Protocol for a Cross-Sectional Study: Effects of a Multiple Sclerosis Relapse Therapy With Methylprednisolone on Offspring Neurocognitive Development and Behavior (MS-Children).

Introduction: Multiple Sclerosis (MS) is the most common neuroimmunological disease in women of childbearing age. Current MS therapy consists of immunomodulatory relapse prevention with disease-modifying therapies (DMTs) and acute relapse therapy with the synthetic glucocorticoid (GC) methylprednisolone (MP). As most DMTs are not approved for use during pregnancy, treatment is usually discontinued, increasing the risk for relapses. While MP therapy during pregnancy is considered relatively save for the fetus, it may be detrimental for later cognitive and neuropsychiatric function. The underlying mechanism is thought to be an epigenetically mediated desensitization of GC receptors, the subsequent increase in stress sensitivity, and a GC-mediated impairment of brain development. The aim of this study is to investigate the associations of fetal MP exposure in the context of MS relapse therapy with later cognitive function, brain development, stress sensitivity, and behavior. Methods and Analysis: Eighty children aged 8-18 years of mothers with MS will be recruited. Forty children, exposed to GC in Ethics and Dissemination: This study was approved by the participating institutions' ethics committees and results will be presented in accordance with the STROBE 2007 Statement. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04832269?id=ZKSJ0130.