Navigating Multiple Sclerosis Through Pregnancy: Protective hormones and DMDs

figure 1: Visualisation of the degradation of the myelin sheath caused by MS. Made with Biorender⁴

Symptoms of MS can vary greatly and progress over time. They generally include²:

• Fatigue

• Numbness and tingling

• Visual impairment

• Bladder and bowel dysfunction

• Cognitive impairment

Possible Causes and Risk Factors

The causes behind MS are unclear ⁵. However, some genetic and environmental factors, including living far north of the equator, smoking, obesity, and low vitamin D levels show a correlation in MS ⁶. The largest risk factor for MS is gender as MS is over twice as prevalent in women than in men. The MS International Foundation reports that over 69% of MS cases are in women¹, ⁷.

figure 2: Ratio of Men to Women affected by MS. Made with Canva²²

Case Study: Postpartum Relapse in a Woman with MS

The aim of this blog is to look into a case study of a woman with MS who had just had a baby. She took teriflunomide(Aubagio) daily before the pregnancy and stopped taking it at about week 15. While she intended to breastfeed the baby, she had an MS relapse about 1 month postpartum and was advised to go back on teriflunomide. She was informed she should not be breast feeding while on teriflunomide.

Disease-Modifying Drugs (DMDs) and Pregnancy

Women with MS commonly stop taking disease-modifying drugs (DMD) during pregnancy due to the lack of information available about their safety  ⁸. In the case of teriflunomide, while no human studies are available, teriflunomide labels often cite that it can excrete into breast milk in animal studies ⁹, ¹⁰, ¹¹.  Moreover, the side effects of teriflunomide, such as diarrhoea, hair thinning, influenza, and nausea ¹², are generally manageable for adults, but are too severe for a newborn or developing foetus to risk passing the drug onto them.

Postpartum Relapse Risk

Findings in a meta-analysis by Charlotte Schubert¹³ suggest that the chances of a relapse are significantly higher in the first 3 months postpartum compared to the pre-pregnancy period. Furthermore, patients who took DMD for MS before pregnancy were more than twice as likely to experience a relapse in the first 3 months postpartum. While patients who exclusively breastfeed showed a reduced risk of relapse, more data is needed to confirm this effect.

One of the key physiological changes postpartum is the reactivation of the immune system. During pregnancy, pregnancy hormones such as oxytocin and progesterone cause a shift in the immune system. ¹⁴. This shift decreases the expression of cell mediated activity, which is a non-specific process for neutralising abnormal cells, and an increase in humoral immunity, where specific antigens found on viruses and antibodies are targeted ¹⁵. These changes protect the foetus from being recognised as a foreign body by the innate immune system. This process is believed to also downregulate the autoimmune activity of MS during the pregnancy, which could be why there is relief in MS symptoms without the need for DMDs ¹⁴.

The Role of Estriol and Hormonal Changes

Estriol is a placenta-made oestrogen hormone that expressed progressively more throughout a pregnancy. As one of the hormones involved in the shift to humoral immunity, estriol promotes anti-inflammatory activity, protecting the foetus and reducing MS activity ¹⁶. After pregnancy, estriol production shows a drastic decline without the placenta. The decrease in estriol is a contributing factor to the immune system reversing to more normal activity. In the case of MS patients, this can lead to an increase in autoimmune myelin breakdown and unfortunately, increases the risk of relapse by MS significantly ¹⁴. This is a possible reason as to why the woman in this case study had a relapse so early in the postpartum period. She likely started taking the DMD again to suppress the cell-mediated immune response.

Preventive Measures and Safer Alternatives

MS patients who are trying for conception should coordinate with their doctor. Several precautions should have been taken to prevent the outcome of this case study and reduce the risk of potential harm to the foetus. There are alternative DMDs for MS that are considered safe to take during pregnancy and the breast-feeding. Glatiramer acetate is a novel treatment for the autoimmune effects of MS ¹⁷ that has shown no adverse effects on breast-fed infants ¹⁸. Many DMD’s for MS have long washout periods. Teriflunomide can take up to 2 years to be completely eliminated from blood plasma ¹⁹. Because she was taking teriflunomide so far into the pregnancy, she should have been prescribed cholestyramine or activated charcoal, which stimulate a rapid washout of teriflunomide in the blood to reduce the risk of passing any teratogenic or hepatotoxic effects onto the foetus ²⁰. She also could have benefited from being recommended an obstetrician to screen for any complications that may come up ²¹.

Conclusion

Multiple sclerosis poses significant challenges for women who are considering pregnancy, are currently pregnant, or are in the postpartum period. Having to make decisions that could impact their infant or their own life, such as going back on DMD postpartum, stopping their DMD before or during pregnancy, or taking the risk to breastfeed without DMD treatment. While the hormonal changes that occur during pregnancy – such as the immunosuppressive effects of oestrogens like Estriol – can alleviate some of these concerns, it is difficult to deal with the rapid shift back to conditions that increase the risk MS relapse. Fortunately, DMDs such as glatiramer acetate, which have far more favourable data available for their safety during not only pregnancy, but also during breastfeeding. This highlights the need for more research in this area, which could reap huge rewards for women with MS who wish to have children.