Exposure to valproic acid during pregnancy: an important cause of fetal trigonocephaly

*Correspondence: [e-mail].

Abstract

Case Presentation: The patient is the third child of a mother with the diagnosis of epilepsy. Who used, during pregnancy, valproic acid until the third month and phenobarbital from there forward. The mother referred to having frequent convulsions during the first three months of pregnancy. The baby was born through vaginal delivery, premature of 35 weeks, weighting 2450 grams, and with Apgar score of 8/9. It presented cardiac insufficiency after birth. The echocardiography identified a broad perimembranous interventricular communication (IVC) of the outflow tract, discrete peripheral pulmonary stenosis, and superior left vena cava draining to the coronary sinus. In the evaluation, were also evidenced: growth retardation, sagittal keel, bilateral epicanthal folds, bilateral tear duct obstruction, well-marked infraorbital fold, anteverted nostrils, long nasal philtrum, thin upper lip, retroverted and low set ears, and right accessory nipple. The cranium computerized tomography confirmed the diagnosis of trigonocephaly. The karyotype was normal. The child was submitted to a surgical correction of the IVC at 8 months old.

Discussion: Valproic acid is a medication frequently used in epilepsy treatment. It is the anticonvulsant that presents a higher association with major malformations in the fetus, including trigonocephaly. All the findings presented, together, constitute the fetal valproate syndrome.

Final Comments: The history of exposure to valproic acid during pregnancy should be remembered in the evaluation of children with trigonocephaly. It represents an important and frequent cause of this type of craniostenosis.

Publication History

Article published online:
12 May 2025