Objectives.— To monitor for a signal of major teratogenicity by determining the risk of all major defects following in utero exposure to sumatriptan and naratriptan. To monitor for unusual patterns of birth defects that might suggest teratogenicity.
Background.— The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to these drugs in pregnancy is likely. The Sumatriptan and Naratriptan Pregnancy Registry captures data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity.
Methods.— Healthcare professionals from anywhere in the world can enroll, on a voluntary basis, women exposed to sumatriptan or naratriptan during their pregnancies in this primarily prospective, observational study. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The percentage of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure.
Results.— Data are available on pregnancy outcomes from 599 exposed women. Among 479 first-trimester exposures to sumatriptan, 20 outcomes with major birth defects were reported (4.6%, 95% confidence interval [CI] 2.9-7.2%). The risk of major birth defects following exposure to sumatriptan during any trimester was 4.7% (95% CI 3.1-7.0%). No distinctive pattern of major birth defects among exposed infants was noted. There were 50 first-trimester exposures to naratriptan with 1 reported birth defect in a fetus with exposure to both sumatriptan and naratriptan.
Conclusions.— The risk of all major birth defects following first-trimester exposure to sumatriptan was 4.6% (95% CI 2.9-7.2%). This coupled with a consistent failure of additional epidemiological studies to observe a signal for major teratogenicity gives a level of reassurance concerning the safety of sumatriptan in pregnancy. There are too few data on naratriptan to draw definitive conclusions, and the sample size for sumatriptan remains too small to detect any but very large increases in specific birth defects.