Association between migraine, migraine subtype, and adverse pregnancy outcomes: A systematic review and meta-analysis

Introduction: Migraine is one of the most prevalent conditions worldwide. This systematic review aimed to evaluate the association between migraine, its subtypes, and adverse pregnancy outcomes. Material and Methods: Eligible cohort and retrospective case–control studies were included from PubMed and Embase databases from their inception to May 2024. Adverse pregnancy outcomes of interest were preeclampsia, preterm birth, low birthweight, small for gestational age, and placental abruption. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses of the outcomes with their odds ratios (ORs) and adjusted ORs (aOR), including a 95% confidence interval (CI), were performed using RevMan. Outcomes were pooled using random effects models, with separate analyses for cohort and retrospective case–control studies. The protocol was registered with PROSPERO (no. CRD42023404759). Results: This meta-analysis included 19 studies (11 cohort and 8 retrospective case–control) encompassing 1 420 690 deliveries. Significant associations were observed between migraine and increased risk of preeclampsia (cohort: aOR 1.28 [95% CI: 1.11–1.47], I² = 0%), (retrospective case–control: aOR 3.4 [95% CI: 1.81–6.4], I² = 83%) and preterm birth (cohort: aOR 1.30 [95% CI: 1.17–1.44], I² = 11%). The meta-analyses of adjusted data on low birthweight and small for gestational age were inconsistent with respect to statistical significance (cohort: aOR 1.27 [95% CI: 0.89–1.82], I² = 36% and cohort: aOR 1.07 [95% CI: 1.03–1.12], I² = 0%, respectively). In addition, migraine without aura (MO) (cohort: OR 1.62 [95% CI: 1.30–2.01], I² = 0%; retrospective case–control: aOR 4.91 [95% CI: 2.78–8.67], I² = 0%) and migraine with aura (MA) (cohort: OR 2.06 [95% CI: 1–4.27], I² = 29%) were significantly associated with the risk of preeclampsia. Similarly, MO (cohort: OR 1.28 [95% CI: 1.11–1.49], I² = 0%) and MA (cohort: OR 1.25 [95% CI: 1.07–1.47], I² = 0%) were associated with preterm birth risk. Conclusions: Pregnant women with migraines have a higher risk of preeclampsia and preterm birth compared with those without migraines. Migraine could be associated with an increased risk of low birth weight and small for gestational age. Sub-analyses indicate an elevated risk of preeclampsia and preterm birth across migraine subtypes. Notably, no previous meta-analyses have differentiated between migraine subtypes. Additional studies are needed to strengthen these findings.