From the Department of Medicine and Neuroscience (F.J.V., T.J.O., J.E.G.), University of Melbourne, Royal Melbourne Hospital, Parkville; and University of Queensland (C.M.L., M.J.E.), Royal Brisbane Hospital, Brisbane, Australia.
Neurology. 2013 Sep 10;81(11):999-1003. doi: 10.1212/WNL.0b013e3182a43e81. Epub 2013 Aug 2.
To study the relationships between maternal valproate dose in pregnancy and the pattern of various fetal malformations.
Analysis of data in the Australian Register of Antiepileptic Drugs in Pregnancy collected from 1999 to 2012. The specific type of fetal malformation in offspring exposed to valproate in utero was correlated with the dose of valproate taken by the mother in the first trimester.
Compared with other malformations, the mean dose of valproate taken during the first trimester was higher in mothers whose offspring had spina bifida (2,000 ± 707 vs 1,257 ± 918 mg/d) and hypospadias (2,417 ± 1,320 vs 1,235 ± 715 mg/d) (both p < 0.05). The overall mean maternal valproate dosage taken by women in the Register decreased over the last 5 years of the study period. This was paralleled by a statistically significant decrease in the rate of occurrence of spina bifida and hypospadias, but not other malformations.
Human fetal malformations associated with valproate exposure during pregnancy do not all seem to bear the same quantitative relationship to drug dose, and reduction in valproate dose in earlier pregnancy is likely to offer greater dividends in protecting against spina bifida and hypospadias than against other types of fetal malformations.
研究妊娠期间母亲丙戊酸剂量与各种胎儿畸形类型之间的关系。
分析 1999 年至 2012 年期间澳大利亚抗癫痫药物妊娠登记处收集的数据。将暴露于子宫内丙戊酸的后代的特定类型胎儿畸形与母亲在妊娠早期服用的丙戊酸剂量相关联。
与其他畸形相比，脊柱裂（2,000 ± 707 比 1,257 ± 918 mg/d）和尿道下裂（2,417 ± 1,320 比 1,235 ± 715 mg/d）患儿母亲在妊娠早期服用的丙戊酸平均剂量更高（均 p < 0.05）。研究期间最后 5 年，登记处女性服用的丙戊酸总体平均剂量呈下降趋势。这与脊柱裂和尿道下裂的发生率呈统计学显著下降平行，但其他畸形发生率没有下降。
与妊娠期间丙戊酸暴露相关的人类胎儿畸形似乎并不都与药物剂量呈相同的定量关系，减少妊娠早期的丙戊酸剂量可能比预防其他类型的胎儿畸形更能有效预防脊柱裂和尿道下裂。
