A cohort study of intrapartum group B streptococcus prophylaxis on atopic dermatitis in 2-year-old children

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Intrapartum group B streptococcus antibiotic prophylaxis was associated with increased atopic dermatitis in vaginally delivered children, but not in those born via cesarean section.

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This retrospective cohort study analyzed 2909 mother-child pairs from Taixing People’s Hospital in Eastern China, following term infants to age 2 years to test whether maternal intrapartum group B streptococcus antibiotic prophylaxis (GBS-IAP) is associated with later atopic dermatitis (AD). GBS-IAP was defined as intravenous penicillin G, ampicillin, or cefazolin administered for at least 4 hours before delivery, and analyses were stratified by mode of delivery with logistic regression adjusting for covariates such as maternal age, allergy history, parity, gestational age, and birth weight. The study found that GBS-IAP was associated with a higher incidence of AD in vaginally delivered children (adjusted OR 6.562, 95% CI 4.302–10.008), while no significant association was observed in cesarean-delivered children. This paper was a preprint and not peer reviewed at the time of posting. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Objective: To understand the occurrence of atopic dermatitis (AD) in children aged 2 years on exposure to maternal group B streptococcus (GBS) antibiotic prophylaxis (IAP). Design Retrospective cohort study of 2909 mother-child pairs. Setting Taixing People's Hospital in Eastern China. Participants Term infants born 2018–2019, followed longitudinally from birth to 2 years. Exposures The GBS-IAP was defined as therapy with intravenous penicillin G or ampicillin or cefazolin ≥ 4 hours from delivery. Reference infants were defined as born with intrapartum antibiotic exposure via cesarean sections. Outcomes The logistic regression models were employed to analyze the effect of intrapartum GBS prophylaxis on AD in 2-year-old children during delivery. Analysis was a priori stratified according to the mode of delivery and adjusted for relevant covariates. Results Univariate and multivariate logistic regression models before and after covariate-adjusted treatment simultaneously showed that preventive GBS-IAP was associated with increased incidence of AD in children delivered vaginally (OR: 6.719,95% CI: 4.730–9.544,P < 0.001;aOR: 6.562,95% CI: 4.302–10.008, P < 0.001), whereas cesarean delivery in 2-year-old children (OR: 0.555,95% CI: 0.276–1.117, P = 0.099;aOR: 0.560,95% CI: 0.271–1.155, P = 0.116) was not related to AD. Conclusion Prophylactic treatment of intrapartum GBS may raise the risk of AD in vaginally delivered children. Children delivered through cesarean section, on the other hand, did not have an elevated risk of AD. These findings highlight the need to better understand the risk between childhood AD and current GBS-IAP intervention strategies.
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A cohort study of intrapartum group B streptococcus prophylaxis on atopic dermatitis in 2-year-old children | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A cohort study of intrapartum group B streptococcus prophylaxis on atopic dermatitis in 2-year-old children Zhang Hong, Ren Jing, Li Hui, Xu Kang, Zhang Chunmei, Wang Yang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1869975/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Objective To understand the occurrence of atopic dermatitis (AD) in children aged 2 years on exposure to maternal group B streptococcus (GBS) antibiotic prophylaxis (IAP). Design Retrospective cohort study of 2909 mother-child pairs. Setting Taixing People's Hospital in Eastern China. Participants Term infants born 2018–2019, followed longitudinally from birth to 2 years. Exposures The GBS-IAP was defined as therapy with intravenous penicillin G or ampicillin or cefazolin ≥ 4 hours from delivery. Reference infants were defined as born with intrapartum antibiotic exposure via cesarean sections. Outcomes The logistic regression models were employed to analyze the effect of intrapartum GBS prophylaxis on AD in 2-year-old children during delivery. Analysis was a priori stratified according to the mode of delivery and adjusted for relevant covariates. Results Univariate and multivariate logistic regression models before and after covariate-adjusted treatment simultaneously showed that preventive GBS-IAP was associated with increased incidence of AD in children delivered vaginally (OR: 6.719,95% CI: 4.730–9.544,P < 0.001;aOR: 6.562,95% CI: 4.302–10.008, P < 0.001), whereas cesarean delivery in 2-year-old children (OR: 0.555,95% CI: 0.276–1.117, P = 0.099;aOR: 0.560,95% CI: 0.271–1.155, P = 0.116) was not related to AD. Conclusion Prophylactic treatment of intrapartum GBS may raise the risk of AD in vaginally delivered children. Children delivered through cesarean section, on the other hand, did not have an elevated risk of AD. These findings highlight the need to better understand the risk between childhood AD and current GBS-IAP intervention strategies. group B streptococcus intrapartum antibiotic prophylaxis atopic dermatitis Figures Figure 1 Figure 2 Highlights ► Maternal group B streptococcus antibiotic prophylaxis (GBS-IAP) was associated with the occurrence of atopic dermatitis in 2-year-old children with vaginal delivery. ► The findings were significant in vaginal delivery before and after adjusting for multiple covariates. Introduction Research over the past decades has revealed the emergence of group B Streptococcus (GBS) is the leading cause of neonatal infections in China [ 1 ]. Intrapartum antibiotic prophylaxis (IAP) was initially introduced in the 1980s to lower the prevalence of perinatal GBS disease and offered to women with particular obstetric risk factors during parturition [ 2 , 3 ]. The treatment of IAP has significantly diminished the incidence of neonatal GBS early-onset disease (GBS-EOD) in newborns [ 1 , 4 ]. However, new research has shown that using maternal antibiotics during pregnancy increases the incidence of atopic dermatitis in offspring [ 5 ]. Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disease that commonly occurs in infancy, is clinically characterized by intense itching and eczematous lesions, and its incidence has increased sharply over the past decade in response to lifestyle changes [ 6 ]. A multicentric study conducted between January and December 2014 showed that the overall point prevalence of AD in infants reached 30.48% in China [ 7 ]. Notably, previous studies evidenced the associations between the occurrence of allergic diseases and gut microbiota after cesarean section in children[ 8 ]. Recent reports also evidenced the shifts of neonatal gut microbiota when intrapartum antibiotics are administered[ 9 , 10 ]. However, whether such antibiotic-mediated effects are related to childhood AD is unknown. To better understand the association between GBS-IAP and AD in children, a retrospective cohort study was administrated in the present project by analyzing 2909 full-term newborns approximately 2 years old to establish a theoretical basis for formulating GBS intervention strategies in China. Methods Design and setting The subjects selected pregnant women and full-term newborns delivered in the present hospital from June 2018 to December 2019. A total of 3500 pregnant women were enrolled in the study. Among them, 320 were excluded from miscarriage and induced labor, 271 for incomplete information on mother-child pairs, and incomplete disease records. Finally, 2909 pairs of mother-child that met the criteria were included and divided into two cohorts, i.e vaginal delivery, and cesarean section according to the mode of delivery. Population Healthy infants with a gestational age of > 37 weeks and a birth weight of > 2500 g were included in the study. The following criteria that may impact the exposure or outcome were excluded for the subjects (Fig. 1 ). Exposure The intrapartum antibiotic prophylaxis (IAP) was defined as the exposure factors that intravenous penicillin G or ampicillin, or cefazolin were being administered ≥ 4 hours before delivery [ 11 , 12 ]. Notably, the IAP was given at the onset of labor or membrane rupture for those pregnant women with positive GBS screening. However, no antibiotics were prescribed when a cesarean section is selected before labor or membrane rupture. The diagnostic of AD in infants was confirmed by > 3 criteria according to Williams standards in Supply Table 1 (10). Table 1 Basic characteristics of the two groups of cohorts. Basic