Jury still out on use of natalizumab for MS in late pregnancy

Multiple sclerosis

By Mardi Chapman

19 Feb 2020

The jury is still out on the use of natalizumab in the latter stages of pregnancy in women with aggressive MS, say neurologists from WA.

While the monoclonal antibody is considered safe in early pregnancy, it crosses the placenta in late pregnancy and has previously been associated with haematological abnormalities.

According to a retrospective review of 15 births from 13 mothers receiving natalizumab throughout their pregnancy, complications occurred in 33% of newborns, according to findings from the Department of Neurology, Sir Charles Gairdner Hospital, Perth. 

Haematological abnormalities – thrombocytopenia and anaemia – were reported in three and two newborns respectively, with one infant having both.

One child required a platelet transfusion and its sibling from a subsequent pregnancy also had a mild thrombocytopenia despite the mother receiving weekly IVIG from week 33. No other reason for the thrombocytopenia could be established.

“The relationship with natalizumab infusions suggested increased risk of haematological abnormalities in newborns whose mothers had more recent and frequent exposure prior to delivery,” the study authors wrote in the journal Multiple Sclerosis and Related Disorders.

“Natalizumab’s impact on fetal hematopoiesis may be compounded by delayed antibody clearance mechanisms in infants, and its presence in breast milk.”

Congenital malformations reported in the study were a renal pelvis dilatation in one child and cardiac abnormalities requiring surgery in a second child. Both also had haematological abnormalities. Another child was born with “congenital hypotonia”.  There were no miscarriages in the cohort.

The study authors said that despite the slight increased frequency of adverse outcomes, there were no consistent abnormalities identified following natalizumab administration. 

“The lack of a clear phenotype makes confirming causality secondary to natalizumab difficult, however ongoing vigilant monitoring of congenital abnormalities is still required until further information is available.”

The study was also unable to confirm that perinatal administration of IVIG, dose reductions and increased dose intervals improve pregnancy outcomes. 

“However the use of these practices and umbilical cord sampling in high-risk pregnancies (i.e. those with previous newborn hematological abnormality) may help mitigate risk,” the authors suggested

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