The risk-mitigation strategies surrounding DMTs in pregnancy haven’t come that far over the last two decades. So far, we have abstain from pregnancy, stop treatment prior to pregnancy, stop if you discover that you’re pregnant, or switch to Copaxone during pregnancy. Albert Einstein once said, “The definition of insanity is doing the same thing over and over again, but expecting different results”.
So why exactly are we stuck??
Sadly, it is because we lack clear long-term pregnancy outcomes from the various pregnancy registries in existence around the world. We know a lot about immediate adverse outcomes in babies, but not of the long-term effects.
Here, Cheraghmakani et al., report of a newborn with a normal term vaginal delivery, but later presenting at the age of 3 with global developmental retardation.
“The baby’s head circumference was normal at birth, but did not grow well in the following years, and at the age of three it was 45 cm (below the 3rd centile, normal range = 48.5 ± 2.7). She did not gain proper head control until 13 months of age and the ability to sit until 17 months.”
Fingolimod exposure in-utero in this specific case was 25 days; exposure to fingolimod particularly during the first trimester of pregnancy has been linked to 7.6% risk of congenital abnormalities. In animal studies, fingolimod demonstrated an increase in malformations (the sphingosine 1-phosphate receptor is known to be involved in vascular formation during embryogenesis) and spontaneous abortions. In a separate case, following in utero exposure, a baby was born prematurely with acrania (absence of the normally ossified skull and abnormal development of the cerebral hemispheres). Therefore, fingolimod must also be affecting the normal migration of neurons during embryogenesis.
Although, there are number of other reasons for the incidence of neurodevelopmental abnormalities in children, when there is a putative agent at play, the risk is entirely avoidable. The question then becomes whether DMTs can be engineered so that they do not to cross the placental barrier? For example, most drugs with a molecular weight (MW)>1000 Da don’t cross the placenta, whilst non-ionized drugs tend to cross more easily than ionized drugs.
Mult Scler Relat Disord. 2019 May 30;33:116-120. doi: 10.1016/j.msard.2019.05.016. [Epub ahead of print]
Neurodevelopmental retardation in a baby born to a multiple sclerosis patient being treated with fingolimod.
Cheraghmakani H, Nasehi MM, Baghbanian SM.
This report is about a female child born to a multiple sclerosis mother who continued fingolimod during her first trimester of pregnancy. The child was born with normal full-term delivery but showed neurodevelopmental retardation in the following years. it is recommended that multiple sclerosis patients undergoing treatment with fingolimod use contraceptive methods for at least two months after discontinuation of the medication.