situation Vaginal birth(n = 1510) Cesarean section(n = 1399) No IAP GBS-IAP t/χ 2 P No IAP GBS-IAP t/χ 2 P (n = 1346) (n = 164) (n = 1279) (n = 120) Mother's age (years) 27.3 ± 3.9 27.5 ± 4.1 -0.379 0.414 29.0 ± 4.4 29.2 ± 4.5 -0.382 0.702 Mother's BMI(x ± s) 20.8 ± 1.6 21.0 ± 1.5 -1.094 0.274 21.0 ± 1.8 21.0 ± 1.9 -0.272 0.786 Parity (n, %) 5.733 0.017 2.521 0.112 One child 724(53.8) 72(43.9) 596(46.5) 65(54.1) Second child or more 622(46.2) 92(56.0) 683(53.4) 55(45.8) GBS Screening(n, %) 1206.195 < 0.001 730.014 < 0.001 Positive 33(2.5) 162(98.7) 65(5.1) 108(90.0) Negative 1313(97.5) 2(1.3) 1214(94.9) 12(10.0) Mother's allergy history(n, %) 128(9.5) 12(7.3) 0.835 0.361 110(8.6) 14(11.7) 1.277 0.258 Whether received higher education(n, %) 1081(80.3) 132(80.5) 0.003 0.957 922(72.1) 91(75.8) 0.770 0.380 Gender (man, n, %) 702(52.1) 103(62.8) 6.662 0.010 711(55.6) 58(48.3) 2.334 0.127 Gestational age(weeks x ± s ) 39.5 ± 1.0 39.2 ± 1.1 1.645 0.100 39.3 ± 1.0 39.4 ± 1.0 -1.210 0.227 Weight of birth (g x ± s ) 3362 ± 396 3416 ± 415 -1.644 0.100 3462 ± 447 3542 ± 473 -1.850 0.065 Feeding method(n, %) 10.846 0.004 1.336 0.113 Breast feeding 1060(78.7) 138(84.1) 963(75.2) 96(80.0) Artificial feeding 12(8.9) 5(3.0) 24(1.8) 2(1.7) Mixed feeding 274(20.4) 21(12.8) 292(22.8) 22(18.3) Whether used antibiotics in infant(n, %) 92(6.8) 68(41.4) 185.044 < 0.001 99(7.7) 46(38.3) 110.521 < 0.001 Incidence of atopic dermatitis in 2 years children(n, %) 150(11.1) 75(45.0) 140.204 < 0.001 163(12.7) 9(7.5) 3.370 0.185 BMI, body mass index; GBS, group B Streptococcus; IAP, intrapartum antibiotic prophylaxis. Covariates In addition to the exposure factors and mode of delivery, potential confounding factors that may affect outcomes were screened including genetic and environmental issues[ 1 , 11 – 14 ]. A questionnaire was used to collect the covariates information of pregnant women and newborns including age, weight, height, parity, mode of delivery, previous GBS colonization, allergies, smoking history, pet ownership, resident place, education level, antibiotic usage, and feeding patterns. The data sources and definitions of model covariates were list in Supply Table 1 . Statistical analysis Initially, chi-square tests and one-way ANOVA were employed for comparison between groups of two cohorts. Then a univariate logistic regression model was performed to analyze the exposure and preselected risk factors for atopic dermatitis in children. To better evaluate the the association between maternal IAP and AD in children, a multivariate logistic regression model was enrolled to adjust the confounding factors such as maternal age, maternal allergy history, parity, gestational age, neonatal birth weight, etc. The Data were imported into Epidata 3.0 database. SPSS 22.0 software was used for statistical analysis. The forest plots were drawn with R 4.1.3. Two-sided tests were employed with an inspection level set at α = 0.05. Results Overview of the cohorts A total of 2909 mother-child pairs were included in the cohort study (Table 1 ). Of these, 1510 cases (52%) were delivered through the vagina and 1399 cases (48%) were by cesarean section. Furthermore, 368 pregnant mothers were screened positive for GBS with a colonization rate of 12.6%, with 284 (9.8%) receiving GBS-IAP, comprising 164 cases from the vaginal group and 120 cases from the cesarean section group. Characteristics of the cohorts Multiple characteristics of mother-child pairs were compared between the IAP and non-IAP groups in the two cohorts. As shown in Table 1 , characteristics were detected across the vaginal birth cohorts in terms of breastfeeding rates, and antibiotics usage within 72 hours after birth (Table 1 ). In the cohort of vaginal delivery, the IAP group had a higher rate of multipara compared with the control group. Moreover, the prenatal IAP group also had higher GBS-positive rate, frequent maternal breastfeeding, and higher antibiotic use within 72 hours of birth in the vaginal delivery cohort (Table 1 ). In the cohort of cesarean section, significances were observed in the IAP group on primipara, GBS-positive rate, maternal breastfeeding and children were more likely to receive antibiotics use with 72 hours after birth in this cohort (Table 1 ). Outcome of the cohorts Atopic dermatitis affected 397 (13.6%) of the children in the present cohorts, of which 225 (56.7%) were delivered vaginally and 172 (43.3%) were delivered by cesarean section (Table 1 ). To be specific, the GBS-IAP group had a higher incidence of atopic dermatitis (45% vs 11.1%) compared with the control group in the vaginal delivery cohort (p 0.05). Analysis of risk factors for atopic dermatitis A univariate logistic regression model was initially performed to analyze the exposure and preselected risk factors for atopic dermatitis in children. Results showed that children exposed to GBS-IAP had an increased incidence of atopic dermatitis in the vaginal delivery cohort compared to those without GBS-IAP exposure (OR: 6.719, 95% CI: 4.730–9.544, Table 2 ). Particularly, the vaginal delivery cohort also revealed an association between childhood AD and other factors such as maternal allergy history (OR: 2.357, 95% CI: 1.575–3.527), mixed feeding rate (OR: 1.479, 95% CI: 1.061–2.061), parity (OR: 1.509, 95% CI: 1.134–2.007), and antibiotic usage (OR: 2.544, 95% CI: 1.793–3.609, Table 2 ). In the cohort of cesarean section, however, only maternal allergy history (OR: 1.721,95% CI: 1.061–2.792) was evidenced to be associated with the incidence of atopic dermatitis while no significance was observed between the GBS-IAP group and control group in 2 years children (OR: 0.555,95% CI: 0.276–1.117, Table 2 ). Table 2 Univariate logistic regression analysis of variables in the cohorts. Variables Vaginal delivery Cesarean section OR 95%CI P OR 95%CI P No IAP Reference Reference GBS-IAP 6.719 4.730–9.544 < 0.001 0.555 0.276–1.117 0.099 Mothers age 1.018 0.982–1.056 0.322 0.997 0.962–1.034 0.873 Mothers without allergic history Reference Reference Mothers with allergic history 2.357 1.575–3.527 < 0.001 1.721 1.061–2.792 0.028 One child Reference Reference Second child and more 1.509 1.134–2.007 0.005 0.906 0.658–1.246 0.543 Gestational age 0.696 0.607–0.798 < 0.001 1.135 0.965–1.335 0.127 BMI 0.976 0.894–1.065 0.584 0.964 0.881–1.054 0.421 Weight of birth 1.238 0.87–1.762 0.236 1.159 0.816–1.646 0.411 Breast feeding Reference Reference Artificial feeding 0.386 0.051–2.929 0.357 2.283 0.899–5.795 0.082 Mixed feeding 1.479 1.061–2.061 0.021 1.207 0.832–1.753 0.321 No antibiotics used within 72h Reference antibiotics used within 72h 2.544 1.793–3.609 < 0.01 0.741 0.417–1.318 0.308 No smoking Reference Reference Smoking 1.420 0.933–2.161 0.102 1.012 0.593–1.728 0.966 No keeping pets Reference Reference keeping pets 1.140 0.849–1.532 0.384 1.329 0.950–1.859 0.097 P value is for the comparison of the GBS IAP groups among vaginal and caesarean cohorts. OR, odds ratio; BMI, body mass index; GBS, group B Streptococcus; IAP, intrapartum antibiotic prophylaxis. Association between the risk factors and atopic dermatitis after adjustment Multivariate logistic regression model was enrolled to explore the association between the cohorts and atopic dermatitis after covariates adjustment. The adjusted results revealed that the vaginal delivery cohort still had a higher occurrence of atopic dermatitis in children with GBS-IAP exposure (adjusted OR: 6. 