• Arne Ohlsson and Janet B Lacy.
• Departments of Paediatrics, Obstetrics and Gynaecology and Institute of Health Policy, Management and Evaluation, University ofToronto, Toronto, Canada. aohlsson@mtsinai.on.ca.
• Cochrane Db Syst Rev. 2013 Jan 1;7:CD001239.

BackgroundNeonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and endogenous synthesis begins several months after birth. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence. Theoretically, infectious morbidity and mortality could be reduced by the administration of IVIG.ObjectivesTo assess the effects of IVIG on mortality/morbidity caused by suspected or proven infection at study entry in neonates. To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection.Search MethodsFor this update, MEDLINE, EMBASE, The Cochrane Library, CINAHL, trial registries, Web of Science, reference lists of identified studies, meta-analyses and personal files were searched in 2013. No language restrictions were applied.Selection CriteriaRandomised or quasi-randomised controlled trials; newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial/fungal infection compared with placebo or no intervention; one of the following outcomes was reported: mortality, length of hospital stay or psychomotor development at follow-up.Data Collection And AnalysisStatistical analyses included typical risk ratio (RR), risk difference (RD), weighted mean difference (WMD), number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH) (all with 95% confidence intervals (CIs) and the I-squared (I(2)) statistic to examine for statistical heterogeneity).Main ResultsThe updated search identified one published study and one ongoing study. A total of eight studies evaluating 3871 infants are included in this review.Mortality during hospital stay in infants with clinically suspected infection at trial entry was not significantly different after IVIG treatment (8 studies (n = 2425); typical RR 0.94, 95% CI 0.80 to 1.12; typical RD -0.01, 95% CI - 0.04 to 0.02 I(2) = 28% for RR and 32% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (one study (n = 1985); RR 0.98, 95% CI 0.88 to 1.09 RD -0.01, 95% CI -0.05 to 0.03). Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry (RR 0.95, 95% CI 0.74 to 1.21 RD -0.01, 95% CI -0.04 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry (RR 1.03, 95% CI 0.91 to 1.18; RD 0.01, 95% CI -0.04 to 0.06). Mortality during hospital stay in infants with clinically suspected or proven infection at trial entry was not significantly different after IVIG treatment (1 study (n = 3493); RR 1.00, 95% CI 0.86 to 1.16; RD 0.00, 95% CI - 0.02 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with suspected or proven infection at trial entry (1 study (n = 3493); RR 1.00, 95% CI 0.92 to 1.09; RD -0.00, 95% CI -0.03 to 0.03). Length of hospital stay was not reduced for infants with suspected/proven infection at trial entry (1 study (n = 3493); mean difference (MD) 0.00 days, 95% CI -0.61 to 0.61). No significant difference in mortality during hospital stay after IgM-enriched IVIG treatment for suspected infection was reported at trial entry (3 studies (n = 164); typical RR 0.57, 95% CI 0.31 to 1.04; RD -0.12, 95% CI -0.24 to 0.00 ; P = 0.06); I(2) = 2% for RR and 0% for RD).Authors' ConclusionsIn previous reviews, we encouraged researchers to undertake well-designed trials to confirm or refute the effectiveness of IVIG in reducing adverse outcomes in neonates with suspected infection. Such a trial has been undertaken. Results of the INIS trial, which enrolled 3493 infants, carry a heavy weight in the current update of this review, and the undisputed results show no reduction in death or major disability at 2 years of age. Routine administration of IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended.

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