Hamdan Medical Journal (previously the Journal of Medical Sciences)

Table of Contents  

Use of Intravenous Immunoglobulin in the Treatment of Neonatal Sepsis: A Pragmatic Review and Analysis

Khalid N Haque
Published in : Journal of Medical Sciences ; Vol 3, No 3 (2010)
DOI : 10.2174/1996327001003030160


Objective: To review literature and assess whether adjunctive therapy with polyclonal and or enriched intravenous immunoglobulin (IVIG) reduces mortality in neonates with sepsis.

Data Source: MEDLINE, EMBASE and Cochrane systematic review.

Study Selection: All studies published in English language evaluating IVIG treatment in neonatal sepsis. Data Synthesis: Effect of all cause mortality was quantified using fixed-effect meta-analysis.

Results: Fifteen studies published between 1986 and 2006 were identified of which fourteen reported mortality and were included in the analysis. Most studies involved small number of neonates, used different preparations and dosing regimens of IVIG, however, there was significant reduction in all cause mortality associated with use of IVIG in neonatal sepsis with pooled odds ratio of 0.41 (95% confidence interval 0.29-0.58) and a risk ratio of 0.52 (95% confidence interval 0.40- 0.67; p < 0.00001). There was no statistically significant difference between-study heterogeneity for the outcome of mortality in the two analyses. I2 = 0%. Number required to treat 7.

Conclusion: This analysis shows that addition of polyclonal or enriched IVIG as adjunct to standard therapy significantly reduces all cause mortality in neonatal sepsis.


Neonatal sepsis; IVIG; Polyclonal IgG Intravenous Immunoglobulin

View article in  :   PDF    


Lawn JE, Cousens S, Zupan J. Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet 2005; 365(9462): 891-900.

Ferrieri P. Neonatal susceptibility and immunity to major bacterial pathogens. Rev Infect Dis 1990; 12(Suppl 4): S394-400.

Haque KN. Year book of Intensive Care and Emergency Medicine. In: Vincent J L. Springer 2007; pp. 55-68.

Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neuro development and growth impairment among extremely low birth-weight infants with neonatal infections. JAMA 2004; 292: 2357-65.

Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson AM. Case control study of ante-natal intra-partum risk for CP in very term preterm babies. Lancet 1995; 346: 1449-54.

Mittendorf R, Covert R, Kohn J, Roizen N, Khoshnood B, Lee KS. The association of CONS isolated from chorioamnion at delivery and subsequent development of CP. J Perinatol 2001; 21: 3-8.

Dammann O, Leviton A. Infections remote from brain; neonatal white matter damage and CP in preterm infants. Semin Pediatr Neurol 1998; 5: 190-201.

Baley JE. Neonatal sepsis: the potential for immunotherapy. Clin Perinatol 1988; 15(4): 755-71.

Christensen RD, Brown MS, Hall DC, Lassiter HA, Hill HR. Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. J Pediatr 1991; 118 (4 Pt 1): 606-14.

Melvan JN, Bagby GJ, Welsh DA, Nelson S, Zhang P. Neonatal sepsis and neutrophil insufficiencies. Int Rev Immunol 2010; 29(3): 315-48.

Mohan PV, Tarnow-Mordi W, Stenson B, Brocklehurst P, Haque K, Cavendish V, et al. Can polyclonal intravenous immunoglobulin limit cytokine mediated cerebral damage and chronic lung disease in preterm infants? Arch Dis Child Fetal Neonatal Ed 2004; 89(1): F5-8.

Jenson HB, Pollock BH. Meta-analyses of the effectiveness of intravenous immune globulin for prevention and treatment of neonatal sepsis. Pediatrics

; 99: 216.

Haque KN. Should Intravenous Immunoglobulin be used in the treatment of neonatal sepsis? Br J Intensive Care 1997; 7: 12-7.

Alejandria MM, Lansang MA, Dans LF, Mantaring JB. Intravenous Immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev 2002; CD001090.

Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and/orvery low birth weight infants. Cochrane Database Syst Rev 2007; 1: CD000361.

Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2010; 3: CD001239.

Norby-Teglund A, Haque KN, Hammarstrom L. Intravenous polyclonal IgM- enriched immunoglobulin therapy in sepsis: a review of clinical efficacy in relation to microbiological aetiology and severity of sepsis. J Int Med 2006; 260: 509-16.

Kreymann KG, deHeer G, Nierhaus A, Kluge S. Use of polyclonal immunoglobulin’s as adjunctive therapy for sepsis or septic shock. Crit Care Med 2007; 35: 2677-85.

Light RJ, Pillemer DB. Summing up: The Science of Reviewing Research. Cambridge, Massachusetts: Harvard University Press 1984.

Egger M, Smith DG, Schneider M, Minder C. Bias in Meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 624-9.

Chen J-Y. Intravenous immunoglobulin in the treatment of full-term and premature newborns with sepsis. J Formos Med Assoc 1996; 95: 839-44.

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. J Pediatr 1991; 118: 606-14.

El-Nawawy A, El-Kinany H, Hamdy El-Sayed M, Boshra N. Intravenous polyclonal immunoglobulin administration to sepsis syndrome patients: A prospective study in a paediatric intensive care unit. J Trop Paed 2005; 51: 271-8.

Erdem G, Yurdakök M, Tekinalp G, Ersoy F. The use of IgM-enriched intravenous immunoglobulin for the treatment of neonatal sepsis in preterm infants. Turk J Pediatr 1993; 35: 277-81.

