early pregnancy use of anti-cgrp monoclonal antibodies and propranolol and spontaneous abortion risk

Overview

• retrospective cohort study (AM-PREGNANT cohort, Merative MarketScan Commercial Database 2018-2021) evaluating the association between early pregnancy exposure to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) or propranolol and the risk of spontaneous abortion (1)
• primary finding: early pregnancy exposure to anti-CGRP mAbs in individuals with pregestational migraine is associated with a statistically significant increase in the risk of spontaneous abortion compared with no exposure (aHR 1.42; 95% CI 1.12 to 1.80) (1)
• comparative finding: early pregnancy exposure to propranolol showed no increased risk of spontaneous abortion (aHR 1.02; 95% CI 0.71 to 1.47), supporting UK consensus guidance to stop anti-CGRP mAbs at least 6 months prior to planned conception (1, 2)

Clinical Context: Anti-CGRP mAbs and Propranolol in Migraine Management

Anti-CGRP Monoclonal Antibodies (mAbs)

• drug class and agents: targeted biological therapies including erenumab, fremanezumab, galcanezumab, and eptinezumab (1, 2)
• clinical indication: prescribed as specialized prophylactic therapy for adults with severe episodic or chronic migraine who have failed standard oral preventive treatments (2)
• mechanism of action: selectively block CGRP ligands or CGRP receptors in the trigeminovascular system, directly inhibiting neurogenic inflammation and nociceptive signalling (1, 2)

Propranolol

• drug class and agents: non-selective beta-adrenergic receptor antagonist (1, 2)
• clinical indication: widely used as a first-line oral prophylactic agent for episodic and chronic migraine in primary care (2)
• mechanism of action: modulates central cortical spreading depression, sympathetic tone, and cerebrovascular autoregulation (2)

Key Study Findings

Exposure and Outcome Rates

• study population: 7,579 singleton pregnancies across 7,119 individuals (mean age 31.6 years) with pregestational migraine followed up to 20 weeks' gestation
• spontaneous abortion rate during anti-CGRP mAb exposure: 28.6% (100 events)
• spontaneous abortion rate during propranolol exposure (without anti-CGRP mAbs): 12.8% (37 events)

Risk Estimates

• anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab):
  • primary multivariable analysis: adjusted hazard ratio (aHR) 1.42 (95% CI 1.12 to 1.80) compared with unexposed time
  • bias-adjusted sensitivity analysis: HR 1.33 (95% simulation interval 1.23 to 1.45)
• propranolol:
  • primary multivariable analysis: aHR 1.02 (95% CI 0.71 to 1.47) compared with unexposed time
  • bias-adjusted sensitivity analysis: HR 1.00 (95% simulation interval 0.96 to 1.03)

Pathophysiological Rationale and Clinical Guidelines

Biological Mechanism

• CGRP role in gestation: CGRP acts as a potent vasodilator and plays a functional role in uteroplacental haemodynamics and early placental development
• therapeutic blockade: monoclonal antibody-mediated inhibition of CGRP signaling during early organogenesis may disrupt vascular adaptation and early placental perfusion, providing a mechanistic basis for elevated spontaneous abortion risks

Current UK Preconception and Pregnancy Guidance

• anti-CGRP mAbs wash-out period:
  • because anti-CGRP mAbs are IgG molecules with long elimination half-lives (several weeks to months), UK guidance recommends discontinuing these agents at least 6 months prior to planned conception
• management of unplanned pregnancy:
  • if an unplanned pregnancy occurs during anti-CGRP mAb therapy, the drug should be stopped immediately, and the case reported to the UK Teratology Information Service (UKTIS) or national pregnancy registries
• alternative prophylactic options:
  • when migraine prophylaxis is required during pregnancy or preconception, options with established fetal safety profiles (or low baseline risk, such as propranolol) should be prioritised alongside non-pharmacological interventions

Reference:

1. Flatman LK, Leal LF, Leroux E, et al. Early Pregnancy Use of Anti-CGRP Monoclonal Antibodies and Propranolol and Spontaneous Abortion Risk. JAMA Neurology. Published online October 12, 2026.
2. British Association for the Study of Headache (BASH). BASH National Management Guidelines for Headache Disorders. 2026.