Interplay between migraine and pregnancy outcomes

Phillips, Katherine Gwyneth ORCID: 0000-0003-0674-605X (2025). Interplay between migraine and pregnancy outcomes. University of Birmingham. Ph.D.

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Abstract

Background: Migraine is highly prevalent in women of reproductive age and there is evidence to suggest that it impacts on the risk of adverse pregnancy outcomes. In particular, an association between migraine and pre-eclampsia has been well described. Links between migraine and other pregnancy outcomes such as miscarriage and preterm birth have been investigated, but findings have been less conclusive. Migraine often requires pharmacological therapy to manage symptoms and prevent episodes, but information about the safety of some migraine medication during pregnancy is lacking. This thesis aims to describe the epidemiology of migraine in pregnancy, determine its associated outcomes, and assess the safety of migraine medication during pregnancy.

Methods: An epidemiological study was carried out using and electronic primary care record database to describe the annual prevalence of migraine in pregnancy and the medications commonly prescribed amongst pregnant women with migraine. An umbrella review was conducted of literature comparing pregnancy outcomes in i) women with migraine to women without migraine ii) women with migraine who were treated to women with migraine who were not treated during pregnancy. A retrospective matched cohort study using the CPRD pregnancy register was conducted to compare the risk of miscarriage in women with migraine to those without migraine. Within the migraine cohort, a nested case-control study was conducted to compare the odds of miscarriage in those exposed to migraine medication in pregnancy compared to women with migraine who were not exposed to medication. Finally, a retrospective cohort study using delivery records from the Hospital Episode Statistics (HES) maternity tail was conducted to compare delivery outcomes (preterm birth, low birth weight, small for gestational age, mode of delivery and stillbirth) in women with migraine to those without migraine.

Results: The age-adjusted prevalence of migraine in pregnancy increased from 11.4% (95% CI 10.3%-12.4%) in 2000 to 17.2% (95% CI 16.7%-17.5%) in 2018. Over the same period, there was an increase in the rates of prescription for numerous medications for the management of migraine, notably, triptans, antidepressants (including amitriptyline) and beta blockers. In the umbrella review, migraine was associated with a higher odds of pre-eclampsia (pooled OR 2.05 (1.47-2.84), peripartum mental illness (pooled OR = 1.75 (1.20-2.54)) and preterm birth (pooled OR 1.26 (1.21-1.32)). Triptan-exposed women had increased odds of miscarriage compared to women without migraine (pooled OR 3.54 (2.24-5.59)). In the matched cohort study, migraine was associated with a 6% higher risk of miscarriage (aRR 1.06 95% CI (1.04-1.08)). Results from the nested case-control study showed that in pregnancies of women with migraine, exposure to triptans, amitriptyline and NSAIDs were associated with a significantly higher odds of miscarriage (aORs 1.24 (1.11-1.38), 1.25 (1.08-1.45) and 1.74 (1.57-1.93), respectively). Migraine was associated with an higher risk of extremely preterm (aRR 1.18 (95% CI 1.01-1.37) and medically-indicated preterm delivery (aRR 1.11 (95% CI 1.02-1.20)) in the matched delivery record cohort.

Conclusion: Prevalence of recorded migraine during pregnancy has increased over the past few decades, as have rates of prescriptions for migraine medications during pregnancy. Migraine was associated with pregnancy complications such as pre-eclampsia, peripartum mental illness, miscarriage and preterm birth (potentially driven by medically indicated preterm birth). Exposure to triptans, NSAIDs and amitriptyline in pregnant women with migraine was associated with miscarriage. Future work should focus on how migraine type and severity impact these outcomes, the associations of migraine drugs with other pregnancy outcomes and potential underlying causative mechanisms.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):