Drug Saf. 2026 Jun 11. doi: 10.1007/s40264-026-01686-2. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: Concerns about modafinil and armodafinil use in pregnancy emerged from animal reproductive toxicity and limited human data, including a US registry suggesting increased risk of major congenital malformations (MCMs). Subsequent studies have reported conflicting findings. This study aimed to evaluate the risk of MCMs and other adverse pregnancy outcomes following prenatal modafinil exposure in the French population.
METHODS: This retrospective cohort study identified pregnancies during 2012-2019 using the French national health database (SNDS). Pregnancies exposed and unexposed to modafinil were identified and propensity score matched (1:4 ratio). Outcomes assessed included MCMs, spontaneous abortion, stillbirth, elective termination, preterm birth, low birth weight, and growth restriction. Prevalence and prevalence ratios (PRs) were calculated and adjusted risk ratios (RR) were estimated using Poisson regression models.
RESULTS: A total of 786 modafinil-exposed pregnancies were matched to 3144 unexposed pregnancies. The prevalence of MCMs among first-trimester modafinil-exposed pregnancies was 4.2%, compared with 3.3% in unexposed pregnancies (PR 1.26; 95% CI 0.77-2.04). After adjustment for potential confounding factors, no statistically significant increase in MCM risk was observed (RR 1.32, 95% CI 0.81-2.15). Most other pregnancy and birth outcomes showed no significant differences. However, elective terminations were 32% more frequent in the exposed group (PR 1.32; 95% CI 1.14-1.51).
DISCUSSION: This large, population-based study found no increased risk of MCMs or most adverse pregnancy outcomes following modafinil exposure. The elevated rate of elective terminations may reflect clinical decisions influenced by underlying maternal conditions such as narcolepsy. While these findings do not indicate an increased risk of MCM, caution remains warranted regarding modafinil use during pregnancy.
PMID:42274903 | DOI:10.1007/s40264-026-01686-2
