IMPORTANCE-The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006. PARTICIPANTS-A total of 3 789 330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders. CONCLUSIONS AND RELEVANCE-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.
OBJECTIVE-To
HHS Public AccessThe high pulmonary vascular resistance characteristic of fetal circulation fails to decrease at birth in 10 to 20 newborns in every 10 000 live births, resulting in right-to-left shunting of blood through fetal channels, diminished pulmonary blood flow, and profound hypoxemia. 1,2 Such persistent pulmonary hypertension of the newborn (PPHN) typically occurs in term or near-term infants and presents within hours of birth with severe respiratory failure requiring intubation and mechanical ventilation. 2 Persistent pulmonary hypertension of the newborn is associated with substantial morbidity and mortality: 10% to 20% of affected infants will not survive, and infants who survive face serious long-term sequelae including chronic lung disease, seizures, and neurodevelopmental problems due to both the hypoxemia and the aggressive treatments it often requires. 1,[3][4][5][6] In 2006, the US Food and Drug Administration (FDA) issued a public health advisory on a potential increased risk of PPHN associated with late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) based on a single epidemiologic study that found a 6-fold increase in risk associated with SSRI use after the 20thweek of pregnancy. 7,8 Based on a review of additional studies with conflicting findings (2 studies reported an increase in risk, whereas 3 did not), the FDA concluded in 2011 that it was premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN and updated the advisory accordingly. [9][10][11][12][13] The negative studies tended to be small, raising the possibility that they had insufficient power to detect an increased risk. 10,11 Given the ongoing controversy regarding the association between SSRI exposure in late pregnancy and the risk of this highly morbid pregnancy outcome, we examined the risk of The approach used for the development of our study cohort has previously been described in detail. 14 We identified all completed pregnancies in women aged 12 to 55 years and linked these pregnancies to ...