562, 95% CI: 4.302–10.008, Table 3 , Fig. 2 ). On the contrary, no significant risk factors were identified for atopic dermatitis in children without GBS-IAP exposure delivered by cesarean section (adjusted OR: 0.560, 95% CI: 0.271–1.155, Table 3 , Fig. 2 ). In addition, the vaginal delivery cohort also witnessed the association between childhood AD and other factors in the multivariate logistic regression model including maternal allergy history (adjusted OR: 2.642, 95% CI: 1.699–4.109), mixed feeding rate (adjusted OR: 1.844, 95% CI: 1.281–2.655), and gestational age (adjusted OR: 0.758, 95% CI: 1.003–2.701) that relate to childhood AD. However, only maternal allergy history was evidenced to be associated with the occurrence of childhood AD in the cesarean section cohort (adjusted OR: 1.646, 95% CI: 1.003–2.701, Table 3 , Fig. 2 ). Table 3 Multivariate logistic regression analysis of variables in the cohorts. Variables Vaginal delivery Cesarean section aOR 95%CI P aOR 95%CI P No IAP Reference Reference GBS-IAP 6.562 4.302–10.008 < 0.001 0.562 0.271–1.155 0.116 Mothers age 0.994 0.953–1.036 0.769 1.011 0.969–1.055 0.614 Mothers without allergic history Reference Reference Mothers with allergic history 2.642 1.699–4.109 0.000 1.645 1.003–2.701 0.049 One child Reference Reference Second child and more 1.495 1.074–2.081 0.017 0.986 0.664–1.472 0.954 Gestational age 0.758 0.653–0.879 0.000 1.172 0.977-1.4 0.087 No smoking Reference Reference Smoking 1.282 0.782–2.101 0.324 1.169 0.675–2.057 0.564 BMI 0.966 0.879–1.061 0.470 0.961 0.877–1.053 0.397 Breast feeding Reference Reference Artificial feeding 0.203 0.025–1.628 0.133 2.245 0.865–5.78 0.097 Mixed feeding 1.844 1.281–2.655 0.001 1.187 0.809–1.734 0.384 No antibiotics used within 72h Reference Reference antibiotics used within 72h 1.234 0.795–1.915 0.348 0.851 0.472–1.564 0.619 No keeping pets Reference Reference Keeping pets 1.276 0.92–1.77 0.144 1.282 0.905–1.831 0.161 aOR, adjusted odds ratio; BMI, body mass index; GBS, group B Streptococcus; IAP, intrapartum antibiotic prophylaxis. Discussion Previous studies have shown an association between postnatal antibiotic exposure and allergic disease in children, while fewer cases of atopic dermatitis were of concern in the context of presumed prenatal antibiotic use. A European cohort report conducted in 2019 revealed a positive association between antenatal antibiotic use and the appearance of AD in the first year of rural-born children [ 15 ]. Simultaneously, a prospective birth cohort in China also demonstrated that maternal antibiotic exposure was significantly associated with AD in postnatal childhood [ 5 ]. However, a recent meta-analysis claimed that no significant evidence that maternal antibiotic exposure in late pregnancy increases the risk of AD in infants [ 16 ]. To better explore the relationship between antibiotic exposure during pregnancy and the risk of atopic dermatitis in children, a retrospective cohort analysis was administrated in this study that identified that vaginal delivery significantly increased the AD risk in children exposed to GBS-IAP. Previous research reported that delivery mode had a greater impact on the establishment of neonatal gut microbiota after birth [ 13 , 17 ]. Microbiota development was affected in infants born vaginally exposed to IAP for up to 6 months [ 18 ]. Specifically, exposure to IAP may change the microenvironment of colonized gut microbiota, leading to a reduction in commensal bacteria but the persistence of pathogenic microorganisms[ 19 ]. In the present study, we assumed that the GBS-IAP exposure might result in the disruption of gut microbiota and further influence the course of allergic diseases such as atopic dermatitis processes in childhood. GBS-IAP interventions are usually administered 4 hours before delivery, which overlaps with the establishment of gut microbes in the first colonized neonate [ 20 ]. Such overlaps may affect the dysregulation of the gut microbiota throughout the neonatal period, and into infancy [ 21 , 22 ]. Contrary to the cohort of vaginal delivery, no significant incidence of AD was detected in infants with IAP exposure at the time of cesarean delivery. Similar results were observed in an American study in which cesarean section was not associated with atopic dermatitis in 4-year-old children and was neither affected by intrapartum antibiotics nor other indications [ 23 ]. Another study showed that delivery by cesarean section may cause food allergy in children, but not atopic dermatitis [ 24 ], which explained why the colonization of infant gut microbiome was less affected by cesarean section than vaginally born children. The antimicrobials administered in this study were narrow-spectrum antibiotics, which may lead to changes in the composition and diversity of gut microbiota during the perinatal period. After therapy with the narrow spectrum penicillin, Nogacka and Aloisio found a decrease in symbiotic bacteria but an increase in pathogen abundance in infants [ 25 , 26 ]. Taipianen revealed that the effect size of IAP was comparable to that caused by postnatal antibiotics in newborn infants [ 27 ]. When narrow-spectrum antibiotics were given to pregnant women, the effects on the newborn gut microbiota were comparable to when broad-spectrum antibiotics were given directly to neonates. Moreover, Cox reported that postnatal administration of low-dose penicillin induces metabolic changes and affects the ileal expression of immune-related genes [ 28 ] Other genetic and environmental factors, such as the history of family allergic disease, climate change, passive smoking, pet ownership, and other confounding factors, were believed to be connected with the incidence of atopic dermatitis [ 29 ]. To better adjust the logistic regression model, these indicators, initially screened by univariate logistic regression, were selected for multivariate regression analysis, and the adjusted results showed that maternal history of allergic disease, in addition to IAP exposure, was an independent risk factor. Parental allergic disease may affect skin barrier function and immune homeostasis, leading to a variety of immunological abnormalities [ 30 ]. Other studies have reported that pet ownership and smoking may be linked with the development of atopic dermatitis in children, however, this was not found in our study [ 31 – 33 ]. There are some limitations to this study. First, this study was a retrospective analysis but relied on parental feedback on a diagnosis of atopic dermatitis. Second, the lack of detailed information on parents was noticed, including a family history of allergies, and smoking history. Therefore, a prospective large-sample study will be established to collect the feces of newborns after IAP intervention and send for metagenome sequence. A longitudinal study will be conducted to investigate the impact of IAP on children to better understand the risks and benefits of the current GBS-IAP intervention strategies. Conclusion GBS-IAP intervention for pregnant mothers significantly increased the incidence of AD in children aged 2 years in vaginal delivery, whereas no significance was observed in cesarean sections. Declarations Ethics approval and consent to participate The study was approved by the Ethics Committees of Taixing People's Hospital (Reference txry2018-003) in Jiangsu Province, China. Written informed consents were obtained from the parents of all the enrolled infants before data collection. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication Not applicable Availability of data and materials All data generated or analyzed during this study are included in this published article and its supplementary information files. Competing interests The authors declare no conflicts of interest. Funding Not applicable Authors' contributions ZH and RJ designed and organized the performance of the study; DX and YX guided and instructed the data analysis. ZH and RJ performed the study, collected and analyzed the data; LH, XK, ZC, WY and ZB participated in the table and figure analysis. ZH and RJ wrote the manuscript. 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Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol. 1994;131(3):383–396. doi: 10.1111/j.1365-2133.1994.tb08530.x Metzler S, Frei R, Schmaußer-Hechfellner E, von Mutius E, Pekkanen J, Karvonen AM, Kirjavainen PV, Dalphin JC, Divaret-Chauveau A, Riedler J, Lauener R, Roduit C; PASTURE/EFRAIM study group. Association between antibiotic treatment during pregnancy and infancy and the development of allergic diseases. Pediatr Allergy Immunol. 2019 Jun;30(4):423–433. doi: 10.1111/pai.13039 . Epub 2019 Mar 5. PMID: 30734960. Huang FQ, Lu CY, Wu SP, Gong SZ, Zhao Y. Maternal exposure to antibiotics increases the risk of infant eczema before one year of life: a meta-analysis of observational studies. World J Pediatr. 2020;16(2):143–151. doi: 10.1007/s12519-019-00301-y Akagawa S, Tsuji S, Onuma C, Akagawa Y, Yamaguchi T, Yamagishi M, Yamanouchi S, Kimata T, Sekiya SI, Ohashi A, Hashiyada M. Effect of delivery mode and nutrition on gut microbiota in neonates. Ann Nutr Metab. 2019;74(2):132–139. doi: 10.1159/000496427 Garcia VR. Impact of Intrapartum Antibiotic Prophylaxis for Group B Streptococcus on the Term Infant Gut Microbiome: A State of the Science Review. J Midwifery Womens Health. 2021;66(3):351–359. doi: 10.1111/jmwh.13245 Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015;17(5):553–564. doi: 10.1016/j.chom.2015.04.006 Dhudasia MB, Spergel JM, Puopolo KM, Koebnick C, Bryan M, Grundmeier RW, Gerber JS, Lorch SA, Quarshie WO, Zaoutis T, Mukhopadhyay S. Intrapartum Group B streptococcal prophylaxis and childhood allergic disorders. Pediatrics. 2021;147(5):e2020012187. doi: 10.1542/peds.2020-012187 Shao Y, Forster SC, Tsaliki E, Vervier K, Strang A, Simpson N, Kumar N, Stares MD, Rodger A, Brocklehurst P, Field N, Lawley TD. