Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2020 Jan 29;1(1):CD001239.
doi: 10.1002/14651858.CD001239.pub6.

Intravenous immunoglobulin for suspected or proven infection in neonates

Arne Ohlsson  1 , Janet B Lacy  2
Affiliations
Meta-Analysis

Intravenous immunoglobulin for suspected or proven infection in neonates

Arne Ohlsson et al. Cochrane Database Syst Rev. .

Abstract

Background: Neonates 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.

Objectives: To assess the effects of IVIG on mortality and 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 methods: For 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 criteria: Randomised or quasi-randomised controlled trials involving newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial or fungal infection compared with placebo or no intervention; and where one of the following outcomes was reported, mortality, length of hospital stay or psychomotor development at follow-up.

Data collection and analysis: Statistical 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 I2 statistic to examine for statistical heterogeneity.

Main results: The updated search identified one published study that was previously ongoing. A total of 9 studies evaluating 3973 infants were included in this review. Mortality during hospital stay in infants with clinically suspected infection was not significantly different after IVIG treatment (9 studies (n = 2527); typical RR 0.95, 95% CI 0.80 to 1.13; typical RD -0.01, 95% CI - 0.04 to 0.02; I2 = 23% for RR and 29% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (1 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 (1 trial (n = 1446); 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 (1 trial (n = 1393); 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 or 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 administration of IgM-enriched IVIG for suspected infection at trial entry was reported in 4 studies (n = 266) (typical RR 0.68, 95% CI 0.39 to 1.20; RD -0.06, 95% CI -0.14 to 0.02; I2 = 17% for RR and 53% for RD).

Authors' conclusions: The undisputable results of the INIS trial, which enrolled 3493 infants, and our meta-analyses (n = 3973) showed no reduction in mortality during hospital stay, or death or major disability at two years of age in infants with suspected or proven infection. Although based on a small sample size (n = 266), this update provides additional evidence that IgM-enriched IVIG does not significantly reduce mortality during hospital stay in infants with suspected infection. Routine administration of IVIG or IgM-enriched IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended. No further research is recommended.

