When resuming a DMT inside the first 14 days post partum, individuals may choose to consider modifying premedications for the first infusion in order that prolactin levels are not affected; for instance, diphenhydramine is recommended for mothers before each ocrelizumab infusion but can cause sedation and irritability in breastfed infants, and decrease milk supply after large/frequent doses.e21,e59 == Figure 3. == Recent Findings == We outline the latest evidence-based data for DMT use during pregnancy and lactation, the effect of MS on fertility and fertility treatments, the risk of adverse pregnancy and delivery outcomes, the risk of postpartum relapse, and immunization and clinical imaging safety during pregnancy and breastfeeding. == Summary == Management of family planning and pregnancy in patients with MS requires the most current information. Health care providers should discuss family planning early and frequently with patients with MS, and partners where practicable. Because management of pregnant people with MS will often require a risk/benefit analysis of their needs, shared decision-making in family planning discussions is emphasized. Additional data are needed for specific and underrepresented populations with MS (e.g., single parents or those from the LGBTQ+ community) and those at risk of racial and socioeconomic disparities in care. Pregnancy registries and the design and conduct of clinical trials L-Azetidine-2-carboxylic acid focused on pregnant and lactating patients should provide additional data to guide the ongoing management of patients with MS. == Introduction == Multiple sclerosis (MS) is typically diagnosed between the ages of 20 and 50 years.e1Because most patients with MS are women (approximately 70%), diagnosis often coincides with patients’ reproductive years.e1Historically, women with MS have been discouraged from pregnancy;e2,e3however, evidence suggests that pregnancy does not adversely affect the long-term course of MS and may even have L-Azetidine-2-carboxylic acid a beneficial effect in MS, with overall better MS outcomes in patients who have been pregnant compared with those who have not.1In the short term, pregnant women with MS often experience a substantial reduction in relapse rates, especially in the third trimester.e4However, risk of postpartum disease rebound requires consideration and careful management. An increased risk of infection and preterm birth was noted in a study of 3,875 pregnant women with MS in US databases, with an unclear association between this risk and the use of disease-modifying therapies (DMTs); however, other pregnancy or fetal complications were not elevated in pregnant women with MS. e5 Although treatment paradigms in MS have evolved rapidly over the past decade, pregnant and lactating women have been excluded from phase 3 trials, and labeling for DMTs precludes their use during pregnancy (Figure 1; additional details are L-Azetidine-2-carboxylic acid summarized in eTable 1,links.lww.com/CPJ/A500). Pregnancy safety evidence is often based on real-world data originating from pharmaceutical company postmarketing registries or claims databases.e5-e7For some treatments, real-world data are often borrowed from other indications. For example, the pyrimidine synthesis inhibitor leflunomide, whose active metabolite is the MS DMT teriflunomide, is indicated for the treatment of rheumatoid arthritis. The safety of teriflunomide use during pregnancy, which is contraindicated, has been informed by pregnancy data from leflunomide.e8Despite this, using DMTs to better control Rabbit Polyclonal to OR2T10 disease in young women, along with active treatment of patients prepregnancy, intrapregnancy, and postpregnancy, has resulted in a significant improvement in outcomes, with a decrease in the risk of disability, an improvement in quality of life, and more autonomy for pregnancy planning for women living with MS.e4,e9,e10 == Figure 1. US FDA/EMA Guidelines for DMT Use During Pregnancy. == *See eTable 1 (links.lww.com/CPJ/A500) for further details and Health Canada guidelines. *Color coding represents the authors’ L-Azetidine-2-carboxylic acid interpretation of agency guidelines and literature to date. Green cells indicate that the DMT can be used during pregnancy; yellow cells indicate that the DMT may be used based on the balance of benefit and risk; red cells indicate that the DMT should not be used during pregnancy. DMT = disease-modifying therapy; EMA = European Medicines Agency; US FDA = US Food and Drug Administration; S1P = sphingosine-1-phosphate. In the past, an escalation treatment strategy has been used in MS.e11With this approach,.