Table 3.

Treatments for multiple sclerosis during pregnancy and breastfeeding (according to Cree,²⁶ Coyle,²⁷ Havla et al.²⁸ and Gold et al.²⁹).

FDA classification	GA30	IFN ß1-a/b26	NAT	FTY	DMF	TER	ALE	CLAD	OCR
	B	C	C	C	C	X	C	D	Not assigned
Fertility	No negative effects in rats No controlled studies in humans	Irregular menstruation in guinea pigs and increased abortion rate in monkeys. No properly controlled studies in humans	Reduced fertility in guinea pigs and increased abortion rate in monkeys. No properly controlled studies in humans	Reduced gestation rate in rats Not reported in humans	Does not appear to impair fertility in animals Not reported in humans	Does not affect the overall fertility in animal studies, despite reducing sperm counts in rats	Data from animal studies showed effects on the fertility of humanized mice	In mice, there were no effects on fertility or the reproductive function of offspring. However, testicular effects were observed in mice and monkeys	Does not appear to impair fertility in humans
Teratogenicity	No malformations in rats and rabbits	No malformations in monkeys	The most recent data from the pregnancy registry showed the rate of spontaneous abortion (SA) and congenital anomalies within the estimates for the general population31	Foetal malformations in rats Not reported in humans	Foetal malformations in rats Not reported in humans	Foetal malforma-tions in rats and rabbits Not observed in humans	Embryotoxic in mice	In preclinical experiments, teratogenic effects of cladribine have been observed	In monkeys at doses similar to or greater than those used clinically, increased perinatal mortality, depletion of B-cell populations, renal, bone marrow, and testicular toxicity were observed
Transfer through the placenta	Unlikely MW = 5000–9000 Da	Unlikely MW = 18 500–22 500 Da	Yes (in guinea pigs)	Yes	Not reported	Yes (in animals)	Can pass through the placental barrier	Unknown	Immunoglobulin G1 subtype are known to cross the placental barrier
Passage into breast milk	Unknown/ Unlikely	Unknown	Yes: IgG4 in second and third trimester	Yes	Not reported	Unknown	Was transferred to newborn mice via breast milk	It is not known whether cladribine is excreted in human breast milk	OCR was excreted in the milk of ocrelizumab-treated monkeys
Breast- feeding	Discuss potential risk with patient	Not recommen-ded; discuss potential risk	Not recommended	Not recommen-ded	Not recommended	Not recommen-ded	Not recommen-ded	Not recommen-ded	Not recommended
Practical recommen-dations	Treatment can be continued until pregnancy is detected*32	Treatment can be continued until pregnancy is detected*25	In rare circumstances treatment can be continued at least until pregnancy is detected33	Treatment has to be discontinued 2 months before conception34	Treatment should be discontinued at the latest when pregnancy is detected35	Pregnancy should be actively ruled out before TER onset and women should be counselled to take appropriate contra-ception36	Contraception is recommen-ded at least 4 months after infusion cycles37	Women of childbearing potential must prevent pregnancy and male patients must prevent the pregnancy of their female partner during cladribine treatment and for at least 6 months after the last dose	Women of child bearing potential should use contraception while receiving ocrelizumab and for 6 months (FDA) or 12 months (EMA) after the last infusion.

For the latest recommendations on treatment of MS during pregnancy and the breastfeeding period, the reader is referred to the regularly updated expert consensus of the Competence Network Multiple Sclerosis (www.kompetenznetz-multiplesklerose.de).

ALE, alemtuzumab; FDA, US Food and Drug Administration; EMA, European Medicines Agency FTY, fingolimod; GA, glatiramer acetate; IFN, interferon; MW, molecular weight; MS, multiple sclerosis; NAT, natalizumab; OCR, ocrelizumab; TER, teriflunomide.

^*Should be based on individual risk/benefit assessment.