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a Department of
Neonatology, Aalborg Hospital, Denmark, b Department of Gynecology
and Obstetrics, c Department of Paediatrics, Hjoerring Hospital,
Denmark
Correspondence to: Dr Ebbesen, Department of Paediatrics, Aalborg Hospital, P O Box 561, 9100 Aalborg, Denmark email: ul9091{at}aas.nja.dk
Accepted 27 March 2000
AIMS
To define, in a
prospective study, the risk of hypoglycaemiadefined as blood glucose
concentration < 1.8 mmol/lin term infants exposed in utero to
valproate and to describe the withdrawal symptoms.
METHODSTwenty
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).
RESULTSThirteen 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).
CONCLUSIONSInfants
exposed to valproate in utero had a significantly elevated risk of
hypoglycaemia, and withdrawal symptoms were often observed.
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