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019;574(7776):117–121. doi: 10.1038/s41586-019-1560-1 Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–227. Published 2012 May 9. doi: 10.1038/nature11053 Richards M, Ferber J, Chen H, Swor E, Quesenberry CP, Li DK, Darrow LA. Caesarean delivery and the risk of atopic dermatitis in children. Clin Exp Allergy. 2020;50(7):805–814. doi: 10.1111/cea.13668 Papathoma E, Triga M, Fouzas S, Dimitriou G. Cesarean section delivery and development of food allergy and atopic dermatitis in early childhood. Pediatr Allergy Immunol. 2016;27(4):419–424. doi: 10.1111/pai.12552 Nogacka A, Salazar N, Suárez M, Milani C, Arboleya S, Solís G, Fernández N, Alaez L, Hernández-Barranco AM, de Los Reyes-Gavilán CG, Ventura M, Gueimonde M. Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates. Microbiome. 2017;5(1):93. Published 2017 Aug 8. doi: 10.1186/s40168-017-0313-3 Aloisio I, Quagliariello A, De Fanti S, Luiselli D, De Filippo C, Albanese D, Corvaglia LT, Faldella G, Di Gioia D. Evaluation of the effects of intrapartum antibiotic prophylaxis on newborn intestinal microbiota using a sequencing approach targeted to multi hypervariable 16S rDNA regions. Appl Microbiol Biotechnol. 2016;100(12):5537–5546. doi: 10.1007/s00253-016-7410-2 Tapiainen T, Koivusaari P, Brinkac L, Lorenzi HA, Salo J, Renko M, Pruikkonen H, Pokka T, Li W, Nelson K, Pirttilä AM, Tejesvi MV. Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants. Sci Rep. 2019;9(1):10635. Published 2019 Jul 23. doi: 10.1038/s41598-019-46964-5 Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Zárate Rodriguez JG, Rogers AB, Robine N, Loke P, Blaser MJ. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158(4):705–721. doi: 10.1016/j.cell.2014.05.052 Brown S, Reynolds NJ. Atopic and non-atopic eczema. BMJ. 2006;332(7541):584–588. doi: 10.1136/bmj.332.7541.584 Guo Y, Li P, Tang J, Han X, Zou X, Xu G, Xu Z, Wei F, Liu Q, Wang M, Xiao F, Zong W, Shen C, Li J, Liu J, Luo Y, Chang J, Sheng N, Dong C, Zhang D, Dai X, Zhou J, Meng C, Niu H, Shi X, Zhang X, Xiang J, Xu H, Ran Q, Zhou Y, Li M, Zhang H, Cheng R, Gao X, Wang H, Gu H, Ma L, Yao Z. Prevalence of Atopic Dermatitis in Chinese Children aged 1–7 ys. Sci Rep. 2016;6:29751. Published 2016 Jul 19. doi: 10.1038/srep29751 Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160(1):1–9. doi: 10.1111/j.1365-2249.2010.04139.x Langan SM, Flohr C, Williams HC. The role of furry pets in eczema: a systematic review. Arch Dermatol. 2007;143(12):1570–1577. doi: 10.1001/archderm.143.12.1570 Fotopoulou M, Iordanidou M, Vasileiou E, Trypsianis G, Chatzimichael A, Paraskakis E. A short period of breastfeeding in infancy, excessive house cleaning, absence of older sibling, and passive smoking are related to more severe atopic dermatitis in children. Eur J Dermatol. 2018;28(1):56–63. doi: 10.1684/ejd.2017.3165 Additional Declarations No competing interests reported. Supplementary Files Supplytable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 16 Aug, 2022 Reviews received at journal 11 Aug, 2022 Reviewers agreed at journal 31 Jul, 2022 Reviewers invited by journal 30 Jul, 2022 Editor assigned by journal 30 Jul, 2022 Editor invited by journal 20 Jul, 2022 Submission checks completed at journal 20 Jul, 2022 First submitted to journal 18 Jul, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1869975","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":122548648,"identity":"d450f566-f525-47ac-b8dc-c9b188e3ba98","order_by":0,"name":"Zhang Hong","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhang","middleName":"","lastName":"Hong","suffix":""},{"id":122548650,"identity":"ca812d08-d6d4-4ca4-b548-3a53e140b0ff","order_by":1,"name":"Ren Jing","email":"","orcid":"","institution":"Children’s Hospital of Soochow University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ren","middleName":"","lastName":"Jing","suffix":""},{"id":122548652,"identity":"0fb99943-428c-4f04-91ca-5d3e35372501","order_by":2,"name":"Li Hui","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Hui","suffix":""},{"id":122548653,"identity":"69ae42ed-945d-4958-b99b-c24e3591977d","order_by":3,"name":"Xu Kang","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xu","middleName":"","lastName":"Kang","suffix":""},{"id":122548655,"identity":"4adb6143-f078-41ba-9a97-6fcaae2cd1c9","order_by":4,"name":"Zhang Chunmei","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhang","middleName":"","lastName":"Chunmei","suffix":""},{"id":122548656,"identity":"b8d0fb2e-78c3-4160-ba7d-b734f3ba3f33","order_by":5,"name":"Wang Yang","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Yang","suffix":""},{"id":122548658,"identity":"42c93ace-3d78-47ab-9d99-7dea983e787b","order_by":6,"name":"Zhou Baojian","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhou","middleName":"","lastName":"Baojian","suffix":""},{"id":122548659,"identity":"3cbf3ecc-88f0-4d0a-8536-e93ed406acb6","order_by":7,"name":"Ding Xin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYDCCwyDCgEEOTDIwMBOvxZgELQcgVGID0Vr4jvMefs1TcCd9/ozkjR8YKqwTG9jPHsCrRfIwX5rlDINnuRtupBVLMJxJT2zgyUvAq8XgMI+ZwQeDw7kbJHIMJBjbDic2SPAYENaSYHA4XX5GjvEPxn/EaTF+ALQlgeFGjpkEYwMRWiSBtjDOMDhsuOHMszKLhGPpxm08Ofi18J0/Y/yZ589hefn25M03PtRYy/azn8GvBQjYJODMBBCXkHogYP5AhKJRMApGwSgYyQAAlwlFlt6HCEkAAAAASUVORK5CYII=","orcid":"","institution":"Children’s Hospital of Soochow University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ding","middleName":"","lastName":"Xin","suffix":""},{"id":122548662,"identity":"05ad8aa7-7f0b-4b28-8444-ebaf8e4a44a0","order_by":8,"name":"Yin Xiaoping","email":"","orcid":"","institution":"Taixing People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yin","middleName":"","lastName":"Xiaoping","suffix":""}],"badges":[],"createdAt":"2022-07-18 12:44:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1869975/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1869975/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":24369222,"identity":"3a19b7ec-2187-4c9d-a4b6-fca45050e675","added_by":"auto","created_at":"2022-07-26 19:40:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":234320,"visible":true,"origin":"","legend":"\u003cp\u003eDesign of study cohorts. Figure describes the process of inclusion and exclusion criteria for the selected pregnant women and infants.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1869975/v1/f6807315a63baa827468add1.jpg"},{"id":24369646,"identity":"1de473c2-19e4-43a8-9258-e6d15420eb5a","added_by":"auto","created_at":"2022-07-26 19:45:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21165,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for multivariate logistic regression analysis of outcomes. Blue square represents vaginal delivery and red symbol represents cesarean section.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-1869975/v1/743f000fc84a5fc59e96e845.png"},{"id":24369647,"identity":"bac3166a-ef9b-472e-8642-0759d73ee958","added_by":"auto","created_at":"2022-07-26 19:45:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":622417,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1869975/v1/ef839d3f-646a-4eda-b267-34ec9977bf52.pdf"},{"id":24369645,"identity":"acb50d31-f640-40e5-9d63-9d43b1d0f315","added_by":"auto","created_at":"2022-07-26 19:45:12","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17876,"visible":true,"origin":"","legend":"","description":"","filename":"Supplytable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-1869975/v1/233c37ebb4b836d414ec7b67.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A cohort study of intrapartum group B streptococcus prophylaxis on atopic dermatitis in 2-year-old children","fulltext":[{"header":"Highlights","content":"\u003cp\u003e► Maternal group B streptococcus antibiotic prophylaxis (GBS-IAP) was associated with the occurrence of atopic dermatitis in 2-year-old children with vaginal delivery.\u003c/p\u003e\n\u003cp\u003e► The findings were significant in vaginal delivery before and after adjusting for multiple covariates.