Abstract & Commentary

Intravenous Immune Globulin for Neonatal Sepsis

By Hal B. Jenson, MD, FAAP, Dean, Western Michigan University School of Medicine, Kalamazoo, MI, is Associate Editor for Infectious Disease Alert.

Synopsis: Intravenous immune globulin for suspected or proven severe neonatal infection had no effect on clinical outcomes including subsequent sepsis, death, or major or non-major disability at 2 years of age.

Source: The INIS Collaborative Group. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 2011;365:1201-1211.

A double-blind, randomized, controlled trial conducted by the International Neonatal Immunotherapy Study (INIS) compared adjunctive therapy of human nonspecific polyvalent IgG intravenous immune globulin to placebo in the treatment of newborn infants with suspected or proven sepsis who were also receiving antibiotic therapy. Newborns receiving antibiotics and having birth weight less than 1500 g, requiring assisted ventilation, or with evidence of infection of a usually sterile body site were randomized to receive intravenous immune globulin (500 mg/kg, 2 doses 48 hours apart) or an identical volume of placebo. Primary outcomes were death or major disability at 2 years of age, including cognitive function using the Parent Report of Children's Abilities-Revised (PARCA-R).

From 2001 to 2007, 3,493 infants were recruited from 113 hospitals in nine countries. Newborn and maternal characteristics were very similar. Outcomes at 2 years of age were available for 97% of surviving infants. In the group receiving intravenous immune globulin, 686 of 1,759 infants (39.0%) either died or had major disability at 2 years of age, compared with 677 of 1,734 infants (39.0%) in the placebo group. There were no significant outcome differences for any secondary outcome, including rates of subsequent episodes of sepsis and by causative organisms. There were 22 adverse events reported with 12 in the group receiving intravenous immune globulin (including 2 deaths) and 10 in the placebo group (including 4 deaths).


There are more than 20 reported trials involving more than 5,000 preterm infants studying the use of polyvalent IgG to treat suspected or proven sepsis in preterm infants. Relatively low numbers of enrollees, small differences in treatment groups, conflicting results even among meta-analyses, and variable scientific quality of many reports have resulted in uncertainty of the value of intravenous immune globulin as adjunctive therapy for neonatal sepsis.

This study is notable for the double-blind and randomized study design with a large number of enrolled infants (3,493), and measurements of both short-term mortality and long-term (at age 2 years) disability outcomes. Based on this trial, intravenous immune globulin has no effect on the outcomes of suspected or proven neonatal sepsis.