Use of antidepressants in late pregnancy may be associated with increased risk of PPHN

An analysis of approximately 3.8 million pregnancies finds that use of antidepressants late in pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN), according to a study in the June 2 issue of JAMA. However, the absolute risk was small and the risk increase appears more modest than suggested in previous studies. PPHN is a rare but life-threatening condition that occurs when a newborn's circulation system doesn't adapt to breathing outside the womb.

Persistent pulmonary hypertension of the newborn is associated with substantial illness and death: 10 percent to 20 percent of affected infants will not survive, and infants who survive face serious long-term consequences, including chronic lung disease, seizures, and neurodevelopmental problems. An association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of PPHN has been controversial since the U.S. Food and Drug Administration issued a public health advisory in 2006. Studies that found no increased risk tended to be small, raising the possibility that they had insufficient power to detect an increased risk, according to background information in the article.

Krista F. Huybrechts, M.S., Ph.D., of Brigham and Women's Hospital, Boston, and colleagues examined the risk of PPHN associated with both SSRI and non-SSRI antidepressants among 3,789,330 pregnant women enrolled in Medicaid (from 46 U.S. states and Washington, D.C.; data from 2000-2010).

Of the study population, 128,950 women (3.4 percent) used an antidepressant during the 90 days before delivery: 102,179 (2.7 percent) were exposed to an SSRI and 26,771 (0.7 percent) to a non-SSRI antidepressant. Overall, 20.8 per 10,000 infants not exposed to antidepressants during the last 90 days of pregnancy had PPHN compared with 31.0 per 10,000 infants exposed to antidepressants. This higher risk among exposed infants was observed for both SSRI (31.5 per 10,000 infants) and non-SSRI (29.1 per 10,000 infants) antidepressants.

Associations between antidepressant use and PPHN were decreased with adjustment for confounders (factors that can influence outcomes that may improperly skew the results).

"Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However the absolute risk was small, and the risk increase appears more modest than suggested in previous studies," the authors write.

"The findings in the largest cohort studied to date, using advanced epidemiologic methods to mitigate confounding by the underlying psychiatric illness and its associated conditions and behaviors, suggest that the risk of PPHN associated with late pregnancy exposure to SSRI antidepressants—if present—is smaller than previous studies have reported. Clinicians and patients need to balance the potential small increase in the risk of PPHN, along with other risks that have been attributed to SSRI use during pregnancy, with the benefits attributable to these drugs in improving maternal health and well-being."