Background Several studies have shown that pregnancy reduces relapse rate in Multiple Sclerosis (MS), followed by an increased relapse rate in the early postpartum period. We re-examined the effect of pregnancy on MS using the international MSBase Registry, examining predictors of early post-partum relapse.

Methods We performed a prospective observational multi-centre case-control study, with self-control. Annualised relapse rate (ARR) and median Expanded Disability Status Scale (EDSS) scores were compared for the 24 months pre-conception, pregnancy and 24 months postpartum periods. Clustered logistic regression was used to investigate predictors of early postpartum relapses.

Results We included 893 pregnancies in 674 females with MS. Mean ARR (SD) for 24 months pre-pregnancy was 0.32 (0.45), decreasing to 0.13 (0.77) by 3rd trimester of pregnancy. ARR rose to 0.61 (1.61) in the 1st 3 months postpartum, and returned to baseline by 24 months. Median EDSS remained stable. Higher pre-conception ARR predicted early postpartum relapse and an independent protective effect was observed with disease-modifying treatment (DMT) use in the 2 years pre-conception.

Conclusion We confirm a favourable effect of pregnancy on relapse rate in MS, strongest in the third trimester, and a peak in relapses in the early postpartum period. In the pre-conception period, DMT exposure and low ARR conferred independent protective effects for postpartum relapse. This novel finding could provide clinicians with a strategy to minimise risk of postpartum relapse in women with MS planning pregnancy.