27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e234141 (32.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25716 (32.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15060 (32.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1834 (31.86%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134177 (18.83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14921 (18.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8947 (19.15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1073 (18.64%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV (lowest)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139551 (19.59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16813 (21.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10089 (21.59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1280 (22.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocioeconomic status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;15840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89488 (12.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12480 (15.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7969 (17.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1051 (18.26%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15841\u0026ndash;25000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e296481 (41.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33444 (42.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19385 (41.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2277 (39.55%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=25001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e326426 (45.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32940 (41.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19377 (41.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2429 (42.19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026dagger; Prematurity complications encompassed chronic lung disease, cerebral palsy, hydrocephalus, and necrotizing enterocolitis\u003c/p\u003e \u003cp\u003eTable III Allergic diseases in male infants across each group\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncidence (per 10\u003csup\u003e5\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCrude HR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted HR\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3287.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3274.4 to 3301.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3274\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3233.3 to 3314.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.98 to 1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99 to 1.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3947.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3894.9 to 4000.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.18 to 1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.17 to 1.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3994.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3843 to 4145.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.15 to 1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.12 to 1.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAtopic dermatitis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1251.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1244.1 to 1259.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1180.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1158 to 1203.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93 to 0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.96 to 1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1173.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1147.1 to 1199.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.92 to 0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.92 to 0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1159.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1085.3 to 1234.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.86 to 0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.86 to 0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAllergic rhinitis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5971.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5952.7 to 5991.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5780.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5722.9 to 5837.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.96 to 0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.98 to 1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6144.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6075 to 6213.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.02 to 1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.01 to 1.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6492.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6289 to 6696.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.05 to 1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.02 to 1.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eFood allergy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.4 to 6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5 to 8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.94 to 1.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.91 to 1.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 to 7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.71 to 1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.68 to 1.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4 to 12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51 to 2.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.41 to 2.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026dagger; Adjusted for age, gender, pregnancy related variables, prematurity complications and other variables mentioned in Table I\u003c/p\u003e \u003cp\u003eTable IV Allergic diseases in female infants across each group\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncidence (per 10\u003csup\u003e5\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCrude HR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted HR\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2466.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2454.5 to 2477.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2485.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2450.4 to 2520.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99 to 1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.00 to 1.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2938.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2888.5 to 2989.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.17 to 1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.15 to 1.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3134.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2984.4 to 3284.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.19 to 1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.14 to 1.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAtopic dermatitis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1093.6 to 1108.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1051.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1029.6 to 1073.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.94 to 0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.96 to 1.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1042.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1014 to 1070.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.92 to 0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.93 to 0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1084.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1001.4 to 1167.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.90 to 1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.88 to 1.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAllergic rhinitis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4577.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4560.4 to 4594\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4510.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4460.2 to 4560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.97 to 1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99 to 1.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4751.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4684.3 to 4818.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.03 to 1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.02 to 1.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5006.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4807.7 to 5204.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.05 to 1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.01 to 1.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eFood allergy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 to 4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5 to 7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.04 to 1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.01 to 1.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm AGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7 to 7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.89 to 1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.75 to 1.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9 to 13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32 to 3.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.22 to 2.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026dagger; Adjusted for age, gender, pregnancy related variables, prematurity complications and other variables mentioned in Table I\u003c/p\u003e "}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Atopic diseases, prematurity, small for gestational age, asthma, allergic rhinitis, atopic dermatitis","lastPublishedDoi":"10.21203/rs.3.rs-4337052/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4337052/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe aim of our study was to conduct a national-wide longitudinal follow-up investigation to elucidate the association between prematurity, small for gestational age (SGA), and later development of atopic diseases in pediatric population.\u003c/p\u003e \u003cp\u003eResearch data was obtained from Taiwan\u0026rsquo;s National Health Insurance Research Database (NHIRD). Our cohort included infants born between 1 January 2004 and 31 December 2019 with exclusion of death during follow-up period and multiple births. Children born prematurely or SGA were identified as study cases and those born term and appropriate for gestational age (AGA) as controls. Data was then analyzed and adjusted for covariates.\u003c/p\u003e \u003cp\u003eA total of 1,758,460 infants comprising 914,713 male and 843,747 female were included in the study. Prematurity was associated with atopic rhinitis (AR) (HR, 1.03, male and HR, 1.03, female), asthma (HR, 1.19, male and HR, 1.17, female) and protective against atopic dermatitis (AD) (HR, 0.94, male and HR, 0.95, female) in both male and female AGA groups. SGA were not associated with atopic diseases in term infants.\u003c/p\u003e \u003cp\u003eFurther investigations are required to clarify the underlying mechanisms and establish the causal relationship of the issue.\u003c/p\u003e","manuscriptTitle":"Atopic diseases in pediatric population: prematurity and small for gestational age","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-10 20:18:06","doi":"10.21203/rs.3.rs-4337052/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e08e3a9-9b03-4bc0-b0da-bf0c9368b69c","owner":[],"postedDate":"May 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":31624336,"name":"Health sciences/Medical research/Epidemiology"},{"id":31624337,"name":"Biological sciences/Immunology/Immunological disorders/Inflammatory diseases/Asthma"},{"id":31624338,"name":"Biological sciences/Immunology/Immunological disorders/Inflammatory diseases/Atopic dermatitis"},{"id":31624339,"name":"Biological sciences/Immunology/Immunological disorders/Inflammatory diseases/Allergy"},{"id":31624340,"name":"Health sciences/Risk factors"},{"id":31624341,"name":"Biological sciences/Developmental biology/Intrauterine growth"}],"tags":[],"updatedAt":"2025-02-13T11:08:38+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-10 20:18:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4337052","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4337052","identity":"rs-4337052","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}