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eResearch over the past decades has revealed the emergence of group B Streptococcus (GBS) is the leading cause of neonatal infections in China [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Intrapartum antibiotic prophylaxis (IAP) was initially introduced in the 1980s to lower the prevalence of perinatal GBS disease and offered to women with particular obstetric risk factors during parturition [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The treatment of IAP has significantly diminished the incidence of neonatal GBS early-onset disease (GBS-EOD) in newborns [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, new research has shown that using maternal antibiotics during pregnancy increases the incidence of atopic dermatitis in offspring [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAtopic dermatitis (AD), a chronic and recurrent inflammatory skin disease that commonly occurs in infancy, is clinically characterized by intense itching and eczematous lesions, and its incidence has increased sharply over the past decade in response to lifestyle changes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A multicentric study conducted between January and December 2014 showed that the overall point prevalence of AD in infants reached 30.48% in China [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Notably, previous studies evidenced the associations between the occurrence of allergic diseases and gut microbiota after cesarean section in children[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Recent reports also evidenced the shifts of neonatal gut microbiota when intrapartum antibiotics are administered[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, whether such antibiotic-mediated effects are related to childhood AD is unknown.\u003c/p\u003e \u003cp\u003eTo better understand the association between GBS-IAP and AD in children, a retrospective cohort study was administrated in the present project by analyzing 2909 full-term newborns approximately 2 years old to establish a theoretical basis for formulating GBS intervention strategies in China.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv class=\"Section2\" id=\"Sec3\"\u003e\n \u003cp\u003e\u003cstrong\u003eDesign and setting\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe subjects selected pregnant women and full-term newborns delivered in the present hospital from June 2018 to December 2019. A total of 3500 pregnant women were enrolled in the study. Among them, 320 were excluded from miscarriage and induced labor, 271 for incomplete information on mother-child pairs, and incomplete disease records. Finally, 2909 pairs of mother-child that met the criteria were included and divided into two cohorts, \u003cem\u003ei.e\u003c/em\u003e vaginal delivery, and cesarean section according to the mode of delivery.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003ePopulation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHealthy infants with a gestational age of \u0026gt;\u0026thinsp;37 weeks and a birth weight of \u0026gt;\u0026thinsp;2500 g were included in the study. The following criteria that may impact the exposure or outcome were excluded for the subjects (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe intrapartum antibiotic prophylaxis (IAP) was defined as the exposure factors that intravenous penicillin G or ampicillin, or cefazolin were being administered\u0026thinsp;\u0026ge;\u0026thinsp;4 hours before delivery [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. Notably, the IAP was given at the onset of labor or membrane rupture for those pregnant women with positive GBS screening. However, no antibiotics were prescribed when a cesarean section is selected before labor or membrane rupture. The diagnostic of AD in infants was confirmed by \u0026gt;\u0026thinsp;3 criteria according to Williams standards in Supply Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e (10).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBasic characteristics of the two groups of cohorts.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eBasic situation\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eVaginal birth(n\u0026thinsp;=\u0026thinsp;1510)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eCesarean section(n\u0026thinsp;=\u0026thinsp;1399)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IAP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGBS-IAP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et/\u0026chi; 2\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IAP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGBS-IAP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et/\u0026chi; 2\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1346)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;164)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1279)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;120)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMother\u0026apos;s age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.414\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.702\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMother\u0026apos;s BMI(x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.786\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParity (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.733\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOne child\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e724(53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72(43.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e596(46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65(54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecond child or more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e622(46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92(56.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e683(53.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55(45.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGBS Screening(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1206.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e730.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e162(98.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108(90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1313(97.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1214(94.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMother\u0026apos;s allergy history(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e128(9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e110(8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhether received higher education(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1081(80.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132(80.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.957\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e922(72.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91(75.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender (man, n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e702(52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e103(62.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e711(55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58(48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational age(weeks x\u0026thinsp;\u0026plusmn;\u0026thinsp;s )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.645\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight of birth (g x\u0026thinsp;\u0026plusmn;\u0026thinsp;s )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3362\u0026thinsp;\u0026plusmn;\u0026thinsp;396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3416\u0026thinsp;\u0026plusmn;\u0026thinsp;415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3462\u0026thinsp;\u0026plusmn;\u0026thinsp;447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3542\u0026thinsp;\u0026plusmn;\u0026thinsp;473\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.850\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFeeding method(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.846\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBreast feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1060(78.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138(84.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e963(75.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96(80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArtificial feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e274(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e292(22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhether used antibiotics in infant(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92(6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68(41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e185.044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46(38.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e110.521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncidence of atopic dermatitis in 2 years children(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e150(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75(45.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e140.