Multiple Sclerosis Relapse Treatment During Pregnancy and Offspring Functional and Structural Neurodevelopment: A...

High-dose methylprednisolone (MP) is the global standard for treating pregnancy-associated relapses in multiple sclerosis (MS). Given that glucocorticoids cross the placenta and may interfere with fetal brain development, concerns remain about their long-term safety. This study assessed whether in utero MP exposure as part of MS relapse therapy affects neurodevelopment in school-aged children.

In this cross-sectional, 2-center study, term-born children with prenatal exposure to MP due to maternal MS relapse treatment were compared with a nonexposed reference group of children, all born to mothers with MS. Participants were primarily identified using the German MS and Pregnancy Registry and assessed at tertiary MS centers. The primary outcome was global cognitive ability, measured using a standardized intelligence test. Secondary outcomes included attention, behavior, motor performance, and electrocortical activity at rest. Structural brain development was assessed using high-resolution MRI, including voxel-based and surface-based morphometry. Deviations from chronological brain age were quantified using a machine learning-based framework. Statistical associations were examined using linear regression models.

The MP-exposed group (n = 30; mean age 9.6 years; 37% female) and the reference group (n = 30; mean age 10.0 years; 40% female) were comparable with respect to demographic and perinatal characteristics. The median cumulative MP dose was 5 g (Q1-Q3: 3-7.5), predominantly administered during the second trimester. Global IQ did not differ between groups (MP: 103.0; 95% CI: 99.2-106.8 vs reference: 101.5; 95% CI: 97.6-105.3). After correction for multiple comparisons, no group differences emerged in secondary neuropsychological outcomes or electrocortical parameters. MRI analyses revealed no differences in gray matter volume, cortical thickness, gyrification, or chronological brain age.

In spite of theoretical concerns that MP exposure during pregnancy might lead to alterations in neurodevelopment, this was not found to be the case in this cohort, with most exposures occurring during the second trimester. However, this study was not powered to detect subtle associations in secondary analyses or to draw definitive conclusions regarding potential dose-response relationships. Given the remaining uncertainties, MP should be used with caution at the lowest effective dose until larger follow-up studies provide further clarity.