Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort
Authors: Tianyang Zhang, Gustaf Brander, Ängla Mantel, Ralf Kuja-Halkola, Olof Stephansson, Zheng Chang, Henrik Larsson, David Mataix-Cols, Lorena Fernández de la Cruz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Recent studies suggest that cesarean delivery (CD) is associated with increased risk of neurodevelopmental disorders in children, although they were unable to control for indications for CD or familial confounding beyond full siblings. <h3>Objective</h3> To examine the association between CD and neurodevelopmental and psychiatric disorders in children. <h3>Design, Setting, and Participants</h3> This Swedish register-based cohort study included 1 179 341 term-birth singletons born between January 1, 1990, and December 31, 2003, and followed up through December 31, 2013. All individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins. Statistical analyses were performed from September 26, 2019, to January 16, 2021. <h3>Exposures</h3> Birth by CD recorded at birth, stratified into planned and intrapartum CD. <h3>Main Outcomes and Measures</h3> Registered diagnoses of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, tic disorders, communication disorders, learning disorders, and any neurodevelopmental disorder; and psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, depressive disorders, eating disorders, bipolar disorders, psychotic disorders, and any psychiatric disorder. <h3>Results</h3> Of 1 179 341 individuals, 1 048 838 (533 140 boys [50.8%]) were delivered vaginally, 59 514 (30 138 boys [50.6%]) were delived via planned CD, and 70 989 (39 191 boys [55.2%]) were delivered via intrapartum CD. Mean (SD) age at follow-up was 17.7 (4.1) years for vaginal delivery, 16.6 (4.2) years for planned CD, and 16.8 (4.1) years for intrapartum CD. Compared with vaginal delivery, and after controlling for measured covariates (parental and neonatal characteristics, maternal comorbidities, and pregnancy complications), CD was associated with higher risk in children of any neurodevelopmental disorder (planned CD, hazard ratio [HR], 1.17; 95% CI, 1.13-1.22; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.14), ADHD (planned CD, HR, 1.17; 95% CI, 1.12-1.23; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.15), and intellectual disability (planned CD, HR, 1.26; 95% CI, 1.14-1.39; intrapartum CD, HR, 1.17; 95% CI, 1.06-1.28). Only planned CD was associated with a higher risk of ASD (HR, 1.20; 95% CI, 1.10-1.31), communication disorders (HR, 1.14; 95% CI, 1.02-1.28), and learning disorders (HR, 1.15; 95% CI, 1.01-1.30). Cesarean delivery was not associated with the remaining disorders. The associations between CD and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated (became nonsignificant) in maternal half siblings and full siblings (risk of any neurodevelopmental disorder in full siblings, planned CD, HR, 0.93; 95% CI, 0.81-1.06; intrapartum CD, HR, 1.07; 95% CI, 0.96-1.21). <h3>Conclusions and Relevance</h3> The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding.