Dihydroergotamine (DHE) Use During Gestation and the Risk of Adverse Pregnancy Outcomes

Authors

  • Anick Bérard PhD,

    Corresponding author
    1. From the Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada (A. Bérard); Research Center, CHU Ste-Justine, Montreal, QC, Canada (A. Bérard); MAP Pharmaceuticals Inc., Mountain View, CA, USA (S. Kori).
    Search for more papers by this author
  • Shashidhar Kori MD

    1. From the Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada (A. Bérard); Research Center, CHU Ste-Justine, Montreal, QC, Canada (A. Bérard); MAP Pharmaceuticals Inc., Mountain View, CA, USA (S. Kori).
    Search for more papers by this author

  • Conflicts of Interest: A. Bérard has no conflicts of interest to disclose. S. Kori is a full-time employee of MAP Pharmaceuticals.

  • Funding Source: This study was funded by MAP Pharmaceuticals Inc.

  • Anick Bérard is the recipient of a career award from the Fonds de la recherche en santé du Québec and is on the endowment research chair on Medications, Pregnancy, and Lactation at the Faculty of Pharmacy of the University of Montreal.

  • The results of this article were presented in part at the American Headache Society Conference in Washington, DC, in June 2011, and at the Annual Teratology Society Conference in San Diego, CA, in June 2011.

A. Bérard, Sainte-Justine Hospital, Research Center, 3175, chemin de la Côte-Ste-Catherine, Montreal, QC, H3T 1C5, Canada, email: anick.berard@umontreal.ca

Abstract

Background.— Dihydroergotamine (DHE) is perceived to be associated with a higher risk of adverse pregnancy events, but it has significantly less vasoconstrictive and uterotonic effects compared with ergotamine, and has demonstrated no teratogenic effect in animals. The objectives of this study were to quantify the risk of major congenital malformations (MCMs), prematurity, low birth weight (LBW), and spontaneous abortions (SAs) associated with gestational use of DHE, triptans, and nonsteroidal anti-inflammatory drugs (NSAIDs).

Methods.— Four independent case–control analyses were conducted within the Quebec Pregnancy Registry: (1) MCM; (2) prematurity (<37 weeks of gestation); (3) LBW (birth weight <2500 g); (4) clinically detected SA. Exposure was defined dichotomously as use of DHE, triptan, and NSAIDs during pregnancy.

Results.— Overall, 59,707 pregnant women met the eligibility criteria and were considered (53 [0.08%] used DHE, 139 [0.23%] triptans, and 2990 [5.01%] NSAIDs). Adjusting for potential confounders, gestational use of DHE was not significantly associated with the risk of MCM (odds ratio [OR]: 0.97; 95% confidence interval [CI]: 0.22-4.28), LBW (OR: 1.41; 95%CI: 0.25-7.80), or SA (OR: 1.97; 95% CI: 0.21-18.57). DHE use was, however, increasing the risk of prematurity (OR: 4.18; 95% CI: 1.34-12.99). In users of triptans, the OR for MCM was 1.49 (95% CI: 0.89-2.52), prematurity 0.76 (95% CI: 0.34-1.66), LBW 0.83 (95% CI: 0.31-2.25), and SA 2.65 (95% CI: 1.57-4.48). In users of NSAIDs, the OR for MCM was 1.20 (95% CI: 1.06-1.36), prematurity 1.10 (95% CI: 0.95-1.26), LBW 1.29 (95% CI: 1.08-1.54), and SA 2.97 (95% CI: 2.63-3.36).

Conclusions.— This study showed that other than for prematurity, DHE use during pregnancy was similar to that of triptan use and was smaller than the risk associated with NSAID use.

Ancillary