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

Abstract

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.

Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Teratogenesis and perinatal outcomes [RETIRED]

“…Using the Cochran Armitage method, 17 we found a significant dose relationship with VPA (exact tests one-sided p ϭ 0.02, two-sided p ϭ 0.04) and with LTG (exact tests one-sided p ϭ 0.01, two-sided p ϭ 0.02), but not with CBZ (exact tests one-sided p ϭ 0.19, two-sided p ϭ 0.31). Two Class II studies 11,12 and six Class III studies [13][14][15][18][19][20] also found a relationship between VPA dose and MCMs. The VPA dose above which MCMs were significantly more likely to occur was not consistent, but was approximately 1,000 mg daily in five studies.…”

“…The VPA dose above which MCMs were significantly more likely to occur was not consistent, but was approximately 1,000 mg daily in five studies. 12,13,[18][19][20] Conclusion. There is probably a relationship between the dose of VPA and LTG and the risk of development of MCMs in the offspring of WWE (one Class I study).…”

Managing Bipolar Disorder during Pregnancy: Weighing the Risks and Benefits

“…These risks are of particular concern because formation of the neural tube occurs within the first month of gestation, often before the pregnancy has been diagnosed. Prenatal exposure to valproate has also been associated with characteristic craniofacial abnormalities, cardiovascular malformations, limb defects, and genital anomalies, as well as other central nervous system (CNS) structural abnormalities, including hydrocephalus (76)(77)(78)89,90).…”

“…It is not known whether the new derivative, oxcarbazepine, is associated with similar fetal risks (88). However, among the anticonvulsants used to treat BD, valproic acid and its various derivatives and preparations, including divalproex, may be even more serious teratogens, with rates of NTDs in the range of 1.0% to 5.0%, or about a two-to tenfold increase in risk above the general-population base rates of about 0.5% (89,90). These risks are of particular concern because formation of the neural tube occurs within the first month of gestation, often before the pregnancy has been diagnosed.…”

Do lamotrigine and levetiracetam solve the problem of using sodium valproate in women with epilepsy?

“…64 The risk of spina bifida (1-2%) 46,65,66 is dose dependent, with the greatest risk for those exposed to doses of greater than 1000 mg per day. Skeletal defects, including radial ray aplasia, rib and vertebral anomalies 67 and polydactyly, have also been reported.…”