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e163(12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.185\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eBMI, body mass index; GBS, group B Streptococcus; IAP, intrapartum antibiotic prophylaxis.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCovariates\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eIn addition to the exposure factors and mode of delivery, potential confounding factors that may affect outcomes were screened including genetic and environmental issues[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. A questionnaire was used to collect the covariates information of pregnant women and newborns including age, weight, height, parity, mode of delivery, previous GBS colonization, allergies, smoking history, pet ownership, resident place, education level, antibiotic usage, and feeding patterns. The data sources and definitions of model covariates were list in Supply Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec7\"\u003e\n \u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eInitially, chi-square tests and one-way ANOVA were employed for comparison between groups of two cohorts. Then a univariate logistic regression model was performed to analyze the exposure and preselected risk factors for atopic dermatitis in children. To better evaluate the the association between maternal IAP and AD in children, a multivariate logistic regression model was enrolled to adjust the confounding factors such as maternal age, maternal allergy history, parity, gestational age, neonatal birth weight, etc. The Data were imported into Epidata 3.0 database. SPSS 22.0 software was used for statistical analysis. The forest plots were drawn with R 4.1.3. Two-sided tests were employed with an inspection level set at \u0026alpha;\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec9\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverview of the cohorts\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eA total of 2909 mother-child pairs were included in the cohort study (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Of these, 1510 cases (52%) were delivered through the vagina and 1399 cases (48%) were by cesarean section. Furthermore, 368 pregnant mothers were screened positive for GBS with a colonization rate of 12.6%, with 284 (9.8%) receiving GBS-IAP, comprising 164 cases from the vaginal group and 120 cases from the cesarean section group.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of the cohorts\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultiple characteristics of mother-child pairs were compared between the IAP and non-IAP groups in the two cohorts. As shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, characteristics were detected across the vaginal birth cohorts in terms of breastfeeding rates, and antibiotics usage within 72 hours after birth (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In the cohort of vaginal delivery, the IAP group had a higher rate of multipara compared with the control group. Moreover, the prenatal IAP group also had higher GBS-positive rate, frequent maternal breastfeeding, and higher antibiotic use within 72 hours of birth in the vaginal delivery cohort (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In the cohort of cesarean section, significances were observed in the IAP group on primipara, GBS-positive rate, maternal breastfeeding and children were more likely to receive antibiotics use with 72 hours after birth in this cohort (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome of the cohorts\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAtopic dermatitis affected 397 (13.6%) of the children in the present cohorts, of which 225 (56.7%) were delivered vaginally and 172 (43.3%) were delivered by cesarean section (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). To be specific, the GBS-IAP group had a higher incidence of atopic dermatitis (45% vs 11.1%) compared with the control group in the vaginal delivery cohort (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). However, in cesarean delivery, the presence of AD was not associated with intrapartum GBS-IAP exposure (7.5% vs. 12.7%, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis of risk factors for atopic dermatitis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA univariate logistic regression model was initially performed to analyze the exposure and preselected risk factors for atopic dermatitis in children. Results showed that children exposed to GBS-IAP had an increased incidence of atopic dermatitis in the vaginal delivery cohort compared to those without GBS-IAP exposure (OR: 6.719, 95% CI: 4.730\u0026ndash;9.544, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Particularly, the vaginal delivery cohort also revealed an association between childhood AD and other factors such as maternal allergy history (OR: 2.357, 95% CI: 1.575\u0026ndash;3.527), mixed feeding rate (OR: 1.479, 95% CI: 1.061\u0026ndash;2.061), parity (OR: 1.509, 95% CI: 1.134\u0026ndash;2.007), and antibiotic usage (OR: 2.544, 95% CI: 1.793\u0026ndash;3.609, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). In the cohort of cesarean section, however, only maternal allergy history (OR: 1.721,95% CI: 1.061\u0026ndash;2.792) was evidenced to be associated with the incidence of atopic dermatitis while no significance was observed between the GBS-IAP group and control group in 2 years children (OR: 0.555,95% CI: 0.276\u0026ndash;1.117, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate logistic regression analysis of variables in the cohorts.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eVaginal delivery\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCesarean section\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo IAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGBS-IAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.730\u0026ndash;9.544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.555\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.276\u0026ndash;1.117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMothers age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.982\u0026ndash;1.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.962\u0026ndash;1.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.873\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMothers without allergic history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMothers with allergic history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.575\u0026ndash;3.527\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.721\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.061\u0026ndash;2.792\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOne child\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecond child and more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.134\u0026ndash;2.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.658\u0026ndash;1.246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.543\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.696\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.607\u0026ndash;0.798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.965\u0026ndash;1.335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.976\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.894\u0026ndash;1.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.964\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.881\u0026ndash;1.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.421\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight of birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.87\u0026ndash;1.762\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.159\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.816\u0026ndash;1.646\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.411\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBreast feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArtificial feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.051\u0026ndash;2.929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.899\u0026ndash;5.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.479\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.061\u0026ndash;2.