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especially if an enzyme-inducing AED is being taken. However, the American Academy of
Neurology updated its practice parameter in 2009, stating that there was insufficient evidence
to determine if infants born to women with epilepsy had increased risk of haemorrhagic
complications, or if prenatal supplementation of vitamin K reduced these risks79. At present
it is not possible to give oral supplementation in the UK as there is no orally available
preparation of vitamin K which can be prescribed in pregnancy. At birth it is recommended,
as is the case for all newborns, that infants receive vitamin K, with 1 mg of vitamin K given
intramuscularly76,77.

The effects of pregnancy on AEDs and seizure control

Studies documenting the natural history of epilepsy during pregnancy have given a wide
range of results.

It is however usually held that women with well controlled epilepsy are unlikely to experience
a significant change in their seizure frequency. This has been confirmed in a report from the
EURAP study group, who reported on the outcomes of 1956 prospectively studied
pregnancies. Using first trimester as reference, seizure control remained unchanged
throughout pregnancy in 63.6% of those studied, 92.7% of whom were seizure free during
the entire pregnancy80.

However, poor compliance with AED treatment because of nausea or the fear of the potential
risks from AEDs to the fetus can result in loss of control. Measuring compliance is
problematic and monitoring serum levels or self-reporting may not be reliable. A study
comparing longer term AED ingestion in pregnant and non-pregnant women using hair
samples is therefore of interest. In this study it was shown that AED levels of carbamazepine
and lamotrigine varied more often in women who were pregnant, with 15% of the cohort of
pregnant women having little or no AED in their proximal compared with distal hair
measurements of AEDs81.

During pregnancy total serum AED levels may fall with less marked reductions in non-
protein bound (free) drug concentrations82,83. Many factors may contribute to this fall
including increased metabolism/excretion, increased plasma volume and reduced protein
binding. Total AED concentrations do not predict response during pregnancy and therefore
if serum assessments are to be made measurement of the unbound fraction is the method of
choice84. This is especially relevant for those AEDs, such as valproate and phenytoin, that are
moderately or highly protein bound.

Several studies have demonstrated pronounced alterations in the pharmacokinetics of
lamotrigine during pregnancy85-89. Apparent clearance increases steadily throughout
pregnancy, peaking at about the 32nd week of gestation, when a 330% increase from baseline
has been observed. The observed fall in lamotrigine levels during pregnancy has been
reported as being associated with a decline in seizure control compared to preconception
baseline in up to 39% of women90.

There is currently no consensus on how best to monitor AED levels during pregnancy. It has
been advocated that a baseline, preconception, unbound (free) AED level, repeated at the
beginning of each trimester and in the last four weeks of pregnancy should be the minimum
level of monitoring76. More frequent measurements will be necessary if seizure control
deteriorates, side effects ensue, or compliance is an issue. For most AEDs routine monitoring
of serum levels is not necessary. For lamotrigine some are of the opinion that close
monitoring is mandatory and that drug levels should be increased if serum levels fall, to
prevent deterioration in seizure control90. Close monitoring may be effective at minimising