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Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants
1Paediatrics, Mount Sinai Hospital, 775A-600 University Avenue, Toronto, Ontario, Canada, M5G 1X5. aohlsson@mtsinai.on.ca
Insights
Intravenous immunoglobulin (IVIG) reduces serious infections in preterm infants but does not impact mortality. The clinical significance of this 3-4% reduction in nosocomial infections is marginal, warranting exploration of alternative prevention strategies.
Area of Science:
- Neonatalogy
- Immunology
- Infectious Diseases
Background:
- Nosocomial infections pose significant risks to preterm and low birth weight (LBW) infants due to limited maternal antibody transfer and delayed endogenous synthesis.
- Intravenous immunoglobulin (IVIG) administration offers potential benefits by providing IgG antibodies that enhance immune responses against pathogens.
Purpose of the Study:
- To evaluate the efficacy and safety of IVIG in preventing nosocomial infections in preterm and/or LBW infants.
- To compare IVIG administration against placebo or no intervention in randomized controlled trials (RCTs).
Main Methods:
- Systematic review and meta-analysis of RCTs identified through comprehensive database searches (MEDLINE, EMBASE, Cochrane Library).
- Inclusion criteria focused on RCTs involving preterm/LBW infants receiving IVIG for infection prevention, with relevant clinical outcomes reported.
- Data extraction and analysis involved pooling results using fixed-effects models, calculating relative risk (RR), risk difference (RD), and number needed to treat (NNT).
Main Results:
- Nineteen RCTs involving approximately 5,000 infants were analyzed.
- IVIG significantly reduced the incidence of sepsis (RR 0.85, NNT 33) and any serious infection (RR 0.82, NNT 25).
- No significant differences were observed in mortality, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or hospital length of stay. No major adverse effects were reported.
Conclusions:
- IVIG administration demonstrates a modest reduction in serious infections but does not improve mortality or other critical outcomes in preterm/LBW infants.
- The clinical benefit of IVIG for infection prevention is considered marginal, with decisions on use depending on cost-effectiveness and assigned outcome values.
- Further RCTs on IVIG for this indication are not justified; focus should shift to alternative infection prevention strategies.
Background:
Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight infants. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks gestation and endogenous synthesis does not begin until several months after birth. Administration of intravenous immunoglobulin provides IgG that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody dependent cytotoxicity, and improve neutrophilic chemoluminescence. Intravenous immunoglobulin thus has the potential of preventing or altering the course of nosocomial infections.
Objectives:
To assess the effectiveness/safety of intravenous immunoglobulin (IVIG) administration (compared to placebo or no intervention) to preterm (< 37 weeks gestational age at birth) and/or low birth weight (LBW) (< 2500 g BW) infants in preventing nosocomial infections.
Search Strategy:
MEDLINE, EMBASE, and the Cochrane Library Databases were searched in February 2001 using the keywords: immunoglobulin and infant-newborn and random allocation or controlled trial or randomized controlled trial (RCT). The reference lists of identified RCTs and personal files were searched. No language restrictions were applied.
Selection Criteria:
The criteria used to select studies for inclusion in this overview were: 1) DESIGN: RCTs in which administration of IVIG was compared to a control group that received a placebo or no intervention. 2) POPULATION: preterm (< 37 weeks gestational age) and/or LBW (<2500 g) infants. 3) INTERVENTION: IVIG for the prevention of bacterial/fungal infection during initial hospital stay (8 days or longer). (Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded as were studies in which the follow-up period was one week or less). 4) At least one of the following outcomes was reported: sepsis, any serious infection, death from all causes, death from infection, length of hospital stay, intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD).
Data Collection And Analysis:
Two reviewers independently abstracted information for each outcome reported in each study, and one researcher (AO) checked for any discrepancies and pooled the results. Relative risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using the fixed effects model are reported. When a statistically significant RD was found the number needed to treat (NNT) was also calculated with 95% CIs. The results include all accepted studies in which the outcome of interest was reported. Statistically significant between study heterogeneity was reported.
Main Results:
Nineteen studies met inclusion criteria. These included aprox. 5,000 preterm and/or LBW infants and reported on at least one of the outcomes of interest for this systematic review. When all studies were combined there was a statistically significant reduction (p = 0.02) in sepsis, RR [0.85 (95% CI 0.74, 0.98)] and RD [-0.03 (95% CI 0.00, -0.05)], NNT 33. There was statistically significant between-study heterogeneity (p = 0.02). A statistically significant reduction was found for any serious infection, one or more episodes, when all studies were combined [RR 0.82 (95% CI 0.74, 0.92); RD -0.04 (95% CI -0.02, -0.06,); NNT 25 (95% CI, 16.7, 50). There was statistically significant between-study heterogeneity (p = 0.0006). There were no statistically significant differences for mortality from all causes, mortality from infection, incidence of NEC, BPD and IVH or length of hospital stay. No major adverse effects of IVIG were reported in any of the studies.
Reviewer'S Conclusions:
IVIG administration results in a 3% reduction in sepsis and a 4 % reduction in any serious infection, one or more episodes, but is not associated with reductions in other important outcomes: sepsis, NEC, IVH, or length of hospital stay. Most importantly IVIG administration does not have any effect on mortality from any cause or from infections. Prophylactic use of IVIG is not associated with any short term serious side effects. From a clinical perspective a 3-4% reduction in nosocomial infections without a reduction in mortality or other important clinical outcomes is of marginal importance. The decision to use prophylactic IVIG will depend on the costs and the values assigned to the clinical outcomes. There is no justification for further RCTs testing the efficacy of previously studied IVIG preparations to reduce nosocomial infections in preterm and/or LBW infants. The results of these meta-analyses should encourage basic scientists and clinicians to pursue other avenues to prevent nosocomial infections.