Evolución de la esclerosis múltiple durante la gestación y tras el partoinfluencia de los tratamientos modificadores de la enfermedad sobre el embarazo, el recién nacido y el curso de la enfermedad

Abstract

Introduction: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory and degenerative disease of the central nervous system and the most common non-traumatic disabling neurological disease in young adults, being 2 to 3 times more frequent in women. Literature data show that disease activity decreases during pregnancy followed by a significant increase after childbirth, even above pre-gestation levels. Even so, 30% of women with MS experience relapses during pregnancy and more than 50% after childbirth. So far, there has been insufficient evidence to reliably support the use of disease modifying treatments (DMT) during pregnancy and guidelines on MS treatment recommend DMT interruption before pregnancy or discontinuing them as soon as a non-scheduled pregnancy is confirmed. The few published series of pregnancies exposed to interferon beta (IFN-?) or glatiramer acetate (GA) have not detected safety problems. Objectives: The objectives of this study were to describe the evolution of MS during pregnancy and after childbirth in a cohort of patients with MS and to assess if there are differences in the disease evolution during pregnancy and after childbirth and in the obstetric and neonatal details according to if there was or not exposure to DMT. Methods: A prospective observational cohort study of 14 women with MS who decide to remain on IFN-? or GA throughout pregnancy. Retrospective observational study of MS patients included in the databases of 6 hospitals in the provinces of Murcia, Alicante and Albacete with planned or unscheduled pregnancy while receiving DMT. Descriptive analysis of the obstetric results, neonatal outcomes and MS evolution during pregnancy and one year after childbirth. Comparative analysis between different groups regarding to DMT exposure was performed. Results: 74 gestations (35.1% unscheduled) from 69 patients were analysed. Assisted reproduction techniques were employed in 5.4%. In 14 pregnancies treatment with GA (n = 7) or IFN-? (n = 7) was maintained throughout pregnancy, in 21 DMT were withdrawn before pregnancy, in 29 DMT were withdrawn when pregnancy was confirmed and in 10 it was decided not to start DMT until postpartum period. There were 2 spontaneous abortions in the first trimester (2.7%), from the remaining 72 pregnancies, 4 of which were twin pregnancies, resulted in 76 live births. The number of relapses 1 and 3 years before pregnancy and a higher score on expanded disability status scale (EDSS) at the beginning of pregnancy were associated with the occurrence of relapses during pregnancy and the first postpartum year. In those patients who stopped DMT before a planned pregnancy the occurrence of relapses before pregnancy increased the risk of relapses during pregnancy. Patients who stopped DMT more than 3 months before pregnancy experienced more relapses after delivery. Relapse rate was reduced during pregnancy but significantly increased in the first trimester postpartum compared to the year before pregnancy. DMT exposed pregnancies showed a lower relapse or disability progression risk in the postpartum year. Maintenance therapy with GA or IFN-? throughout pregnancy was associated with a significant decrease in relapse or disability progression risk in the postpartum year. Pregnancies in which DMT was stopped for 3 months or longer before pregnancy had a five-fold increased risk of relapses during pregnancy and a six-fold increased risk of relapses in the postpartum year. The mean gestational age of live-born infants was 38.14 ± 2.4 weeks and the mean birth weight was 2995 grams. Eighteen percent of the deliveries were preterm, 15.8% of the newborns had low birth weight and 5.2% were small for gestational age. No congenital anomalies were found. Caesarean section was performed in 29.16% of deliveries. Patients with EDSS ? 1.5 at the beginning of pregnancy and more relapses in the year prior to pregnancy had an increased risk of caesarean section. No differences were found in the mean birth weight, gestational age, percentages of preterm birth, low birth weight, or caesarean section among pregnancies with or without DMT exposure. Conclusions: Stopping or delaying DMT to plan a pregnancy does not seem to be appropriate and may have consequences on the course of the disease, causing relapses and future disability progression. Pregnancy in patients with MS does not seem to be associated with an increased risk of adverse maternal-fetal effects. Our results confirm the maternal-fetal safety of IFN-? and GA in the first weeks of pregnancy and even during the entire gestation period. The maintenance of these treatments at least until the pregnancy is confirmed seems to be safe, well tolerated and probably convenient. In case of active MS, treatment with GA or IFN-? throughout pregnancy could be considered. Key words: multiple sclerosis, pregnancy, disease modifying treatments, disability progression, relapsing-remitting, clinical relapses, cohort study, interferon, glatiramer acetate.