Does cesarean delivery increase risk of neurodevelopmental and psychiatric disorders?

A study by European researchers suggests that there may be a link between birth by cesarean delivery and autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). The authors cautioned, however, that their results do not show causation and there may be multiple underlying reasons for the connection they found.

Published in JAMA Network Open, the findings reflect outcomes from more than 20 million deliveries and are from a systematic review and meta-analysis of 61 studies. The researchers’ objective was to evaluate the association between cesarean delivery and risk of neurodevelopmental and psychiatric disorders in offspring. In previous studies, a connection has been found between ASD and cesarean delivery but whether such births are connected to other mental disorders remans unclear. 

To fill that gap in understanding, the authors searched Ovid MEDLINE, Embase, Web of Science, and PsycINFO from inception to December 19, 2018 on all main mental disorders in the DSM-5 and selected studies with outcomes diagnoses assessed through structured interviews or using standardized diagnostic criteria. Of the 61 studies analyzed, associations between cesarean delivery and ASD were reported in 27 studies; ADHD in 13 studies; intellectual disabilities, tic disorders, and obsessive-compulsive disorder in three studies each; four studies with eating disorders; and seven studies with non-affective psychoses.

The authors then calculated odds ratios for offspring with any neurodevelopmental or psychiatric disorder born via cesarean delivery and compared them with those for offspring born via vaginal delivery. They also looked at whether there was a differential association between those outcomes and type of cesarean delivery or assisted vaginal delivery versus unassisted vaginal delivery.

Odds of ASD and ADHD were not significantly higher in the children born via cesarean delivery versus those born via vaginal delivery. (ASD OR, 1.33; 95% CI, 1.25-1.41; I² = 69.5%; ADHD OR, 1.17; 95% CI, 1.07-1.26; I² = 79.2%). There were no significant associations between cesarean delivery and  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%).

The researchers found no significant associations between cesarean delivery and depression/affective psychoses or nonaffective psychoses. Estimates were comparable for emergency and elective cesarean delivery and both were associated with increase odds of ASD and ADHD, but heterogeneity was low.

Of their results, the authors said that “for the first time, to our knowledge, we were able to examine elective cesarean delivery separately from emergency delivery in association with neurodevelopmental and psychiatric disorders.” The main limitation of the study, they noted, was the “high level of heterogeneity in all outcomes except for depression and affective psychoses,” which was not fully explained by any of their analyses.

In conclusion, the researchers said, “future research should include further adjustment for potential confounders and consider genetically sensitive designs, such as sibling comparisons or twin and adoption studies.”