Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn

N Engl J Med. 2006 Feb 9;354(6):579-87. doi: 10.1056/NEJMoa052744.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Case-Control Studies
  • Depressive Disorder / drug therapy
  • Female
  • Fetus / drug effects
  • Humans
  • Infant, Newborn
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Persistent Fetal Circulation Syndrome / etiology*
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use

Substances

  • Antidepressive Agents
  • Serotonin Uptake Inhibitors