Enzyme-inducing antiepileptic drugs in pregnancy and the risk of bleeding in the neonate.
BACKGROUND
Case reports suggest that maternal hepatic enzyme-inducing antiepileptic drugs (AED) increase the risk for neonatal bleeding. Antenatal administration of vitamin K(1) to mothers using these drugs therefore is widely recommended. There are, however, no studies on the incidence of this complication.


OBJECTIVE
To assess the occurrence of bleeding complications in newborns exposed to maternal enzyme-inducing AED in utero.


METHODS
The authors prospectively followed 662 pregnancies in women with epilepsy who used enzyme-inducing AED. Of the 667 neonates, 463 were exposed to carbamazepine, 212 to phenytoin, 44 to phenobarbital, 11 to primidone, and 7 to oxcarbazepine. The control subjects were 1,324 nonepileptic pregnancies (1,334 neonates) matched for maternal age, parity, number of fetuses, and delivery date. None of the mothers received vitamin K(1) during pregnancy, but all infants received 1 mg vitamin K(1) intramuscularly at birth.


RESULTS
A bleeding complication was observed in five (0.7%) of the offspring exposed to maternal enzyme-inducing AED and in five (0.4%) control subjects (p = 0.3). After logistic regression analysis was performed, bleeding was associated with birth at <32 weeks of gestation (adjusted OR = 13; 95% CI = 2.7 to 64) and alcohol abuse (adjusted OR = 17; 95% CI = 1.8 to 162) but not with exposure to enzyme-inducing AED (adjusted OR = 1.1; 95% CI = 0.3 to 4.6; p = 0.8).


CONCLUSIONS
These data do not support the hypothesis that maternal enzyme-inducing AED increase the risk for bleeding in the offspring. Antenatal administration of vitamin K to these mothers may still be needed in selected cases.
Kaaja
Erja
E
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Kaaja
Risto
R
Matila
Riitta
R
Hiilesmaa
Vilho
V
D000328:Adult; D000437:Alcoholism / Q000150:complications; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D016001:Confidence Intervals; D004790:Enzyme Induction / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn / Q000502:physiology; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D016015:Logistic Models; D016017:Odds Ratio; D011247:Pregnancy / Q000187:drug effects* / Q000706:statistics & numerical data; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric
D000927:Anticonvulsants