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The prevalence of anti-epileptics use in women of child bearing age
ranges between 0.2 % to 0.5%. Prenatal exposure to anti-epileptics has
been associated with many adverse events such as neurodevelopmental
disorders and congenital malformations in a dose dependent manner.
Neuro developmental disorders include
autistic spectrum disorders (ASD),
attention deficit hyperactivity disorder
(ADHD) and dyspraxia which are also
more prevalent following prenatal
exposure to a number of teratogenic
substances. Congenital malformations
include characterised dysmorphic
features. Sodium valproate in particular
has been associated with a reduction
in cognitive function.3 To date, there
are conflicting results with regard to
the degree of risk of anti-epileptics,
making it difficult to counsel women
regarding their choice of treatment
during pregnancy and hence the above
mentioned review was undertaken.
The studies included in the above
mentioned review were both
randomised controlled trials including
women with epilepsy requiring
treatment who were randomised to
a particular anti-epileptic drug prior
to conception or to a control group.
Prospective observational cohort
studies were also included from either
a single or multiple participating sites,
where information regarding the
pregnancy and history were collected
before to knowledge of the outcome.
Quality of the research
Studies included in the report were of
varied methodological quality. Biases
such potential selection bias and
reporting of confounding factors were
the major drawbacks.
The following databases were
searched; the Cochrane Epilepsy
Group Specialized Register (May
2014), Cochrane Central Register
of Controlled Trials (CENTRAL) in
The Cochrane Library (2014, Issue
4), MEDLINE (via Ovid) (1946 to May
2014), EMBASE (May 2014), Pharmline
(May 2014) and Reprotox (May 2014).
The review included a total of 28
studies, 10 of them were included in
the final analysis and the remainder
were described in a narrative format.
The drugs evaluated included;
carbamazepine (CBZ), sodium
valproate (VPA), lamotrigine (LTG) and
The main outcome measures
included; Global cognitive functioning
or ability measured as an IQ test;
the proportion of children with
autistic spectrum disorders; attention
deficit-hyperactivity disorder (ADHD)
and dyspraxia and cognitive domains
such as attention; executive function,
language, memory and visuospatial.
The management of
epilepsy during pregnancy
BY DR HANAN KHALIL
» EVIDENCE SUMMARIES
Dr Hanan Khalil is the Director of the Centre for
Chronic Disease Management, a collaborating centre
of the Joanna Briggs Institute, Faculty of Medicine,
Nursing and Health Sciences, Monash University, and
a reviewer for the consumer group of the Cochrane
Collaboration. Hanan is also the Editor in Chief of the
International Journal of Evidenced Based Health Care.
The purpose of this evidence summary is to provide
the best available evidence for the management of
epilepsy during pregnancy. For the full review, please
refer to: Bromley R, Weston J, Adab N, Greenhalgh J,
Sanniti A, McKay AJ, et al. Treatment for epilepsy in
pregnancy: neurodevelopmental outcomes in the
child. Cochrane Database of Systematic Reviews 2014,
Issue 10. Art. No.: CD010236. DOI: 10.1002/14651858.
The developmental quotient (DQ)
was lower in children exposed to
carbamazepine (CBZ) (n = 50) than
in children born to women without
epilepsy (n = 79).
The DQ of children exposed to CBZ
(n = 163) was also lower compared
to children of women with untreated
epilepsy (n = 58). Children exposed
to VPA (n = 89) also had lower IQ
than children born to women with
untreated epilepsy (n = 87), Moreover,
Children exposed to VPA (n = 89)
also had lower IQ than children born
to women with untreated epilepsy
When comparing CBZ and VPA; there
was no significant difference in the DQ
of children exposed to CBZ (n = 210)
versus VPA (n=160) (MD 4.16, 95% CI
- 0.21 to 8.54, P = 0.06). However the IQ
of children exposed to VPA (n = 112)
was significantly lower than for those
exposed to CBZ.
When comparing CBZ versus (LTG), the
IQ of children exposed to CBZ (n = 78)
versus lamotrigine (LTG) (n = 84) was
not significantly different (MD -1.62,
95% CI -5.44 to 2.21, P =0.41).
When comparing CBZ versus PHT,
there was no significant difference
in both the DQ and IQ of children
exposed to CBZ (n = 172) versus (PHT)
(n = 87).
When comparing VPA versus LTG, the
IQ was significantly lower for children
exposed to VPA (n = 74) versus LTG
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