May 20, 2014

Newer antidepressants and pediatric pulmonary hypertension

Query 12-10: Newer antidepressants and Persistent Pulmonary Hypertension of the Newborn (PPHN).

This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Anick Bérard, Odile Sheehy, Jinping Zhao, Michal Abrahamowicz, Mona Loutfy, Isabelle Boucoiran, Sasha Bernatsky.


  • Recent research has linked antidepressant use during pregnancy with an increased risk of spontaneous abortions, major congenital malformations, prematurity, low birth weight, and cognitive delay.
  • Limited data are available on the risk of pulmonary hypertension of the newborn (PPHN) associated with other types of antidepressants such as SNRI (venlafaxine, desvenlafaxine, duloxetine), bupropion, and mirtazapine.
  • Given that PPHN is a rare condition, large population-based cohorts are needed to quantify its association with gestational use of antidepressants.

Study aim:

  • To determine whether the use of SSRIs and SNRIs in late pregnancy is associated with an increased risk of PPHN.

Study description:

  • Using data from the Quebec Pregnancy Cohort between 1998 and 2015, we included women covered by the provincial drug plan with a singleton live birth. Exposure categories were SSRI, SNRI and other antidepressant use; non-users were considered as the reference category.
  • Cases of PPHN were identified in the RAMQ/MedEcho databases from both maternal and infant files and defined based on the presence of the International Classification of Diseases, Ninth Revision diagnostic codes (ICD‐9: 416, 747.8) and the International Statistical Classification of Diseases, 10th Revision diagnostic codes (ICD‐10: I27, I521, P293) within the first 6 weeks of life in newborns not transferred to another hospital after birth.

Study findings:

  • The use of SSRIs in the second half of pregnancy was associated with the risk of PPHN.
  • SNRI use was not statistically significantly associated with an increased risk of PPHN, which could be explained by the small sample size and lack of statistical power.
  • Given our results, we do not know at this point whether SNRIs are associated with the risk of PPHN.


  • The authors conducted a population-based cohort study to evaluate the correlation between the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in late pregnancy and the risk of persistent pulmonary hypertension (PPHN) of the newborn.
  • Our data suggest that the use of SSRIs in the second half of pregnancy was associated with the risk of PPHN. However, given our results on SNRIs and the lack of statistical power for these analyses, it is unclear whether SNRI use during pregnancy also increases the risk of PPHN.

Results were discussed at the June 2015 Reseau Quebecois de Recherche sur les Medicaments (RQRM) meeting and the International Society for Pharmacoepidemiology (ICPE) meeting in August 2015.

Our manuscript is published:

Berard A, Sheehy O, Zhao JP, Vinet E, Bernatsky S, Abrahamowicz M. SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. Br J Clin Pharmacol. 2017 May;83(5):1126-1133.

For more information, contact: Autumn Neville, Research Coordinator.