Objective: Early-onset neonatal seizures are a strong predictor of later morbidity and mortality in term infants. Although an association of noninfectious intrapartum fever with neonatal seizures in term infants has been reported, it was based on only a small number of neonates with seizures. We therefore conducted a case control study to investigate this association further.
Methods: All term infants with neonatal seizures born at Brigham and Women's Hospital between 1989 and 1996 were identified. For this study, cases consisted of all term neonates with a confirmed diagnosis of seizure born after a trial of labor for whom no proximal cause of seizure could be identified. Infants with sepsis or meningitis were excluded. Four controls matched by parity and date of birth were identified for each case. The rate of intrapartum maternal temperature >100.4 degrees F was compared for case infants and controls. Potential confounding was controlled in logistic regression analysis.
Results: Cases comprised 38 term infants with unexplained seizures after a trial of labor. We identified 152 controls. Infants with seizures were more likely to be born to mothers who were febrile during labor (31.6% vs 9.2%). In almost all cases, the fever developed during labor (94.7% cases, 97.4% controls). At admission, mothers of infants with seizures were not significantly more likely to have factors associated with concern about infection such as a white blood cell count >15 000/mm(3) (28. 9% vs 19.1%) and premature rupture of the membranes (15.8% vs 17.8%). In a logistic regression analysis controlling for confounding factors, intrapartum fever was associated with a 3.4-fold increase in the risk of unexplained neonatal seizures (odds ratio = 3.4, 95% confidence interval = 1.03-10.9).
Conclusion: Our data indicate that intrapartum fever, even when unlikely to be caused by infection, is associated with a fourfold increase in the risk of unexplained, early-onset seizures in term infants.