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VOL. 28, NO. 6, NOVEMBER/DECEMBER 2009 363
NEONATAL N ETWORK
SODIUM VALPROATE (VALPROATE) IS WIDELY USED FOR
epilepsy, but is increasingly prescribed for such non-
epileptic conditions as bipolar disease, migraine, pain relief,
and sleep disorders.1–3 Valproate,
however, is teratogenic, causing
a w ide ra nge of abnormalities
in offspring of many treated
mothers.4–6 A par ticular facial
dysmorphism and spina bifida
in combination with other mus-
culoskeletal disorders have been
described as “feta l valproate
syndrome.” Major abnormali-
ties have been reported in 11
percent of exposed pregnancies
in the U.S.,7 6.2–14.4 percent
in the U.K.,8 and 17.1 percent
in Australia by the Australian
Pregnancy Register for Women
on Anti-Epileptic Medication.9
Women of childbearing age
taking valproate should be counseled regarding its terato-
genic effects, and modification of therapy should be consid-
ered. Folic acid supplementation has been shown to reduce
the recurrence of myelomeningocele in mothers who have
given birth to a previously affected child.10 Although this
effect has not been demonstrated in mothers taking val-
proate, supplementation in a dose of 4–5 mg/day of folic acid
is recommended.11
We present a case of a mother prescribed valproate for
bipolar disease in which neither warning of teratogenicity
nor advice on the need for folic acid supplementation was
recorded. She produced a child with myelomeningocele.
CASE REPORT
A fema le in fant weighing
2,870 g was born at term to a
25-year-old, gravida 1, para 0,
mother. Diagnosed with bipolar
disorder and from a remote
town in Queensland, Australia,
the mother had been taking val-
proate 1,500 mg/day. Her care
had been shared by a general
practitioner and a psychiatrist,
who had prescribed the val-
proate. She had been taking
valproate for about four years;
it was discontinued because of
an improvement in the mother’s
psychological condition with the
fetus at 11 weeks gestation. The
obstetrician had not advised the mother regarding the use of
valproate because the pregnancy was unexpected.
An ultrasound examination at 20 weeks gestation revealed
a myelomeningocele. Termination of pregnancy was offered
but refused. There was no record of discussion about the
teratogenic effects of valproate, and the mother could recall
no such discussions. There was no record of advice on the
value of folate supplementation to reduce the risk of neural
tube defects in general or with special relevance to valproate
therapy. The mother took no folate or vitamin supplementation
Accepted for publication September 2008. Revised November 2008.
Sodium Valproate and the Fetus:
A Case Study and Review
of the Literature
Jacqueline Smith, RSCN, MSc, NNP
Dr. John Whitehall
ABSTRACT
Sodium valproate is a teratogen responsible for a wide
range of abnormalities, including neural tube defects.
It has traditionally been prescribed for epilepsy, but is
increasingly used for such psychiatric conditions as bipolar
disease. Women of childbearing age taking valproate
should be warned of its teratogenicity and advised to plan
pregnancies, take a higher dose of folate, discuss reducing
the dose of valproate or changing the medication with
their physician, and have antenatal screening. After birth,
the infant should be examined for a wide range of reported
abnormalities. Neurodevelopmental assessment should
continue throughout childhood. We present a case that
illustrates the need for better education of mothers taking
valproate and the medical staff prescribing it.
364 NOVEMBER/DECEMBER 2009, VOL. 28, NO. 6
NEONATAL N ETWORK
until she realized she was pregnant. She then began the usual
pregnancy folate supplementation dose of 0.5 mg/day, not
the higher dose of 4–5 mg/day recommended for women at
high risk for neural tube defects.12
The female infant was delivered by cesarean section because
of failure to progress, with a brow presentation. She required
no resuscitation and was admitted to the neonatal unit for
surgical closure of the myelomeningocele (Figure 1).
There were no signs of infant withdrawal from the val-
proate because it had been discontinued at 11 weeks of ges-
tation, nor were there disturbances in hepatic or glucose
homeostasis, which have been reported in infants of mothers
taking valproate throughout pregnancy.13,14 The half-life of
valproate depends on whether the drug is used on its own
or in conjunction with another anti-epileptic drug (AED).
