Summary by Vilija G. Jokubaitis,1,2 Wei Yeh,1,2 Anneke van der Walt,1,2 Helmut Butzkueven1,2 and Orla Gray3

1Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; 2Department of Neurology, Alfred Health, Melbourne Australia; 3South Eastern HSC Trust, Belfast, Northern Ireland


Maintaining brain health before, during and after pregnancy is important for a woman living with MS; she will need to consult with her MS care team to make decisions about treatment and lifestyle. The guidance below has been provided by the MSBase Pregnancy Research Group. It is based on a comprehensive summary of recommendations published in 2021.1 Review articles by Van der Walt et al.2 and Dobson et al.3 also provide comprehensive summaries of the area.

Details relating to the use of specific disease-modifying treatments (DMTs) can be found on the websites of the European Medicines Agency, the US Food and Drug Administration and the Australian Government Department of Health Therapeutic Goods Administration.


Pre-pregnancy counselling

  • All women of child-bearing age with MS should have pre-pregnancy counselling, ideally soon after an MS diagnosis.
  • Women considering pregnancy should be advised to discuss this with their MS team before trying to conceive.
  • Women with MS should be aware that:
    • MS does not affect fertility; contraception should be used if pregnancy is undesirable
    • pregnancy itself does not increase the risk of worsening disability, independent of relapses in MS
    • relapse rates may reduce during pregnancy but increase in the 3 months following childbirth;4,5 the relapse rate over 1 year, including 9 months of pregnancy and 3 months postpartum, is the same as for a woman with MS who is not pregnant.
  • Women should not defer taking a DMT if considering pregnancy in the future.6
  • When prescribing or starting treatment in women of childbearing age, MS teams should consider some relevant issues, to inform the choice of an appropriate DMT:
    • the likely timing of a planned pregnancy
    • the safety profile of all treatments to be used during pregnancy
    • the risks associated with stopping MS treatment, including rebound relapses and risk of postpartum relapse.
  • MS teams should be aware of the possibility of unplanned pregnancies.

Prenatal advice

  • Women with MS should be given the same prenatal advice as women without MS, including advice about healthy living and not smoking.
  • In accordance with normal obstetric advice, women who are planning pregnancy should take prenatal supplements, including vitamin D and folic acid.
  • Women with MS currently receiving a DMT should consult with their neurologist about whether to continue taking it or when to stop; the decision will depend on their level of disease activity, the individual safety profile of their DMT and the risk of relapse.
  • A woman who plans to stop taking her DMT prior to conceiving should understand the potential impact of this on her MS and also be aware of the average length of time from trying to conceive to conception in women of her age (see UK National Health Service guidance: How long does it usually take to get pregnant?).

Pregnancy

  • Pregnancy in women with MS does not necessarily carry a high risk.
  • Some DMTs are safe to use in pregnancy; they should be considered in women with highly active MS. Alternatively, planned pre-pregnancy use of a DMT with a long-lasting effect may provide effective disease control whilst minimizing drug exposure during pregnancy.
  • Corticosteroids can be used for treatment of relapse in pregnancy; methylprednisolone either orally or intravenously is the treatment of choice.
  • MRI is not contraindicated in pregnancy, but use of contrast dye should be avoided if possible. Routine scans can be deferred until after pregnancy.7
  • Having MS should not influence the choice of delivery method; however, significant disability (such as spasticity) should be taken into account.

Postpartum

  • There is a higher risk of relapse in the postpartum period than before or during pregnancy.
    • All women with MS are at increased risk of postpartum relapse; however, the risk is greatest in women with high disease activity or those not receiving treatment.8
  • Women with active disease should be encouraged to restart their DMT promptly to reduce postpartum relapse risk.8
  • Women with MS should be encouraged to breastfeed because of the known benefits to mother and baby.1,8
    • There is some evidence that breastfeeding may be beneficial in preventing postpartum relapse.8
    • Some DMTs are considered safe to use while breastfeeding, others are considered not safe, and for some there is currently insufficient evidence to assess their safety.9–13
  • Choice of DMT during breastfeeding should be discussed with the clinical care team to weigh health and safety concerns.
  • MS teams should give advice about storing breast milk in a freezer in case of fatigue or relapse.3
  • Women should be aware that there is no indication to stop breastfeeding if methylprednisolone is required to treat a postpartum relapse; however, they should wait for 4–8 hours after steroids are given before they breastfeed.
  • Physiotherapy may help with pelvic floor rehabilitation after delivery.

References

1. Krysko KM, Bove R, Dobson R et al. Treatment of women with multiple sclerosis planning pregnancy. Curr Treat Options Neurol 2021;23:11.

2. Van Der Walt A, Nguyen A-L, Jokubaitis V. Family planning, antenatal and post partum care in multiple sclerosis: a review and update. Med J Aust 2019;211:230–6.

3. Dobson R, Dassan P, Roberts M et al. UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines. Pract Neurol 2019;19:106–14.

4. Dobson R, Jokubaitis VG, Giovannoni G. Change in pregnancy-associated multiple sclerosis relapse rates over time: a meta-analysis. Mult Scler Relat Disord 2020;44:102241.

5. Langer-Gould A, Smith JB, Albers KB et al. Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort. Neurology 2020;94:e1939–e49.

6. De Stefano N, Giorgio A, Battaglini M et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology 2010;74:1868–76.

7. Ray JG, Vermeulen MJ, Bharatha A et al. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA 2016;316:952–61.

8. Yeh WZ, Widyastuti PA, Van der Walt A et al. Natalizumab, fingolimod and dimethyl fumarate use and pregnancy-related relapse and disability in women with multiple sclerosis. Neurology 2021;96:e2989–e3002.

9. Ciplea AI, Langer-Gould A, Stahl A et al. Safety of potential breast milk exposure to IFN-beta or glatiramer acetate: One-year infant outcomes. Neurol Neuroimmunol Neuroinflamm 2020;7:e757.

10. Krysko KM, LaHue SC, Anderson A et al. Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions. Neurol Neuroimmunol Neuroinflamm 2020;7:e637.

11. LaHue SC, Anderson A, Krysko KM et al. Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases. Neurol Neuroimmunol Neuroinflamm 2020;7:e769.

12. Ciplea Al, Langer-Gould A, de Vries A et al. Monoclonal antibody treatment during pregnancy and/or lactation in women with MS or neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm 2020;7:e723.

13. Datta P, Ciplea AI, Rewers-Felkins K et al. Cladribine transfer into human milk: A case report. Mult Scler 2021;27:799–801.