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Maternal antidepressant exposure does not increase autism, ADHD risk

Use of antidepressants during pregnancy was significantly associated with preterm birth, but not with being small for gestational age, autism spectrum disorder or attention-deficit/hyperactivity disorder, according to research published in JAMA.

“Given the increasing prevalence of antidepressant use among pregnant women, gaining knowledge on the safety of use during pregnancy is a public health priority,” Ayesha C. Sujan, MA, from department of psychological and brain sciences at Indiana University, and colleagues wrote.

“Prenatal antidepressant exposure has been associated with adverse outcomes,” they added. “Previous studies, however, may not have adequately accounted for confounding.”

Sujan and colleagues conducted a retrospective cohort study of 1,580,629 Swedish offspring (mean gestational age, 279 days; 48.6% female) born between 1996 and 2012 to assess alternative explanations for associations between use of antidepressants during the first trimester, and birth and neurodevelopmental issues, including preterm birth (< 37 gestational weeks), small for gestational age (birthweight < 2 SDs below the mean for gestational age) and first inpatient or outpatient clinical diagnosis of autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD). Offspring were followed until 2013, death or emigration. The researchers controlled the analysis for potential confounding factors, including pregnancy and maternal and paternal covariates, as well as sibling, timing of exposure and paternal comparisons.

Antidepressant use during the first trimester was self-reported by 1.4% of mothers (n = 22,544). Overall, children exposed to maternal antidepressant use showed trends toward greater risk for preterm birth, small for gestational age, autism and ADHD.

However, sibling comparison models adjusting for pregnancy and maternal and paternal traits revealed that such data were not statistically significant. Rather, these models indicated that maternal antidepressant use during the first trimester 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 (HR = 0.83; 95% CI, 0.62-1.13) or ADHD (HR = 0.99; 95% CI, 0.79-1.25). These findings were consistent with assessments of associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations.

In an accompanying editorial, Tim F. Oberlander, MD, from the division of developmental pediatrics at the University of British Columbia, Vancouver, and Lonnie Zwaigenbaum, MSc, MD, from the department of pediatrics at the University of Alberta, Edmonton, highlighted that this study did not account for maternal psychiatric illness severity variations during pregnancy or postnatally, and the next step is to determine the impact of maternal mood disorders on the fetus compared with shared genetic predisposition to mental and neurodevelopmental disorders.

These findings are a reminder that offspring of mothers with depression are at a heightened risk for developmental disturbances regardless of antidepressant exposure, they added.

“Identifying how maternal mood and related genetic and environmental factors shape developmental risk is needed, moving away from a focus on antidepressant medications alone and toward whether some mothers and their children might actually benefit from prenatal maternal antidepressant treatment,” they wrote.

“Not all children with antidepressant exposure experience developmental adversity and identifying why some children do remains a challenge,” Oberlander and Zwaigenbaum concluded. “Regardless of whether associations between antidepressant use during pregnancy and autism spectrum disorder reflect drug effects or risks inherent to maternal mental health, efforts should focus on how best to promote optimal child health in ways that harness a child’s inherent developmental plasticity.” – by Alaina Tedesco

Disclosures: Sujan and colleagues report receiving research support from the National Institute of Mental Health of the NIH and the National Institute on Drug Abuse of NIH. Oberlander reports receiving support from the BC Children’s Hospital Research Institute, the Canadian Institutes for Health Research, Brain Canada and the Kids Brain Health Network. Zwaigenbaum reports receiving support from the Women’s and Children’s Health Research Institute, the Glenrose Rehabilitation Hospital Foundation, the Canadian Institutes for Health Research, Brain Canada and the Kids Brain Health Network. Please see full study for complete list of all authors’ financial disclosures.