It is unlikely that birth by cesarean delivery is a causal risk factor for autism spectrum disorder (ASD), according to a new study by researchers in Cork, Ireland, who have examined this issue previously.
In a meta-analytic review of relevant studies published last year in the Journal of Child Psychology and Psychiatry, they found that birth by cesarean delivery was associated with about a 20% increased risk for ASD, compared with vaginal birth.
“However, the studies were limited, and we were unable to determine what was driving this association,” Ali Khashan, PhD, Department of Epidemiology and Public Health, University College Cork said.
Their latest study published June 24 in JAMA Psychiatry, confirms the researchers’ earlier finding that children born by cesarean delivery are roughly 20% more likely to be diagnosed with ASD. However, the association did not persist in a sibling control analysis, which implies that this association is due to familial confounding by genetic and/or environmental factors, they note.
“The overall risk of ASD is very small, and this most recent work suggests that most, if not all, the risk is not to do with the cesarean section at all, which is reassuring for parents,” Louise Kenny, PhD, consultant obstetrician and gynecologist at Cork University Maternity Hospital, who worked on both studies said.
In this latest study, the largest to date on the topic, the investigators studied the association between delivery mode and ASD diagnosis in children born in Sweden between 1982 and 2010. The conventional cohort analysis included nearly 2.7 million children and 28,290 cases of ASD.
In this analysis, compared with unassisted vaginal delivery, elective cesarean delivery was associated with ASD (adjusted hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.15 – 1.27), as was emergency cesarean delivery (HR, 1.15; 95% CI, 1.10 – 1.20).
But in the sibling control analysis, elective cesarean delivery was not associated with ASD in partially (odds ratio [OR] 0.97; 95% CI, 0.85 – 1.11) or fully adjusted (OR, 0.89; 95% CI, 0.76 – 1.04) models.
Emergency cesarean delivery was associated with ASD in the partially adjusted model (OR, 1.20; 95% CI, 1.06 – 1.36), but this effect disappeared in the fully adjusted model (OR, 0.97; 95% CI, 0.85 – 1.11).
This analysis included 13,411 sibling pairs discordant for ASD, including 2555 pairs discordant on mode of delivery. With the sibling pairs analysis, “we were able to account for many factors that most previous studies could not,” Dr Khashan said.
Although the traditional cohort analysis revealed birth by cesarean delivery to be associated with ASD, “it is not necessarily a cause because the association could be due to residual confounding,” the investigators write.
Because the association between birth by cesarean delivery and ASD did not persist in the sibling control analysis, “we can conclude that there is no causal association.” It is more likely that birth by cesarean is related to some unknown genetic or environmental factor that leads to increased risk for both cesarean delivery and ASD, they conclude.
“This is a valuable study that highlights the importance of using large, population-based samples and appropriate controls when evaluating potential risk factors for ASD,” Alex Kolevzon, MD, clinical director of the Seaver Autism Center, Icahn School of Medicine at Mount Sinai, in New York City, who was not involved in the study said.
“The results provide evidence that while cesarean section delivery may be associated with ASD, it is not likely to be a causal risk factor. Many, many risk factors have been associated with ASD, and the field would benefit greatly from similarly rigorous analyses to further clarify the difference between association and causation as it relates to these factors and the risk for ASD,” Dr Kolevzon said.