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Articles » Toxic exposure » Fetal valproate syndrome

2006-04-06-15 Fetal valproate syndrome © Cuillier www.thefetus.net/


Fetal valproate syndrome

Cuillier F, MD*, Fernet A, MD**, Alessandri JL, MD***, Samperiz S***

* Department of Gynecology, Félix Guyon’Hospital, ** Department of Obstetric, Intercommunal Hospital ** Department of Neonatology, Hôpital Félix Guyon, Reunion Island, France

Definition: Fetal valproate syndrome is due to maternal valproic acid exposure during pregnancy. Valproic acid is an anti convulsivant drug used initially to control certain types of psychiatric illness and then seizure in the treatment of epilepsy. Fetal valproate syndrome is characterized by different anomalies:  

  • central nervous anomalies
  • intrauterine  growth restriction
  • cardiac anomalies
  • facial anomalies

Synonyms: Acid valproic exposure; Depakine exposure; Dalpro fetal effects; Depakene fetal effects

Case report:  This is a 36-year-old-woman, with an epileptic disease and hemiplegia (caused by neonatal effects). She has been taking valproic acid since the age of six. In 2003, she delivered one girl vaginally. In 2004, she delivered another baby at 26 weeks, who died three days later.

The conception occurred on January 2005. She had been taking pills of valproic acid (500mg) three times per day. The first scan was performed at 13 weeks. The patient refused to perform the triple test. During the second trimester, the patient did not undergo the anomaly scan. The ultrasound examination was performed at 32 weeks. The sonographer detected a discordance of size between the ventricular chambers. The patient was referred to our level III unit. Our scan performed at 33 weeks revealed: 

  • Discordance of size between ventricular chambers
  • Small ventricular septal defect
  • Normal pulmonary artery
  • Normal aortic isthmus
  • In the right ventricle, just below the tricuspid valve, there was a hyperechoic mass. This mass seemed muscular, hyperechogenic, but avascular
  • We could not see the penis, but the scrotum seemed normal
  • There was no cleft lip
  • The kidneys were normal
  • There was a single umbilical artery

The baby born at 37 weeks (3400g).  A hypospadias and a posterior cleft palate were diagnosed. The skeletal radiography was normal and also the kidney scan. An echocardiography was performed at day 5 and 10. The cardio pediatrician confirmed the small ventricular septal defect (membrane type). The atrio-ventricular valves were normal. Below the tricuspid valve, there was a right muscular hypertrophy. The aorta and pulmonary valves were normal. The pulmonary artery seemed normal. At the level of the aorta isthmus, they was a anterior notch but the flux was normal. The femoral pulse was present.

The face was dimorphic.  There were:

  • Thick and long superior lip with shallow philtrum
  • Cleft palate 
  • Small broad nose
  • Flat philtrum with coarse face
  • Bi-temporal narrowness

During the hospitalization, the baby had several episode of apnea. The oxygen-dependance was present up to October. The electroencephalogram and the cerebral sonography were normal. The kidney scan and the skeletal radiography were also normal. On November, the baby was discharge the neonatal unit. He will be schedule to visit the the pediatric surgeon (for hypospadias surgery), the neonatologist (for neurological follow up), the maxillofacial surgeon (cleft palate) and the neonatal cardiologist. Three months later, a left inguinal hernia and right muscular diastase were diagnosed.

 

4-chamber view at 33 weeks showing marked echo-reflectivity near the tricuspid valve

Pulmonary artery at 33 weeks

Aorta at 33 weeks

3D view at 33 weeks of the sex showing hypospadias

Cardiac examination at 34 weeks. Note the interventricular septal defect.

Doppler examination at 33 weeks showing interventricular septal defect

Four- chamber view at 34 weeks showing marked echo-reflectivity near the tricuspid valve

Transverse scan of the umbilical cord.

Four chamber view at 34 weeks. Note the echo-reflectivity near the tricuspid valve and right ventricular hypertrophy.

Parasagittal cardiac view showing pulmonary artery and aorta.

2D view of the profile and 3D view of the face at 36 weeks

 

History: