Antidepressants during pregnancy tied to ASD without intellectual disability risk
Children of mothers on antidepressants during pregnancy appear to have a higher risk of autism spectrum disorder (ASD) without intellectual disability compared with children of mothers with psychiatric conditions but without exposure to antidepressants during pregnancy, a recent observational prospective cohort study has found.
“This points to a potential effect of antidepressant use on the risk of autism beyond any effect caused by confounding by the underlying condition. It is important to note, however, that the absolute risk was small,” researchers said.
The investigators retrieved relevant medical and psychiatric data of 254,610 individuals aged 4 to 17 years from the Stockholm youth cohort. Adopted children, those born before 1996 and those who could not be linked to their biological mothers were excluded from the study.
Both the medical birth and the prescribed drug registers were consulted to identify use of antidepressants during pregnancy. The national patient and the habilitation registers were included in the validation of autism diagnoses.
There were 3,342 children exposed to antidepressants during pregnancy, 4.1 percent (n=136) of which developed ASD. In comparison, 2.9 percent (n=353) of the 12,325 children of mothers with psychiatric disorders but not on antidepressants developed ASD. [BMJ 2017;358:j2811]
Of the 238,943 children of mothers without psychiatric disorders and no exposure to antidepressants during pregnancy, 2.1 percent (n=4,889) had ASD.
Regression analysis showed that antidepressant exposure during pregnancy was associated with higher risks of ASD (odds ratio [OR], 1.45; 95 percent CI, 1.13 to 1.85), specifically ASD without intellectual disability (OR, 1.57; 1.21 to 2.04) after adjusting for birth year, maternal psychiatric disorders, other medications used, sex, maternal age and other confounders.
Propensity score and sibling matched analyses showed that children exposed to antidepressants during pregnancy had higher risks of ASD (OR, 1.68; 1.23 to 2.30 and OR, 1.36; 0.84 to 2.20, respectively) and ASD without intellectual disability (OR, 1.76; 1.26 to 2.46 and OR, 1.57; 0.92 to 2.66, respectively).
In contrast, paternal antidepressant use did not have significant impact on ASD (OR, 1.13; 0.68 to 1.88) and ASD without intellectual disability (OR, 1.18; 0.68 to 2.06), according to negative control analysis adjusted for maternal psychiatric disorders, paternal depression, age, sex, and other confounders.
“The findings seemed to be consistent across traditional regression methods, propensity score matching and a sibling set comparison, and maternal exposure to antidepressants during pregnancy had a strong association with the outcomes, whereas no such association was observed with paternal exposure,” according to researchers.
Limitations of the present study include the lack of detailed measurements of depression during pregnancy and the failure to determine dose-response and trimester-specific effects of the medication. Among its strengths, on the other hand, were the large sample size and the use of several analyses, both of which improve the statistical power and reliability of the obtained data.
“The different analyses we used have different strengths and limitations, but their findings seemed to triangulate, pointing towards an association between maternal antidepressant use in pregnancy and autism in offspring,” researchers said.