When used in monotherapy, valporate’s half-life is approxi-
mately 10–12 hours. When used with other agents, its half-
life may be as short as 5–6 hours.15 The myelomeningocele
extended from the second to the fifth lumbar vertebrae and
was associated with mild hydrocephalus and prominent
Arnold-Chiari (Arnold Type II) malformation. Although
the lesion was severe, there was surprising preservation of
movement in the legs; the anus, however, was patulous. The
kidneys and heart were normal on ultrasound examination,
and no other abnormalities were noted. The infant tolerated
surgery and recovered well. She was discharged on day of life
(DOL) 11, but was readmitted on DOL 42 because of rapidly
progressing hydrocephalus that required a ventriculoperito-
neal shunt.
At three months of age, this infant had reached her appro-
priate milestones, though movement of the legs was impaired
in accordance with a myelomeningocele at S1–S4. She was
smiling, following with her eyes, showing interest in people
and her surroundings, and reaching appropriately. Further
follow-up for assessment of growth, intellectual and behav-
ioral development, eyesight, and hearing will be done.
DISCUSSION
The teratogenicity of valproate was reported soon after
this drug became available for treatment of epilepsy in the
late 1970s.16 In 1982, a significant association with spina
bifida was noted.17 In 1984, fetal valproate syndrome was
described.18 Our case emphasizes the teratogenic effect of
certain drugs that may not be well appreciated by physicians
working in subspecialties that are distant from the intricacies
of fetal development.
STATISTICS
In major studies in various countries, maternal treat-
ment with valproate has been associated with a collection
of major and minor anomalies in the neonate. In the U.S.,
two studies reported major congenital anomalies in 10.7 and
20.3 percent of exposed pregnancies.19,20 In Australia, major
and minor anomalies have been described in 17.1 percent, in
England, 14 percent, in Finland, 10.7 percent, in Sweden, 9.7
percent, and in the Netherlands, 6 percent.9,21–24 The rate of
major anomalies in the general population is 1–3 percent.25
There is a slightly higher rate of anomalies in offspring of
mothers with epilepsy because of genetic influences.26 Thus,
the overall relative risk for major anomalies in offspring of
mothers treated with valproate is considered to be 3.77 times
higher than the risk in the general population. When com-
pared with offspring of mothers treated with other AEDs,
the relative risk is considered to be a factor of 2.59.11 By way
of comparison, thalidomide is believed to have been associ-
ated with a 20–30 percent rate of anomalies in offspring of
treated mothers.27
ANOMALIES
Antenatal screening should be performed for major anom-
alies. Short-term effects of maternal valproate use that would
be of particular concern to neonatal nurses include not only
congenital anomalies, but signs of withdrawal, which occur
soon after birth. These signs and symptoms include hypo-
glycemia, irritability, jitteriness, hypotonia or hypertonia,
feeding problems, and seizures.14 One study reported with-
drawal symptoms in 20 percent of exposed neonates. These
infants require follow-up developmental studies that should
continue beyond infancy through childhood to identify late-
presenting problems such as joint laxity, connective tissue
weakness, otitis media with effusion, and minor malforma-
tions of the digits.4
A particular facial dysmorphism of thin arched eyebrows
with medial deficiency, broad nasal bridge, short anteverted
nose, and smooth, long philtrum with thin upper lip has been
described.21 A wide range of anomalies, including neural tube
defects, has also been described (Table 1). A review of 69
cases in the literature from 1978 to 2000 reported consistent
facial phenotype and abnormalities in the musculoskeletal
system (43 cases), the cardiovascular system (18 cases), the
genitourinary tract (15 cases), the skin (21 cases), the respira-
tory tract (11 cases), and the eyes and ears. Abnormalities in
FIGURE 1 ■ Myomeningocele
VOL. 28, NO. 6, NOVEMBER/DECEMBER 2009 365
NEONATAL N ETWORK
the neurologic system included neural tube defects (2 cases)
and problems in neuronal migration and organization that
resulted in intellectual and behavioral difficulties, including
autism spectrum disorder, in as many as 20 of the infants.28
Verbal intelligence quotients, in particular, have been reported
to be reduced.29,30
Comparison between studies is difficult because of varying
methods of reporting, inexact amount of drug exposure, age
of the child at examination, mode of evaluation of develop-
ment, and such confounding influences as cultural differ-
ences and social status.31 Data from a 20-year study period
in India revealed that 8.9 percent of those exposed to val-
proate in utero became autistic.32 In Canada and the U.K.,
a lengthy review revealed that 28 percent of exposed infants
suffered developmental delay, and another 10.9 percent expe-
rienced behavioral disorders with normal development.4 (See:
Pharmacokinetics—Anticonvulsant, Antipsychotic.)
