Loading ...

ORLANDO, Fla. — Use of calcitonin gene-related peptide (CGRP) monoclonal antibodies for migraine during early pregnancy was associated with an increased risk for miscarriage, results of a retrospective observational study.

Results of a retrospective observational study showed risk for spontaneous abortion was approximately 45% greater in those taking CGRP monoclonal antibodies while pregnant than in those not taking CGRPs or the beta-blocker propranolol.

“These findings were robust across multiple sensitivity analyses, suggesting that confounding by migraine severity is unlikely to fully explain the observed association overall,” study investigator Leah K. Flatman, PhD, of the Centre Hospitalier Universitaire Sainte-Justine in Montreal, Quebec, Canada, told attendees.

“These results support cautious use of anti-CGRP therapies and emphasize the importance of preconception counseling for women of childbearing potential. They also highlight the need for future safety research of pregnancy, including studies of fetal and long-term offspring outcomes.”

The findings were presented on June 5 at the American Headache Society (AHS) Annual Meeting 2026.

Few Treatment Options

Despite a documented disproportionate burden of migraine among women of reproductive age, options for treating migraine during pregnancy are limited because of teratogenicity and other safety concerns, Flatman said.

“Anti-CGRP monoclonal antibodies have transformed migraine prevention since their introduction in 2018 but their use in pregnancy remains uncertain as CGRP is involved in placental and vascular development,” she said, adding that existing evidence on their safety in pregnancy is sparse and inconsistent, relying primarily on case reports and pharmacovigilance data.

To determine whether exposure to anti-CGRP monoclonal antibodies during early pregnancy was associated with an increased risk for spontaneous abortion, the researchers conducted a retrospective study of the AM-PREGNANT cohort using US MarketScan commercial claims data from 2018 to 2021. 

They examined the claims data for 7579 singleton pregnancies in 7119 women aged 15-45 years who had a migraine diagnosis before pregnancy and had at least 6 months of continuous health insurance enrollment before their last menstrual period.

They compared spontaneous abortion up until 20 weeks gestation for 318 people taking anti-CGRP monoclonal antibodies with or without propranolol, 201 people taking propranolol without CGRP monoclonal antibodies, and 7060 people unexposed to either medication class. The results were adjusted to account for age, comorbidities, other medications, and healthcare utilization.

The groups were similar in average age (31-32 years) and in diagnoses of renal disease, epilepsy, diabetes, and thyroid disorders, but depression was higher in those receiving CGRP monoclonal antibodies and hypertension was higher in those receiving propranolol. Depression was also higher in both groups taking migraine medications but highest in those taking CGRP monoclonal antibodies.

Use of antidepressants was higher in those taking propranolol and/or CGRP monoclonal antibodies, and more women taking CGRP monoclonal antibodies were also taking triptans, nonsteroidal anti-inflammatory drugs, ondansetron, and antiepileptic medications than those in the other two groups. The women taking CGRP monoclonal antibodies also had higher healthcare utilization than the other two groups. 

Up until 8 weeks gestation, there were no instances of spontaneous abortion across all three groups. Incidence of spontaneous abortion increased among those taking CGRP monoclonal antibodies between 8-12 weeks to a greater extent than in the other groups, and then rates were similar again for gestational weeks 12-20.

Overall, 2% of those taking propranolol alone had spontaneous abortions, for an incidence rate of 0.77 per person-year, compared to 5% of those taking CGRP monoclonal antibodies, with a rate of 1.13 per person-year.

The rate of spontaneous abortion was 0.73 per person-year in those unexposed to either medication class.

Compared to unexposed pregnancies, risk for spontaneous abortion was greater in those taking CGRP monoclonal antibodies (adjusted hazard ratio [aHR], 1.45; 95% CI, 1.14-1.85) but not in those taking propranolol alone (aHR, 1.04; 95% CI, 0.72-1.5). With additional adjustment for bias, risk remained higher in those taking CGRP monoclonal antibodies compared to unexposed pregnancies (aHR, 1.38; 95% CI, 1.2-1.55).

Experts Urge Caution

Vincent Martin, MD, professor of clinical medicine and director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience Institute in Cincinnati, Ohio, who was not involved in the research, told Medscape Medical News the findings are noteworthy.

“When you give CGRP therapies by injection, they stay in the body for 5 months, so this is an issue that could come up with a lot of different patients that are on CGRP therapies where they have an unexpected pregnancy, or maybe they don’t even know that they should be off of therapy for five months before trying to get pregnant,” Martin said.

He acknowledged that those taking CGRP monoclonal antibodies likely have more severe migraine than others and that this finding is early and need to be replicated, “but I think it’s one that needs to be discussed with patients as well.”

His colleague, Brinder Vij, MD, professor of clinical medicine and division director of headache medicine at the University of Cincinnati College of Medicine, Cincinnati, said it’s unclear whether anti-CGRP therapies should be used during pregnancy based on the FDA label and that he personally does not recommend pregnant patients take them.

“The interesting finding here was that propranolol was not affecting the outcomes, which I think has become a little norm to use during pregnancy,” Vij added.

No external funding was noted, and Flatman reported having no disclosures. Vij reported speaker fees from AbbVie, Amgen, and Biohaven Pharmaceuticals, and Martin reported consulting and/or speaking fees and research support from AbbVie, Eli Lilly, Pfizer, Tonix, and Teva Pharmaceuticals.