Association of caesarean delivery with offspring health outcomes in full-cohort versus sibling-comparison studies: a comparative meta-analysis and simulation study

BMC Medicine

Research Article

Yu-bo Zhou¹  Zhen-yu Guo¹  Zhi Lin¹  Hong-zhao Yu¹  Xiao-wei Wang¹  Hong-tian Li²  Jian-meng Liu² 

[1] Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing, China;Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China;Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing, China;Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China;Center for Intelligent Public Health, Institute for Artificial Intelligence, Peking University, Beijing, China;

关键词: Caesarean delivery;    Offspring health outcomes;    Cohort;    Sibling comparison;    Systemic review;    Meta-analysis;    Simulation;   

DOI  :  10.1186/s12916-023-03030-2

 received in 2023-04-05, accepted in 2023-08-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFull-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery.MethodsA systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis.ResultsEighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study.ConclusionsSibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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