TERATOGENIC EFFECTS
The teratogenic effects of valproate are not well under-
stood and appear to be multifactorial. These include an
effect on genes that control the early patterning of the fetus,
a direct disruption of cell differentiation and proliferation
that could interfere with the development of the neural tube
and neuronal development, and an interference with folate
metabolism, which is necessary for cell division. Widespread,
dose-dependent, neuronal apoptosis has been observed in the
rat model exposed to valproate.33 The therapeutic effect of
valproate appears to involve an increase in inhibitory neuro-
transmitters and alteration in ion channels that may indi-
rectly interfere with neuronal migration and organization
in the developing brain.34–39 The development of the brain
may thus be interrupted by exposure in all trimesters of preg-
nancy.40 The embryopathy has been seen to be repeated in
siblings, so there may be a congenital susceptibility in some
families.41
Folic acid is known to reduce the incidence of neural
tube defects in the offspring of women not receiving anti-
epileptic drugs.25 A dose of 0.5 mg/day is recommended for
all women likely to become pregnant. A dose of 5 mg/day is
recommended for those at high risk as suggested by a family
history of neural tube defect.11 It is recommended that 5 mg
be ta ken daily by women who are receiving valproate for
whatever reason and who intend to become pregnant, but
there is more hope than evidence for effect.2,9,19
COMMUNICATION
Fai lure to inform t he mother fully about t he risks of
valproate therapy is not unusual. According to a review of
records of women attending a mental health institution in
England, 138 women of childbearing age were prescribed
mood-stabilizing drugs including valproate, but documented
warning of teratogenicity was found in only 29 cases (21
percent). Thirty-three women (24 percent) had been advised
about contraception, and 14 (10 percent) conceived while on
TABL E 1 ■ Major and Minor Malformations Seen with Maternal
Valproate Use
Epicanthal folds
Upturned nose/flat nasal bridge
Shallow philtrum
Thin upper vermillion border
Low-set ears
Hypospadias
Neural tube defects
Congenital heart disease
Genitourinary abnormalities
Laxity in joints
Glue ear
Valproate Pharmacok i netics
Anticonvulsant, Antipsychotic
Site and mode
of action
Not yet fully established. Valproate’s
anticonvulsant effect is attributed to the
blockage of voltage-dependent sodium
channels. However, there are some
inconsistencies in the data. A combination
of mechanisms that involves the excitatory
amino acids, sodium flux, and potassium-
mediated inhibition may be operative.
Absorption Rapidly, almost completely absorbed in
fasting patients following oral dosing with
Epilim plain tablets, syrup, and sugar-free
liquid. Absorption is delayed, however, if the
medicine is taken with food. Peak blood levels
occur within 1–4 hours.
Distribution Rapidly distributed and most likely restricted
to the circulation and rapidly exchangeable
extracellular water. Cerebrospinal fluid and
breast milk levels were found to be 5–15%
and 1–10%, respectively, with 90% bound
to plasma proteins, but only 60% bound to
albumin.
Excretion Valproate almost completely metabolized
prior to excretion
Use in lactation Only about 5% of valproate passes through
to the breast milk, and even less enters
through the baby’s bloodstream. How
valproate affects the infant is unknown, and
most breastfed infants whose mothers are
on valproate experience no side effects. The
American Academy of Neurology and the
American Epilepsy Society both recommend
breastfeeding in women with epilepsy, and
neurologists have the veiw that the benefits
far outweigh the risk.
Adapted from: www.sanofi-aventis.com.au/products/aus_pi_epilim.pdf
366 NOVEMBER/DECEMBER 2009, VOL. 28, NO. 6
NEONATAL N ETWORK
the mood-stabilizing drugs. Extrapolating to the whole of
the U.K., it was predicted that between 7,000 and 11,000
women of childbearing age would have been prescribed such
drugs without documented discussion of risks.1
In Australia, prescriptions for valproate (presumably for
psychiatric reasons) increased by 10 percent in 2004, reach-
ing an approximate total of 660,000 in 2006. If each patient
had four prescrptions each over a year, a quarter of women of
childbearing age may be using this drug in 2008.42
War nings of the d rug’s teratogenic ef fects should be pro-
vided and recorded in the patient’s medical record. Ideally,
pregnancy should be planned and folate supplementation
taken. The health care provider should work with the patient
to find an alternate neuropsychiatric medication if possible.
