Craniosynostosis and fetal exposure to sodium valproate

• Published in: Journal of neurosurgery Vol. 95; no. 5; pp. 778 - 782
• Main Authors: LAJEUNIE, Elizabeth, BARCIK, U. L. I, THORNE, John A, EL GHOUZZI, Vincent, BOURGEOIS, Marie, RENIER, Dominique
• Format: Journal Article
• Language: English
• Published: Park Ridge, IL American Association of Neurological Surgeons 01-11-2001
• Subjects: Anticonvulsants - adverse effects; Biological and medical sciences; Child; Child, Preschool; Craniosynostoses - chemically induced; Craniosynostoses - pathology; Craniosynostoses - psychology; Drug toxicity and drugs side effects treatment; Epilepsy - drug therapy; Female; Fetus - drug effects; Genetics; Human genetics; Humans; Infant; Intelligence; Life Sciences; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Pregnancy; Pregnancy Complications - drug therapy; Valproic Acid - adverse effects; Human; Nervous system diseases; Pregnancy disorders; 4-Aminobutyrate transaminase; Enzyme; Toxicity; Transferases; Craniosynostosis; Diseases of the osteoarticular system; Enzyme inhibitor; Dysostosis; Anticonvulsant; Exposure; Maternal diseases; Valproic acid; Chemotherapy; Mother; Transaminases; Skull disease; Teratogen; Child
• ISSN: 0022-3085; 1933-0693
• DOI: 10.3171/jns.2001.95.5.0778

Fetal valproate syndrome affects one in 10 children born to mothers who ingest sodium valproate regularly during pregnancy. It has been described as producing a combination of typical dysmorphic features and major organ system anomalies. Trigonocephaly is caused by premature fusion of the metopic suture and has not previously been described as a typical feature of the syndrome. The authors reviewed the cases of 2,220 children with craniosynostosis to examine the effect of maternal sodium valproate use on the fetus.
Case files of all 2,220 children were reviewed. The type and severity of each patient's craniosynostosis was assessed. Information about maternal health and medication use was obtained, and family interviews were conducted. Children underwent mental development assessment performed using standard tests both pre- and postoperatively. Detailed maternal health information was obtained in 1,676 cases. Of these, 17 mothers were found to have undergone regular treatment with sodium valproate monotherapy at the time of their pregnancies. No other antiepileptic medical regimen was found. All 17 children exhibited trigonocephaly. These patients' intelligence quotients (JQs) at the time of the most recent follow-up examination ranged from 45 to 100, with a mean of 75; IQs were significantly higher in patients who underwent surgery before reaching 6 months of age.
Ideally any pregnancy in a woman being treated for epilepsy should be planned, and both an obstetrician and a neurologist should be consulted. In children born with fetal valproate syndrome, it is important to be aware of the possibility of metopic suture synostosis, which we believe should be considered part of the syndrome, because early surgical intervention may improve cognitive outcome.