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

Katherine Phillips; Krishna Gokhale; Christine Damase-Michel; Helen Dolk; Catherine Nelson-Piercy; Benjamin R Wakerley; Francesca Crowe; Krishnarajah Nirantharakumar

doi:10.1177/03331024251414634

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

Katherine Phillips
, Krishna Gokhale
, Christine Damase-Michel
, Helen Dolk
, Catherine Nelson-Piercy
, Benjamin R Wakerley
, Francesca Crowe
, Krishnarajah Nirantharakumar

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective
To 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.
Design
Matched cohort study and nested case-control.
Setting
Clinical Practice Research Datalink (CPRD) GOLD pregnancy register. All pregnancies meeting data quality requirements between 2000 and 2019 were eligible for inclusion.
Participants
Cohort 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 measures
Cohort study: miscarriage recorded in primary care. Nested case-control: odds of miscarriage amongst migraineurs using migraine medication.
Results
Miscarriage 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.
Conclusions
Migraine and triptan, amitriptyline and NSAID exposure were all associated with higher risk of miscarriage. Further work is needed to understand the potential causative mechanisms.

Original language	English
Pages (from-to)	1-12
Number of pages	12
Journal	Cephalalgia
Volume	46
Issue number	1
Early online date	28 Jan 2026
DOIs	https://doi.org/10.1177/03331024251414634
Publication status	Published (in print/issue) - 28 Jan 2026

Bibliographical note

Data Access Statement

The data that support the findings of this study are available from CPRD but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was not specifically funded but was supported by the MuMPreDiCT consortium which is funded by the Strategic Priority Fund “Tackling multimorbidity at scale” programme (grant number MR/W014432/1) delivered by the Medical Research Council and the National Institute for Health Research (NIHR) in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council. KP, NIHR Clinical Lecturer, is funded by the NIHR for this research project. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, National Health Service (NHS) or the UK Department of Health and Social Care. This work was also supported by Health Data Research UK (HDRUK2023.0030), which is funded by UK Research and Innovation, the Medical Research Council, the British Heart Foundation, Cancer Research UK, the National Institute for Health and Care Research, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Funders	Funder number
Economic and Social Research Council
Medical Research Council
Cancer Research UK
British Heart Foundation
Engineering and Physical Sciences Research Council
MR/W014432/1
HDRUK2023.0030

Keywords

pharmacoepidemiology
miscarriage
pregnancy
migraine
Humans
Risk Factors
Case-Control Studies
Pregnancy
Pregnancy Complications/epidemiology
Female
Adult
Registries
Abortion, Spontaneous/epidemiology
Migraine Disorders/drug therapy
Cohort Studies
Migraine Disorders - drug therapy - epidemiology
Pregnancy Complications - epidemiology - drug therapy
Abortion, Spontaneous - epidemiology

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Cite this

@article{b4efe2e9370245e097af18a6de43cb28,

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

abstract = "Objective To 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. Design Matched cohort study and nested case-control. Setting Clinical Practice Research Datalink (CPRD) GOLD pregnancy register. All pregnancies meeting data quality requirements between 2000 and 2019 were eligible for inclusion. Participants Cohort 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 measures Cohort study: miscarriage recorded in primary care. Nested case-control: odds of miscarriage amongst migraineurs using migraine medication. Results Miscarriage 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. Conclusions Migraine and triptan, amitriptyline and NSAID exposure were all associated with higher risk of miscarriage. Further work is needed to understand the potential causative mechanisms.",

keywords = "pharmacoepidemiology, miscarriage, pregnancy, migraine, Humans, Risk Factors, Case-Control Studies, Pregnancy, Pregnancy Complications/epidemiology, Female, Adult, Registries, Abortion, Spontaneous/epidemiology, Migraine Disorders/drug therapy, Cohort Studies, Migraine Disorders - drug therapy - epidemiology, Pregnancy Complications - epidemiology - drug therapy, Abortion, Spontaneous - epidemiology",

author = "Katherine Phillips and Krishna Gokhale and Christine Damase-Michel and Helen Dolk and Catherine Nelson-Piercy and Wakerley, \{Benjamin R\} and Francesca Crowe and Krishnarajah Nirantharakumar",

note = "{\textcopyright} International Headache Society 2026.",

year = "2026",

month = jan,

day = "28",

doi = "10.1177/03331024251414634",

language = "English",

volume = "46",

pages = "1--12",

number = "1",

}

TY - JOUR

T1 - Migraine, associated treatments and risk of miscarriage: A matched cohort study and nested case-control study using the CPRD pregnancy register

AU - Phillips, Katherine

AU - Gokhale, Krishna

AU - Damase-Michel, Christine

AU - Dolk, Helen

AU - Nelson-Piercy, Catherine

AU - Wakerley, Benjamin R

AU - Crowe, Francesca

AU - Nirantharakumar, Krishnarajah

N1 - © International Headache Society 2026.

PY - 2026/1/28

Y1 - 2026/1/28

N2 - Objective To 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. Design Matched cohort study and nested case-control. Setting Clinical Practice Research Datalink (CPRD) GOLD pregnancy register. All pregnancies meeting data quality requirements between 2000 and 2019 were eligible for inclusion. Participants Cohort 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 measures Cohort study: miscarriage recorded in primary care. Nested case-control: odds of miscarriage amongst migraineurs using migraine medication. Results Miscarriage 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. Conclusions Migraine and triptan, amitriptyline and NSAID exposure were all associated with higher risk of miscarriage. Further work is needed to understand the potential causative mechanisms.

AB - Objective To 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. Design Matched cohort study and nested case-control. Setting Clinical Practice Research Datalink (CPRD) GOLD pregnancy register. All pregnancies meeting data quality requirements between 2000 and 2019 were eligible for inclusion. Participants Cohort 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 measures Cohort study: miscarriage recorded in primary care. Nested case-control: odds of miscarriage amongst migraineurs using migraine medication. Results Miscarriage 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. Conclusions Migraine and triptan, amitriptyline and NSAID exposure were all associated with higher risk of miscarriage. Further work is needed to understand the potential causative mechanisms.

KW - pharmacoepidemiology

KW - miscarriage

KW - pregnancy

KW - migraine

KW - Humans

KW - Risk Factors

KW - Case-Control Studies

KW - Pregnancy

KW - Pregnancy Complications/epidemiology

KW - Female

KW - Adult

KW - Registries

KW - Abortion, Spontaneous/epidemiology

KW - Migraine Disorders/drug therapy

KW - Cohort Studies

KW - Migraine Disorders - drug therapy - epidemiology

KW - Pregnancy Complications - epidemiology - drug therapy

KW - Abortion, Spontaneous - epidemiology

UR - https://www.scopus.com/pages/publications/105028817333

U2 - 10.1177/03331024251414634

DO - 10.1177/03331024251414634

M3 - Article

C2 - 41603448

VL - 46

SP - 1

EP - 12

JO - Cephalalgia

JF - Cephalalgia

IS - 1

ER -

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

Abstract

Bibliographical note

Data Access Statement

Funding

Keywords

Access to Document

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