Risks and management recommendations: Fetal exposure to disease-modifying therapiesa
| Medication | First-trimester exposure recommendations | Exposure risks |
|---|---|---|
| Interferons Interferon beta-1a14,15 Peginterferon beta-1a16 Interferon beta-1b13,17 | No additional fetal or neonatal monitoring | With interferons, slight risk of decreased birthweight and increased embryo or fetal death based on animal data |
| Glatiramer acetate18,19 | No additional fetal or neonatal monitoring | None |
| Fumarates Dimethyl fumarate28 Diroximel fumarate29 Monomethyl fumarate30 | Early ultrasonography for major malformations | Dimethyl fumarate: uncertain risk to fetus; animal studies have shown low birthweight, delayed development, delayed ossification, spontaneous abortions, decreased fetal viability, and impaired learning and memory Diroximel fumarate: based on animal data, may cause fetal harm including skeletal abnormalities, increased mortality, decreased body weight, and neurobehavioral impairment Monomethyl fumarate: Based on animal data, may cause fetal harm including adverse embryotoxicity, reduction in body weight, and delayed sexual maturation |
| S1Pr modulators Fingolimod32 Siponimod33 Ozanimod34 Ponesimod35 | Early ultrasonography for major malformations | All: teratogenic effect likely; risk of neural tube defects, fetal loss and fetal abnormalities Fingolimod: based on animal studies, increased risk of congenital malformations and embyrolethality, fetal growth retardation, and neurobehavioral deficits Siponimod: based on animal studies, increased risk of congenital malformations and embyrolethality, increased incidence of skeletal variations, decreased body weight, and delayed sexual maturation Ozanimod: based on animal studies, increased risk of congenital malformations and embyrolethality, skeletal variations, vascular malformations, and neurobehavioral deficits Ponesimod: based on animal studies, increased risk of congenital malformations and embyrolethality, visceral , cardiac, and skeletal malformations |
| Cladribine10 | Follow up with high-risk obstetrician | Risk of congenital malformations and embyrolethality based on animal studies |
| Teriflunomide31 | Early screening for major and minor malformations; option to follow up with high-risk obstetrician | Highly teratogenic; risk of serious birth defects in fetus; risk of preterm labor; risk of low birthweight |
| Natalizumab21 | Screen neonate for liver dysfunction, pancytopenia | Risk of mild to moderate hematologic alterations (pancytopenia with late pregnancy exposure) |
| B-cell–depleting agents Ocrelizumab22 Ofatumumab23 Rituximab24,25 Ublituximab26 | Screen neonate for B-cell depletion, pancytopenia | With B-cell–depleting agents, there is a risk of B-cell depletion in fetus or infant with second-trimester and third-trimester exposure Rituximab: risk of congenital malformations in fetus, and neonatal infections |
| Alemtuzumab27 | Monitor thyroid studies | Risk of thyroid disease in mother (autoimmune thyroiditis in up to 40%); risk of low birthweight, preterm birth, preeclampsia; risk of neonatal Graves disease and cognitive impairment |
↵a This table reflects our clinical practice and review of combined recommendations of prescribing information and key articles.
S1Pr = sphingosine 1-phosphate receptor
Based on information in references 1,5,10,11, and 13–41.