Neurologists managing women with Multiple Sclerosis (MS) need information about the safety of disease modifying drugs (DMDs) during pregnancy. However, this knowledge is limited.
The aim of this systematic review and meta-analysis was to evaluate pregnancy outcomes in women with MS treated with DMDs.
The term “multiple sclerosis” combined with DMDs and pregnancy terms were searched in Embase and Medline databases to identify studies published between Jan 2000 and Jul 2019. Only studies in which the exposure occurred in utero and compared patients exposed to a DMD versus MS patients without treatment were included, regardless of the study design. 1260 studies were identified, and ten studies met our inclusion criteria. MS treated patients were analysed overall and stratified by DMDs class and by type. Pooled relative risk (RR) of pregnancy and birth outcomes in pregnancies exposed to DMDs compared to those not exposed was calculated using a random effects model.
Overall, for MS patients exposed to DMDs the RR (95% confidence interval) for spontaneous abortion was 1.14, (0.99-1.32), for preterm births 0.93 (0.72-1.21) and for major congenital malformations (MCM) in live births 0.86 (0.47-1.56) when compared to MS without treatment. The pooled prevalences of each pregnancy outcome in MS patients exposed to any DMD were: spontaneous abortions 11.6% (7.4-16.7), premature births 12.1% (9.0-15.6) and MCM 3.0% (1.8-4.4). The most common major congenital malformations reported in MS patients exposed to DMDs were atrial septal defect (ASD) (N=4), polydactyly (N=4) and club foot (N=3), which are among the most prevalent birth defects observed in the general population. Each case of ASD was present in patients exposed to different drugs (natalizumab, beta-interferon, glatiramer acetate and mitoxantrone).
Interferons, glatiramer acetate or natalizumab, do not appear to increase the risk for spontaneous abortions, preterm births or MCM. Future studies that assess the effect of individual DMDs are needed to enable decisions on the best treatment options.