Alternative medications for maternal epilepsy include lamo-
trogine and carbamazepine, and alternative medication for
psychological disorders, such as bipolar disorder, include
lithium. Adverse effects have been described with these med-
ications also, but at a rate lower than with valproate.43 If an
alternative medication cannot be used, the minimum dose of
valproate for effect should be given, divided into several daily
doses to minimize peak levels. Embryopathy is reported to
be unlikely if the mother is receiving less than 1,000 mg/day,
but the rate increases with dose, especially beyond 1,400 mg/
day, when normal metabolism of the drug might be saturated
and breakdown products accumulate.44 Risks and benefits,
therefore, need careful assessment, and full understanding by
the mother and by the whole team of providers is essential.
(R. Schwarz, perinatal psychiatrist, personal communication,
2008).
Contrary to other reviews,24,30,45,46 Vajda reports that
monotherapy is associated with a higher rate of abnormali-
ties in Australia than polytherapy, but considers the higher
rate due to higher doses of valproate (Personal communica-
tion, 2008). Rat models, however, suggest greater apoptosis
with polytherapy because of damaging synergism between
various anti-epileptic drugs.33 Some studies have reported
lower developmental quotients in infants of mothers on
polytherapy.46
CONCLUSION
A major adverse effect in any change of established therapy
is destabilization of the mother, and the underlying principle
should not be forgotten: The infant needs a healthy mother.
It is important to remember that withdrawal of anti-epileptic
drugs for the mother may precipitate a catastrophic recur-
rence of seizures in which the fetus may be damaged from
hypoxia. Indeed the overall death rate is higher in epileptic
mothers, and uncontrolled seizures are considered a cause.26
There is a need for more study of the effects of anti-epilep-
tic drugs in pregnancy. Health care providers should consider
encouraging affected mot hers to join national registries.
Valproate has been prescribed for epilepsy for almost 30 years,
during which time its teratogenic effects have been recog-
nized. Those effects, however, may not be well known by
those who prescribe valproate for psychological conditions.
The effects of congenital abnormalities and withdrawal are of
immediate concern to neonatal nurses, who are also in the
position to advocate for long-term developmental assessment.
Awareness of these effects should encourage consideration of
alternative or reduced therapy.
REFERENCES
1. James, L., Barnes, T. R., Lelliott, P., Taylor, D., & Paton, C. (2007).
Informing patients of the teratogenic potential of mood stabilising
drugs: A case note review of the practice of psychiatrists. Journal of
Psychopharmacology, 21, 815–819.
2. Kennedy, D., & Koren, G. (1998). Valproic acid use in psychiatry:
Issues in treating women of reproductive age. Journal of Psychiatry &
Neuroscience, 23, 223–228.
3. Yonkers, K. A., Wisner, K., Stowe, Z., Leibenluft, E., Cohen, L., Miller,
L., et al. (2004). Management of bipolar disorder during pregnancy and
the postpartum period. The American Journal of Psychiatry, 161, 608–
620.
4. Dean, J. C., Hailey, H., Moore, S. J., Lloyd, D. J., Turnpenny, P. D., &
Little, C. (2002). Long term health and neurodevelopment in children
exposed to antiepileptic drugs before birth. Journal of Medical Genetics,
39, 251–259.
5. Janz, D. (1975). The teratogenic risk of anti epileptic drugs. Epilepsia,
16, 159–162.
6. Meador, K. J. (2002). In utero effects of antiepileptic drugs. Epilepsy
Currents, 2, 164–165.
7. Broomfield, E. B., Dworetzky, B. A., Wyszynski, D. F., Smith, C. R.,
Baldwin, E. J., & Holmes, L. B. (2008). Valproate teratogenicity and
epilepsy syndrome. Epilepsia, 49, 2122–2124.
8. Perucca, E. (2005). Birth defects after prenatal exposure to antiepileptic
drugs. Lancet Neurology, 4, 781–786.
9. Vajda, F. J., & Eadie, M. J. (2005). Maternal valproate dosage and foetal
malformations. Acta Neurologica Scandinavica, 112, 137–143.
10. Czeizel, A. E., & Dudas, I. (1992). Prevention of the first occurrence
of neural-tube defects by preconceptional vitamin supplementation. The
New England Journal of Medicine, 327, 1832–1835.
11. Koren, G., Goh, I., & Klieger, C. (2008). Folic acid, the right dose.
Canadian Family Physician, 11, 1545–1547.
12. Wilson, R. D., Davies, G., Desilets, V., Reid, G. J., Summers, A., & Wyatt,
P. (2003). The use of folic acid for the prevention of neural tube defects
and other congenital anomalies. Journal of Obstetrics and Gynaecology
Canada, 25, 959–973.
