Prepregnancy Migraine, Migraine Phenotype, and Risk of Adverse Pregnancy Outcomes

Background And Objective: Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of prepregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes.

Methods: We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses' Health Study II (1989-2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RRs) and 95% CIs for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight.

Results: The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, prepregnancy 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 with no 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 somewhat higher among participants with migraine with aura (RR vs no migraine = 1.51; 95% CI = 1.22-1.88) than migraine without aura (RR vs no migraine = 1.30; 95% CI = 1.04-1.61; heterogeneity = 0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular prepregnancy aspirin use had lower risks of preterm delivery (<2×/week RR = 1.24; 95% CI = 1.11-1.38; ≥2×/week RR = 0.55; 95% CI = 0.35-0.86; -interaction < 0.01) and preeclampsia (<2×/week RR = 1.48; 95% CI = 1.25-1.75; ≥2×/week RR = 1.10; 95% CI = 0.62-1.96; -interaction = 0.39); however, power for these stratified analyses was limited.

Discussion: Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine.