Pregnancy and multiple sclerosis: the initial results from a Brazilian database

Abstract

-Purpose: Pregnancy management poses an extra challenge to physicians and their multiple sclerosis (MS) patients. There are few papers reporting databases on the subject. Method: Brazilian database from nine MS clinical and research units, with complete data on 47 pregnant women (49 pregnancies). Results: Despite relatively high exposure to MS medications, no birth defects were reported. Low birth weight and prematurity were similar to those for developing countries. Three complications may have been associated with these medications, while three others were considered to be of purely obstetric nature. Conclusion: Our results confirm previous findings on lower relapse rate during pregnancy and add to the present literature informing on data related to drug exposure.Key wOrDS: multiple sclerosis, pregnancy, prematurity, low birth weight, obstetric complications, interferon beta, glatiramer acetate. gravidez e esclerose múltipla: resultados preliminares de base de dados Brasileira resumo -Propósito: O manejo da gravidez cria um desafio extra aos médicos e aos pacientes com esclerose múltipla (eM). existem poucos trabalhos relatando bases de dados neste tema. Método: Base de dados brasileira de nove centros clínicos e de pesquisa na eM, com dados completos de 47 mulheres grávidas (49 gestações). Resultados: Apesar da exposição a drogas para eM ter sido relativamente alta, não foram registradas malformações. Baixo peso e prematuridade foram semelhantes àqueles de países em desenvolvimento. Três complicações podem ter sido associadas a drogas, enquanto outras três foram consideradas como sendo de natureza puramente obstétrica. Conclusão: Nossos resultados confirmam os achados de menor taxa de surtos na gestação e adicionam dados relacionados a exposição a drogas, na literatura atual.PALAvrAS-chAve: esclerose múltipla, gravidez, prematuridade, baixo peso, complicações obstétricas, interferon beta, acetato de glatirâmer.

Fertility, Pregnancy and Childbirth in Patients with Multiple Sclerosis: Impact of Disease-Modifying Drugs

“…Moreover, the occurrence of malformations or developmental abnormalities has been described in some studies, but the overall frequency does not seem to be different from that of the normal population [83,90,[102][103][104]. Finally, a lower body weight has been observed in some studies [83,[103][104][105] but not confirmed by others [106,107]. On the whole, the best evidence (level 3) suggested that IFN exposure was associated with a lower mean birth weight, a shorter mean birth length and preterm birth, but not with spontaneous abortion [101].…”

“…The transfer of these compounds should be limited by their molecular weight [71]. Moreover, it is likely that they are depolymerized after oral ingestion [106]. In one recent report [113], IFN transfer to human breast milk was assessed in six women receiving intramuscular IFN-b1a.…”

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

“…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).…”

“…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. In addition, some studies investigated DMD exposure late in pregnancy; three small studies (n = 9 [14], 11 [16] and 12 [15] pregnancies) reported on GA exposure up to the third trimester of pregnancy, whereas others followed long-term developmental outcomes beyond the immediate perinatal period in offspring exposed to GA [16] or IFN-β [12,26] in utero. Individual studies have also investigated maternal natalizumab exposure during pregnancy [17] and paternal DMD use around conception [28] -both represent the first cohort studies published on these topics.…”