Department of pediatrics, JJM Medical College, Davangere, Karnataka, India

Abstract

Fetal Valproate Syndrome results from prenatal exposure to valproic acid. It is characterized by distinctive facial appearance, a cluster of minor and major anomalies and central nervous system dysfunction. Here we report a 4-year-old boy with typical facial features of Fetal Valproate Syndrome.

Keywords: Fetal valproate syndrome; Valproic acid

Anticonvulsants taken during pregnancy are associated with an increased risk of malformations and developmental delay. Sodium valproate is a widely used antiepileptic drug and mood stabilizer. It was licensed to use in 1978 and the first adverse report of fetus exposed to this drug was published in 1980.[1] Since then the potential teratogenic and dysmorphogenic effect of valproic acid have been emphasized.

Here we report a 4-year-old boy with dysmorphic features suggestive of Fetal Valproate Syndrome and also review the literature.

Case report

A 4-year-old boy was brought to our out patient department for evaluation of hypospadiasis. He was the only child born to a non-consanguineously married couple. Mother was on anticonvulsant sodium valproate monotherapy since 22 years. She continued the dose of 900 mg/day throughout her pregnancy. Delivery was by emergency LSCS, indication being fetal distress. His birth weight was 2.8 kg. Baby did not cry immediately after birth. Apgar score was not known. He was admitted to NICU for 3 days. Except for mild motor developmental delay his growth was normal.

Now at the age of 4 years, on examination, he had flat occiput, low set ears, slanting forehead, broad nasal bridge, hypertelorism, epicanthal folds, depressed nasal bridge, long philtrum, upturned nose, thin upperlip, small mouth. Figure1 Broad hands and feet, broad thumb deep set nails, loose skin, hypospadiasis Figure2 were other features.

His intelligence quotient was 70, with mild motor developmental delay. His weight was 18 Kg and height 104 cm (on 25th centile, NCHS). His neonatal follow-up record showed the presence of secundum ASD, but now cardiovascular system was completely normal. Echocardiogram showed normal heart without ASD. Ultrasound abdomen and CT of head did not show any abnormality. With maternal history of intake of sodium valproate throughout pregnancy and dysmorphic features typical of Fetal Valproate Syndrome, a diagnosis of FVS was made.

Discussion

Sodium valproate is a widely used antiepileptic drug and is also increasingly used for managing bipolar and other affective disorders. It is a salt of dipropyl acetic acid. It is thought to act either by inhibiting GABA metabolism or by a direct effect on mitochondria, thereby impairing cellular energy metabolism.[2] It is 80-90% bound to plasma proteins and may displace other drugs if used in combinations giving rise to toxicity. Long term valproate therapy may lead to carnitine depletion, which impairs mitochondrial fatty metabolism and leads to hepatotoxicity.

Various factors contribute to the teratogenecity of valproic acid. These include the number of drugs that are coadministered, drug dosage, differences in maternal and / or infant metabolism, the gestational age of the fetus at exposure. Valproic acid crosses the placenta and is present in a higher concentration in the fetus than in the mother.[3],[4] Various congenital malformations are associated with FVS. There is 6 to 7 times increase of malformations in babies of mothers exposed to valproate. The most frequent major congenital malformation are neural tube defects, congenital heart defects, oral clefts, genital abnormalities and limb defects. Other less frequent abnormalities include inguinal and umblical hernia, supernumerary nipple, postaxial polydactyly, bifid ribs, preaxial defect of feet.[5]