Abstract
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. To examine the association between CD and neurodevelopmental and psychiatric disorders in children. 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. Birth by CD recorded at birth, stratified into planned and intrapartum CD. 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. 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). 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.
Highlights
Neurodevelopmental disorders are a group of childhood-onset disorders that often persist into adulthood.[1]
After controlling for measured covariates, cesarean delivery (CD) was associated with higher risk in children of any neurodevelopmental disorder, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability
The associations between CD and any neurodevelopmental disorder, ADHD, autism spectrum disorders (ASD), and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated in maternal half siblings and full siblings
Summary
Neurodevelopmental disorders are a group of childhood-onset disorders that often persist into adulthood.[1] Family studies suggest that these disorders are familial and highly heritable,[2,3,4,5,6,7] their specific etiology remains unknown.[8] Birth by cesarean delivery (CD) has been suggested to represent an environmental risk factor for neurodevelopmental and psychiatric disorders. Previous studies have suggested that the described associations between CD and ASD or ADHD may not be causal but due to familial confounding.[16,17,18,19] a potential genetic overlap between psychiatric disorders and the likelihood of delivering via CD has been suggested,[20,21] indicating that CD may reflect the child’s genetic predisposition to develop psychiatric disorders rather than being a causal risk factor
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