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. 2015 Jun 2;313(21):2142-51.
doi: 10.1001/jama.2015.5605.

Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn

Krista F Huybrechts  1 , Brian T Bateman  2 , Kristin Palmsten  3 , Rishi J Desai  4 , Elisabetta Patorno  1 , Chandrasekar Gopalakrishnan  4 , Raisa Levin  4 , Helen Mogun  4 , Sonia Hernandez-Diaz  5
Affiliations

Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn

Krista F Huybrechts et al. JAMA. .

Abstract

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.

Objective: To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy.

Design and setting: Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010.

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. EXPOSURES FOR OBSERVATIONAL STUDIES: SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use.

Main outcomes and measures: Recorded diagnosis of PPHN during the first 30 days after delivery.

Results: A total of 128,950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102,179 (2.7%) used an SSRI and 26,771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10,000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10,000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10,000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74).

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.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Figures

Figure 1
Figure 1
Risk of Persistent Pulmonary Hypertension of the Newborn Among Infants of Women Who Were and Were Not Exposed to Selective Serotonin Reuptake Inhibitors (SSRIs) During Pregnancy Results are presented with different levels of confounding adjustment and varying the outcome definition. PPHN indicates persistent pulmonary hypertension of the newborn
Figure 2
Figure 2
Risk of Persistent Pulmonary Hypertension of the Newborn Among Infants of Women Who Were and Were Not Exposed to Antidepressants Other Than Selective Serotonin Reuptake Inhibitors (SSRIs) During Pregnancy Results are presented with different levels of confounding adjustment and varying the outcome definition.
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Comment in

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