The prevalence of neurodevelopmental disorders
in children prenatally exposed to antiepileptic drugs
Rebecca Louise Bromley,1George E Mawer,2Maria Briggs,2Christopher Cheyne,3
Jill Clayton-Smith,2Marta García-Fiñana,3Rachel Kneen,4,5Sam B Lucas,2
Rebekah Shallcross,6Gus A Baker,1On Behalf of the Liverpool and Manchester
1Department of Molecular and
University of Liverpool,
2Genetic Medicine, Manchester
Academic Health Sciences
Centre, University of
Manchester, Manchester, UK
3Department of Biostatistics,
University of Liverpool,
4Department of Neurology,
Alder Hey Children’s NHS
Foundation Trust, Liverpool, UK
5Institute of Infection and
Global Health, University of
Liverpool, Liverpool, UK
6Department of Clinical
Psychology, University of
Liverpool, Liverpool, UK
Dr Rebecca Louise Bromley,
Department of Molecular and
Clinical Pharmacology, Clinical
Sciences Centre for Research
and Education, Lower Lane,
Liverpool L9 7LJ, UK;
Received 4 October 2012
Revised 18 December 2012
Accepted 21 December 2012
To cite: Bromley RL,
Mawer GE, Briggs M, et al.
J Neurol Neurosurg
Psychiatry Published Online
First: [please include Day
Month Year] doi:10.1136/
The aim of this study was to compare the prevalence of
diagnosed neurodevelopmental disorders in children
exposed, in utero, to different antiepileptic drug
treatments. A prospective cohort of women with epilepsy
and a control group of women without epilepsy were
recruited from antenatal clinics. The children of this
cohort were followed longitudinally until 6 years of age
(n=415). Diagnosis of a neurodevelopmental disorder
was made independently of the research team. Multiple
logistic regression analysis revealed an increase in risk of
neurodevelopmental disorders in children exposed to
monotherapy sodium valproate (VPA) (6/50, 12.0%; aOR
6.05, 95%CI 1.65 to 24.53, p=0.007) and in those
exposed to polytherapy with sodium VPA (3/20, 15.0%;
aOR 9.97, 95% CI 1.82 to 49.40, p=0.005) compared
with control children (4/214; 1.87%). Autistic spectrum
disorder was the most frequent diagnosis. No significant
increase was found among children exposed to
carbamazepine (1/50) or lamotrigine (2/30). An
accumulation of evidence demonstrates that the risks
associated with prenatal sodium VPA exposure include
an increased prevalence of neurodevelopmental
disorders. Whether such disorders are discrete or
represent the severe end of a continuum of altered
neurodevelopmental functioning requires further
investigation. Replication and extension of this research
is required to investigate the mechanism(s) underpinning
the relationship. Finally, the increased likelihood of
neurodevelopmental disorders should be communicated
to women for whom sodium VPA is a treatment option.
Prenatal exposure is associated for the majority of
antiepileptic drugs (AEDs), with an increased risk
of major congenital malformations in a dose
dependent manner.1There is also evidence demon-
strating that prenatal exposure to sodium valproate
(VPA) is associated with reduced cognitive func-
tioning in the exposed child.2–4This has increased
concern about the longer term influences of pre-
natal exposure to AEDs.
Neurodevelopmental disorders, such as autistic
spectrum disorders (ASD), attention deficit hyper-
activity disorder (ADHD) and dyspraxia, are report-
edly more prevalent following prenatal exposure to a
number of teratogenic substances.5–10The question
remains as to whether prenatal exposure to AEDs is
associated withanincreasedlikelihood of
development is regarded as a pathological cause of
ASD11and AEDs have been shown to alter neuronal
development,12 13in a manner that is consistent with
Additionally, there is evidence from case series17–20
and retrospective human studies2 21–23that neurode-
velopmental disorders are more prevalent in children
exposed to VPA. Adab et al2observed five cases of
neurodevelopmental disorder in children exposed to
VPA monotherapy (5/41; 12.1%) in a retrospective
cohort. This increase was not found in the groups
exposed to carbamazepine (CBZ) or phenytoin
(PHT). A systematic review of children with a history
of prenatal exposure to AEDs revealed that 8.9% of
children exposed to VPA and 2.5% of children
exposed to CBZ met the diagnostic criteria for
ASD,23although no adjustment for potential con-
founding variables was undertaken. High rates of
reported in children diagnosed with Fetal Valproate
Syndrome.21This is a condition characterised by a
pattern of major and minor congenital malforma-
tions, dysmorphic features and cognitive deficits,24 25
and is likely to represent the severely effected end of
a spectrum of difficulties associated with prenatal
exposure to VPA. Preliminary findings regarding the
prevalence of ASD within this cohort have previously
been published,26and highlight an increased risk of
neurodevelopmental disorders following VPA expos-
ure. Further, Cohen et al27documented significantly
higher maternal ratings of inattention, hyperactivity
and reduced social skills in children prenatally
exposed to VPA at 3 years of age.
An association between prenatal CBZ exposure
and ASD has been reported in one study,23which is
not consistent with another.2There have been no
reports of a significant association between other
AEDs and neurodevelopmental disorders to date.
Prospective observational studies using a control
group provide the most reliable evidence to test
this possible association as randomised controlled
trials to establish teratogenic risk are thought to be
unethical. The final results of this 11-year prospect-
ive study are reported here.
A prospective study of the children born to women
with epilepsy (WWE) was initiated in 2000, aiming
Bromley RL, et al. J Neurol Neurosurg Psychiatry 2013;0:1–7. doi:10.1136/jnnp-2012-3042701
development. Between 2000 and 2004, 628 pregnant women
were recruited from antenatal clinics in the northwest of
England. Over 99% of the cohort was Caucasian. Twenty preg-
nancies were excluded due to fetal or child death, or on the
basis that the children or mothers had conditions likely to influ-
ence neurodevelopmental outcome (including chromosomal dis-
orders and hydrocephalus). Eighty women (29 WWE and 51
controls) were never accessible to the research team, even by
telephone and were excluded. Therefore the total number of eli-
gible pregnancies between 2000 and 2004 was 528 (243 WWE
and 285 controls). Of those exposed to AEDs in utero 59 were
exposed to CBZ, 59 to VPA, 36 to lamotrigine (LTG), 14 to
Thirty-four children were born to WWE who were not taking
medication during their pregnancy.
At recruitment each woman provided information relating to
education, occupation and lifestyle issues such as smoking and
alcohol use during pregnancy. Maternal health and pregnancy
information was recorded from maternal interview and checked
against medical records. An epilepsy specialist (GEM) confirmed
seizure type, syndrome diagnosis (symptomatic/cryptogenic
focal, idiopathic generalised epilepsy (IGE) or not classifiable),
current seizure frequency as well as AED type and dose.
Treatment was classed as polytherapy if a second AED (includ-
ing a benzodiazepine) had been prescribed even for a short
period. Seizure frequency was ascertained from the patient and,
where possible a family member. The study methodology has
been detailed in the earlier paper describing the immediate
Children from this cohort were assessed at 1year, 3 years and
6 years of age to monitor their physical and cognitive develop-
ment.4 28Thirty-nine per cent of children born to WWE were
also enrolled into a US/UK study.3 27 29 30This collaborative
study has reported on behaviour in infants at 3 years of age27
which included earlier age data on 21% (n=86) of children
reported here. Structured interviews with the parents were con-
ducted by a trained research assistant or authors MB, RLB, RS
or JC-S, blinded as to whether the mother had epilepsy and
whether the child had been exposed to medication during preg-
nancy. It was recorded whether the child had been ill, attended
hospital or whether a professional had been consulted regarding
the health, development, behaviour or educational progress of
the child. Information was specifically collected on ASD,
ADHD and dyspraxia due to their increased prevalence in an
earlier retrospective cohort.2Indication that a child had seen a
specialist pertaining to a developmental difficulty or neurodeve-
lopmental disorder was documented and followed up with the
diagnosing health professional, family doctor or school nurse.
The researchers played no clinical role in the treatment of the
WWE or in the diagnosis of the child. Children were referred
to specialist services following contact with the research team if
there were significant concerns about development. In one case
a referral was made following concerns regarding speech
quality, which led to a diagnosis of ASD. The referring
researcher in this case was blind to the exposure type. Outcome
at 6 years of age was the end point of this longitudinal study
and the presence of a confirmed diagnosis of a neurodevelop-
mental disorder (ASD, ADHD or dyspraxia) at the time of the
6-year assessment is reported here.
Data analyses were conducted in two stages, by author SBL
using SPSS V . 17.0, and by author CC under the supervision of
MG-F using R V .2.12.1. Multiple logistic regression analysis was
applied to explore the likelihood of neurodevelopmental dis-
order of the offspring of WWE exposed to AED treatments
and 41to polytherapy.
(CBZ, LTG, VPA, other monotherapy and polytherapy) com-
pared with controls and to identify the demographic and clinical
variables associated with the diagnosis of a neurodevelopmental
disorder. Due to the relatively low frequency of diagnosis this
was only possible for the overall category of neurodevelopmen-
tal disorder category and not for the individual types (ASD,
ADHD or dyspraxia). A similar analysis was applied to compare
the likelihood of neurodevelopmental disorder across maternal
epilepsy types. A preliminary exploratory data analysis was used
to identify candidate variables for consideration in the logistic
model by individually exploring their association with the
occurrence of neurodevelopmental disorder. The variables
included seizures during pregnancy, maternal IQ, maternal age,
socioeconomic status, alcohol or nicotine exposure, gender and
gestational age at birth. Paternal date of birth was missing in
over 25% of cases and was therefore not included.
Ethical approval for this cohort study was awarded by the
Northwest Regional Ethics Committee and research approval
was obtained from individual participating hospitals. All families
Preliminary findings regarding the prevalence of ASD within
this cohort have previously been reported.26
to participatein the study.
Of the 528 children who actively participated in the longitudinal
follow-up, 415 (214 controls and 201 children born to WWE)
were assessed at the main outcome age of 6 years (78.6%). The
majority of missing cases were lost to follow-up with less than
5% formally withdrawing or indicating that they were emigrat-
ing. Significant differences were found between the demograph-
ics of those assessed and those not, with lower maternal IQ
(p=0.01), socioeconomic status (p=0.01) and maternal age
(p=0.02) associated with non-completion. Further, mothers
whose child participated in the 6-year assessments were less
likely to have smoked during the pregnancy (p=0.04).
The demographics of the cohort completing assessment at
6 years of age are displayed in table 1. WWE were marginally
younger than the control women (28 vs 29 years, p=0.002) and
had a lower full scale IQ as measured by the National Adult
Reading Test (p<0.001). Significantly more control women
reported drinking alcohol during the pregnancy (30.8% vs
17.9%, p=0.004), but significantly more WWE reported
smoking (27.9% vs 15.9, p=0.008). There was no significant
difference in the gestational age of the child at birth (p=0.5) or
in the distribution of gender between the groups of children
born to WWE and controls (p=0.3).
Nineteen children had a diagnosis of a neurodevelopmental
disorder at the 6-year assessment (table 2). Twelve were diag-
nosed with ASD; one of which was also diagnosed with ADHD.
Three children had ADHD in isolation. The four remaining
children had a diagnosis of dyspraxia. Of the 19 with a diagno-
sis of neurodevelopmental disorders, physical malformations
were noted in three cases (16%) all of whom were prenatally
exposed to AEDs (table 2).
