Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

Abstract

Objective To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. Design Cohort study nested in the Medicaid Analytic eXtract for 2004-13. Setting Publicly insured pregnancies in the United States. Participants Pregnant women 18 to 55 years of age and their liveborn infants. Interventions Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. Main outcome measures Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. Results Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. Conclusions On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. Trial registration EUPAS 15946.

Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases

“…This was based on World Health Organization criteria and identified as at least 2 ICD-9/10 codes for the same congenital malformations in the newborn (Supplementary Table 1); this definition has been validated with a positive predictive value of >80% and used in prior studies. [18][19][20][21] Secondary outcomes of interest included risk of (1) preterm birth (<37 weeks of gestation) and ( 2) low birth weight (<2500 g at birth). All were identified using 2 ICD-9/-10 codes reported within 90 days after the birth date in the infant records.…”

Affective disorders: A question of continuing treatment during pregnancy (Review)

“…Duloxetine is unlikely to be a major teratogen although it may slightly increase the risk of cardiovascular malformations. It has also been associated by some researchers with postpartum hemorrhage (36).…”

Duloxetine Exposure During Pregnancy and the Risk of Spontaneous and Elective Abortion: A Danish Nationwide Observational Study

“…The decision is likely multifactorial if an elective abortion is chosen [ 30 ], with health issues related to the fetus among the factors. A recent US-based study did not find an increased risk for malformation after duloxetine exposure [ 55 ]. In the present study, the duration of pregnancies was similar across comparators, and most were very early in pregnancy.…”