13. Moore, S. J., Turnpenny, P., Quinn, A., Glover, S., Lloyd, D. J.,
Montgomery, T., et al. (2000). A clinical study of 57 children with fetal
anticonvulsant syndrome. Journal of Medical Genetics, 37, 489–497.
14. Thisted, B., & Ebbeson, F. (1993). Malformations, withdrawal
manifestations, and hypoglycaemia after exposure to valproate in utero.
Archives of Disease in Childhood, 69, 288–291.
15. Bazil, C. W., & Pedley, T. A. (2003). Clinical pharmacology of antiepileptic
drugs. Clinical Neuropharmacology, 26, 38–52.
16. Dalens, D., Raynaud, E. J., & Gaulme, J. (1980). Teratogenicity of
valproic acid. The Journal of Pediatrics, 97, 332–333.
17. Robert, E., & Guibard, P. (1982). Maternal valproic acid and congenital
neural tube defects. Lancet, 2, 937.
18. DiLiberti, J. H., Farndon, P. A., Dennis, N. R., & Curry, C. J. (1984).
The fetal valproate syndrome. American Journal of Medical Genetics, 19,
473–481.
VOL. 28, NO. 6, NOVEMBER/DECEMBER 2009 367
NEONATAL N ETWORK
19. Wyszynski, D. F., Nambisam, N., Surve, T., Alsdorf, R. M., Smith,
C. R., & Holmes, L. B. (2005). Increased rate of major malformations
in offspring exposed to valproate during pregnancy. Neurology, 64, 961–
965.
20. Meador, K. J., Baker, G. A., Finnell, R. H., Kalayjian, L. A., Liporace,
J. D., Loring, D.W., et al. (2006). In utero antiepileptic drug exposure:
fetal death malformations. Neurology, 67, 407–412.
21. Kini, U., Adab, N., Vinten, J., Fryer, A., Clayton-Smith, J., & Coyle,
H. (2006). Liverpool and Manchester neurodevelopmental study group.
Dysmorphic features: An important clue to the diagnosis and severity
of fetal anticonvulsant syndromes. Archives of Disease in Childhood. Fetal
and Neonatal Edition, 91, F90–F95.
22. Gorry, J., Gregg, J., Mawer, G., Nicolaides, P., Pickering, L., Tunnicliffe,
L., et al. (2005). Antiepileptic drug use of women with epilepsy and
congenital malformations in offspring. Neurology, 64, 1874–1878.
23. Wide, K., Winbladh, B., & Kallen, B. (2004). Major malformations
in infants exposed to antiepileptic drugs in utero, with emphasis on
carbamazepine and valproic acid: A nation-wide, population based
register study. Acta Paediatrica, 93, 174–176.
24. Samren, E. B., van Duijn, C. M., Christiaens, G. C., Hofman, A., &
Lindhout, D. (1999). Antiepileptic drug regimens and major congenital
abnormalities in the offspring. Annals of Neurology, 46, 739–746.
25. Koren, G., Mava-Ocampo, A. A., Moretti, M. E., Sussman, R., &
Nulman, I. (2006). Major malformations with valproic acid. Canadian
Family Physician, 52, 441–447.
26. Battino, D., & Tomson, T. (2007). Management of epilepsy during
pregnancy. Drugs, 67, 2727–2746.
27. Koren, G., Pastuszak, A, & Ito, S. (1998). Drugs in pregnancy. The New
England Journal of Medicine, 16, 1128–1137.
28. Kozma, C. (2001). Valproic acid embryopathy: Report of two siblings
with further expansion of the phenotypic abnormalities and a review of
the literature. American Journal of Medical Genetics, 98, 168–175.
29. Adab, N., Kini, U., Vinten, J., Ayres, J., Baker, G., Clayton-Smith, J., et
al. (2004). The longer term outcome of children born to mothers with
epilepsy. Journal of Neurology, Nerurosurgery and Psychiatr y, 75, 1575–
1583.
30. Vinten, J., Adab, I., Kini, U., Gorry, J., Gregg, J., & Baker, G. (2005).
Neuropsychological effects of exposure of anticonvulsant medication in
utero. Neurology, 64, 949–954.
31. French, J. A. (2007). When should we pay attention to unfavourable
news from pregnancy registrars? Epilepsy Currents, 7(2), 36–37.