Diagnosis by group
Neurodevelopmental disorders were more frequently reported in
the children of WWE (15/201; 7.46%) than in the control group
(4/214; 1.87%). Prevalence of neurodevelopmental disorders dif-
fered across the AED groups (figure 1). Children exposed to VPA
showed a high prevalence of neurodevelopmental disorders (6/50:
12.0% for VPA monotherapy and 3/20: 15.0% for VPA polyther-
apy). Prevalence of neurodevelopmental disorder differed for the
other exposures. The small ‘other monotherapy group’, which
2Bromley RL, et al. J Neurol Neurosurg Psychiatry 2013;0:1–7. doi:10.1136/jnnp-2012-304270
Cohort demographics in the Liverpool and Manchester neurodevelopment group prospective study
age at birth
*Figures are inclusive of children recruited between 2000 and 2004 who attended at least one appointment or completed one phone visit with investigators (actively enrolled).
†Two sets of dizygotic twins included.
‡Five sets of twins—three exposed to monotherapy VPA (one dizygotic pair and one unconfirmed) and two exposed to monotherapy CBZ (one dizygotic pair). Alcohol—any level of consumption during pregnancy (including prior to conception).
Nicotine—including prior to knowledge of conception.
CBZ, carbamazepine; F, focal; IGE, idiopathic generalised epilepsy; LTG, lamotrigine; UC, unclassified; VPA, valproate; WWE, women with epilepsy.
Bromley RL, et al. J Neurol Neurosurg Psychiatry 2013;0:1–7. doi:10.1136/jnnp-2012-304270
comprised of a number of different AEDs had a prevalence of
14.29% (2/14), with one case prenatally exposed to PHTand the
other vigabatrin. A single case of ADHD was found in the group
of children exposed to CBZ (1/50: 2.0%). This child also had
IGE with active seizures. For the LTG exposed group there were
two cases with a diagnosis (2/30: 6.67%), one child with a diag-
nosis of Asperger’s syndrome and another of dyspraxia. There
were no reported cases of neurodevelopmental disorder in the
children born to untreated WWE. A single case of dyspraxia was
found in the group of children exposed to polytherapy without
VPA (1/11: 9.1%). Finally, four control children (4/214: 1.87%)
were diagnosed with a neurodevelopmental disorder, which was
ASD in all cases.
Multiple logistic regression analysis revealed that children
born to WWE exposed to VPA monotherapy and VPA polyther-
apy were, respectively, six times (aOR 6.05, 95% CI 1.65 to
24.53, p=0.007) and 10 times (aOR 9.97, 95% CI 1.82 to
49.40, p=0.005) more likely to be diagnosed with a neurodeve-
lopmental disorder than controls (table 3).
The ‘other monotherapy group’ also showed a significantly
higher risk compared with controls (aOR 8.17, 95% CI 1.1 to
49.4, p=0.02) but, similarly to what is observed for the VPA
polytherapy group, the low sample sizes in these two groups
are linked to wide CIs and large SE of the corresponding aORs
(table 3). For the other AED groups, the risk of neurodevelop-
mental disorder was not statistically significant when compared
with the control group (CBZ, LTG and polytherapy without
When the VPA exposed groups were split by dose the preva-
lence of neurodevelopmental disorder appeared to increase with
dose (table 4). A logistic regression analysis, unadjusted for
other factors due to the low number of cases per dose and VPA
exposure groups, showed a positive association between the
prevalence of neurodevelopmental disorder and the preconcep-
tual dose of VPA in monotherapy but this failed to attain signifi-
The prevalence of neurodevelopmental disorder was similar
across maternal epilepsy type: focal 8.33%; IGE 6.15% and
Individual cases of neurodevelopmental disorder alongside demographic information
ASD* Alcohol Nicotine
Autistic spectrum disorders
8M PHT 300F0 None 35
MControl N/AN/AN/ANone 32 NoneYes
ADHDM VPA+LTG2000+50 IGE0 1 major 27402 Siblings
16DyspraxiaMLTG 100F2 TCNone 22Not
19DyspraxiaM VPA1000 UC2TCNone 40None NoNo
*ASD was the only reported diagnosed disorder in siblings.
†Case was included in the preliminary report from this cohort.26
‡Child also has idiopathic generalised epilepsy.
