Migraine, associated treatments and risk of miscarriage: A matched cohort study and nested case-control study using the CPRD pregnancy register

ObjectiveTo estimate the risk of miscarriage amongst pregnant women with migraine compared to pregnant women without migraine. To compare the odds of miscarriage in women taking medication for migraine to women with migraine who did not take medication and to explore this association with different types of medications.DesignMatched cohort study and nested case-control.SettingClinical Practice Research Datalink (CPRD) GOLD pregnancy register. All pregnancies meeting data quality requirements between 2000 and 2019 were eligible for inclusion.ParticipantsCohort study: 193,208 pregnancies of women with migraine were matched one-to-one to women without migraine. Nested case-control: 20,778 pregnancies of women with migraine that ended in miscarriage were matched to 40,122 pregnancies of women with migraine that did not end in miscarriage.Main outcome measuresCohort study: miscarriage recorded in primary care. Nested case-control: odds of miscarriage amongst migraineurs using migraine medication.ResultsMiscarriage occurred in 10% (n = 19,233) of women without migraine compared to 10.8% (n = 20,778) of women with migraine. Having migraine was associated with an 8% higher relative risk of miscarriage (risk ratio (RR) 1.08, 95% confidence interval (CI) 1.06-1.10, p < 0.001) and remained significant after adjustment for demographic factors, body mass index (BMI), smoking and comorbidities (aRR 1.06 95% CI [1.04-1.08][p = 0.001]).Of the pregnancies ending in miscarriage, 719 (3.46%), 380 (1.83%), 173 (0.83%) and 733 (3.52%) were exposed to triptans, amitriptyline, beta-blockers and non-steroidal anti-inflammatory drugs (NSAIDs), respectively. Of the matched pregnancies that did not end in miscarriage, 1099 (2.74%), 542 (1.35%), 294 (0.73%) and 780 (1.94%) were exposed to these medications, respectively.Exposure to triptans, amitriptyline and NSAIDs were associated with a significantly higher odds of miscarriage (aORs 1.24 [1.11-1.38][p < 0.001], 1.25 [1.08-1.45][p = 0.003] and 1.74 [1.57-1.93][p < 0.001] respectively). Beta-blockers were not associated with a higher risk of miscarriage.ConclusionsMigraine and triptan, amitriptyline and NSAID exposure were all associated with higher risk of miscarriage. Further work is needed to understand the potential causative mechanisms.