Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study

Abstract

Our findings suggest that neither GA nor IFN constitutes a major risk for prenatal developmental toxicity.

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance

“…Although considered a progressive disease, the severity and rate of progression is highly variable; some patients may only experience occasional relapses of MS disease interspersed with periods of relatively stable Pregnancy loss: conflicting findings (observed in n = 23 [25] and n = 69 [IFN-β 1b only [13]], but not in n = 88 [12]) Decreased fetal growth: conflicting findings (observed in n = 88 [12] and n = 69 [13], but not in n = 78 [59]) Teratogenicity not observed (n = 88 [12], n = 78 [59] and n = 69 [13] Recommend discontinuation prior to conception or once pregnancy is known [7,8] with some suggesting a washout period of at least 1 month prior to conception [60] for women with mild MS Recommend continuation until conception or through pregnancy [6] for women with severe or highly active MS Use not recommended in breastfeeding [6,8,10] Glatiramer acetate Pregnancy loss: unknown Decreased fetal growth not observed in rats with 18-36× human dose [110] Teratogenicity not observed in rats or rabbits with 18-36× human dose [110] Decreased newborn survival: unknown…”

“…Pregnancy loss not observed (n = 31 [13], n = 46 [61] and n = 17 [62]) Decreased fetal growth not observed (n = 31 [13] and n = 17 [62]) Teratogenicity not observed (n = 31 [13], n = 46 [61] and n = 17 [62]) Impaired development of the newborn not observed (n = 11 [16] Recommend discontinuation prior to conception or once pregnancy is known [7,8] with some suggesting a washout period of at least 1 month prior to conception [60] for women with mild MS Use until conception or into pregnancy may be recommended for women with severe or highly active MS [6] Use not recommended in breastfeeding [6] Natalizumab Contraception required for women with childbearing potential; recommend discontinuation at least 3 months prior to conception [6] Use not recommended in breastfeeding [6,11] MS: Multiple sclerosis.…”

“…IFN-β exposure was not associated with low birthweight (<2500 g), cesarean delivery, congenital anomaly or spontaneous abortion [12]. Fewer studies (with limited sample size) were available regarding the safety of GA [13][14][15][16] or natalizumab [17]. Therefore, while GA exposure was not associated with lower mean birthweight, congenital anomaly, preterm birth or spontaneous abortion [13], and natalizumab did not appear to increase the risk of shorter birth length, lower birthweight or lower gestational age [17], conclusive statements surrounding safety cannot be made.…”

“…For example, when classifying DMD exposure, some defined in utero DMD exposure as within 1 month prior to conception, whereas others used the estimated time of conception. All these issues outlined here could contribute to the differences in reported findings between studies -with some studies reporting harm [12,13,[25][26][27] and others not [14][15][16][17][27][28][29][30][31][32][33]. Some of the best available studies are prospective, which, by their nature, minimize reporting and recall bias (a common challenge in pregnancy-related pharmacovigilance studies).…”

“…Some of the best available studies are prospective, which, by their nature, minimize reporting and recall bias (a common challenge in pregnancy-related pharmacovigilance studies). Three such cohort studies have been published to date and all examined IFN-β exposure [12,13,25]. Of these, two had relatively large sample sizes (n = 69 [13] and 88 [12]), which also allowed for adjustment of important confounders (including gestational age, parity, socioeconomic status and smoking or alcohol use) to better estimate the true effect of IFN-β exposure.…”