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Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis.

ABSTRACT: BACKGROUND:Numerous studies indicate caesarean delivery is associated with childhood asthma. Sex-specific associations were reported in four of these studies, and in all four studies, the estimated association between caesarean delivery and asthma was of greater magnitude among girls, although most report a lack of evidence of multiplicative interaction. METHODS:We assessed potential effect modification by sex, on the additive and multiplicative scales, of the association between caesarean delivery and asthma by ages 2 through 6 in up to 17 075 racially diverse children from a retrospective birth cohort, the Kaiser Air Pollution and Pediatric Asthma (KAPPA) Study. We also conducted a random-effects meta-analysis, combining our sex-stratified results (using the odds ratio for compatibility with previous studies) with previously published results. RESULTS:Adjusted risk differences for caesarean delivery and asthma in the KAPPA cohort were higher among girls than boys at every follow-up age. By age 5, caesarean delivery was associated with an absolute 3.8% (95% confidence interval [CI] 0.4%, 7.3%) higher asthma risk among girls and a 1.9% (95% CI -1.7, 5.4) higher risk among boys. The summary odds ratio from the meta-analysis for caesarean delivery and asthma among girls was 1.26 (95% CI 1.14, 1.39) and 1.08 (95% CI 0.98, 1.20) among boys (P = 0.036). CONCLUSIONS:Higher, but imprecise, estimates for females across five studies should motivate investigators to estimate sex-specific associations for caesarean delivery and asthma and to explore biological mechanisms or sex-dependent biases that could explain this possible heterogeneity.

SUBMITTER: Pennington AF

PROVIDER: S-EPMC6261703 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis.

Pennington Audrey Flak AF Strickland Matthew J MJ Klein Mitchel M Drews-Botsch Carolyn C Hansen Craig C Darrow Lyndsey A LA

Paediatric and perinatal epidemiology 20180928 6

<h4>Background</h4>Numerous studies indicate caesarean delivery is associated with childhood asthma. Sex-specific associations were reported in four of these studies, and in all four studies, the estimated association between caesarean delivery and asthma was of greater magnitude among girls, although most report a lack of evidence of multiplicative interaction.<h4>Methods</h4>We assessed potential effect modification by sex, on the additive and multiplicative scales, of the association between ...[more]

PMID: 30266042

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Project description:BackgroundResults from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery.MethodsWe pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis.FindingsThe studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]).InterpretationOur results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism.FundingNational Cancer Institute.

Project description:ObjectiveTo compare the risk of stillbirth and miscarriage in a subsequent pregnancy in women with a previous caesarean or vaginal delivery.DesignSystematic review of the published literature including seven databases: CINAHL; the Cochrane library; Embase; Medline; PubMed; SCOPUS and Web of Knowledge from 1945 until November 11(th) 2011, using a detailed search-strategy and cross-checking of reference lists.Study selectionCohort, case-control and cross-sectional studies examining the association between previous caesarean section and subsequent stillbirth or miscarriage risk. Two assessors screened titles to identify eligible studies, using a standardised data abstraction form and assessed study quality.Data synthesis11 articles were included for stillbirth, totalling 1,961,829 pregnancies and 7,308 events. Eight eligible articles were included for miscarriage, totalling 147,017 pregnancies and 12,682 events. Pooled estimates across the stillbirth studies were obtained using random-effect models. Among women with a previous caesarean an increase in odds of 1.23 [95% CI 1.08, 1.40] for stillbirth was yielded. Subgroup analyses including unexplained stillbirths yielded an OR of 1.47 [95% CI 1.20, 1.80], an OR of 2.11 [95% CI 1.16, 3.84] for explained stillbirths and an OR of 1.27 [95% CI 0.95, 1.70] for antepartum stillbirths. Only one study reported adjusted estimates in the miscarriage review, therefore results are presented individually.ConclusionsGiven the recent revision of the National Institute for Health and Clinical Excellence guidelines (NICE), providing women the right to request a caesarean, it is essential to establish whether mode of delivery has an association with subsequent risk of stillbirth or miscarriage. Overall, compared to vaginal delivery, the pooled estimates suggest that caesarean delivery may increase the risk of stillbirth by 23%. Results for the miscarriage review were inconsistent and lack of adjustment for confounding was a major limitation. Higher methodological quality research is required to reliably assess the risk of miscarriage in subsequent pregnancies.

Project description:BackgroundCaesarean delivery has increased worldwide, however, the effects on fertility are largely unknown. This systematic review aims to compare subsequent sub-fertility (time to next pregnancy or birth) among women with a Caesarean delivery to women with a vaginal delivery.MethodsSystematic review of the literature including seven databases: CINAHL; the Cochrane Library; Embase; Medline; PubMed; SCOPUS and Web of Knowledge (1945 - October 2012), using detailed search-strategies and reference list cross-checking. Cohort, case-control and cross-sectional studies were included. Two assessors reviewed titles, abstracts, and full articles using standardised data abstraction forms and assessed study quality.Results11 articles were eligible for inclusion in the systematic review, of these five articles which adjusted for confounders were combined in a meta-analysis, totalling 750,407 women using fixed-effect models. Previous Caesarean delivery was associated with an increased risk of sub-fertility [pooled odds ratio (OR) 0.90; 95% CI 0.86, 0.93]. Subgroup analyses by parity [primiparous women: OR 0.91; 95% CI 0.87, 0.96; not limited to primiparous women: OR 0.81; 95% CI 0.73, 0.90]; by publication date (pre-2000: OR 0.80, 95% CI 0.68, 0.94; post-2000: OR 0.90, 95% CI 0.86, 0.94); by length of follow-up (<10 years: OR 0.81, 95% CI 0.73, 0.90; >10 years: OR 0.91, 95% CI 0.87, 0.96); by indication for mode of delivery (specified: 0.92, 95% CI 0.88, 0.97; not specified: OR 0.81, 95% CI 0.73, 0.90); by cohort size (<35,000: OR 0.79, 95% CI 0.67, 0.92; >35,000: OR 0.90, 95% CI 0.87, 0.95), by definition of sub-fertility used divided into (birth interval [BI]: OR 0.89, 95% CI 0.84, 0.94; inter-pregnancy interval [IPI]: OR 0.91, 95% CI 0.85, 0.97; and categorical measures: OR 0.81, 95% CI 0.73, 0.90); continuous measures: OR 0.91, 95% CI 0.87, 0.96) were performed. Results of the six studies not included in the meta-analysis (which did not adjust for confounders) are presented individually.ConclusionsThe meta-analysis shows an increased waiting time to next pregnancy and risk of sub-fertility among women with a previous Caesarean delivery. However, included studies are limited by poor epidemiological methods such as variations in the definition of time to next pregnancy, lack of confounding adjustment, or details of the indication for Caesarean delivery. Further research of a more robust methodological quality to better explore any underlying causes of sub-fertility and maternal intent to delay childbearing is warranted.

Dataset Information

Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis.

Publications

Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis.

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