Gokalp AS, Toksoy HB, Turkay S, Bakici MZ, Kaya R. Intravenous immunoglobulin in the treatment of Salmonella typhimurium infections in preterm neonates. Clin Pediatr 1994; 33: 349-52.

Gunes T, Koklu E, Buyukkayhan D, Kurtoglu S, Karakukcu M, Patiroglu T. Exchange transfusion or intravenous immunoglobulin therapy as an adjunct to antibiotics for neonatal sepsis in developing countries: a pilot study. Ann Trop Paediatr 2006; 26: 39-42.

Haque KN, Zaidi MH, Bahakim H. IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis. Am J Dis Child 1988; 142: 1293-6.

Haque KN, Remo C, Bahakim H. Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis. Clin Exp Immunol 1995; 101: 328-33.

Mancilla-Ramirez J, Gonzalez-Yunes R, Castellanos- Cruz C, Garcia-Roca P, Santos-Preciado JI. Immunoglobulina intravenosa en el tratamiento de

septicemia neonatal. Bol Med Hosp Infant Mex 1992; 49: 4-11.

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 Pediatr J 1997; 11: 1-6.

Hellwege HH, Thuresson EM, Grosse R, Damman O, Seitz RC. IgM enriched intravenous immunoglobulin in the treatment of neonatal sepsis. J Neonatol 1997; 49: 44.

Shenoi A, Nagesh NK, Maiya PP, Bhat SR, Subba Rao SD. Multicentre randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis. Indian Pediatr 1999; 36: 1113-8.

Sidiropoulos D, Boehme U, von Muralt G, Morell A, Barandun S. Immunoglobulin supplementation in prevention or treatment of neonatal sepsis. Pediatr Inf Dis 1986; 5: S193-194.

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. J Pediatr 1992; 121: 434-43.

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. J Bangladesh Coll Phys Surg 2006; 24: 97-104.

Stoll BJ, Gordon T, Korones SB, Shankaran S, Tyson JE, Bauer CR, 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. J Pediatr 1996; 129: 72-80.

Escobar GJ. The neonatal ‘sepsis workup’: Personal reflections on the development of an evidence based approach toward newborn infections in a managed care organisation. Pediatrics 1999; 103: 360-73.

Beyry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV. Intravenous immunoglobulin for infectious diseases: back to pre-antibiotic and passive prophylaxis era. Trends Pharmacol 2004; 25: 306-10.

Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory disease with intravenous immunoglobulin. N Engl J Med 2001; 345: 745-55.

Andersson J, Skansen-Saphir U, Sparrelid E, Andersson U. Intravenous Immunoglobulin affects cytokine production in T lymphocytes and monocytes/macrophages. Clin Exp Immunol 1996; 104(Suppl 1): 10-20.

Aukrust P, Muller F, Svenson M, Nordoy I, Bendtzen K, Froland SS. Administration of intravenous immunoglobulin (IVIG) in vivo down regulatory effects of the IL-1 system. Clin Exp Immunol 1999; 115: 136-43.

Ross C, Svenson M, Hansen MB, Vejlsgaard GL, Bendtzen K. High avidity IFN-neutralizing antibodies in pharmaceutically prepared IgG. J Clin Invest 1995; 95: 1974-8.

Stangel M, Schumacher HC, Ruprecht K, Boegner F, Marx P. Immunoglobulin for intravenous use inhibit TNFAlpha cytotoxicity in vitro. Immunol Invest 1997; 26: 569-78.

Kondo N, Kasahara K, Kameyama T, Suzuki Y, Shimozawa N, Tomatsu S, et al. Intravenous immunoglobulins suppress immunoglobulin productions by suppressing Ca(2+)-dependent signal transduction through Fc gamma receptors in B lymphocytes. Scand J Immunol 1994; 40: 37-42.

Kaveri S, Vassilev T, Hurez V, Lengagne R, Lefranc C, Cot S, et al. Antibodies to a conserved to a region of HLA class I molecule, capable of modulating CD8 T cell mediated function are present in pooled normal immunoglobulin for therapeutic use. J Clin Invest 1996; 97: 865-9.

Teeling JL, De Groot ER, Eerenberg AJ, Bleeker WK, Van Mierlo G, Aarden LA, et al. Human Intravenous Immunoglobulin (IVIG) preparations degranulate human neutrophils in vitro. Clin Exp Immunol 1998; 114: 264-70.

Lutz HU, Stammler P, Jelezarova E, Nater M, Späth PJ. High doses of immunoglobulin G attenuate aggregate mediated complement activation by enhancing physiological cleavage of C3b in C3bn-IgG complexes. Blood 1996; 88: 184-93.

Kyllonen KS, Clapp DW, Kliegman RM, Baley JE, Shenker N, Fanaroff AA, Berger M. Dosage of intravenously administered immunoglobulin and dosing interval required to maintain target levels of immunoglobulin G in low birth weight infants. J Pediatrics 1989; 115(6): 1013-6.

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.

Jenson HB, Pollock BH. The role of Intravenous Immunoglobulin for prevention and treatment of neonatal sepsis. Semin Perinatol 1998; 22: 50-63.

Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF, et al. Improving the quality of reports of metaanalyses of randomized controlled trials: the QUOROM statement: Quality of reporting of meta-analyses. Lancet 1999; 354: 1896-900.

Add comment 

Home  Editorial Board  Search  Current Issue  Archive Issues  Announcements  Aims & Scope  About the Journal  How to Submit  Contact Us
Find out how to become a part of the HMJ  |   CLICK HERE >>
© Copyright 2012 - 2013 HMJ - HAMDAN Medical Journal. All Rights Reserved         Website Developed By Cedar Solutions INDIA