ADHD, attention deficit hyperactivity disorder; ASD, autistic spectrum disorders; CBZ, carbamazepine; F, focal; IGE, Idiopathic generalised epilepsy; PHT, phenytoin; PS, partial seizures;
TC, tonic clonic seizures; UC, unclassified; VGB, vigabatrin. Alcohol includes intake prior to knowledge of conception. Nicotine—smoking even prior to knowledge of conception.
4 Bromley RL, et al. J Neurol Neurosurg Psychiatry 2013;0:1–7. doi:10.1136/jnnp-2012-304270
unclassified (UC) type 7.14% (table 3). A significant aOR was
demonstrated for maternal focal epilepsy (aOR 4.76, 95% CI
1.42 to 15.94, p=0.01) in comparison with the control group,
but the aOR remained similar to that for IGE and UC type
(table 3). Differences due to epilepsy type are unavoidably con-
founded with differences due to AED treatment. After exclusion
of all cases exposed to VPA there were five cases of NDD in the
children of 86 women with focal epilepsy. The corresponding
figures for IGE were 0/25 and for UC epilepsy 1/22. There were
no cases of neurodevelopmental disorder in the children of
women with untreated epilepsy.
In terms of demographic influences, boys tend to be three
times more likely than girls to be diagnosed with a neurodeve-
lopmental disorder (aOR 3.2, 95% CI 1.0 to 10.1, p=0.05),
but no significant association was found for maternal age, mater-
nal IQ, gestational age at birth, seizure exposure or any other
demographic variable (data not shown).
The prevalence of ASD in the control group (1.87%) was com-
parable with population rates reported for the UK (1%),31sug-
gesting that the control group was representative. Furthermore
the association of neurodevelopmental disorder and male
gender is consistent with a large existing body of evidence.32
No diagnosis of dyspraxia or ADHD was reported in the
control group, which may be related to the relatively young age
of this cohort and the average age of diagnosis for these condi-
tions in the UK, 5–11 years of age for ASD and 7 years of age
for ADHD.33–35No cases of neurodevelopmental disorder were
reported in the children of women with untreated epilepsy. This
is likely linked to the small size of the group (n=26), as all
groups displayed similar mean child age.
This is the first prospective report regarding prevalence, and
replication and extension is required. A 6 or 10 times increased
prevalence of neurodevelopmental disorders is reported here for
children with a history of prenatal VPA exposure respectively
for monotherapy and polytherapy exposure. The most common
neurodevelopmental disorder at 6 years of age for VPA exposed
children was ASD. The increased prevalence of ASD within this
research21–23and reports from animal studies.14–16
Consistent with previous research, a dose effect for VPA was
indicated but such an association failed to reach statistical sig-
nificance for monotherapy VPA, possibly due to limited power.
Prevalence of neurodevelopmental disorder by group.
Crude and adjusted ORs for antiepileptic drug (AED) type and maternal epilepsy type
Group TotalNDDs No NDDs Incidence rate (%) Unadjusted OR Adjusted OR* (95% CI)p Value
Polytherapy with VPA
6.05 (1.65 to 24.53)
1.09 (0.06 to 7.39)
4.06 (0.55 to 22.20)
8.17 (1.09 to 49.40)
9.97 (1.82 to 49.40)
4.95 (0.25 to 40.45)
4.76 (1.42 to 15.94)
3.15 (0.76 to 13.09)
3.74 (0.65 to 21.67)
Note: significant results are highlighted in bold.
*Separate regression models were created for AED and maternal epilepsy type regressions due to the limited numbers of cases per drug by maternal epilepsy type.
CBZ, carbamazepine; VPA, valproate.
