Giuseppe
Emeritus
[Source: The New England Journal of Medicine, full text: (LINK). Abstract, edited.]
Treatment of Neonatal Sepsis with Intravenous Immune Globulin
The INIS Collaborative Group
N Engl J Med 2011; 365:1201-1211 - September 29, 2011
Background
Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality.
Methods
At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years.
Results
There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events.
Conclusions
Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis. (Funded by the United Kingdom Medical Research Council and others; INIS Current Controlled Trials number, ISRCTN94984750.)
The members of the writing committee (Peter Brocklehurst, M.B., Ch.B., Barbara Farrell, Dip. Bus. Stud., Andrew King, B.A., and Edmund Juszczak, M.Sc., University of Oxford, Oxford, United Kingdom; Brian Darlow, M.D., University of Otago, Christchurch, New Zealand; Khalid Haque, F.R.C.P.C.H., University of London, London, and Children's Hospital Complex, Multan/Lahore, Pakistan; Alison Salt, F.R.C.P.C.H., University College London, London; Ben Stenson, M.D., Royal Infirmary of Edinburgh, Edinburgh; and William Tarnow-Mordi, M.B., Ch.B., University of Sydney, Sydney) take full responsibility for the content and integrity of this article.
Supported by the United Kingdom Medical Research Council, the National Health and Medical Research Council of Australia, and the Health Research Council of New Zealand.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Source Information
Address reprint requests to Dr. Brocklehurst at the National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Headington, Oxford OX3 7LF, United Kingdom, or at peter.brocklehurst@npeu.ox.ac.uk.
Additional members of the International Neonatal Immunotherapy Study (INIS) Collaborative Group are listed in the Supplementary Appendix, available at NEJM.org.
- -------The INIS Collaborative Group
N Engl J Med 2011; 365:1201-1211 - September 29, 2011
Background
Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality.
Methods
At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years.
Results
There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events.
Conclusions
Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis. (Funded by the United Kingdom Medical Research Council and others; INIS Current Controlled Trials number, ISRCTN94984750.)
The members of the writing committee (Peter Brocklehurst, M.B., Ch.B., Barbara Farrell, Dip. Bus. Stud., Andrew King, B.A., and Edmund Juszczak, M.Sc., University of Oxford, Oxford, United Kingdom; Brian Darlow, M.D., University of Otago, Christchurch, New Zealand; Khalid Haque, F.R.C.P.C.H., University of London, London, and Children's Hospital Complex, Multan/Lahore, Pakistan; Alison Salt, F.R.C.P.C.H., University College London, London; Ben Stenson, M.D., Royal Infirmary of Edinburgh, Edinburgh; and William Tarnow-Mordi, M.B., Ch.B., University of Sydney, Sydney) take full responsibility for the content and integrity of this article.
Supported by the United Kingdom Medical Research Council, the National Health and Medical Research Council of Australia, and the Health Research Council of New Zealand.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Source Information
Address reprint requests to Dr. Brocklehurst at the National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Headington, Oxford OX3 7LF, United Kingdom, or at peter.brocklehurst@npeu.ox.ac.uk.
Additional members of the International Neonatal Immunotherapy Study (INIS) Collaborative Group are listed in the Supplementary Appendix, available at NEJM.org.