Objective:

To assess whether exposure to anti-CGRP monoclonal antibodies or propranolol was associated with spontaneous abortion among pregnancies in patients with pregestational migraine.

Approach:

• Design and population: Retrospective cohort study of 7,579 singleton pregnancies among 7,119 patients aged 15–45 years, recorded from November 2018 through December 2021 in a US commercial insurance database.
• Exposure and outcome: Claims identified time-varying exposure to anti-CGRP monoclonal antibodies or propranolol and clinically detected spontaneous abortion at or before 20 weeks.
• Analysis: Cox models adjusted for maternal age, comorbidities, concomitant medications, and health care utilization; sensitivity and bias analyses assessed exposure duration and potential confounding by migraine severity.

Key Findings:

• There were 1,862 clinically detected spontaneous abortions (24.6%) among 7,579 pregnancies.
• Anti-CGRP-exposed person-time included 350 pregnancies and 100 spontaneous abortions (28.6%); the adjusted hazard was 42% higher than during unexposed person-time.
• The adjusted estimated risk by 20 weeks was 28.7% under a hypothetical all-exposed scenario, compared with 24.5% without exposure.
• Propranolol-exposed person-time included 283 pregnancies and 37 spontaneous abortions (12.8%); propranolol was not associated with an increased hazard compared with unexposed person-time.
• Adjustment for potential confounding by migraine severity modestly attenuated the anti-CGRP association, which remained elevated.

Interpretation:

The observational findings indicate an association between anti-CGRP monoclonal antibody exposure around conception or early pregnancy and spontaneous abortion, but do not establish causality. The authors called for further research on pregnancy safety and longer-term offspring outcomes.

Limitations:

• Claims did not directly measure migraine frequency or severity, leaving potential residual confounding by indication.
• The number of anti-CGRP-exposed pregnancies was relatively small, and prescription claims could not confirm medication administration.
• Very early unrecognized losses may have been missed, and gestational age was imputed for many losses.
• The commercially insured US population may limit generalizability; pregnancy intention and treatment history could also have influenced findings.

Conclusion:

The authors advised that clinicians consider the limited pregnancy-safety evidence when discussing anti-CGRP monoclonal antibody treatment with people who may become pregnant.

Sources:

• JAMA Neurology (study source named in article context)