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17α-Hydroxyprogesterone Caproate and the Risk of Glucose Intolerance in Pregnancy

A Systematic Review and Meta-analysis

Eke, Ahizechukwu C., MD, MPH; Sheffield, Jeanne, MD; Graham, Ernest M., MD

doi: 10.1097/AOG.0000000000003115
Contents: Preterm Birth: Review
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OBJECTIVE: To evaluate whether 17α-hydroxyprogesterone caproate use in preventing preterm birth increases the risk of gestational diabetes mellitus (GDM).

DATA SOURCES: Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) were searched for studies published before October 2018. Keywords included “gestational diabetes,” “preterm birth,” “pregnancy,” and “17-hydroxyprogesterone caproate.”

METHODS OF STUDY SELECTION: Studies comparing 17α-hydroxyprogesterone caproate with unexposed control groups in women with singleton gestation and a history of a prior spontaneous preterm birth were included. The primary outcome was the development of GDM. Secondary outcomes included abnormal 1-hour, 50-g glucose screen results and mean venous blood glucose levels. Summary estimates were reported as mean differences and 95% CI for continuous variables or relative risk (RR) with 95% CI for dichotomous outcomes. Meta-analysis was performed using the random effects model of DerSimonian and Laird.

TABULATION, INTEGRATION AND RESULTS: Six studies, four of which were cohort studies, met inclusion criteria and were included in the final meta-analysis. Of the 5,053 women, 1,538 (30.4%) received 17α-hydroxyprogesterone caproate and 3,515 (69.6%) were in unexposed control groups. The overall rate of GDM in women exposed to 17α-hydroxyprogesterone caproate was 10.9% vs 6.1% in women who were not exposed (RR 1.77, 95% CI 1.22–2.55). After exclusion of the cohort studies, the summary estimate of effect was nonsignificant among women who had been randomly allocated to 17α-hydroxyprogesterone caproate (RR 1.21, 95% CI 0.63–2.36).

CONCLUSION: Women with singleton gestations receiving weekly 17α-hydroxyprogesterone caproate for recurrent preterm birth prevention had a significantly higher incidence of abnormal glucose test results and GDM compared with those in unexposed control groups, a finding that did not hold among women who had been randomly allocated to 17α-hydroxyprogesterone caproate.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016041694.

Women receiving weekly 17α-hydroxyprogesterone caproate for recurrent preterm birth prevention may have a higher incidence of abnormal glucose test results.

Division of Maternal Fetal Medicine and Clinical Pharmacology, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine; and Doctoral (PhD) Program in Clinical Investigation, Graduate Training Program in Clinical Investigation (GTPCI), Johns Hopkins University School of Public Health, Baltimore, Maryland.

Corresponding author: Ahizechukwu C. Eke, MD, MPH, Division of Maternal Fetal Medicine & Clinical Pharmacology, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287; email: aeke2@jhu.edu.

Financial Disclosure The authors did not report any potential conflicts of interest.

Each author has confirmed compliance with the journal's requirements for authorship.

Peer reviews and author correspondence are available at http://links.lww.com/AOG/B280.

© 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.