Page 441 - ILAE_Lectures_2015

childhood autism (2.95%; 95% CI 1.42–6.11%) compared to those exposed to other AEDs
(2.44%; 95% CI 1.88–3.16% and 1.02%; 95% CI 0.70–1.49% respectively). Exposure to
carbamazepine, lamotrigine, oxcarbazepine or clonazepam was not associated with a
significantly higher risk for these disorders160.

Data for the other newer AEDs are restricted to levetiracetam. Studies from the Liverpool
and Manchester Neurodevelopmental Group and the UK Epilepsy and Pregnancy Register,
which compared cognitive development up to three years of age in children exposed to
levetiracetam and valproate, children exposed to levetiracetam in utero were not at an
increased risk of delayed early development compared with control children. In contrast those
exposed to valproate scored significantly worse161.

Management of labour and postpartum management of mother and child

Most women with epilepsy will have a normal uncomplicated vaginal delivery65. However,
in approximately 24% the stress of labour may result in an increased risk of seizures during
labour or in the following 24 hours102,162. Tonic-clonic seizures may result in fetal hypoxia
and it is therefore generally recommended that delivery takes place in a unit equipped with
facilities for maternal and neonatal resuscitation76,77.

Breastfeeding is generally to be encouraged and may even have the additional advantage that
it ensures the baby is gradually withdrawn from the AED. AEDs are excreted in breast milk
at a level inversely proportional to the degree of maternal serum protein binding. Hence the
amount transferred to the infant in breast milk varies substantially between AEDs. In addition,
concentrations of AEDs can differ substantially between the start and end of a meal, and
between the right and left breast depending on the fat and protein contents of the milk. For
some AEDs, such as phenobarbitone and primidone, reduced neonatal serum protein binding
and immature elimination mechanisms can also result in drug accumulation. This can result
in sedation of the infant and necessitate the discontinuation of breastfeeding. However, for
most AEDs including phenytoin, carbamazepine and valproate, breastfeeding is usually
without problems as these drugs are highly protein bound and therefore are poorly excreted
into breast milk. Information on the concentration in breast milk of the newer AEDs is rather
limited as yet163, however preliminary data indicate that lamotrigine passes into breast milk
at 4045% of the level in plasma, with levels comparable to those seen in patients having
been noted164. For levetiracetam, plasma concentrations in breastfed infants are low despite
extensive transfer of levetiracetam into breast milk165.

There has been some concern that breastfeeding during AED therapy might have a
detrimental effect on cognitive development. Data from the Neurodevelopmental Effects of
Antiepileptic Drugs Study is therefore reassuring, albeit the numbers studied were small. At
age six years, breastfed children had higher IQ and enhanced verbal abilities compared to
those that were not breastfed. The analysis found no evidence of an adverse effect on
cognitive development either for all AEDs combined or for those exposed to the individual
AEDs studied (phenytoin, carbamazepine, lamotrigine or valproate)166.

Risk of injury to the infant largely depends on seizure type and frequency. Any such risk can
be minimised if time is allocated to training mothers with epilepsy on safe handling, bathing
techniques, feeding, and safe practice around the home.

Epilepsy and the menopause

The effects of epilepsy on the menopause and the effects of the hormonal changes of the
menopause on epilepsy cannot be reliably predicted. Women with epilepsy are at increased