In utero antidepressant exposure not associated with neurodevelopmental disorders
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Antidepressant use in pregnancy was not associated with neurodevelopmental disorders in offspring, according to a cohort study published in JAMA Internal Medicine.
“There has been a lot of research in this area, but results are conflicting and do not offer a lot of clarity for patients and providers,” Elizabeth A. Suarez, MPH, PhD, who was a postdoctoral research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School at the time of the study, told Healio. “Many studies did not properly account for other factors that could explain an association between antidepressant use in pregnancy and neurodevelopmental disorders in children, such as the indication for the medication (eg, depression, anxiety) and genetic or environmental causes. We had an opportunity to address these limitations in a very large population of pregnant patients in the United States.”
Data collection
Suarez and colleagues used Medicaid Analytic eXtract (MAX) data from 2000 to 2014 and data from the MarketScan Commercial Claims and Encounters database (IBM) from 2003 to 2015 to create a cohort of pregnant patients who had Medicaid and private insurance, respectively. They identified 145,702 pregnancies exposed to antidepressants at 19 weeks’ gestation or later, and 3,032,745 pregnancies that were not exposed to antidepressants. The researchers followed children until one of the following events was reached:
- diagnosis of autism spectrum disorder (ASD), ADHD, specific learning disorders, developmental speech/language disorder, developmental coordination disorder, intellectual disability, behavioral disorder or any neurodevelopmental disorder;
- disenrollment from insurance;
- death; or
- end of the study.
Risk for neurodevelopmental disorders
The MAX cohort had a higher cumulative incidence of neurodevelopmental disorders compared with the MarketScan cohort.
Disorders were common among antidepressant-exposed children in both groups, with 46.8% of children (95% CI, 45.6-48.1) in the MAX cohort and 24.9% (95% CI, 23-26.9) in the MarketScan cohort having at least one neurodevelopmental disorder by age 12 years. In unexposed children, the incidence rate was 31.4% (95% CI, 31.1-31.6) in the MAX cohort and 15.1% (95% CI, 14.7-15.4) in the MarketScan cohort.
“The incidence of neurodevelopmental disorders in children who were exposed to antidepressants during pregnancy is quite high, especially for children in the Medicaid population,” Suarez said. “While we do not believe this is due to the medications, antidepressant use in pregnancy could be a marker for identifying children that may be at higher risk and could benefit from early screening and intervention.”
Although crude HRs for neurodevelopmental disorder outcomes suggested that antidepressants increased the risk for all outcomes, adjusted analyses largely attenuated the difference.
For instance, the risk for specific learning disorders — for which antidepressant-exposed children had a 32% greater risk in unadjusted analyses — were not significantly different between children who were vs. were not exposed to antidepressants in adjusted analyses (adjusted HR = 1.01; 95% CI, 0.87-1.17). The HRs for ADHD — for which antidepressant-exposed children had the greatest risk compared with unexposed children — were 2.02 (95% CI, 1.96-2.08) in unadjusted analyses and 1.2 (95% CI, 1.15-1.25) in adjusted analyses.
Comparisons of siblings who were and were not exposed to antidepressants in utero revealed a similar risk for all neurodevelopmental disorder outcomes between siblings.
Of note, the findings were largely consistent between antidepressant classes and drugs, as well as across different timings of exposures.
“Hopefully these findings will help patients and providers make difficult treatment decisions in pregnancy,” Suarez said. “Given that we have evidence that untreated depression and anxiety in pregnancy may increase the risk of adverse outcomes, treatment discontinuation should not be the default option. These results suggest that neurodevelopmental disorders in children are not a potential risk that patients and providers have to consider when deciding to take antidepressants in pregnancy.”
Perspective
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In this study, Suarez and colleagues utilized data from two large claims databases in the U.S. and concluded that antidepressant use during pregnancy does not increase the risk for neurodevelopmental disorders in children. The investigators conducted a methodologically strong study addressing many limitations of previous research. While results support the study conclusions for several of the neurodevelopmental outcomes investigated (ie, autism, ADHD, specific learning disorders, intellectual disability), the results suggest a potential increased risk associated with antidepressant use during pregnancy for others (ie, developmental speech and language disorders, developmental coordination disorders and behavioral disorders).
Depression is the most common complication of pregnancy and, if left untreated, is associated with adverse maternal, pregnancy and child developmental outcomes. Women, especially women of color, report a preference for non-pharmaceutical treatment options for perinatal depression. This is of significance given that access to preferred treatment choice improves treatment initiation, adherence and outcomes.
Findings from the current study are an important contribution to the body of research for clinicians and patients to make informed treatment decisions. However, these findings underscore the continued need for evidence-based research into alternative treatment options (eg, mindfulness, exercise or peer support) and training of mental health care clinicians from diverse backgrounds to address inequities in perinatal mental health.
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