Modest SSRI-Associated Risk of Persistent Pulmonary Hypertension of the Newborn

June 3, 2015

By Will Boggs, MD

NEW YORK - The risk of persistent pulmonary hypertension of the newborn (PPHN) following maternal selective serotonin reuptake inhibitor (SSRI) use late in pregnancy may be more modest than previous studies indicated, according to an analysis of Medicaid data.

A 2006 US Food and Drug Administration advisory suggested that there may be as much as a sixfold increased risk of PPHN associated with late pregnancy exposure to SSRIs, but after further studies yielded conflicting results, the FDA concluded in 2011 that it was premature to reach any conclusions about a possible link.

Given the ongoing controversy, Dr. Krista F. Huybrechts, from Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues used data extracted from the Medicaid Analytic eXtract (MAX) to examine the risk of PPHN associated with SSRI and non-SSRI antidepressants in nearly four million pregnancies.  

A total of 128,950 women (3.4%) filled at least one prescription for antidepressants during the 90 days before delivery: 102,179 (2.7%) used an SSRI and 26,771 (0.7%) a non-SSRI.

They found PPHN in 20.8 infants per 10,000 not exposed to antidepressants during the last 90 days of pregnancy, compared with 31.0 infants per 10,000 exposed to antidepressants during this period.

In unadjusted analyses, the risk of PPHN was increased by 51% in the SSRI group and 40% in the non-SSRI group, compared with infants not exposed to antidepressants, according to the June 2 JAMA report.

After adjusting for other factors, including a diagnosis of depression, the increased risk associated with SSRIs and non-SSRIs was no longer statistically significant.

The risk of PPHN was also significantly increased in association with maternal diabetes, obesity, cesarean delivery, and black race.

"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," the researchers conclude.

Dr. Nancy Byatt, from the University of Massachusetts Medical School and medical director of Massachusetts Child Psychiatry Access Project for Moms, Worcester, Massachusetts, told Reuters Health by email, "When considering whether to prescribe an antidepressant during pregnancy, it is extremely important to consider the risks of untreated illness. It is well established that depression during pregnancy is common and has adverse effects on birth outcomes, mother-infant attachment, and the behavior and development in infants and children. Although important, non-pharmacologic treatments are often inadequate for women with moderate-to-severe depression. Although the study suggests that there may be a modest association between PPHN and maternal use of antidepressants in late pregnancy, the absolute risk is small. This small risk must be considered in the context of the risk of untreated illness."

"It is also a point to consider that depression during pregnancy increases the risk of postpartum depression," Dr. Byatt said. "Thus, late pregnancy is an important time in which it is essential to provide the best possible mental health treatment. It is vital to optimize the mental health department in order to promote maternal and child health."

"SSRIs are generally considered first-line in pregnancy," Dr. Byatt added. "SSRIs are well characterized, and although risks have been reported, the overall data is reassuring."

"Nothing much has changed," Dr. Megan Galbally, from the University of Melbourne's Mercy Hospital for Women, Heidelberg, Victoria, Australia, told Reuters Health by email. "Women need as part of informed consent to understand there may be a small increased risk of PPHN after exposure to SSRI antidepressants in later pregnancy. While findings to date have been mixed and there are still many questions to be answered, this has now been found in a number of studies and one did control for mode of delivery and a number of other key confounding variables."

"The study has a number of significant limitations, which discount its value for clinical practice," Dr. Galbally said. "These include imprecise measures of exposure (SSRI) and imprecise measures of outcome (PPHN) as well as not controlling for cesarean section."

"There is a real need to undertake robust research into antidepressant exposure in pregnancy for answers on these important matters such as the risk of PPHN," Dr. Galbally concluded. "These studies need robust measures of exposure and outcome as well as accounting for the key potential confounding variables. Continuing to examine these important health concerns using data not designed to answer these questions only creates confusion for women and clinicians."

"These studies have previously been useful in identifying potential areas of concern for further examination, but there is now the urgent need for higher quality and purpose designed studies," she said.

Dr. Huybrechts was unable to provide comments in time for this report.

The Agency for Healthcare Research and Quality and the National Institutes of Health supported this research. The authors reported no disclosures.


JAMA 2015.

(c) Copyright Thomson Reuters 2015. Click For Restrictions -