Maternal use of antidepressants during pregnancy is unrelated to autism spectrum disorder in the offspring, according to two separate, population-level cohort studies that used sophisticated statistical techniques to account for numerous confounding factors.
Both studies were reported online April 18 in JAMA.
Some previous studies have reported a possible link between in utero exposure to antidepressants, particularly SSRIs, and autism. But they had limited ability to control for key confounders, notably the mother’s underlying depression.
Hilary K. Brown, PhD, and her associates studied the issue by analyzing data for 35,906 singleton pregnancies in Ontario during an 8-year period in which the mothers’ medication use was documented. A total of 2,837 of these mothers (7.9%) used serotonergic antidepressants during pregnancy. The children were followed for a mean of 5 years for the development of autism.Overall, 1.1% of these children were diagnosed as having autism spectrum disorder. This prevalence is consistent with current population estimates, indicating that few if any cases of the disorder were missed, said Dr. Brown of Women’s College Research Institute in Toronto and the division of epidemiology, University of Toronto, and her associates.
In initial, unadjusted analyses of the data, the risk of autism was higher in exposed than in nonexposed children. However, that association disappeared once the data were adjusted to account for numerous potential confounders.
Further analysis comparing the exposed children with their unexposed siblings also found that after adjusting for confounding factors, prenatal exposure to antidepressants did not affect the risk of developing autism. In addition, this lack of association also was found in the subgroup of children whose mothers took antidepressants shortly before but not during pregnancy.
Taken together, these findings “suggest that confounding by indication for the medication may explain previously observed associations between in utero serotonergic antidepressant exposure and autism spectrum disorder,” Dr. Brown and her associates said (JAMA. 2017 Apr 18. doi: 10.1001.jama.2017.3415). In the other study, Ayesha C. Sujan and her associates analyzed data in several nationwide Swedish registries to examine whether first trimester exposure to any antidepressants raised the risk of a range of neurodevelopmental problems, including autism. This study involved 1,580,629 offspring, including 22,544 (1.4%) whose mothers took antidepressants during the first trimester.
As with Dr. Brown’s study, the initial unadjusted analysis showed an association between antidepressant exposure and autism, but that association disappeared once the data were adjusted to account for confounding factors. In the final data analysis, first trimester exposure was associated with preterm birth (odds ratio, 1.34) but not with small-for-gestational-age size (OR, 1.01), autism spectrum disorder (hazard ratio, 0.83), or attention deficit/hyperactivity disorder (HR, 0.99), said Ms. Sujan of the department of psychological and brain sciences, Indiana University, Bloomington, and her associates.
“These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both, account for the population-wide associations between first-trimester antidepressant exposure and these outcomes,” they noted (JAMA. 2017 Apr 18. doi: 10.1001/jama.2017.3413).