SSRI Exposure During Later Pregnancy May Increase Risk of Persistent Pulmonary Hypertension of Newborn
DynaMed Weekly Update - Volume 7, Issue 7
Persistent pulmonary hypertension of newborn (PPHN) is a life threatening condition in which the infant fails to transition from high pulmonary vascular resistance and low pulmonary blood flow characteristic of fetal circulation to low pulmonary vascular resistance and high pulmonary blood flow of postnatal circulation. It occurs in 0.1%-0.2% of live births, with death in 10%-20% of cases (N Engl J Med 2006 Feb 9;354(6):579). To date, evidence for a link between maternal use of selective serotonin reuptake inhibitors (SSRIs) for depression and risk of PPHN has been inconsistent, and in December, 2011, the FDA recommended that health care providers not alter their current practice for treating depression during pregnancy (FDA MedWatch 2011 Dec 14). However, a new large retrospective cohort study published 1 month after the FDA statement strongly suggests that SSRI exposure does increase PPHN risk (level 2 [mid-level] evidence).
A total of 1,618,255 infants born > 33 weeks gestational age in 5 Nordic countries were evaluated for maternal use of any SSRIs. Mothers were stratified by date of SSRI exposure (at > 20 weeks gestational age, prior to pregnancy or before 8 weeks gestational age, or no exposure). PPHN developed in 0.29% of infants with later pregnancy exposure, 0.19% of infants with early pregnancy exposure, and 0.12% of infants with no exposure. Later exposure to any SSRI was associated with a significant increase in PPHN risk compared to no exposure (adjusted hazard ratio 2.1, 95% CI 1.5-3, NNH 416-1,666). Early exposure was associated with a trend toward increased risk. Results of subgroup analyses for individual SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were similar to the overall analysis (BMJ 2012 Jan 12;344:d8012). While there now appears to be a significantly increased risk, the condition is rare and the absolute risk remains low. These risks must be weighed against the benefits of treating the depression and compared to alternative options for the mother.