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.832\u0026ndash;1.753\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo antibiotics used within 72h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eantibiotics used within 72h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.793\u0026ndash;3.609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.741\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.417\u0026ndash;1.318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo smoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.933\u0026ndash;2.161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.593\u0026ndash;1.728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo keeping pets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ekeeping pets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.849\u0026ndash;1.532\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.384\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.950\u0026ndash;1.859\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eP value is for the comparison of the GBS IAP groups among vaginal and caesarean cohorts.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eOR, odds ratio; BMI, body mass index; GBS, group B Streptococcus; IAP, intrapartum antibiotic prophylaxis.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAssociation between the risk factors and atopic dermatitis after adjustment\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eMultivariate logistic regression model was enrolled to explore the association between the cohorts and atopic dermatitis after covariates adjustment. The adjusted results revealed that the vaginal delivery cohort still had a higher occurrence of atopic dermatitis in children with GBS-IAP exposure (adjusted OR: 6. 562, 95% CI: 4.302\u0026ndash;10.008, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). On the contrary, no significant risk factors were identified for atopic dermatitis in children without GBS-IAP exposure delivered by cesarean section (adjusted OR: 0.560, 95% CI: 0.271\u0026ndash;1.155, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, the vaginal delivery cohort also witnessed the association between childhood AD and other factors in the multivariate logistic regression model including maternal allergy history (adjusted OR: 2.642, 95% CI: 1.699\u0026ndash;4.109), mixed feeding rate (adjusted OR: 1.844, 95% CI: 1.281\u0026ndash;2.655), and gestational age (adjusted OR: 0.758, 95% CI: 1.003\u0026ndash;2.701) that relate to childhood AD. However, only maternal allergy history was evidenced to be associated with the occurrence of childhood AD in the cesarean section cohort (adjusted OR: 1.646, 95% CI: 1.003\u0026ndash;2.701, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate logistic regression analysis of variables in the cohorts.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eVaginal delivery\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCesarean section\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo IAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGBS-IAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.302\u0026ndash;10.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.271\u0026ndash;1.155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMothers age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.953\u0026ndash;1.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.769\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.969\u0026ndash;1.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMothers without allergic history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMothers with allergic history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.642\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.699\u0026ndash;4.109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.645\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.003\u0026ndash;2.701\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOne child\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecond child and more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.074\u0026ndash;2.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.664\u0026ndash;1.472\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.653\u0026ndash;0.879\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.977-1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo smoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.782\u0026ndash;2.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.675\u0026ndash;2.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.879\u0026ndash;1.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.470\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.961\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.877\u0026ndash;1.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.397\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBreast feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArtificial feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.025\u0026ndash;1.628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.865\u0026ndash;5.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.281\u0026ndash;2.655\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.809\u0026ndash;1.734\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.384\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo antibiotics used within 72h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eantibiotics used within 72h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.795\u0026ndash;1.915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.851\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.472\u0026ndash;1.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo keeping pets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKeeping pets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.92\u0026ndash;1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.905\u0026ndash;1.831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eaOR, adjusted odds ratio; BMI, body mass index; GBS, group B Streptococcus; IAP, intrapartum antibiotic prophylaxis.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrevious studies have shown an association between postnatal antibiotic exposure and allergic disease in children, while fewer cases of atopic dermatitis were of concern in the context of presumed prenatal antibiotic use. A European cohort report conducted in 2019 revealed a positive association between antenatal antibiotic use and the appearance of AD in the first year of rural-born children [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Simultaneously, a prospective birth cohort in China also demonstrated that maternal antibiotic exposure was significantly associated with AD in postnatal childhood [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, a recent meta-analysis claimed that no significant evidence that maternal antibiotic exposure in late pregnancy increases the risk of AD in infants [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo better explore the relationship between antibiotic exposure during pregnancy and the risk of atopic dermatitis in children, a retrospective cohort analysis was administrated in this study that identified that vaginal delivery significantly increased the AD risk in children exposed to GBS-IAP. Previous research reported that delivery mode had a greater impact on the establishment of neonatal gut microbiota after birth [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Microbiota development was affected in infants born vaginally exposed to IAP for up to 6 months [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Specifically, exposure to IAP may change the microenvironment of colonized gut microbiota, leading to a reduction in commensal bacteria but the persistence of pathogenic microorganisms[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In the present study, we assumed that the GBS-IAP exposure might result in the disruption of gut microbiota and further influence the course of allergic diseases such as atopic dermatitis processes in childhood. GBS-IAP interventions are usually administered 4 hours before delivery, which overlaps with the establishment of gut microbes in the first colonized neonate [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Such overlaps may affect the dysregulation of the gut microbiota throughout the neonatal period, and into infancy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eContrary to the cohort of vaginal delivery, no significant incidence of AD was detected in infants with IAP exposure at the time of cesarean delivery. Similar results were observed in an American study in which cesarean section was not associated with atopic dermatitis in 4-year-old children and was neither affected by intrapartum antibiotics nor other indications [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Another study showed that delivery by cesarean section may cause food allergy in children, but not atopic dermatitis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], which explained why the colonization of infant gut microbiome was less affected by cesarean section than vaginally born children.