Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn

Abstract

Persistent pulmonary hypertension of the newborn (PPHN), which occurs once or twice in every thousand live births, produces substantial morbidity and results in death in 10% to 20% of cases despite treatment. A small cohort study found that the risk of PPHN may be increased when the mother takes fluoxetine, a selective serotonin reuptake inhibitor (SSRI), late in the third trimester. The investigators enrolled 377 women whose infants had PHN and 836 matched control women with their infants in the years 1998 through 2003. Nurses lacking knowledge of the study goal interviewed mothers regarding their use of SSRIs. Criteria for entry into the study included a gestational age exceeding 34 weeks, severe respiratory failure (requiring intubation and mechanical ventilation) shortly after birth, and pulmonary hypertension as evidenced by either a gradient of at least 5% between pre- and postductal oxygen saturation or characteristic echocardiographic findings. More than half the PPHN births were preterm (34-37 weeks gestation). The study women took a variety of SSRIs, including fluoxetine, citalopram, paroxetine, and sertraline, as well as tricyclics, bupropion, venlafaxine, and trazodone. After adjusting for maternal diabetes, race, ethnic group, and body mass index, the risk of PPHN associated with any use of an antidepressant any time during pregnancy was not significantly increased. However, when the analysis was limited to those women who used any antidepressant after 20 weeks gestation, the risk of PHN was significantly increased (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.3-7.4). This increased risk was entirely the result of the use of SSRIs after 20 weeks (6.1; 2.2-16.8). When SSRI treatment was limited to the first half of pregnancy, the risk of PPHN was not increased. The association between PPHN and use of an SSRI persisted when using a cutoff point of 26 rather than 20 weeks gestation. These findings support an association between use of a SSRI in late pregnancy and PHN. The increased risk of this serious disorder should be considered when deciding whether to continue use of a SSRI during pregnancy.