Foetal/child perspective: risks related to drug exposure and breastfeeding

In general, around 60% of pregnant women take prescribed medication during pregnancy, 50% during the first trimester, with even more patients using over-the-counter medication. For most drugs, it is known whether they are safe for the foetus or not. However, data is lacking for MS treatments specifically.

Fortunately, teratogenic effects have only been demonstrated with 30 treatments in humans, some of which are used in neurology, such as the anti-epileptic drug valproic acid, and some off-label use of the neuroimmunological agents mycophenolate mofetil and methotrexate.

MS drugs and pregnancy

Specific treatments are relatively new in MS, with the first drugs approved “only” 30 years ago, and the last drug in 2017. In the publications regarding the use of DMTs during pregnancy, the sample sizes are much larger for patients who had first trimester exposure compared to those with exposure throughout pregnancy. The former meaning: becoming pregnant, taking a pregnancy test, and then stopping medication. “This is what generally happens”, Dr Kerstin Hellwig (Ruhr-Universität Bochum, Germany) stated. “Most data we have is for IFN-beta and glatiramer acetate, with several thousand pregnancies evaluated. Both drugs have the best safety profile. We are awaiting a new EMA label. Dimethyl fumarate seems to have a good safety profile, but only 300 pregnancies have been analysed. Recently, the EMA published an updated restriction to use fingolimod during pregnancy [1]. So far, no teratogenicity is found for teriflunomide in humans, but data is missing.” With respect to the monoclonal antibodies (mAb) and cladribine, a lot of data is still missing, especially with the newer drugs. Despite a lack of data, Dr Hellwig argues to opt for depleting antibodies, at least in patients with highly active MS, “because they have a long-lasting effect. This might also be true for cladribine.” In patients with highly active disease who became pregnant on natalizumab, she advises to consider continuing natalizumab. “In the case of stopping natalizumab, there might be a risk of rebound, but the exact magnitude of the rebound risk, especially of severe rebounds, is not known yet. There might be the possibility to continue natalizumab, but then there is a risk for haematological abnormalities in the baby and there might be an aberrant birth weight.” Therefore, it is advised to stop treatment in gestational week 34 and check haematology. Dr Hellwig concluded that none of the current MS drugs justifies an elective termination of pregnancy per se.

Breastfeeding

It is recommended by the WHO that women breastfeed, and Dr Hellwig thinks that more women using MS medication should be recommended to breastfeed. “At least for mild MS, there is no reason to believe that breastfeeding is harmful. A systematic review published a couple of years ago [2], that is also supported by more recent data, showed that breastfeeding is not harmful. Women who want to breastfeed, should be supported to do so.”

She advised that not all MS patients need medication during or after pregnancy, meaning that they can safely breastfeed. But breastfeeding should also not be discouraged in favour of resuming MS medications in most women. The size of a molecule mainly determines if it enters the breastmilk, so there is the possibility to choose treatments compatible with breastfeeding (injectables and mAbs), even in patients with highly active MS. With respect to the oral DMTs, cladribine is the first drug which advises on the label that breastfeeding is safe 1 week after the intake of the last tablet. If a woman does not want to breastfeed, Dr Hellwig advised to begin with MS treatment early after delivery (after 7-14 days), especially in cases of active disease. More data on breastfeeding under medication and a longer follow up of exposed children is needed.

1. https://www.ema.europa.eu/en/news/updated-restrictions-gilenya-multiple-sclerosis-medicine-not-be-used-pregnancy
2. Pakpoor J, et al. J Neurol. 2012;259:2246-8.

Posted on 8 November, 201915 February, 2024