Bromley RL, et al. J Neurol Neurosurg Psychiatry 2013;0:1–7. doi:10.1136/jnnp-2012-3042705
Analysis of monotherapy and polytherapy VPA combined was
not undertaken due to the potential bias. Further research is
required to confirm a VPA dose dependent effect. The demon-
stration of dose dependency strengthens the case against a sus-
pected teratogen36and dose effects have been reported for rates
of malformations and impaired cognitive abilities following VPA
In earlier publications from this cohort, increased risk of
major congenital malformations and reduced early cognitive
ability were documented.4 28Further investigation is required
into whether an increased prevalence of neurodevelopmental
disorders are discretely diagnosable conditions or whether they
represent the severe end of a continuum of altered neurodeve-
research has documented that prenatal exposure to VPA is asso-
ciated with verbal, social and attentional difficulties,2 4 27 30and
it is proposed here the raised prevalence of neurodevelopmental
disorders is due to severe difficulties with language, social and
attentional abilities, which meet a threshold level for diagnosis
of a neurodevelopmental disorder. The majority of children
received a diagnosis between 3 years and 5 years of age. Of
interest, global or specific developmental difficulties were noted
under the age of 2 years in six out of seven VPA (monotherapy
or polytherapy) exposed infants previously assessed. Such an
observation demonstrates that the early developmental trajec-
tory of these children is altered and surveillance through the
early childhood years is necessary. Deficits in neurodevelopment
of this nature can have a large impact on the child and their
families, and present increased costs to society through
increased health and educational support.
The use of VPA was associated with maternal IGE (66.7%),
an expected association due to its efficacy in this epilepsy syn-
drome.38Therefore the effects of one could not be viewed in
isolation of the other in the logistic regression analysis.
However, no significant aOR was found for IGE. Maternal focal
epilepsy and not IGE, was associated with an increased rate of
neurodevelopmental disorders in the offspring. Of the cases in
offspring born to women with focal epilepsy, four out of nine
were treated with VPA in either monotherapy or polytherapy
form, with the remaining cases exposed to other monotherapy
or polytherapy AEDs.
The suggestion that VPA exposure is associated with an
increased prevalence of neurodevelopmental disorders, which is
independent of the maternal epilepsy type is consistent with the
results of animal work, where there is no maternal epilepsy influ-
ence.12 14–16Studies are now required into the mechanism by
whichVPA isassociated with
neurodevelopmental disorders, considering that environmental
(in utero) and genetic influences may not be mutually
This study does not replicate the finding of Rasalam et al23in
relation to CBZ, as there was only a single case of ADHD
among the CBZ-exposed children. Single cases of neurodevelop-
mental disorder were also noted following exposure to PHTand
vigabatrin, and two cases exposed to LTG. Larger studies includ-
ing wider dose ranges for individual AEDs are called for in
order to provide reliable evidence with regards to AED treat-
ment other than VPA exposure and potential occurrence of neu-
A major strength of this study is its prospective design. The
enrolment of mothers during pregnancy reduces the bias asso-
ciated with knowledge of outcome and selective recall of health
information. The utilisation of a control group representative of
the general population provides risk information relevant to the
effects of AEDs in epilepsy and in other conditions (eg, mood
disorders and pain). Ascertainment of diagnosis independently
of the research team, through routine clinical practice, where
other causes are likely to have been considered and excluded
(eg, chromosomal syndromes) helps to ensure objectivity.
Additional strengths of this study include its: (i) follow-up into
middle childhood; (ii) inclusion of multiple AED groups; (iii)
blinding of researchers to exposure type and epilepsy type and
(iv) control for a number of influential confounding variables.
A potential weakness was the setting of the final study
outcome at 6 years of age which, as discussed above, has impli-
cations for prevalence of diagnosis. It is possible that reassess-
ment at an older age would reveal an even higher prevalence of
neurodevelopmental disorder. Furthermore, only 79% of those
actively enrolled, completed the assessment at 6 years. It could
be suggested that families of a child with difficulties would be
more likely to bring their child for assessment. This however is
unlikely to account for a selective rise in prevalence for the VPA
exposed only, as the dropout rate did not differ significantly
across AED groups.
Although the within data correlation from twin pairs was not
taken into account in the analysis, it is felt to be justified on the
relative infrequency and the lack of association with neurodeve-
lopmental disorder (only a single case of ASD). Further limita-
tions are (i) low sample size of disorder cases (n=19) were
involved in the analysis, (ii) due to the low number of cases, the
individual types of neurodevelopmental disorder (ASD, ADHD
and dyspraxia) were not investigated through regression analysis,
(iii) the limitations imposed by the relationship between maternal
epilepsy and type of prescribed medication (eg, VPA and IGE and
CBZ and focal epilepsy), discussed above. Further a binary
outcome (presence or absence of a disorder) was taken as a
measure of prevalence. Questionnaires completed by parents and
formal systematic clinical observations could provide graded
information on children experiencing mild–moderate levels of
difficulty and should be considered in future work.
