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

TLDR

Persistent pulmonary hypertension of the newborn (PPHN) causes significant infant mortality and morbidity, and a prior cohort study linked late‑trimester use of the SSRI fluoxetine to increased PPHN risk. This case‑control study aimed to determine whether maternal exposure to SSRIs during late pregnancy is associated with PPHN in the infant. Researchers enrolled 377 PPHN cases and 836 matched controls from 1998‑2003, collected blinded maternal interview data on medication use and confounders, and compared SSRI exposure after 20 weeks of gestation between groups. The analysis revealed that 14 of 377 PPHN infants were exposed to an SSRI after 20 weeks versus 6 of 836 controls (adjusted OR 6.1, 95 % CI 2.2‑16.8), while early SSRI use or non‑SSRI antidepressants showed no increased risk, supporting a link between late‑pregnancy SSRI exposure and PPHN and suggesting caution in continuing SSRIs during pregnancy.

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant mortality and morbidity. A previous cohort study suggested a possible association between maternal use of the selective serotonin-reuptake inhibitor (SSRI) fluoxetine late in the third trimester of pregnancy and the risk of PPHN in the infant. We performed a case-control study to assess whether PPHN is associated with exposure to SSRIs during late pregnancy.Between 1998 and 2003, we enrolled 377 women whose infants had PPHN and 836 matched control women and their infants. Maternal interviews were conducted by nurses, who were blinded to the study hypothesis, regarding medication use in pregnancy and potential confounders, including demographic variables and health history.Fourteen infants with PPHN had been exposed to an SSRI after the completion of the 20th week of gestation, as compared with six control infants (adjusted odds ratio, 6.1; 95 percent confidence interval, 2.2 to 16.8). In contrast, neither the use of SSRIs before the 20th week of gestation nor the use of non-SSRI antidepressant drugs at any time during pregnancy was associated with an increased risk of PPHN.These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy.