Objectives:Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) predominantly affect women of reproductive age. During the last few decades many disease-modifying therapies (DMTs) have been approved. It is therefore important to provide epidemiological structures for the collection of safety information on exposed pregnancies. Data on disease activity after withdrawal of DMTs are in high demand especially as severe relapses have been described after ceasing highly effective DMTs. Although breastfeeding is recommended, it is still unclear if the early reintroduction, especially of highly effective DMTs, has a beneficial effect on postpartum relapse risk or a combination of both, however safety data are lacking.Methods:The German MS and Pregnancy Registry (DMSKW) is a nationwide, observational, cohort study of pregnant women with MS or NMOSD, founded in 2006. As the study procedure has undergone important adaptation in recent years, described here is the updated methodology including data source and acquisition as well as variables collected within the DMSKW.Results:As of December 2020, the DMSKW database comprises 2579 pregnancies, 2568 with MS and 11 with NMOSD. Women are enrolled at a median gestational week of 11 (range: 0.02–42.1), have a median postpartum follow up of 1.2 years (range: 0–9.2) with 76% of all pregnancies being exposed to a DMT, mostly in the first trimester. Spontaneous abortion and preterm birth occurred in 7% and 10%, respectively; 19% of all women suffered from at least one relapse during pregnancy, with a minimum of 6% during the third trimester of pregnancy.Conclusion:The DMSKW is a valuable structure in providing safety data on drug exposure during pregnancy and lactation in combination with information on disease activity up to 6 years postpartum. This article will be the reference for describing the methods of future publications from the DMSKW.