Intravenous immunoglobulin therapy for prevention of infection in high-risk premature infants: report of a multicenter, double-blind study. Intravenous gammaglobulin therapy for prophylaxis of infection in high-risk neonates.
The effectiveness of intravenously administered immunoglobulin (Ig) therapy for prophylaxis of infection was evaluated in high-risk preterm infants. Two hundred thirty-five premature newborns were randomly assigned, in a double-blind controlled trial, to treatment and placebo groups. Thirty-five infants (29%) of the Ig group and 29 (25%) of the placebo group had one or more episodes of certain infection. Thirty infants (25%) of the Ig group and 18 (16%) of the placebo group had one or more episodes of probable infection. No significant differences were observed in the incidence of certain or probable infection in treated and control infants. Nevertheless, among the infants who had one or more certain or probable episodes of infection, more of them belonged to the Ig group than to the placebo group. The possible deleterious effect of the administration of large amounts of polyspecific Ig is discussed. The safety and effectiveness of intravenously administered gammaglobulin therapy for prophylaxis of infection was evaluated in 133 high-risk neonates. The infants were stratified into two groups: infants with birth weight less than or equal to 1500 g and gestational age less than or equal to 34 weeks, and infants with birth weight greater than 1500 g and receiving intensive care and assisted ventilation. Forty-three infants in group 1 and 25 in group 2 were given gammaglobulin at a dose of 0.5 g/kg/wk, for 1 month in group 1 and during intensive care in group 2. Forty infants in group 1 and 25 in group 2 served as controls. Serum total IgG and group B streptococcus-, Escherichia coli-, and CMV-specific IgG levels similar to those in adult controls were observed in the treated infants 2 hours after gammaglobulin administration. In the treated infants in group 1, the incidence of infection was 51%, and of septicemia 5%; in the controls the incidence of infection was 77% (P less than 0.02), and of septicemia 20% (P less than 0.05). Infection was the main cause of death in one treated and six control infants in group 1 (P less than 0.04). In the infants with birth weight greater than 1500 g receiving intensive care and assisted ventilation, no significant differences were observed in the incidence of infection or septicemia in treated and control infants. No side effects were observed after intravenous gammaglobulin administration. These data show that intravenously administered gammaglobulin is both safe and effective for prophylaxis of infection in preterm very low birth weight infants.
Intrapartum antibiotic prophylaxis appeared to reduce EOGBSD, but this result may well be a result of bias as we found a high risk of bias for one or more key domains in the study methodology and execution. There is lack of evidence from well designed and conducted trials to recommend IAP to reduce neonatal EOGBSD.
Ideally the effectiveness of IAP to reduce neonatal GBS infections should be studied in adequately sized double-blind controlled trials. The opportunity to conduct such trials has likely been lost, as practice guidelines (albeit without good evidence) have been introduced in many jurisdictions.