\u003c/p\u003e \u003cp\u003eThe antimicrobials administered in this study were narrow-spectrum antibiotics, which may lead to changes in the composition and diversity of gut microbiota during the perinatal period. After therapy with the narrow spectrum penicillin, Nogacka and Aloisio found a decrease in symbiotic bacteria but an increase in pathogen abundance in infants [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Taipianen revealed that the effect size of IAP was comparable to that caused by postnatal antibiotics in newborn infants [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. When narrow-spectrum antibiotics were given to pregnant women, the effects on the newborn gut microbiota were comparable to when broad-spectrum antibiotics were given directly to neonates. Moreover, Cox reported that postnatal administration of low-dose penicillin induces metabolic changes and affects the ileal expression of immune-related genes [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOther genetic and environmental factors, such as the history of family allergic disease, climate change, passive smoking, pet ownership, and other confounding factors, were believed to be connected with the incidence of atopic dermatitis [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. To better adjust the logistic regression model, these indicators, initially screened by univariate logistic regression, were selected for multivariate regression analysis, and the adjusted results showed that maternal history of allergic disease, in addition to IAP exposure, was an independent risk factor. Parental allergic disease may affect skin barrier function and immune homeostasis, leading to a variety of immunological abnormalities [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Other studies have reported that pet ownership and smoking may be linked with the development of atopic dermatitis in children, however, this was not found in our study [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are some limitations to this study. First, this study was a retrospective analysis but relied on parental feedback on a diagnosis of atopic dermatitis. Second, the lack of detailed information on parents was noticed, including a family history of allergies, and smoking history. Therefore, a prospective large-sample study will be established to collect the feces of newborns after IAP intervention and send for metagenome sequence. A longitudinal study will be conducted to investigate the impact of IAP on children to better understand the risks and benefits of the current GBS-IAP intervention strategies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eGBS-IAP intervention for pregnant mothers significantly increased the incidence of AD in children aged 2 years in vaginal delivery, whereas no significance was observed in cesarean sections.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committees of Taixing People\u0026apos;s Hospital (Reference txry2018-003) in Jiangsu Province, China. Written informed consents were obtained from the parents of all the enrolled infants before data collection. All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZH and RJ designed and organized the performance of the study; DX and YX guided and instructed the data analysis. ZH and RJ performed the study, collected and analyzed the data; LH, XK, ZC, WY and ZB participated in the table and figure analysis. ZH and RJ wrote the manuscript. DX and YX revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhu Y, Huang J, Lin XZ, Chen C. Group B streptococcus colonization in late pregnancy and invasive infection in neonates in China: A Population-Based 3-Year Study. Neonatology. 2019;115(4):301\u0026ndash;309. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000494133\u003c/span\u003e\u003cspan address=\"10.1159/000494133\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHasperhoven GF, Al-Nasiry S, Bekker V, Villamor E, Kramer B. 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Arch Dermatol. 2007;143(12):1570\u0026ndash;1577. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archderm.143.12.1570\u003c/span\u003e\u003cspan address=\"10.1001/archderm.143.12.1570\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFotopoulou M, Iordanidou M, Vasileiou E, Trypsianis G, Chatzimichael A, Paraskakis E. A short period of breastfeeding in infancy, excessive house cleaning, absence of older sibling, and passive smoking are related to more severe atopic dermatitis in children. Eur J Dermatol. 2018;28(1):56\u0026ndash;63. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1684/ejd.2017.3165\u003c/span\u003e\u003cspan address=\"10.1684/ejd.2017.3165\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"group B streptococcus, intrapartum antibiotic prophylaxis, atopic dermatitis","lastPublishedDoi":"10.21203/rs.3.rs-1869975/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1869975/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo understand the occurrence of atopic dermatitis (AD) in children aged 2 years on exposure to maternal group B streptococcus (GBS) antibiotic prophylaxis (IAP).\u003c/p\u003e\u003ch2\u003eDesign\u003c/h2\u003e \u003cp\u003eRetrospective cohort study of 2909 mother-child pairs.\u003c/p\u003e\u003ch2\u003eSetting\u003c/h2\u003e \u003cp\u003eTaixing People's Hospital in Eastern China.\u003c/p\u003e\u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eTerm infants born 2018\u0026ndash;2019, followed longitudinally from birth to 2 years.\u003c/p\u003e\u003ch2\u003eExposures\u003c/h2\u003e \u003cp\u003eThe GBS-IAP was defined as therapy with intravenous penicillin G or ampicillin or cefazolin\u0026thinsp;\u0026ge;\u0026thinsp;4 hours from delivery. Reference infants were defined as born with intrapartum antibiotic exposure via cesarean sections.\u003c/p\u003e\u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe logistic regression models were employed to analyze the effect of intrapartum GBS prophylaxis on AD in 2-year-old children during delivery. Analysis was a priori stratified according to the mode of delivery and adjusted for relevant covariates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eUnivariate and multivariate logistic regression models before and after covariate-adjusted treatment simultaneously showed that preventive GBS-IAP was associated with increased incidence of AD in children delivered vaginally (OR: 6.719,95% CI: 4.730\u0026ndash;9.544,P\u0026thinsp;\u0026lt;\u0026thinsp;0.001;aOR: 6.562,95% CI: 4.302\u0026ndash;10.008, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas cesarean delivery in 2-year-old children (OR: 0.555,95% CI: 0.276\u0026ndash;1.117, P\u0026thinsp;=\u0026thinsp;0.099;aOR: 0.560,95% CI: 0.271\u0026ndash;1.155, P\u0026thinsp;=\u0026thinsp;0.116) was not related to AD.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eProphylactic treatment of intrapartum GBS may raise the risk of AD in vaginally delivered children. Children delivered through cesarean section, on the other hand, did not have an elevated risk of AD. These findings highlight the need to better understand the risk between childhood AD and current GBS-IAP intervention strategies.\u003c/p\u003e","manuscriptTitle":"A cohort study of intrapartum group B streptococcus prophylaxis on atopic dermatitis in 2-year-old children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-26 19:40:10","doi":"10.21203/rs.3.rs-1869975/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-08-16T08:44:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-08-11T10:41:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"b7b194af-84d2-468e-ae4e-a86c5b2360cf","date":"2022-08-01T00:05:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-07-30T14:07:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-07-30T14:01:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-07-20T09:42:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-07-20T09:35:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2022-07-18T12:43:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8ab9cf35-0146-40e0-a391-471d49b83b9f","owner":[],"postedDate":"July 26th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-11-18T06:44:27+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-26 19:40:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1869975","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1869975","identity":"rs-1869975","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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