Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to valproate

Ebbesen, Finn; Joergensen, Annemette; Hoseth, Eva; Kaad, P. H.; Moeller, Margrethe; Holsteen, V; Rix, Mariane

doi:10.1136/fn.83.2.f124

Cited by 56 publications

(45 citation statements)

References 33 publications

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“…It is noteworthy that Glut1 is also highly expressed in placenta responsible for glucose delivery to the fetus. Consistent with the Glut1-inhibiting actions of the compound, sodium valproate consumption during pregnancy has been associated with an increased risk of infantile hypoglycemia [Ebbesen et al, 2000].…”

Section: Discussionmentioning

confidence: 97%

Sodium valproate inhibits glucose transport and exacerbates Glut1‐deficiency in vitro

Wong

Chu

Lai

et al. 2005

J of Cellular Biochemistry

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Anticonvulsant sodium valproate interferes with brain glucose metabolism. The mechanism underlying such metabolic disturbance is unclear. We tested the hypothesis that sodium valproate interferes with cellular glucose transport with a focus on Glut1 since glucose transport across the blood-brain barrier relies on this transporter. Cell types enriched with Glut1 expression including human erythrocytes, human skin fibroblasts, and rat astrocytes were used to study the effects of sodium valproate on glucose transport. Sodium valproate significantly inhibited Glut1 activity in normal and Glut1-deficient erythrocytes by 20%-30%, causing a corresponding reduction of Vmax of glucose transport. Similarly, in primary astrocytes as well as in normal and Glut1-deficient fibroblasts, sodium valproate inhibited glucose transport by 20%-40% (P < 0.05), accompanied by an up to 60% downregulation of GLUT1 mRNA expression (P < 0.05). In conclusion, sodium valproate inhibits glucose transport and exacerbates Glut1 deficiency in vitro. Our findings imply the importance of prudent use of sodium valproate for patients with compromised Glut1 function.

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Section: Discussionmentioning

confidence: 97%

Sodium valproate inhibits glucose transport and exacerbates Glut1‐deficiency in vitro

Wong

Chu

Lai

et al. 2005

J of Cellular Biochemistry

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“…Recently, a prospective study of 22 VPA-exposed pregnancies in Denmark found an inverse correlation between third trimester maternal VPA levels and the infants' plasma glucose level [64]. This study sought to determine the risk of hypoglycaemia (defined as blood glucose concentration < 1.8 mmol/l), as well as identify withdrawal symptoms, in term infants exposed prenatally to VPA.…”

Section: Hypoglycaemia and Coagulation Factorsmentioning

confidence: 97%

Teratogenicity of sodium valproate

Alsdorf

Wyszynski

2005

Expert Opinion on Drug Safety

171

100

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The teratogenicity of the widely popular antiepileptic drug (AED) and mood stabiliser sodium valproate (also known as valproate, VPA) has been evidenced by previous research; however, these findings have often been limited by a small population sample of exposed women and a retrospective study design. Many factors contribute to the teratogenicity of VPA. These include the number of drugs that are co-administered, drug dosage, differences in maternal and/or infant metabolism, the gestational age of the fetus at exposure, and hereditary susceptibility. VPA has been associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism. It has been suggested that polytherapy treatment in epileptic pregnant women increases the risk of teratogenicity in offspring. Furthermore, there is an established relationship between VPA dose and adverse outcome. Large single doses of VPA potentially cause high peak levels in the fetal serum resulting in deleterious effects. Currently there is an increase in the number of national and international pregnancy registries being formed in an effort to better identify the teratogenic effects of AEDs. These efforts hope to enhance our understanding of AEDs and their associated risks by addressing past study limitations.

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“…23 Neonatal hypoglycaemia is common following valproate exposure and may be asymptomatic. 36 Although it can cause cerebral damage and adverse neurodevelopmental outcome in other circumstances, 37 it is not known whether this is important in *Significantly different from non-exposed group by Cox's proportional hazards regression (p <0.05).…”

Section: Neurodevelopmentmentioning

confidence: 99%

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth

Dean

Hailey²,

Moore³

et al. 2002

Journal of Medical Genetics

210

145

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Objective: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. Design: Retrospective population based study. Setting: Population of the Grampian region of Scotland. Participants: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. Results: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). Conclusion: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.

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Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to valproate

Cited by 56 publications

References 33 publications

Sodium valproate inhibits glucose transport and exacerbates Glut1‐deficiency in vitro

Sodium valproate inhibits glucose transport and exacerbates Glut1‐deficiency in vitro

Teratogenicity of sodium valproate

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth

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