PubMed Disclaimer

Conflict of interest statement

None

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 IVIG versus placebo or no intervention for suspected infection, outcome: 1.1 Mortality from any cause.
4
4
Forest plot of comparison: 1 IVIG versus placebo or no intervention for suspected infection at trial entry, outcome: 1.4 Death or major disability at 2 years corrected age.
5
5
Forest plot of comparison: 2 IVIG versus placebo or no intervention for proven infection at trial entry, outcome: 2.3 Death or major disability at 2 years corrected age.
6
6
Forest plot of comparison: 3 IVIG versus placebo for suspected or proven infection at trial entry, outcome: 3.7 Death or major disability at 2 years corrected age.
7
7
Forest plot of comparison: 4 IgM‐enriched IVIG for suspected infection at trial entry, outcome: 4.1 Mortality from any cause during initial hospitalisation.
1.1
1.1. Analysis
Comparison 1 IVIG versus placebo or no intervention for suspected infection at trial entry, Outcome 1 Mortality from any cause during initial hospitalisation.
1.2
1.2. Analysis
Comparison 1 IVIG versus placebo or no intervention for suspected infection at trial entry, Outcome 2 Length of hospital stay.
1.3
1.3. Analysis
Comparison 1 IVIG versus placebo or no intervention for suspected infection at trial entry, Outcome 3 Death at 2 years corrected age.
1.4
1.4. Analysis
Comparison 1 IVIG versus placebo or no intervention for suspected infection at trial entry, Outcome 4 Death or major disability at 2 years corrected age.
2.1
2.1. Analysis
Comparison 2 IVIG versus placebo or no intervention for proven infection at trial entry, Outcome 1 Mortality from any cause during hospital stay.
2.2
2.2. Analysis
Comparison 2 IVIG versus placebo or no intervention for proven infection at trial entry, Outcome 2 Death at 2 years corrected age.
2.3
2.3. Analysis
Comparison 2 IVIG versus placebo or no intervention for proven infection at trial entry, Outcome 3 Death or major disability at 2 years corrected age.
3.1
3.1. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 1 Mortality from any cause during hospital stay.
3.2
3.2. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 2 Use of supplemental oxygen on day 28.
3.3
3.3. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 3 Major cerebral abnormality.
3.4
3.4. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 4 Necrotizing enterocolitis (new episode).
3.5
3.5. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 5 Duration of hospital stay (days).
3.6
3.6. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 6 Death at 2 years corrected age.
3.7
3.7. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 7 Death or major disability at 2 years (corrected age).
3.8
3.8. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 8 Nonmajor disability at 2 years corrected age.
3.9
3.9. Analysis
Comparison 3 IVIG versus placebo for suspected or proven infection at trial entry, Outcome 9 Major disability at 2 years corrected age.
4.1
4.1. Analysis
Comparison 4 IgM‐enriched IVIG for suspected infection at trial entry, Outcome 1 Mortality from any cause during initial hospitalisation.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Ahmed 2006 {published data only}
    1. Ahmed SS, Chowdhury MAKA, Hoque MM, Begum D, Ahmed ASMNU. Role of intravenous immunoglobulin (IVIG) as an adjuvant in the treatment of neonatal sepsis in preterm babies. Journal of Bangladesh College of Physicians and Surgeons 2006;24(3):97‐104.
Akdag 2014 {published data only}
    1. Akdag A, Dilmen U, Haque K, Dilli D, Erdeve O, Goekmen T. Role of pentoxifylline and/or IgM enriched intravenous immunoglobulin in the management of neonatal sepsis. American Journal of Perinatology 2014;31(10):905‐12. [PUBMED: 24515621] - PubMed
Christensen 1991 {published data only}
    1. Christensen RD, Brown MS, Hall DC, Lassiter HA, Hill HR. Effect of neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early‐onset sepsis. Journal of Pediatrics 1991;118(4 Pt 1):606‐14. [PUBMED: 1901083] - PubMed
Erdem 1993 {published and unpublished data}
    1. Erdem G, Yurdakök M, Tekinalp G, Ersoy F. The use of IgM‐enriched intravenous immunoglobulin for the treatment of neonatal sepsis in preterm infants. Turkish Journal of Pediatrics 1993;35(4):277‐81. [PUBMED: 8160279] - PubMed
Haque 1988 {published and unpublished data}
    1. Haque KN, Zaidi MH, Bahakim H. IgM‐enriched intravenous immunoglobulin therapy in neonatal sepsis. American Journal of Diseases of Children 1988;142(12):1293‐6. [PUBMED: 3195529] - PubMed
INIS 2011 {published data only}
    1. INIS Collaborative Group, Brocklehurst P, Farrell B, King A, Juszczak E, Darlow B, et al. Treatment of neonatal sepsis with intravenous immune globulin. New England Journal of Medicine 2011;365(13):1201‐11. [PUBMED: 21962214] - PubMed
Samatha 1997 {published data only}
    1. Samatha S, Jalalu MP, Hegde RK, Vishwanath D, Maiya PP. Role of IgM enriched intravenous immunoglobulin as an adjuvant to antibiotics in neonatal sepsis. Karnataka Pediatric Journal 1997;11:1‐6.
Shenoi 1999 {published and unpublished data}
    1. Shenoi A, Nagesh NK, Maiya PP, Bhat SR, Rao SD. Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis. Indian Pediatrics 1999;36(11):1113‐8. [PUBMED: 10745332] - PubMed
Sidiropoulos 1981 {published data only}
    1. Sidiropoulos D, Boehme U, Muralt G, Morell A, Barandun S. Immunoglobulin supplementation in prevention or treatment of neonatal sepsis. Pediatric Infectious Disease 1986;5(3 Suppl):S193‐4. [PUBMED: 3714523] - PubMed
    1. Sidiropoulos D, Bohme U, Muralt G, Morell A, Barandun S. Immunoglobulin substitution in the treatment of neonatal septicemia [Immunoglobulinsubstitution bei der Behandlung der neonatalen Sepsis]. Schweizerische Medizinische Wochenschrift 1981;111(44):1649‐55. [PUBMED: 7302548] - PubMed