Consideration of the results here, in the context of already pub-
lished work, suggests that the risks associated with VPA treat-
ment during pregnancy include neurodevelopmental disorders.
The extent to which such conditions are discrete or are part of
the wider neurobehavioural effects of prenatal exposure to VPA
requires further investigation. If VPA is the treatment of choice,
women should be provided with as much information as pos-
sible to enable them to make an informed decision. This should
take place prior to conception as the evidence suggests that the
Prevalence of neurodevelopmental disorders by dose of
Dose of valproate
mg/daily*Yes No% YesNo% Yes No%
†Monotherapy and polytherapy combined.
6 Bromley RL, et al. J Neurol Neurosurg Psychiatry 2013;0:1–7. doi:10.1136/jnnp-2012-304270
neuropathology of ASD develops early in gestation.39
Further, these findings have implications for the care of children
with a history of prenatal exposure to AEDs. Children exposed
to AEDs in utero, particularly VPA, should be monitored closely
during early childhood to allow for early intervention, diagnosis
and support, should it be required.
Acknowledgements The authors would like to acknowledge the families for their
participation in this longitudinal study and also Dr Kimford Meador for his
comments on the manuscript and ongoing collaboration as part of the NEAD study.
Collaborators Members of the Liverpool and Manchester Neurodevelopment
Group: Professor Gus Baker, Maria Briggs, Dr Rebecca Bromley, Professor Jill
Clayton-Smith, Dr Pete Dixon, Dr Alan Fryer, Alison Gummery, Dr Rachel Kneen,
Loretta Kerr, Dr Sam Lucas, Professor George Mawer, Dr Rebekah Shallcross.
Contributors RLB and GEM, GAB and JC-S were involved in the conception,
design, analysis, interpretation and the writing of the manuscript. CC, MG-F and
SBL were involved in the analysis, interpretation and the writing of the manuscript.
RS, RK and MB were involved in data collection and the writing of the manuscript.
Funding Supported by grants from Epilepsy Research UK RB219738 (National
Lottery Charities Board) and through two educational grants from Sanofi Aventis
pharmaceutical company. The research group was also in receipt of funding from the
National Institute of Health (NIH grant #NS038455) as part of the NEAD study,
these funds were not directly used for the collection of data included in this paper,
however the study group was supported more generally by such funding.
Competing interests Dr Bromley has received honorarium from Sanofi-Aventis for
presenting to their Advisory Panel on two occasions. Dr Bromley has also provided
expert testimony regarding fetal exposure to antiepileptic drugs. Travel support for
two conferences has also been received from UCB Pharma and she has worked on
projects supported by Educational grants from Sanofi Aventis and UCB Pharma.
Professor Mawer has provided expert testimony regarding fetal exposure to
antiepileptic drugs. Ms Briggs has no disclosures. Dr Cheyne has no disclosures.
Professor Jill Clayton-Smith has provided expert testimony regarding fetal exposure to
antiepileptic drugs and has received honorarium from GSK. Dr García-Fiñana has no
disclosures. Dr Kneen has no disclosures. Dr Lucas has no disclosures. Dr Shallcross
has received honorarium from UCB pharma for a lecture and also travel support from
UCB pharma for conference attendance. Professor Baker has received educational
grants for this research from Sanofi-Aventis and has also received an educational
grant from UCB Pharma for work not reported here. Professor Baker has also provided
expert testimony regarding fetal exposure to antiepileptic drugs and has received
honorarium from UCB pharma, GSK and Sanofi Aventis for lectures given.
Ethics approval NRES Commitee North West.
Provenance and peer review Not commissioned; externally peer reviewed.
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