Anti-CGRP antibodies associated with higher spontaneous abortion risk

A retrospective cohort study published in JAMA Neurology examined whether early pregnancy exposure to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies or propranolol is associated with spontaneous abortion in individuals with migraine. Migraine affects people of reproductive age, and preventive options during pregnancy are limited by safety concerns. Anti-CGRP monoclonal antibodies are effective for migraine prevention, but CGRP plays a role in placental development.

The analysis used data from the AM-PREGNANT cohort, derived from the Merative MarketScan Commercial Database, from 2018 to 2021. Participants were followed through 20 weeks' gestation or until spontaneous abortion or censoring. Of 7,991,200 pregnancies identified in the cohort, 7119 individuals contributing 7579 singleton pregnancies met the predefined eligibility criteria.

Eligible participants were aged 15 to 45 years, had continuous insurance enrollment, and had a last menstrual period (LMP) on or after November 1, 2018. Pregnancy end or 20-week censoring had to occur by December 31, 2021. Pregestational migraine was defined as a migraine diagnosis or triptan or ergot prescription within 6 months before LMP. Data were analyzed in early 2026.

Exposures were anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) or propranolol. Each was defined as 1 or more filled prescriptions or injection procedure claims during follow-up and modeled as time-varying. The main outcome was spontaneous abortion at 20 weeks' gestation or less, estimated with multivariable Cox proportional hazards models adjusted for comorbidities and concomitant medications.

Key data

• 7579 pregnancies in 7119 individuals (mean [SD] age, 31.6 [5.5] years) were included, and 1862 spontaneous abortions occurred
• 100 spontaneous abortions (28.6%) occurred during anti-CGRP monoclonal antibody-exposed person-time
• 37 events (12.8%) occurred during propranolol-exposed person-time without anti-CGRP monoclonal antibodies
• Anti-CGRP monoclonal antibody exposure was associated with increased risk of spontaneous abortion vs unexposed individuals (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.12-1.80)
• The association remained similar in bias-adjusted analyses (HR, 1.33; 95% simulation interval [SI], 1.23-1.45)
• Propranolol exposure was not associated with increased risk (aHR, 1.02; 95% CI, 0.71-1.47; bias-adjusted HR, 1.00; 95% SI, 0.96-1.03)

Anti-CGRP exposure showed an association that held after bias adjustment

The elevated risk tied to anti-CGRP monoclonal antibody exposure persisted when the investigators applied bias-adjusted analyses, with the hazard ratio moving only modestly from 1.42 to 1.33. The consistency across both approaches adds weight to the signal, which the authors said supports further evaluation of the safety of these agents during pregnancy.

Propranolol showed no association with spontaneous abortion

Propranolol, another migraine preventive, served as a comparison exposure and showed no association with spontaneous abortion in either the standard or bias-adjusted models. The hazard ratios sat at or near 1.00, in contrast to the elevated estimates for anti-CGRP monoclonal antibodies.

Findings point to counseling for individuals of childbearing potential

The authors framed the results as relevant to treatment decisions for people with migraine who may become pregnant, stating “These findings support further evaluation of anti-CGRP mAb safety and emphasize counseling for individuals of childbearing potential.”

Reference:

Flatman LK, Leal LF, Leroux E, Lipton RB, Bérard A. Early Pregnancy Use of Anti-CGRP Monoclonal Antibodies and Propranolol and Spontaneous Abortion Risk. JAMA Neurol. Published online October 12, 2026. doi:10.1001/jamaneurol.2026.3573