In the 32nd Congress, organized by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of London, England, the paper was reviewed: Multiple options for the treatment of Multiple Sclerosis.
The objective of this review is to highlight the problems faced by women affected by multiple sclerosis (MS) when facing a pregnancy, highlighting the steps that follow from the moment they want to get pregnant until their pregnancy, as well as during the follow-up of the same and the moment of delivery.
Management considerations during these stages are multiple.
Before pregnancy, the woman raises several questions such as the genetic risk that her offspring present the disease, as well as the impact that pregnancy may have on the prognosis of the disease, or the impact of the use of disease-modifying drugs (DMDs). In turn doubts arise during the course of pregnancy such as the activity of the disease, on the use of DMDs during the same, the evaluation and treatment of relapses and finally the choice of anesthesia for delivery. In the postpartum stage there are also relevant issues such as the activity of the disease, breastfeeding, the use of DMDs and their effects on the development of the newborn (1).
Effect of pregnancy on the course of the disease
Until the 1980s, women with MS were advised not to become pregnant. In 1998 the prospective study PRIMS (Pregnancy in MS) showed that the activity of the disease was significantly reduced during pregnancy, especially in the third trimester of pregnancy, while in the first trimester postpartum the relapse rate increased again, although decreasing later until reaching the same activity that was before pregnancy (2). In fact, it has been seen that women with greater activity of the disease during the year before and during pregnancy present a higher risk of relapse in the 3 months after delivery (3).
In other studies it has been shown that pregnancy could have a protective effect since it slows the progression of the disease in the long term (4).
Gestation and treatment of MS
As with any other disease, the potential risks associated with any therapy should be weighed carefully with the potential benefit obtained in each of the affected patients. In this specific case, the risk of relapse and disability of the mother with MS should be evaluated and weighed against the risk to the fetus, the possible teratogenic effects of the treatment, risk of spontaneous abortion and fetal development.
According to the technical specifications of the different DMDs, there are no data on the effect of these drugs on fertility, while the data on pregnancy are limited. Regarding interferon Beta there are contradictory data on its effect on the weight and height of the newborn (5,6). Therefore, according to the technical information of the different products, most DMDs are not recommended or even contraindicated during pregnancy. However, the clinical data that we have so far show that pregnancies in women treated with these drugs develop in a similar way to those in the general population, although for some drugs there is controversy about their effects on weight and height of the newborn
Impact of MS on pregnancy
Pregnancy in women with MS presents a normal course (8); at fetal level, there are no differences in gestational age or birth weight, nor does it differ in the frequency of vaginal births or caesarean sections with the general population; On the other hand, neither epidural anesthesia nor caesarean section are associated with adverse effects that interfere in the course of MS (8). However, it is very important to offer advice on a regular basis to be able to discuss all aspects related to pregnancy and to alleviate those fears that may persist (9); Communication and collaboration is therefore essential (9).
Risk of postpartum relapse
Most women are afraid of relapsing after childbirth. Currently there are good predictors; The relapse rate before and during pregnancy is a good predictor of relapse in the early postpartum period (3, 10, 11). In turn, it has been shown that treatment with DMDs during the two years prior to conception predicts postpartum relapse (11).
Regarding the restoration of treatment with DMDs indicate that so far there are no data available, only the recommendation to make the decision based on the willingness or not of the patient to breastfeed their child; in fact, the available data on the excretion of these drugs in breast milk are scarce. Therefore, the decision must always be individualized and shared with the patient, always assessing three important aspects: the activity of the disease before pregnancy, the desire of the patient to restore the treatment and her decision to breastfeed (11).
Regarding the latter aspect, if the patient finally wishes to breastfeed her child, indicate that this fact does not increase the risk of postpartum relapse. This is what is known following the German Registry in which the percentage of patients with relapses was analyzed in the first 6 postpartum months, observing a slight difference between women in exclusive breastfeeding and women who breast-fed their children together with supplementation . 24.2% and 38.3%, respectively, suffered a relapse at 6 months postpartum (HR equals 1.7, p equals 0.04) (10). Therefore, in case of not giving exclusive breastfeeding, it would be advisable to re-establish treatment with DMDs as soon as possible, at least 30-40 days postpartum.
> It is unlikely that MS has an adverse impact on pregnancy or on the baby’s health.
> The impact of pregnancy on MS is limited:
– The frequency of relapses varies over time, although in general it stabilizes until at least 3 months after gestation, reaching the same rate as before pregnancy.
– The effect of pregnancy on long-term progression is unknown, although most studies show no harm.
> Therapy with disease modifying drugs (DMDs) during pregnancy is not recommended or contraindicated; the benefits must be evaluated and compared with the risks for each patient in particular.
> Advice to patients is crucial in each of the phases; for this it is important to create multidisciplinary centers that allow to address all these aspects.
1. Coyle PK. Management of women with multiple sclerosis through pregnancy and after childbirth. Ther Adv Neurol Disord. 2016 May;9(3):198-210.
2. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998 Jul 30;339(5):285-91.
3.Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004 Jun;127(Pt 6):1353-60.
4.Masera S, Cavalla P, Prosperini L, Mattioda A, Mancinelli CR, Superti G, et al. Parity is associated with a longer time to reach irreversible disability milestones in women with multiple sclerosis. Mult Scler. 2015 Sep;21(10):1291-7.
5. Thiel S, Langer-Gould A, Rockhoff M, Haghikia A, Queisser-Wahrendorf A, Gold R, et al. Interferon-beta exposure during first trimester is safe in women with multiple sclerosis-A prospective cohort study from the German Multiple Sclerosis and Pregnancy Registry. Mult Scler. 2016 May;22(6):801-9.
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7. Herbstritt S, Langer-Gould A, Rockhoff M, Haghikia A, Queisser-Wahrendorf A, Gold R, et al. Glatiramer acetate during early pregnancy: A prospective cohort study. Mult Scler. 2016 May;22(6):810-6.
8. Miller DH, Fazekas F, Montalban X, Reingold SC, Trojano M. Pregnancy, sex and hormonal factors in multiple sclerosis. Mult Scler. 2014 Apr;20(5):527-36.
9. Vukusic S, Marignier R. Multiple sclerosis and pregnancy in the ‘treatment era’. Nat Rev Neurol. 2015 May;11(5):280-9.
10. Hellwig K, Rockhoff M, Herbstritt S, Borisow N, Haghikia A, Elias-Hamp B, et al. Exclusive Breastfeeding and the Effect on Postpartum Multiple Sclerosis Relapses. JAMA Neurol. 2015 Oct;72(10):1132-8.
11. Hughes SE, Spelman T, Gray OM, Boz C, Trojano M, Lugaresi A, et al. Predictors and dynamics of postpartum re sMay;20(6):739-46.