Abstract
BACKGROUND: Migraine is common among females of reproductive age (estimated prevalence:17-24%) and may be associated with reproductive health through underlying central nervous system excitability, autoimmune conditions, and autonomic dysfunction. We evaluated the extent to which pre-pregnancy migraine diagnosis and medication use are associated with risk of spontaneous abortion (SAB). METHODS: We analyzed data from a preconception study of pregnancy planners (2013-2021). Eligible participants self-identified as female, were aged 21-45 years, resided in the USA or Canada, and conceived during follow-up (n = 7890). Participants completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever occurred first. Pregnant participants then completed questionnaires during early (~ 8-9 weeks) and late (~ 32 weeks) gestation. We defined migraineurs as participants who reported a migraine diagnosis or use of a medication to treat migraine. Preconception questionnaires elicited migraine medication use during the past 4 weeks, and SAB on follow-up and pregnancy questionnaires. We used Cox regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations among preconception migraine, migraine medication use, and SAB, controlling for potential demographic, medical, and lifestyle confounders. RESULTS: Nineteen percent of study pregnancies ended in SAB. History of migraine before conception was not appreciably associated with SAB risk (HR = 1.03, 95% CI: 0.91-1.06). Use of any migraine medication was associated with a modest increase in SAB risk overall (HR = 1.14, 95% CI: 0.96-1.36). We observed the greatest increase in risk among those taking migraine medications daily (HR = 1.38, 95% CI: 0.81-2.35) and those taking prescription migraine prophylaxis (HR = 1.43, 95% CI: 0.72-2.84) or combination analgesic and caffeine medications (HR = 1.42, 95% CI: 0.99-2.04). CONCLUSIONS: Migraine medication use patterns suggesting greater underlying migraine severity were associated with increased risk of SAB. This research adds to the limited information available on the reproductive effects of migraine.