Maternal antidepressant use during the first trimester of pregnancy and offspring neurodevelopmental problems

Previous studies have found associations between maternal antidepressant use during pregnancy and offspring neurodevelopmental problems, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder... [ view full abstract ]

Previous studies have found associations between maternal antidepressant use during pregnancy and offspring neurodevelopmental problems, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, these studies may not have adequately accounted for confounding factors, such as maternal depression.

The present study of 1,580,629 Swedish offspring used two sources of information on maternal antidepressant use (self-reports and dispensation records) and four designs to account for confounding factors to assess associations between maternal first-trimester antidepressant use and offspring ASD and ADHD. The designs were (1) statistical controls to adjust for measured pregnancy, maternal, and paternal characteristics; (2) sibling comparisons to account for unmeasured genetic and environmental factors that make siblings similar; (3) timing-of-exposure comparisons to account for factors related to maternal antidepressant treatment around the time of pregnancy; and (4) paternal comparisons as another approach to account for familial confounding.  

In the population, first-trimester antidepressant exposure based on maternal report was associated with ASD (HR = 2.0, 95% CI, [1.8-2.3]) and ADHD (HR = 2.2, 95% CI, [2.0-2.4]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester exposure was not associated with ASD (HR = 0.8, 95% CI [0.6-1.1]) or ADHD (HR = 1.0, 95% CI [0.8-1.3]. For both ASD and ADHD, the associations with maternal antidepressant dispensations before but not during or after pregnancy did not statistically differ significantly from the associations with first-trimester maternal dispensations. Paternal first-trimester dispensations were associated with ASD (HR = 1.3, 95% CI [1.1-1.6]) and ADHD (HR = 1.7, 95% CI [1.4-2.2]).

Results from the present study suggest that maternal first-trimester antidepressant use does not increase the risk of offspring ASD and ADHD. These findings can help pregnant women and their doctors more accurately weigh the risks and benefits of treating maternal depression early in pregnancy with antidepressants.