Association of Neurodevelopmental Disorders and Congenital Anomalies With Prenatal Multiple Sclerosis Treatment-Real-World Historical Cohort Study.

There is a paucity of data regarding the effects of prenatal disease-modifying therapies (DMTs) for multiple sclerosis (MS), on congenital anomalies in the offspring. Moreover, data on the association with neurodevelopmental disorders are lacking. This is an historical cohort study, within the Israeli Clalit Health Services database (2005-2024) that included all children, born to mothers carrying a diagnosis of MS. Mothers' demographic and clinical characteristics were used to account for potential confounders. A marginal model used for the association between prenatal dispensed DMTs and neurodevelopmental disorders. A log-binomial regression model used to estimate relative risks (RR), 95% CI for the association between exposure and major congenital anomalies (MCAs). The cohort included 1374 children: 484 exposed prenatally to DMTs (237, 85, 56, 49, 25, 32 exposed to interferon-β, glatiramer, monoclonal antibodies, fumarates, sphingosine-1-phosphate receptor (S1PR) modulators, or a combination of therapies, respectively). In a mean follow-up of 7.5 years (maximum 19.8 years), prenatal exposure to DMTs was not associated with significant risk for neurodevelopmental disorders, in univariate and in multivariate models. Within 1252 children with 2 years of follow-up, 50 (3.9%) children were identified with MCAs. There was higher rate of MCAs among S1PR modulator-exposed children 2(8%). Due to the small group risk estimates for S1PR modulators had wide CIs, with RR = 2.0 (95% CI 0.51-8.1, P = 0.314); RR = 5.16 (95% CI 1.47-18.2, P = 0.011) in the univariate and sensitivity analysis, respectively. In conclusion, in the current cohort, prenatal exposure to DMTs was not associated with neurodevelopmental disorders. Exposure to S1PR modulators in pregnancy was associated with higher risk for congenital anomalies. Prospective larger studies are warranted.