References to studies excluded from this review

Chen 1996 {published data only}
    1. Chen J‐Y. Intravenous immunoglobulin in the treatment of full‐term and premature newborns with sepsis. Journal of the Formosan Medical Association 1996;95(11):839‐44. [PUBMED: 8990771] - PubMed
Gökalp 1994 {published and unpublished data}
    1. Gökalp AS, Toksoy HB, Tũrkay S, Bakici MZ, Kaya R. Intravenous immunoglobulin in the treatment of Salmonella typhimurium infections in preterm neonates. Clinical Pediatrics 1994;33(6):349‐52. [PUBMED: 8200169] - PubMed
Haque 1995 {published data only}
    1. Haque KN, Remo C, Bahakim H. Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis. Clinical and Experimental Immunology 1995;101:328‐33. [PUBMED: 7648717] - PMC - PubMed
Mancilla‐R 1992 {published and unpublished data}
    1. Mancilla‐Ramirez J, Gonzalez‐Yunes R, Castellanos‐Cruz C, Garcia‐Roca P, Santos‐Preciado JI. Intravenous immunoglobulin in the treatment of neonatal septicemia [Immunoglobulina intravenosa en el tratamiento de septicemia neonatal]. Boletín Médico del Hospital Infantil de México 1992;49(1):4‐11. [PUBMED: 1304766] - PubMed
Salihoglu 2013 {published data only}
    1. Salihoglu Ö, Can E, Koç MÖ, Durmus E, Hatipoglu S. Pentaglobin as an adjunct therapy in very low birthweight neonates with nosocomial sepsis. Journal of the Pakistan Medical Association 2013;63(11):1353‐7. - PubMed
Weisman 1992 {published data only}
    1. Weisman LE, Stoll B, Kuesar T, Rubio T, Frank G, Heiman H. Intravenous immunoglobulin (IVIG) therapy of neonatal sepsis. Pediatric Research 1990;27:277A.
    1. Weisman LE, Stoll BJ, Kueser TJ, Rubio TT, Frank CG, Heiman HS, et al. Intravenous immune globulin therapy for early‐onset sepsis in premature neonates. Journal of Pediatrics 1992;121(3):434‐43. [PUBMED: 1517923] - PubMed

