Prenatal diagnosis of spina bifida aperta after first-trimester valproate exposure

Prenat Diagn. 1992 Nov;12(11):893-7. doi: 10.1002/pd.1970121107.


In the context of a prospective study on the adverse effects of anti-epileptic drugs on fetal outcome, we evaluated our experience with prenatal diagnosis by ultrasonography and alpha-fetoprotein (AFP) determination in amniotic fluid. We compared these results with AFP values in maternal serum obtained prior to amniocentesis. From November 1985 to July 1990, amniocentesis at 16-18 weeks of gestation was performed in 267 pregnancies of 237 different women using anti-epileptic drugs. Among 92 pregnancies with maternal valproic acid use, five (including one concordantly affected monozygotic twin-pair) were terminated because of a spina bifida aperta, all prenatally diagnosed by AFP determination and acetylcholinesterase electrophoresis in amniotic fluid. The maternal serum AFP level was raised (> or = 2.5 multiples of the median (MOM) for singleton pregnancies and > or = 4.5 MOM for twin pregnancies) in only two of these five affected pregnancies. We emphasize that maternal serum AFP levels may be unreliable for prenatal screening for fetal neural tube defects in women taking valproate and recommend that amniocentesis and fetal ultrasound examination should be offered directly.

MeSH terms

  • Acetylcholinesterase / analysis
  • Amniotic Fluid / chemistry
  • Female
  • Humans
  • Pregnancy
  • Pregnancy Trimester, Second
  • Prenatal Diagnosis*
  • Prospective Studies
  • Spina Bifida Cystica / chemically induced
  • Spina Bifida Cystica / diagnosis*
  • Spina Bifida Cystica / diagnostic imaging
  • Ultrasonography
  • Valproic Acid / adverse effects*
  • alpha-Fetoproteins / analysis


  • alpha-Fetoproteins
  • Valproic Acid
  • Acetylcholinesterase