Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring: A Systematic Review and Meta-analysis.

Importance: Birth by cesarean delivery is increasing globally, particularly cesarean deliveries without medical indication. Children born via cesarean delivery may have an increased risk of negative health outcomes, but the evidence for psychiatric disorders is incomplete. Objective: To evaluate the association between cesarean delivery and risk of neurodevelopmental and psychiatric disorders in the offspring. Data Sources: Ovid MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception to December 19, 2018. Search terms included all main mental disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Study Selection: Two researchers independently selected observational studies that examined the association between cesarean delivery and neurodevelopmental and psychiatric disorders in the offspring. Data Extraction and Synthesis: Two researchers independently extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines and assessed study quality using the Newcastle-Ottawa Scale. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% CIs for each outcome. Sensitivity and influence analyses tested the robustness of the results. Main Outcomes and Measures: The ORs for the offspring with any neurodevelopmental or psychiatric disorder who were born via cesarean delivery compared with those were born via vaginal delivery. Results: A total of 6953 articles were identified, of which 61 studies comprising 67 independent samples were included, totaling 20 607 935 deliveries. Compared with offspring born by vaginal delivery, offspring born via cesarean delivery had increased odds of autism spectrum disorders (OR, 1.33; 95% CI, 1.25-1.41; I2 = 69.5%) and attention-deficit/hyperactivity disorder (OR, 1.17; 95% CI, 1.07-1.26; I2 = 79.2%). Estimates were less precise for intellectual disabilities (OR, 1.83; 95% CI, 0.90-3.70; I2 = 88.2%), obsessive-compulsive disorder (OR, 1.49; 95% CI, 0.87-2.56; I2 = 67.3%), tic disorders (OR, 1.31; 95% CI, 0.98-1.76; I2 = 75.6%), and eating disorders (OR, 1.18; 95% CI, 0.96-1.47; I2 = 92.7%). No significant associations were found with depression/affective psychoses or nonaffective psychoses. Estimates were comparable for emergency and elective cesarean delivery. Study quality was high for 82% of the cohort studies and 50% of the case-control studies. Conclusions and Relevance: The findings suggest that cesarean delivery births are associated with an increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder, irrespective of cesarean delivery modality, compared with vaginal delivery. Future studies on the mechanisms behind these associations appear to be warranted.