Ebbesen F, Joergensen A, Hoseth E, Kaad P H, Moeller M, Holsteen V, Rix M
Department of Neonatology, Aalborg Hospital, Denmark.
Arch Dis Child Fetal Neonatal Ed. 2000 Sep;83(2):F124-9. doi: 10.1136/fn.83.2.f124.
To define, in a prospective study, the risk of hypoglycaemia-defined as blood glucose concentration < 1.8 mmol/l-in term infants exposed in utero to valproate and to describe the withdrawal symptoms.
Twenty epileptic women were treated with valproate only during pregnancy and two were treated with valproate and carbamazepine. In the first trimester, the daily median dose of valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3-4.8).
Thirteen of the 22 infants became hypoglycaemic. One infant had eight episodes of hypoglycaemia, one had three episodes, two had two episodes, and nine had one episode each. The lowest blood glucose concentration was 1.0 mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of total valproate during the third trimester correlated negatively with blood glucose concentration one hour after delivery (p < 0.0003) and with the development of hypoglycaemia (p < 0.0001). There was no evidence for hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal symptoms, which correlated positively with the mean dose of valproate in the third trimester and the concentration of the free fraction of valproate in maternal plasma at delivery (p < 0.02).
Infants exposed to valproate in utero had a significantly elevated risk of hypoglycaemia, and withdrawal symptoms were often observed.
在一项前瞻性研究中，确定孕期暴露于丙戊酸盐的足月儿发生低血糖（定义为血糖浓度<1.8 mmol/L）的风险，并描述戒断症状。
20名癫痫女性在孕期仅接受丙戊酸盐治疗，2名接受丙戊酸盐和卡马西平治疗。孕早期丙戊酸盐的每日中位剂量为1.0 g（范围0.3 - 4.2），孕晚期为1.2 g（范围0.3 - 4.8）。
22名婴儿中有13名发生低血糖。1名婴儿有8次低血糖发作，1名有3次，2名有2次，9名各有1次。最低血糖浓度为1.0 mmol/L。所有发作均无症状。孕晚期母体总丙戊酸盐的平均血浆浓度与分娩后1小时的血糖浓度呈负相关（p < 0.0003），与低血糖的发生呈负相关（p < 0.0001）。没有证据表明高胰岛素血症是低血糖的原因。10名婴儿出现戒断症状，这与孕晚期丙戊酸盐的平均剂量和分娩时母体血浆中丙戊酸盐游离部分的浓度呈正相关（p < 0.02）。
宫内暴露于丙戊酸盐的婴儿发生低血糖的风险显著升高，且常观察到戒断症状。
