New research suggests that a recently developed class of migraine medications may be associated with a higher risk of miscarriage when used around conception and during early pregnancy. The findings raise further safety concerns for people of reproductive age who rely on these increasingly prescribed treatments.
The medications, known as CGRP-targeted monoclonal antibodies, are designed to prevent migraines by blocking calcitonin gene-related peptide, a molecule involved in migraine attacks. They are generally prescribed to patients whose migraines have not responded adequately to older treatments and are valued for their relatively limited side effects.
How the migraine drugs work
CGRP is a neuropeptide involved in blood vessel dilation and the transmission of pain signals, both of which play important roles in migraine. By blocking CGRP or its receptor, these biological medications can reduce the frequency and severity of migraine attacks in many patients.
However, CGRP also contributes to several processes during pregnancy, including regulation of blood flow to the uterus, embryo implantation and placental development. These overlapping functions have raised theoretical concerns that prolonged CGRP blockade could interfere with the early stages of pregnancy.
Details of the JAMA Neurology study
The new study, led by epidemiologist Anick Bérard at CHU Sainte-Justine in Montreal, examined US insurance claims collected between 2018 and 2021. Researchers followed 7,579 pregnancies among women diagnosed with migraine or recently prescribed triptans or ergot medications.
Some participants were exposed to anti-CGRP monoclonal antibodies, including erenumab, fremanezumab, galcanezumab or eptinezumab, during pregnancy or within six months before conception. Others received propranolol, a beta blocker commonly used as a first-line preventive treatment for migraine.
Using person-time analyses, the researchers compared miscarriage rates during periods with and without medication exposure. During the first 20 weeks of pregnancy, exposure to anti-CGRP antibodies was associated with approximately a 40 percent higher risk of spontaneous abortion compared with unexposed periods. No comparable increase was observed with propranolol.
Limitations and remaining uncertainties
The authors emphasize that the study was observational and cannot establish that CGRP-blocking medications directly cause miscarriage. Women prescribed these biological treatments often experience more severe, treatment-resistant migraines, which may be associated with underlying health conditions that also influence pregnancy outcomes.
The analysis relied on commercial insurance claims, which do not provide detailed information about migraine severity, adherence to prescribed treatment, lifestyle factors or whether pregnancies were planned. Consequently, unmeasured confounding factors could partly account for the observed association.
Additionally, the data primarily represent a privately insured US population and may not apply equally to people with different insurance coverage, lower incomes or more limited access to specialist care. The number of pregnancies involving exposure to these relatively new medications also remains modest compared with established treatments.
Implications for patients and clinicians
Despite these uncertainties, the findings reinforce existing recommendations to avoid anti-CGRP monoclonal antibodies during pregnancy and while actively trying to conceive. Most regulatory agencies already advise discontinuing these medications well before conception because pregnancy safety data remain limited.
Experts caution that patients should not discontinue treatment abruptly without consulting a healthcare professional, particularly when migraines are severe or disabling. Instead, neurologists and obstetric specialists can work together to evaluate alternatives, including propranolol, behavioral therapies and other approaches with a longer history of use during pregnancy.
The authors recommend larger prospective studies and pregnancy registries to monitor fetal development, birth outcomes and children’s long-term health following exposure to anti-CGRP medications. Until more comprehensive evidence becomes available, clinicians are encouraged to discuss the available data, uncertainties and potential risks with migraine patients who could become pregnant.
The findings also contribute to broader discussions about the safety of newer biological therapies during pregnancy, particularly as drug development increasingly targets immune and neurovascular pathways. For now, individualized discussions of potential benefits and risks remain essential for patients balancing effective migraine prevention with plans for pregnancy.