Additional references

Alejandria 2001
    1. Alejandria MM, Lansang MA, Dans LF, Mantaring JBV. Intravenous immunoglobulin for treating sepsis or septic shock. Cochrane Database of Systematic Reviews 2002, Issue 1. [DOI: 10.1002/14651858.CD001090; PUBMED: 11869591] - DOI - PubMed
Alejandria 2013
    1. Alejandria MM, Lansang MAD, Dans LF, Mantaring III JB. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database of Systematic Reviews 2013, Issue 9. [DOI: 10.1002/14651858.CD001090.pub2; PUBMED: 24043371] - DOI - PMC - PubMed
Baker 1990
    1. Baker CJ. New uses of intravenous immune globulin in newborn infants. Journal of Clinical Immunology 1990;10 Suppl:47S‐55S. [PUBMED: 2081789] - PubMed
Baley 1988
    1. Baley JE. Neonatal sepsis: the potential for immunotherapy. Clinics in Perinatology 1988;15(4):755‐71. [PUBMED: 3061698] - PubMed
Baley 1992
    1. Baley JE, Fanaroff AA. Neonatal infections, Part 2: Specific infectious diseases and therapies. In: Sinclair JC, Bracken MB editor(s). Effective Care of the Newborn Infant. Oxford: Oxford University Press, 1992:477‐506.
Franco 2012
    1. Franco AC, Torrico AC, Moreira FT, Sá FP, D'Elia HV, Bernardo WM. Adjuvent use of intravenous immunoglobulin in the treatment of neonatal sepsis: a systematic review with meta‐analysis. Jornal de Pediatria (Rio J) 2012;88(5):377‐83. [PUBMED: 23002082] - PubMed
Friedman 1990
    1. Friedman CA, Wender DF, Temple DM, Rawson JE. Intravenous gamma globulin as adjunct therapy for severe group B streptococcal disease in the newborn. American Journal of Perinatology 1990;7(1):1‐4. [PUBMED: 2104748] - PubMed
Haque 1997
    1. Haque K. Should intravenous immunoglobulins be used in the treatment of neonatal sepsis?. British Journal of Intensive Care 1997;7:12‐6.
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [PUBMED: 12958120] - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. www.cochrane‐handbook.org, [updated March 2011].
Hozo 2005
    1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BioMed Central Medical Research Methodology 2005;5:13. [PUBMED: 15840177] - PMC - PubMed
INIS 2008
    1. INIS Study Collaborative Group. The International Neonatal Immunotherapy Study: non‐specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: an international, placebo controlled, multicentre randomised trial. BioMed Central Pregnancy and Childbirth 2008;8:52. [PUBMED: 19063731] - PMC - PubMed
Jenson 1997
    1. Jenson HB, Pollock BH. Meta‐analyses of the effectiveness of intravenous immune globulin for prevention and treatment of neonatal sepsis. Pediatrics 1997;99(2):e2. [PUBMED: 9099759] - PubMed
Jenson 1998
    1. Jenson HB, Pollock BH. The role of intravenous immunoglobulin for the prevention and treatment of neonatal sepsis. Seminars in Perinatology 1998;22(1):50‐63. [PUBMED: 9523399] - PubMed
Lacy 1995
    1. Lacy JB, Ohlsson A. Administration of intravenous immunoglobulins for prophylaxis or treatment of infection in preterm infants: meta‐analyses. Archives of Disease in Childhood 1995;72(3):F151‐5. [PUBMED: 7796228] - PMC - PubMed
Ohlsson 2013a
    1. Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2013, Issue 7. [DOI: 10.1002/14651858.CD000361.pub3; PUBMED: 23821390] - DOI - PubMed
RevMan 2014 [Computer program]
    1. Version 5.3.3 Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3.3 Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2014.
Shah 2009
    1. Shah PS, Kaufman DA. Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD006449.pub2; PUBMED: 19370635] - DOI - PubMed
Stoll 1996a
    1. Stoll BJ, Gordon T, Korones SB, et al. Early‐onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. Journal of Pediatrics 1996;129(1):72‐80. [PUBMED: 8757565] - PubMed
Stoll 1996b
    1. Stoll BJ, Gordon T, Korones SB, et al. Late‐onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. Journal of Pediatrics 1996;129(1):63‐71. [PUBMED: 8757564] - PubMed

References to other published versions of this review

Ohlsson 1998b
    1. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database of Systematic Reviews 1998, Issue 4. [DOI: 10.1002/14651858.CD001239] - DOI - PubMed
Ohlsson 2001
    1. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates (Cochrane Review). Cochrane Database of Systematic Reviews 2001, Issue 3. [DOI: 10.1002/14651858.CD001239] - DOI - PubMed
Ohlsson 2004
    1. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD001239.pub2] - DOI - PubMed
Ohlsson 2010
    1. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database of Systematic Reviews 2010, Issue 3. [DOI: 10.1002/14651858.CD001239.pub3] - DOI - PubMed
Ohlsson 2013
    1. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane Database of Systematic Reviews 2013, Issue 7. [DOI: 10.1002/14651858.CD001239.pub4] - DOI - PubMed

Substances

LinkOut - more resources