Preconceptional optimization of women with neurological disorders

Many neurological conditions can affect women in the preconcep­tional period; this chapter will focus on two common condi­tions that affect women during pregnancy: epilepsy and multiple sclerosis (MS).

Epilepsy

Though more than 90% of women with epilepsy have a normal preg­nancy, women with epilepsy have an increased risk of serious peri­natal complications, including pre-eclampsia, preterm labour, and congenital malformations, and therefore should be discussed in the preconception period (64). Particular consideration should be taken regarding the management of epilepsy in relation to pregnancy, the effect of pregnancy on seizure frequency, the potential effects of epi­lepsy treatment on the fetus, the increased risks of obstetrical com­plications, and the preparation for the postpartum period.

Many women of childbearing age with epilepsy use antiepileptic drugs (AEDs) to control their condition. One of the principles of treatment with AEDs for women of reproductive age is optimiza­tion of AED therapy most appropriate for the seizure type at least 6 months in advance of the preconception period, and continu­ation of the same treatment regimen from the preconception pe­riod throughout pregnancy, as changes in AEDs during pregnancy are contraindicated (64). Although approximately 25% of women have increased seizures in pregnancy, there is evidence to show that if a woman has been seizure free for more than 9 months, there is a high likelihood (84-92%) of remaining seizure free during pregnancy (65).

The risk of major fetal structural malformations in the general population is 2-3%, which increases to 4-6% for women taking AEDs (65). Specific AEDs have higher rates of major fetal struc­tural malformations, including divalproex sodium and valproic acid, and should therefore be avoided in women of reproductive age for initiation of AED therapy.

It is important to discuss some of the increased risk for obstetrical complications that women with epilepsy have. Historically, it was theorized that women with epilepsy are at increased risk of devel­oping pre-eclampsia and eclampsia in pregnancy. However, recent studies have not shown evidence of an increased risk for develop­ment of pre-eclampsia, although these were insufficiently sensitive to rule out the increased risk (65). There is evidence to show that women with epilepsy have an increased risk of preterm labour, how­ever recent studies demonstrate that smoking may be a confounder, as the risk is substantially higher in those women with epilepsy who also smoke (65).

In preparation for pregnancy and the postpartum period, coun­selling should be undertaken for women taking AEDs regarding the need for vitamin K supplementation in the third trimester, as well as transmission of AEDs through breast milk. Decreased levels of vitamin K in neonates born to women taking some enzyme­inducing AEDs have been reported, and therefore supplementa­tion is indicated in the third trimester (67). Although breastfeeding is not contraindicated for women taking AEDs, for those taking sedating AEDs, special monitoring of the neonate for sedation is recommended (67).

Multiple sclerosis

The disease course of MS is variable in nature, typically character­ized by relapse exacerbations and remissions of neurological deficits.

The disease course of MS in pregnancy is a controversial topic, however a meta- analysis published in 2011 reported a significant de­crease in disease activity during pregnancy, and an overall increase in disease activity during the postpartum period (70). Although there is no net effect of overall increase in exacerbations during pregnancy and postpartum combined, the two reports of the PRIMS study in 1998 and 2004 demonstrate decreased incidence of disease exacerbation in the preconception, and pregnancy periods, and an increased relapse rate in the first 3 months postpartum (71, 72). These reports also demonstrate that pregnancy does not have an ef­fect on the ultimate disease course of MS, specifically no effect on the disease progression overall (72).

In the preconception period, it is advised that women discontinue disease-modifying agents, as some of these are known to be terato­genic (methotrexate, teriflunomide). Current evidence suggests that women discontinue disease-modifying agents in the preconception period from 1 to 6 months prior to conception, depending on the drug, and this decision should be discussed with a neurologist (73). Similarly, women are cautioned against using disease-modifying agents in the postpartum period if breastfeeding, and this schedule should be discussed with a neurologist.