Migraine Symptom Progression During Pregnancy and Associations with Fetal Growth Patterns and Placental-Mediated Complications in Women with Pre-Existing Migraine: A Prospective Cohort Study.

Background: Migraine has been associated with vascular dysfunction and adverse pregnancy outcomes. However, the relationship between changes in migraine manifestations during pregnancy and fetal growth remains incompletely understood. This prospective study aimed to investigate whether migraine symptom progression during pregnancy is associated with abnormal fetal growth patterns and placental-mediated pregnancy complications among women with pre-existing migraine. Methods: This prospective cohort study included 400 pregnant women with a pre-pregnancy diagnosis of migraine who received antenatal care at the Department of Obstetrics and Gynecology, University Hospital "Dr Dragiša Mišović", Belgrade, Serbia, between 2024 and 2026. Maternal migraine characteristics, pregnancy complications, and fetal growth assessments were evaluated. Fetal growth was categorized according to estimated fetal weight percentiles adjusted for gestational age. Univariable and multivariable logistic regression analyses were performed to identify factors associated with abnormal fetal growth. Because of the relatively small number of events, Firth's penalized logistic regression was additionally performed as a sensitivity analysis. Results: Persistent or worsening migraine symptoms during pregnancy were more frequently observed among pregnancies complicated by impaired fetal growth, pregnancy-induced hypertension, gestational diabetes mellitus, abnormal gestational weight gain, and preterm birth. In univariable analyses, migraine worsening was associated with increased odds of abnormal fetal growth. However, after adjustment for maternal and obstetric factors, migraine worsening was no longer independently associated with abnormal fetal growth. Pregnancy-induced hypertension and inadequate gestational weight gain remained the strongest independent predictors. Findings were confirmed in sensitivity analyses using Firth's penalized logistic regression. Conclusions: Among women with pre-existing migraine, persistent or worsening migraine manifestations during pregnancy were associated with a higher burden of placental-mediated complications and abnormal fetal growth patterns in unadjusted analyses. However, migraine worsening was not independently associated with abnormal fetal growth after adjustment for maternal and obstetric factors, suggesting that migraine symptom progression may represent a clinical marker of shared vascular, inflammatory, endothelial, and metabolic processes rather than an independent causal factor. Further prospective multicenter studies incorporating non-migraine control groups and detailed migraine phenotyping are warranted.