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BMJ. 2020 Feb 19;368:m237. doi: 10.1136/bmj.m237.

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

Author information

1
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
2
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
3
Eli Lilly and Company, Indianapolis, IN, USA.
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

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.

PMID:
32075794
DOI:
10.1136/bmj.m237
[Indexed for MEDLINE]
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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: the study was funded by an unrestricted grant to Brigham and Women’s Hospital from Eli Lilly and Company; KFH was an investigator on grants from GSK and Pfizer outside the submitted work; BTB was an investigator on grants from Baxalta, Pfizer, GSK, and Pacira outside the submitted work and has received personal fees from Aetion and the Alosa Foundation outside the submitted work; SHD was an investigator on grants from GSK and Pfizer outside the submitted work and has received personal fees from Bayer outside the submitted work; HL, SM, MFSF, and HPU were employees of Eli Lilly during the conduct of the study; no other relationships or activities that could appear to have influenced the submitted work.

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