In this article we look at how data presented at EAN 2019 or published recently may inform the advice given to a patient with MS who is planning a pregnancy.Currently, prepregnancy counselling is frequently overlooked: in a survey of people with MS (pwMS) who wanted to start a family, 60% (188/311) did not receive any prepregnancy counselling at all, and 16% (55/349) were discouraged to become a parent, most frequently by medical personnel. The Association of British Neurologists (ABN) recommends that at or soon after diagnosis, all women with MS of childbearing age should be offered prepregnancy counselling and this should be repeated at regular intervals (at least annually), particularly for those who are on or considering starting medication.1,2 The ABN recommends covering the following:

  • No effect of MS on fertility
  • Do not routinely defer DMT
  • Consider effect of exposure in males
  • Pregnancy does not affect long-term disability outcomes
  • Relapse risk during and after pregnancy.

There appears to be an unmet need for educational information to complement or facilitate prepregnancy counselling: a survey presented at EAN of educational resources from 51 countries identified 13,321 individual resources, but the category including information on pregnancy planning (‘resources for families’) accounted for only 5.7% (753/13,321) of these resources.3

There is currently limited evidence to inform prepregnancy counselling.2 This year at EAN, several presentations provided further evidence to increase the reliability of advice given to patients and to support the treatment plan.

“It’s becoming more and more important to discuss planning a pregnancy with both female and male patients. The MS population today is very different from the population from the 1990s … they want to have a normal life, which includes a pregnancy”

Doriana Landi, University of Rome Tor Vergata, Italy

How pregnancy affects disease activity

It is thought that the increases in levels of gestation-related steroid hormones reduce the risk of relapses during pregnancy (particularly the third trimester) and that the risk then increases in the postpartum period. For example, in a recent retrospective administrative claims database study including 2,158 patients treated in the USA, the odds of relapse declined during pregnancy, but the monthly adjusted relapse rate increased from 0.99% in the third trimester to 2.56% in the 6-week puerperium period. At EAN 2019, a systematic review of 27 articles showed that relapse rates decreased in pregnancy, with reported annualised relapse rates of 0.0 ± 0.0 to 0.4 ± 0.6. Although it is usually thought that relapse risk decreases most during the third trimester, the relapse rates reported in the systematic review were similar in the first, second and third trimesters. Five studies confirmed a higher relapse rate in the postpartum period compared with both before and after pregnancy. Four studies showed that disease activity before and during pregnancy may be an indicator of postpartum relapse.4-6

The effect of breastfeeding on relapse risk is controversial because studies that have suggested a protective effect may have been biased by the fact that patients with more active disease may be less likely to breastfeed. In the systematic review, two studies indicated that exclusive breastfeeding may reduce the risk of relapse while one study found no effect on MS activity. In addition, there is evidence that exclusive breastfeeding may offer the infant protection from MS later in life. A recent study of 2,055 pwMS showed that those who had been breastfed for at least 6 months had a 4.2-year later age of MS onset than those who had been fed with formula milk.6–10

How pregnancy could affect the treatment plan

Vukusic et al suggest that as soon as a woman with MS is considering pregnancy, a treatment plan should be established. Such treatment plans should balance the risk posed by the DMT with regard to teratogenicity and fetotoxicity with the risk for potential for further disease progression. DMTs are often discontinued in patients planning a pregnancy: in a study presented at EAN 2019, among 80 pwMS who discontinued their oral DMT, patient preference or pregnancy planning was the reason for discontinuation in 34.6%. Discontinuation was associated with clinical and/or MRI activity in 75.7%, among whom 54% discontinued owing to patient preference or pregnancy planning.11,12

The EAN/ECTRIMS consensus recommendations provide some suggestions for DMTs that may be considered prior to or during pregnancy (see recommendations for details), but the majority of DMTs are FDA category C for use in pregnancy (‘risk not ruled out’; no studies in humans but potential benefits may warrant use of the drug in pregnant women). Glatiramer acetate is FDA category B (‘no risk in other studies’; either no risk in animal studies or no risk demonstrated in controlled studies in pregnant women) and the summary of product characteristics states ‘Current data on pregnant women indicate no malformative or feto/neonatal toxicity of glatiramer acetate. To date, no relevant epidemiological data are available. As a precautionary measure, it is preferable to avoid the use of glatiramer acetate during pregnancy unless the benefit to the mother outweighs the risk to the foetus.’ Data presented at EAN 2019 reported pregnancy outcomes in pwMS who were exposed to DMTs prior to or during pregnancy, as well as pwMS who were treated throughout pregnancy. These data may provide some guidance for neurologists deciding to continue DMT during pregnancy in pwMS at high risk of relapse.2,13–16

As mentioned above, the relapse risk generally increases after parturition, and consequently Coyle and colleagues advise rapid reintroduction of DMT in patients with at relatively high risk of postpartum relapse (very active disease before pregnancy, poor prognostic profile, relapse during pregnancy, and/or no previous DMT use). In the systematic review presented at EAN 2019, two studies supported early reintroduction of DMTs while two others showed no benefit of this strategy.4-6

Conclusion

Women with MS do not seem to present a significantly higher risk of obstetric and neonatal complications.17 At this stage of a patient’s journey, providing accurate advice is an important part of a neurologist’s role, and gradually, more data are accumulating to inform this advice.

References

  1. Lavorgna L, et al. Factors interfering with parenthood decision-making in an Italian sample of people with multiple sclerosis: an exploratory online survey. J Neurol 2019;266:707–16.
  2. Dobson R, et al. UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines. Pract Neurol 2019;19:106–14.
  3. Vermersch P, et al. A sub-analysis of global mapping data on the availability of online educational resources for multiple sclerosis patients. Eur Acad Neurol 2019;EPO1148.
  4. Houtchens MK, et al. Relapses and disease-modifying drug treatment in pregnancy and live birth in US women with MS. Neurology 2018;91:e1570–8.
  5. Coyle PK, et al. Management strategies for female patients of reproductive potential with multiple sclerosis: An evidence-based review. Mult Scler Relat Disord 2019;32:54–63.
  6. Sabidó M, et al Systematic review of relapse rates in patients with relapsing multiple sclerosis during pregnancy and breastfeedingitle. In: European Academy of Neurology. 2019:EPO3194.
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  9. Costa GD, et al. Caesarean section and infant formula feeding are associated with an earlier age of onset of multiple sclerosis. Mult Scler Relat Disord 2019. DOI:10.1016/j.msard.2019.05.010.
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  14. Pregnancy Study Group, et al. No increased risk of spontaneous abortion and ectopic pregnancy after exposure to interferon-beta prior to or during pregnancy: Results from register-based Nordic study among women with MS. In: European Academy of Neurology. 2019: EPR2074.
  15. Landi D, et al. Natalizumab use during entire pregnancy in women with Multiple Sclerosis: an Italian case series. In: European Academy of Neurology. 2019: EPO2204.
  16. Teva Pharmaceuticals Ltd. Copaxone 20mg/ml, Solution For Injection, Pre-Filled Syringe. 2019.
  17. Finkelsztejn A, et al. What can we really tell women with multiple sclerosis regarding pregnancy? A systematic review and meta-analysis of the literature. BJOG An Int J Obstet Gynaecol 2011;118:790–7.