Abstract
Migraine is prevalent during pregnancy. Antimigraine medications such as dihydroergotamine (DHE) and triptans have been associated with adverse pregnancy outcomes in individual studies but lack of consensus remains. We compared the risk of prematurity, low birth weight (LBW), major congenital malformations (MCM), and spontaneous abortions (SA) associated with gestational use of DHE or triptans. Three cohort and one nested-case–control analyses were conducted within the Quebec Pregnancy Cohort to assess the risk of prematurity, LBW, MCM, and SA. Exposure was defined dichotomously as use of DHE or triptan during pregnancy. Generalized estimation equations were built to quantify the associations, adjusting for potential confounders. 233,900 eligible pregnancies were included in the analyses on prematurity, LBW, and MCM; 29,104 cases of SA were identified. Seventy-eight subjects (0.03%) were exposed to DHE and 526 (0.22%) to triptans. Adjusting for potential confounders, DHE and triptans were associated with increased risks of prematurity, LBW, MCM, and SA but not all estimates were statistically significant. DHE was associated with the risk of prematurity (aRR: 4.12, 95% CI 1.21–13.99); triptans were associated with the risk of SA (aOR: 1.63, 95% CI 1.34–1.98). After considering maternal migraine, all antimigraine specific medications increased the risk of some adverse pregnancy outcomes, but estimates were unstable.
Highlights
A retrospective analysis of DHE exposures among subjects within a large human pregnancy cohort found that DHE exposure did not statistically significantly increase the risk of low birth weight (LBW), major congenital malformations (MCM), or spontaneous abortions (SA); DHE exposure was associated with a four-fold increased risk of prematurity[8]
Of the 441,575 pregnancies included in the QPC between 1998 and 2015, 233,900 met inclusion criteria and were considered for the analyses on prematurity, LBW, and MCM; 78 (0.03%) were exposed to DHE, and 526 (0.22%) to triptans (Fig. 1)
15,688 (6.7%) pregnant women had a premature delivery (Table 1); deliveries were mostly between 32 and 36 weeks’ gestation (Table 2). Those with a preterm delivery were older; less likely to be on welfare; were hypertensive or diabetics; more likely to be smokers or be using illicit drugs; had more hospitalizations, physician visits and use medications other than the ones studied here; they were more likely to be followed by an obstetrician and take high dose folic acid (Table 1)
Summary
Despite being commercially available since the mid-1940s, there is limited data on the safety of DHE in human pregnancy, likely because DHE is not recommended during pregnancy as a result of potential teratogenic effects reported in reproductive toxicology studies in rats and rabbits undertaken in the course of developing a liquid nasal spray formulation during the 1980s and 1990s. Ergot alkaloids, such as DHE, have a contractile effect on uterine smooth muscle and may cause decreased uterine blood flow[7]. A meta-analysis showed that gestational use of triptans was not associated with the risk of MCM but did suggest an increased risk of SA15
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