Research Submission Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From The Norwegian Mother and Child Cohort Study Kater ˇina Nezvalová-Henriksen, MS; Olav Spigset, MD, PhD; Hedvig Nordeng, MS, PhD Objective.—To evaluate the safety of triptan therapy during pregnancy. Background.—Information on the safety of triptan therapy during pregnancy is scarce and only available for sumatriptan, naratriptan, and rizatriptan. No associations with congenital malformations have been detected so far, but one study found a significant association between sumatriptan exposure during pregnancy and prematurity. Methods.—The study population consisted of 69,929 pregnant women and their newborn children for whom data on drug exposure and pregnancy outcome were available. Information on triptan therapy and potential socio-demographic and medical confounding factors was obtained from the Norwegian Mother and Child Cohort Study. Information on congenital malforma- tions and other adverse pregnancy outcomes was obtained from the Norwegian Medical Birth Registry. The datasets were linked via the women’s personal identification number. Pearson’s c 2 tests and logistic regression analyses were used to identify associations between triptan therapy and pregnancy outcome. Results.—No significant associations between triptan therapy during the first trimester and major congenital malforma- tions (unadjusted OR: 1.0; 95% CI 0.8-1.3, adjusted OR: 1.0; 95% CI 0.7-1.2) or other adverse pregnancy outcomes were found. Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1-1.9, adjusted OR: 1.4; 95% CI 1.1-1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1-1.5, adjusted OR: 1.3; 95% CI 1.1-1.5). Conclusions.—Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malforma- tions. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters. Although the present findings are reassuring, confirmation in independent studies is warranted. Key words: triptans, pregnancy, major congenital malformations, adverse pregnancy outcomes Abbreviations: 5-HT 5-hydroxytryptamine (serotonin); BMI body mass index; CYP1A2 cytochrome P450 1A2; CYP3A4 cytochrome P450 3A4; NSAIDs nonsteroidal anti-inflammatory drugs (Headache 2010;50:563-575) From the Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Norway (K. Nezvalová- Henriksen and H. Nordeng); Department of Clinical Pharmacology, St Olav’s University Hospital, Trondheim, Norway (O. Spigset); Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway (O. Spigset); The Division for Mental Health, National Institute of Health, Oslo, Norway (H. Nordeng). Address all correspondence to K. Nezvalová-Henriksen, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, PO Box 1065 Blindern, Oslo N-0316, Norway. Accepted for publication November 13, 2009. Conflict of Interest: None ISSN 0017-8748 doi: 10.1111/j.1526-4610.2010.01619.x Published by Wiley Periodicals, Inc. Headache © 2010 the Authors Journal compilation © 2010 American Headache Society 563