Over the past few years, multiple reports have raised questions regarding the safety of selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy. Chambers and colleagues reported that exposure to SSRIs late in pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN). In the general population, PPHN affects about 1 to 2 per 1000 live births. Infants with PPHN are typically full-term or near-term and present shortly after delivery with severe respiratory distress. In the worst cases, PPHN requires intubation and mechanical ventilation and may result in long-term morbidity. In 2006, Chambers and colleagues published an article linking SSRI use during late pregnancy to an increased risk of persistent pulmonary hypertension in the newborn. Based on the results of this analysis, the authors estimated the risk of PPHN to be about 1% in infants exposed to SSRIs late in pregnancy (after 20 weeks).

This study raised significant anxiety and prompted many to question the use of SSRIs during pregnancy. However, the findings of the Chambers study have been difficult to reconcile with other studies. While earlier reports of neonatal symptoms documented cases of respiratory distress (usually tachypnea or rapid breathing), the observed symptoms were relatively mild, transient, and did not require specific medical intervention, suggesting that these cases were not PPHN, a more serious complication. Furthermore, informal surveys of sites specializing in the treatment of women during pregnancy did not reveal any cases of PPHN related to SSRI exposure.

Two more recent studies help to shed light on the risk of PPHN in infants exposed to SSRIs during pregnancy. The first study, presented at the annual meeting of American Psychiatric Association in 2007 did not report any association between SSRI use and PPHN. Researchers at the Mayo Clinic in Rochester, Minnesota reviewed the medical records of 25,214 deliveries, including 745 mothers who had been treated with SSRIs during their pregnancies. They found no association between SSRI use during pregnancy and the occurrence of PPHN. Of the 16 infants diagnosed with persistent pulmonary hypertension in this cohort, none had been exposed to SSRIs. Furthermore, the study did not demonstrate any association between SSRI use and any type of cardiovascular malformation.

The second study from the Slone Epidemiology Center was a case-control study designed to identify possible predictors of PPHN. In this study, 377 mothers of infants with PPHN and 836 mothers of matched control subjects were enrolled. The maternal factors that were most strongly associated with an elevated risk for persistent pulmonary hypertension of the newborn were black or Asian race, high pre-pregnancy BMI (>27 vs. <20), diabetes and asthma. The risk for PPHN was about seven times higher for those who were born by cesarean section. The risk was also moderately elevated for male infants, for infants who were born either late preterm (born between 34 and 37 weeks) or post-term (born after 41 weeks), and for infants who were large for gestational age at birth. While this study did not rule out SSRI use as a potential risk factor for PPHN, it does indicate that there are many other factors that are stronger predictors of risk.

Ruta Nonacs, MD PhD

Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med 2006; 354(6):579-87.

Hernández-Díaz S, Van Marter LJ, Werler MM, et al. Risk Factors for Persistent Pulmonary Hypertension of the Newborn. Pediatrics 2007; 120: e272 – e282.

*This post was originally published as an article in our March 2008 Newsletter.

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