Findings from a retrospective study involving over 1.5 million Swedish offspring showed that first-trimester exposure to antidepressants was associated with a slight increase in risk of preterm birth but no increase in risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder after adjusting for confounders. The full study is published in JAMA.

Although antidepressant exposure during the prenatal period  has been linked to adverse outcomes, the studies may not have adjusted for confounding factors. A team of researchers, led by Ayesha C. Sujan, MA, from Indiana University, Bloomington, IN, analyzed Swedish offspring born between 1996–2012 that were followed up through 2013 or censored by death or emigration. They controlled for pregnancy, maternal and paternal covariates, sibling comparisons, timing of exposure comparisons, and paternal comparisons to evaluate the associations. 

The study’s main outcome measures were preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations [SDs] below the mean for gestational age), and first inpatient/outpatient clinical diagnosis of autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD) in offspring. 

The results showed of the 1,580,629 babies born to 943,776 mothers, more maternal first-trimester exposed babies were preterm vs. unexposed babies (6.98% vs. 4.78%), and 2.54% of exposed babies were small for gestational age vs. 2.19% of unexposed babies. 

Autism spectrum disorder was diagnosed by age 15 in 5.28% of exposed vs. 2.14% of unexposed babies; 12.63% of exposed vs. 5.46% of unexposed babies were diagnosed with ADHD by age 15.  

First-trimester exposure was generally associated with all main outcomes at the population level when compared with unexposed offspring as seen with the following odds ratios [OR]: preterm birth (OR 1.47, 95% CI: 1.40–1.55); small for gestational age (OR 1.15, 95% CI: 1.06–1.25); autism spectrum disorder (hazard ratio [HR] 2.02, 95% CI: 1.80–2.26); ADHD (HR 2.21, 95% CI: 2.04–2.39). 

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However, when comparing siblings (with adjustments for covariates), first-trimester antidepressant exposure was associated with preterm birth (OR 1.34, 95% CI: 1.18–1.52) but not with small for gestational age (OR 1.01, 95% CI: 0.81–1.25), autism spectrum disorder (HR 0.83, 95% CI: 0.62–1.13), or ADHD (HR, 0.99, 95% CI: 0.79–1.25).

“Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons,” the authors concluded.

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