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seizure deterioration. In a study of 42 women receiving lamotrigine, monthly monitoring
followed by a 20–25% increase in lamotrigine dose if levels fell below preconception or first
trimester baseline was associated with only 19% having an increased seizure frequency91.
Whether such practices expose the fetus to additional risk has not however been established.

AED levels quickly revert to pre-pregnancy levels after birth85. Hence, if the dose of an AED
has been increased during pregnancy because of falling AED levels it may be useful to
measure serum levels during the first month after delivery to predict for toxicity. The decision
to reduce the AED dosage if the increase has been made solely because of worsening seizure
control during pregnancy should be made on an individual basis. In particular, if the increase
has resulted in a sustained improvement in seizure control with no evidence of toxicity the
dose should not be changed.

The effects of epilepsy and in particular seizures on the developing embryo/fetus

The fetus seems relatively resistant to the effects of seizures although anecdotal evidence
suggests that tonic-clonic seizures may cause fetal bradycardia92 or miscarriage but definitive
data are lacking. There is no evidence that simple partial, complex partial, absence or
myoclonic seizures are harmful to the fetus93. Likewise, prospective studies have not shown
an association between tonic-clonic seizures and malformations94,95. Nevertheless, the risk of
seizure recurrence, injury, status epilepticus, or even death needs to be considered. That the
effects of status epilepticus in pregnancy were previously felt to be particularly dramatic is
well illustrated by Teramo and Hiilesmaa who compiled 29 cased from the literature, of which
nine of the mothers and 14 of the fetuses died96. In contrast, in the prospective study of seizure
control during pregnancy, the EURAP study group did not find such an effect. Of 36 cases
of status epilepticus (12 convulsive) there was one stillbirth, but no cases of miscarriage or
maternal mortality80.

That women with epilepsy who have seizures during pregnancy may be more likely to have
preterm, a small or low birth weight baby compared with women without epilepsy has also
been shown in a study from Taiwan97. More recent studies of the Danish Medical Birth
Registry98 and the Medical Birth Registry of Norway99 have also observed higher risk of
infants with low birth weight (<2500 g) or small for gestational age in women with epilepsy
who were taking an AED during pregnancy. In both studies this effect was most pronounced
in the children of women taking topiramate, with topiramate also being associated with
microcephaly in the Norwegian study. A smaller study from the Oppland Perinantal
Database100 also found increased risk of infants born to mothers with epilepsy being small for
gestational age and having lower ponderal index (kg/m3) compared to controls. This risk was
highest for mothers taking carbamazepine and lamotrigine, although the numbers in
individual drug groups were small. Only three pregnancies exposed to topiramate were
included but these had the lowest values for mean head circumference and birth weight in the
epilepsy group. Unfortunately, information on seizure control during pregnancy was not
included in these studies and it remains unclear whether this effect was due to AED
consumption or seizures.

The effects of AEDs on the developing fetus/embryo

There is some, albeit largely indirect, evidence from human pregnancies that AEDs have an
effect on fetal and embryonic development. For example, it is a consistent finding that women
with epilepsy who are not on AEDs have a lower risk of having children with major
malformations than those who are taking AEDs97,101. However, whether the two groups are
directly comparable is controversial, as women reported as having epilepsy, but who do not
require AEDs usually either have very mild epilepsy or epilepsy in remission. It has also been