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Alexandra Purdue-Smithe, PhD






Brigham and Women's Hospital and Harvard Medical School


Division of Women's Health


Alexandra C. Purdue-Smithe, Jennifer J. Stuart, Leslie V. Farland, Jae H. Kang, Andrea M. Harriott, Janet Rich-Edwards, Kathryn M. Rexrode

Principal Investigator

Kathryn M. Rexrode


Pre-pregnancy migraine, aura phenotype, and risk of adverse pregnancy outcomes: a prospective cohort study

Migraine is a common neurovascular disorder that exhibits striking sex differences. Women of reproductive age are substantially more likely to experience migraine than similarly aged men. Yet, the degree to which migraine might serve as a clinically meaningful marker of obstetric risk is unknown. Here, we show that migraine diagnosed before pregnancy is an independent risk marker for preterm delivery, gestational hypertension, and preeclampsia in a large prospective study. We also show that aspirin may reduce risks of preterm delivery and preeclampsia among women with migraine. These findings highlight the need to include migraine history in obstetric risk assessment, and for further research on aspirin prophylaxis to reduce risk of APOs in pregnant women with a history of migraine. Considering the high prevalence of migraine in women of childbearing age, combined with the substantial contribution of preeclampsia to maternal morbidity and mortality, these findings have important implications for women’s health.

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Women are 2-3 times more likely than men to experience migraine in their lifetime, and the prevalence of migraine is highest (23.5%) among women aged 18-44 years. Migraine and adverse pregnancy outcomes (APOs) share common pathophysiology, and both are associated with cardiovascular disease risk. Whether pre-pregnancy migraine and aura phenotype might serve as clinically useful markers of obstetric risk is unclear, as large prospective studies are lacking.



To examine longitudinal associations of pre-pregnancy migraine and aura phenotype with risks of APOs.



Prospective cohort study.



Nurses’ Health Study II (1989-2009).

Participants 30,555 incident pregnancies among 19,694 women without a history of cardiovascular disease, diabetes, or cancer.



Self-reported physician-diagnosed migraine prior to pregnancy and aura phenotype.


Outcome measures

Relative risks (RR) and 95% confidence intervals (CI) for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight.



After adjusting for health and behavioral factors, pre-pregnancy migraine (11%) was associated with higher risks of preterm delivery (RR=1.17; 95% CI=1.05-1.30), gestational hypertension (RR=1.28; 95% CI=1.11-1.48), and preeclampsia (RR=1.40; 95% CI=1.19, 1.65) compared to women without pre-pregnancy migraine. Migraine was not associated with low birthweight (RR=0.99; 95% CI=0.85-1.16) or GDM (RR=1.05; 95% CI=0.91-1.22). Risk of preeclampsia was slightly higher among women with migraine with aura (RR versus no migraine=1.51; 95% CI=1.22-1.88) than migraine without aura (RR versus no migraine=1.29; 95% CI=1.04-1.61). Regular pre-pregnancy aspirin use modified the association of pre-pregnancy migraine with preterm delivery (<2x/wk RR=1.24; 95% CI=1.11-1.38; ≥2x/wk RR=0.55; 95% CI=0.35-0.86) and preeclampsia (<2x/wk RR=1.48; 95% CI=1.25-1.75; ≥2x/wk RR=1.10; 95% CI=0.62-1.96).



Migraine history, and to a lesser extent aura phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should elucidate the mechanisms underlying these associations and further explore aspirin prophylaxis to reduce risks of APOs in women with migraine.

Research Context