In a study published in JAMA Neurology, researchers found a link between exposure to anticalcitonin gene-related peptide monoclonal antibodies around conception and early pregnancy, and a higher risk of spontaneous abortion in individuals with migraine. Analyzing 7579 singleton pregnancies among 7119 people with pregestational migraine in the AM-PREGNANT cohort, the investigation spanned pregnancies with last menstrual periods on or after November 1, 2018, through 20 weeks of gestation.
Data analysis shows higher risk with specific treatment
Among the 1862 pregnancies that ended in spontaneous abortion, the overall rate was 24.6 percent. The data showed that compared with periods of no drug exposure, use of anti-CGRP mAbs carried an adjusted hazard ratio of 1.42. Propranolol, included as a comparison, showed no statistically significant association with the risk of spontaneous abortion.
The study defined exposure periods based on the long half-lives of these agents, counting 135 to 155 days after each dose or infusion. Among the 350 pregnancies exposed to anti-CGRP mAbs, 172 occurred before and during pregnancy, 147 before pregnancy only, and 31 during pregnancy only. Under a modeled scenario where all pregnancies were exposed, the adjusted risk by 20 weeks would be 28.7 percent, compared with 24.5 percent with no exposure.
Confounding factors and study limitations
Individuals with migraine who took anti-CGRP monoclonal antibodies showed higher healthcare engagement prior to pregnancy and exhibited more indicators of severe migraine episodes. This group had raised usage of triptans, nonsteroidal anti-inflammatory drugs, and ondansetron, as well as higher rates of depression. When researchers adjusted for migraine severity using chronic migraine as a measure, the risk estimate dropped slightly to a hazard ratio of 1.33.
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The authors noted that claims data do not capture migraine frequency or severity, leaving room for residual confounding by indication. Pregnancy intention was also unavailable. The authors cautioned that findings may not generalize beyond commercially insured populations and that outcome timing was partly imputed. Very early losses that were not clinically detected were likely missed. Among the 1862 spontaneous abortions, 1097 (58.9%) had no gestational age code and were assigned an 8-week gestational age to estimate the last menstrual period.
While the data suggests a link between early use of anti-CGRP mAbs and spontaneous abortion, it does not prove causation. The use of these drugs in early pregnancy may reflect an unplanned pregnancy or residual drug levels rather than the medication itself causing the loss. This distinction matters because patients who plan their pregnancies may use these therapies differently than those who conceive unintentionally. Anti-CGRP mAb exposure in early pregnancy may reflect an unplanned pregnancy or residual drug around conception, whereas propranolol may be continued intentionally when clinically indicated.
Clinical guidance for patients of reproductive age
Current recommendations advise discontinuing anti-CGRP monoclonal antibodies 5 to 6 months before attempting pregnancy. The researchers emphasized that their findings justify additional studies on the safety of these drugs during pregnancy. Until stronger evidence emerges, doctors should weigh the available—but limited—data when discussing treatment options with patients who might conceive.
Migraine heavily impacts individuals in their reproductive years, and therapies targeting the CGRP pathway have become standard for prevention since 2018. Globally, migraine ranks as the second-leading cause of disability and the top cause among young women, according to GBD2019 data. With anti-CGRP monoclonal antibodies increasingly prescribed to reproductive-age patients, more research is critical to assess their effects on pregnancy outcomes, including spontaneous abortion risks, fetal development, and long-term child health. Clinicians should factor in these uncertainties when advising patients who may become pregnant.