Planning a pregnancy for people with MS can raise various concerns to do with (for example) fertility, the possibility of transmitting MS to the child, the impact of disease modifying therapies (DMTs) on pregnancy, the influence of pregnancy on MS activity, and the mother’s capability to breastfeed and raise the child. It is therefore very important that family planning and pregnancy is discussed proactively at the earliest opportunity and ideally at least 6 months before attempts at conception so neurologic assessment of stability and specific recommendations for stopping DMTs can be made based on known risk guidelines.
The impact of pregnancy on MS activity
MS is typically least likely to relapse during pregnancy. Natural history studies in mainly untreated populations have suggested that relapse frequency reduces during pregnancy, especially in the third trimester, but about a quarter of women will experience a relapse during the first 3 months postpartum. There is also some indication that treatment with a DMT for at least one year prior to conception, reduces the risk and severity of a relapse following birth.
The impact of MS on pregnancy
Having MS does not affect fertility and should not affect a woman’s chance of getting pregnant. Women with MS can be reassured that they do not have an increased risk of pregnancy complications due to MS; the risks of experiencing miscarriage, stillbirth or birth abnormalities are similar between women with and without MS. In general, there is no evidence of an association between maternal MS and adverse effects on foetal development and babies born to mothers with MS are just as likely to develop normally as those born to women who don’t have MS.
Disease modifying treatments and pregnancy
The decision of which DMT to start, and then to either stop or continue throughout pregnancy, needs to be made based on considerations of how active MS is in any particular individual in the context of risk vs benefit, both to mother and baby. In general, discontinuation of DMTs is recommended before conception to minimise risk of foetal harm. Women with very active MS before pregnancy who stop second-line treatments may show an increase in disease activity during pregnancy. Therefore, it might be discussed to maintain patients on DMTs until pregnancy is confirmed, and sometimes throughout pregnancy, to avoid a rebound of disease activity and severe relapses during pregnancy in very active patients.
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DMT
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Recommendations for use before and during pregnancy1-3
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IFN-B and Glatiramer acetate
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- Safe to continue until conception
- No evidence of harm to foetus
- Benefits of breastfeeding on treatment outweigh risks
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Teriflunomide
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- Teratogenic animal studies, contraindicated in pregnancy
- Potential exposure in females via transfer in seminal fluid
- 2 years washout or accelerated elimination
- Unplanned pregnancies: accelerated elimination and treat pregnancy as high risk
- Breastfeeding contraindicated
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Dimethyl fumarate
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- Not recommended during pregnancy, appropriate contraception should be used
- Consider effect of GI upset on oral contraception
- May use during pregnancy only if potential benefit justifies risk to the foetus
- Breastfeeding: unknown whether metabolites excreted in human milk; decision to continue/discontinue taking into account benefit for baby and mother
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Natalizumab
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- High risk of relapse/rebound if stopped
- No specific pattern of birth defects
- Highly active MS: continue in pregnancy (every 8 weeks and last dose ~34 weeks), evaluate neonate for haematological abnormalities
- Low absorption in breastfeeding; should be discontinued
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Fingolimod
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- Contraindicated without effective contraception and during pregnancy
- Before initiation of treatment in women of childbearing potential, negative pregnancy test must be available
- Stop 2 months before conception, discuss bridging with another DMT
- Unplanned pregnancy: immediately stop; treat pregnancy as high risk
- Should not be used during breastfeeding
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Siponimod
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- Contraindicated without effective contraception and during pregnancy
- Before initiation of treatment in women of childbearing potential, negative pregnancy test must be available
- Stop ≥10 days before conception, discuss bridging with another DMT
- If accidental pregnancy exposure: stop and organ screening ultrasound
- Should not be used during breastfeeding
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Ozanimod
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- Contraindicated without effective contraception and during pregnancy
- Before initiation of treatment in women of childbearing potential, negative pregnancy test must be available
- Stop 3 months before planning pregnancy, discuss bridging with another DMT
- If accidental pregnancy exposure: stop and organ screening ultrasound
- Should not be used during breastfeeding
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Ponesimod
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- Contraindicated without effective contraception and during pregnancy
- Before initiation of treatment in women of childbearing potential, negative pregnancy test must be available
- Effective contraception must be used during and for 1 week after stopping treatment
- If pregnancy occurs during treatment, discontinue immediately and perform follow-up examinations
- Should not be used during breastfeeding
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Ocrelizumab
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- Use contraception while receiving ocrelizumab and for 12 months after the last infusion
- Avoid during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus
- Discontinue use during breastfeeding
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Alemtuzumab
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- Can be used in pregnancy only if the possible benefit justifies the potential risk to the foetus
- Use contraception while receiving alemtuzumab and for 4 months after each course of treatment
- Conception can be attempted 4 months after course of alemtuzumab
- Pregnancy test required before each treatment course
- Monitor for autoimmune disease during pregnancy
- Breastfeeding should be discontinued during treatment and for up to 4 months after
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Ofatumumab
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- Use contraception while receiving ofatumumab and for 6 months after the last treatment
- Treatment with ofatumumab should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus
- If the patient was treated with ofatumumab up to the last few months of pregnancy, breast-feeding can be started immediately after birth
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Cladribine
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- Contraindicated in pregnancy; pregnancy must be excluded before treatment and prevented by effective contraception during treatment and for ≥6 months after the last dose
- Male patients must take precautions to prevent pregnancy of their partner during cladribine treatment and ≥6 months after the last dose
- Women using systemically acting hormonal contraceptives must also use mechanical contraception for ≥4 weeks after last dose in each treatment year
- Pregnancy safe 6 months after last dose
- Treatment should be discontinued immediately in the event of pregnancy
- Breastfeeding contraindicated during treatment and for 1 week after the last dose
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Given rapidly evolving data in MS therapy management in pregnancy, it is important to keep up-to-date when advising women with MS around pregnancy. As the complexity and range of available DMTs increase, further data gathering via MS pregnancy registers is recommended.
Sources:
- UK Consensus on pregnancy in multiple sclerosis: Association of British Neurologists guidelines. Dobson R, et al. Pract Neurol. 2019;19:106–114
- Treatment of women with multiple sclerosis planning pregnancy. Krysko KM, et al. Curr Treat Options Neurol. 2021;23:11
- Latest summary of product characteristics for all treatments. Available at https://www.ema.europa.eu/en