32. Rasalam, A. D., Hailey, H., Williams, J. H., Moore, J. J., Turnpenny,
P. D., Lloyd, D. J., et al. (2005). Characteristics of fetal anticonvulsant
syndrome associated with autistic disorder. Developmental Medicine and
Child Neurology, 47, 551–555.
33. Meador, K. J., Baker, G., Cohen, M. J., Gaily, E., & Westerveld, M.
(2007). Cognitive/behavioral teratogenetic effects of antiepileptic
drugs.. Epilepsy & Behavior: E&B, 11, 292–302.
34. Johannessen, C. U., & Johannessen, S. I. (2003). Valproate: Past, present
and future. CNS Drug Review, 9, 199–216.
35. Kostrouchova, M., & Kostrouch, Z. (2007). Valproic acid, a molecular
lead to multiple regulatory pathways. Folia Biologica (Praha), 53, 37–
49.
36. Manent, J. B., Jorquera, I., Mazzaccheli, I., Depaulis, A., Perucca, E.,
Ben-Ari, Y., et al. (2007). Fetal exposure to GABA-acting anti epileptic
drugs generates hippocampal and cortical dysplasias. Epilepsia, 48, 684–
693.
37. Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007).
Elevated NMDA receptor levels and enhanced postsynaptic long term
potentiation induced by prenatal exposure to valproic acid. Proceedings
of the National Academy of Sciences of the United States of America, 104,
13501–13506.
38. Stodgell, C. J., Ingram, J. L., O’Bara, M., Tisdale, B. K., Nau, H., &
Rodier, P. M. (2006). Induction of the homeotic gene Hoxa 1 through
valproic acid’s teratogenic mechanism of action. Neurotoxicology and
Ter ato lo gy, 28 , 617–624.
39. Wegner, C., & Nau, H. (1992). Alteration of embryonic metabolism
by valproic acid during organogenesis: Implications for mechanism of
teratogenesis. Neurology, 42, 17–24.
40. Motamedi, G. K., & Meador, K. J. (2006). Anti-epileptic drugs and
neurodevelopment. Current Neurology and Neuroscience Reports, 6,
341–346.
41. Duncan, S., Mercho, S., Lopes-Cendes, I., Seni, M., Benjamin, A.,
Dubeau, F., et al. (2001). Repeated neural tube defects and valproate
monotherapy suggest a pharmacogenetic abnormality. Epilepsia, 42,
750–753.
42. Australian Government: Department of Health and Aging. (n.d.)
Australian statistics on medicines 2006. Retrieved July 8, 2009, from
http://www.health.gov.au/internet/main/publishing.nsf/Content/
pbs-pubs-asm2006
43. Grover, S., Avasthi, A., & Sharma, Y. (2006). Psychotropics in pregnancy:
Weighi ng the risks . The Indian Journal of Medical Research, 123, 497–
512.
44. Vajda, F. J., Hitchcock, A., Graham, J., O’Brien, T., Lander, C., &
Eadie, M. J. (2007). The Australian Register of Antiepileptic Drugs in
Pregnancy: The first 1002 pregnancies. The Australian & New Zealand
Journal of Obstetrics & Gynaecology, 47, 468–474.
45. Koch, S., Titze, K., & Zimmermann, R. B. (1999). Long term
neuropsychological consequences of maternal epilepsy and anticonvulsant
treatment during pregnancy for school age children and adolescents.
Epilepsia, 40, 1237–1243.
46. Thomas, S. V., Ajaykumar, B., Sindhu, K., Nair, M. K. C., George, B., &
Sarma, P. S. (2008). Motor and mental development of infants exposed
to antiepileptic drugs in utero. Epilepsy & Behavior, 13, 229–236.
About the Authors
Jacqueline Smith is an NNP at a Level III tertiary neonatal unit
in Queensland, Australia. She has worked in the neonatal specialty for
many years and still has the enthusiasm and dedication she had on her
first day. She is currently working toward a doctorate in nursing science
at James Cook University; her main work is thermoregulation and tem-
perature taking in the preterm and term neonate.
Dr. John Whitehall is the director of neonatology at The Townsville
Hospital, North Queensland, and a professor in the School of Public
Health and Tropical Medicine at James Cook University, Queensland.
He is a graduate of Sydney University, trained and worked as a general
pediatrician in Africa and Australia, and then subspecialized in
neonatology.
For further information, please contact:
Jacqueline Smith RSCN, MSc, NNP
E-mail: jacquelinej_smith@health.qld.gov.au
