Neurodevelopmental Problems Not Linked to Antidepressant Exposure In Utero

iStock/Mohammed Haneefa Nizamudeen

Children who were exposed to antidepressants in the womb do not appear to have an increased risk of neurodevelopmental disorders, according to a comprehensive analysis of health insurance data. The results were published in JAMA Internal Medicine.

This study is part of a larger project on medication use during pregnancy being led by the Harvard Program on Perinatal and Pediatric Pharmacoepidemiology (H4P). Though numerous studies have explored the potential risks of exposure to psychiatric medications in utero, the results have been conflicting and confusing, noted Elizabeth Suarez, Ph.D., M.P.H., an instructor at the Center for Pharmacoepidemiology and Treatment Science at Rutgers University. “These studies were limited by small sample sizes that skewed the results or analyses that weren’t adjusted for important variables,” said Suarez, who joined Rutgers following a postdoctoral fellowship at H4P.

By conducting rigorous statistical testing on millions of claims from both a public (Medicaid Analytic eXtract) and private (MarketScan Commercial Claims Database) insurance database, the H4P project aims to provide more clarity on neurodevelopmental risks associated with taking these medications during pregnancy for both patients and physicians, she said. Earlier this year, the H4P team reported that most antipsychotic use during pregnancy was not linked to a range of neurodevelopmental disorders in offspring (Most Antipsychotics During Pregnancy Do Not Increase Neurodevelopmental Risks).

For this analysis, Suarez and colleagues made use of data on 1.93 million pregnancies in the Medicaid database and 1.25 million pregnancies in the MarketScan database. In total, 145,702 pregnancies involved antidepressant use during the second half of pregnancy. (Week 19 of pregnancy is typically when brain development increases dramatically.)

The researchers compared the rates of the following neurodevelopmental disorders in children who were or were not exposed to antidepressants: autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), learning disorder, developmental speech disorder, developmental coordination disorder, intellectual disability, and behavioral disorder.

Overall, children who were exposed to antidepressants during pregnancy had a 1.76-fold increased risk of being diagnosed with any neurodevelopmental disorders. The risk ranged from a 1.32-fold increased risk of learning disorder to a 2.02-fold increased risk of ADHD.

After adjusting for over 70 variables, such as the mother’s underlying mental health diagnoses, sociodemographic factors, and lifestyle behaviors (such as smoking or drinking), the neurodevelopmental risk associated with antidepressants dropped to 1.15-fold increased risk of any disorder.

The overall risk dropped to 1.10-fold when comparing women who took antidepressants during pregnancy with women who took antidepressants shortly before pregnancy and then stopped. Among individual disorders, only developmental speech and coordination disorders showed a modest elevated risk by continuing antidepressants.

Finally, to factor in familial factors, Suarez and colleagues compared families where some siblings had been exposed to antidepressants while others had not. In these sibling analyses, there was no evidence of increased risk of any neurodevelopmental disorder from antidepressant exposure.

“Having these different comparisons addresses clinically relevant questions, as physicians see patients with a range of medication and pregnancy histories,” Suarez told Psychiatric News.

The researchers also compared the neurodevelopmental risks of in utero exposure to different antidepressant classes (selective serotonin reuptake inhibitors, serotonin norepinephrine uptake inhibitors, and tricyclics) as well as the five most prescribed agents (sertraline, fluoxetine, bupropion, citalopram, and escitalopram). They identified no significant differences in risk of neurodevelopmental disorder according to the antidepressant class. Additionally, no medications were associated with any neurodevelopmental risks except for escitalopram (1.29-fold increased risk of any disorder).

Suarez said the escitalopram findings could be a statistical anomaly, but since the risk was present across among multiple outcomes the potential risk is worth exploring further.

She added that she hopes these findings offer reassurance that for women with depression or anxiety, these medications are likely not adding any substantial risk during pregnancy.

“That’s not to imply that the people who need these medications don’t face extra risks,” Suarez continued. “One of the surprising findings in our study was just how high the raw incidence rate of neurodevelopmental disorders was among children exposed to these medications.” In the Medicaid cohort, for example, over 46% of exposed children were diagnosed with at least one neurodevelopmental disorder by age 12. “Therefore, we need to make sure to carefully screen children who were exposed so we can offer early interventions if needed.”

The H4P group is continuing their efforts with an examination of stimulant use during pregnancy and will follow that up with an analysis of antiepileptics. This large project is funded by a grant from the National Institute of Mental Health. ■