Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2019

Open Access 01-12-2019 | Septicemia | Research article

Effects of immunotherapy on mortality in neonates with suspected or proven sepsis: a systematic review and network meta-analysis

Authors: Yuhang Li, Shulong Yang, Guiyue Wang, Miao Liu, Zhaodi Zhang, Haitao Liu, Kaijiang Yu, Changsong Wang

Published in: BMC Pediatrics | Issue 1/2019

Login to get access

Abstract

Background

To investigate the efficacies of different immunotherapies in neonates with suspected or proven sepsis.

Methods

We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2019 that investigated different immunotherapies in neonates with suspected or proven sepsis. Comparisons were among immunotherapies and between immunotherapy and placebo. The review was registered in the PROSPERO CRD database.

Results

All-cause mortality was not significantly different between patients who received the immunoglobulin (IgG), IgM-enriched immunoglobulin (IgGAM), granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) immunotherapies and those who received placebo. The RRs of the immunotherapies were 0.80 (95% CI: 0.57 to 1.1), 0.45 (95% CI: 0.17 to 1.0), 0.93 (95% CI: 0.64 to 1.2) and 0.67 (95% CI: 0.39 to 1.1), respectively. Compared with placebo, none of the interventions showed statistically significant differences in the duration of hospital stay. The MDs of the immunotherapies were − 2.7 (95% CI: − 8.4 to 3.5), − 0.18 (95% CI: − 7.3 to 7.7), − 1.7 (95% CI: − 7.3 to 3.9) and − 7.2 (95% CI: − 28 to 13), respectively.

Conclusions

No significant differences in all-cause mortality or the duration of hospital stay were found in neonates with suspected or proven sepsis treated with the four types of immunotherapies and those treated with placebo.
Appendix
Available only for authorised users
Literature
1.
Shane AL, Stoll BJ. Neonatal sepsis: progress towards improved outcomes. J Inf Secur. 2014;68(Suppl 1):S24–32.
2.
Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60:367–89.CrossRef
3.
Wynn JL, Wong HR, Shanley TP, Bizzarro MJ, Saiman L, Polin RA. Time for a neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med. 2014;15:523–8.CrossRef
4.
Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390(10104):1770–80.CrossRef
5.
Wynn JL, Scumpia PO, Winfield RD, Delano MJ, Kelly-Scumpia K, Barker T, et al. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood. 2008;112:1750–8.CrossRef
6.
7.
Kollmann TR, Crabtree J, Rein-Weston A, Blimkie D, Thommai F, Wang XY, et al. Neonatal innate TLR-mediated responses are distinct from those of adults. J Immunol. 2009;183:7150–60.CrossRef
8.
Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007;7:379–90.CrossRef
9.
Rieben R, Roos A, Muizert Y, Tinguely C, Gerritsen AF, Daha MR. Immunoglobulin M-enriched human intravenous immunoglobulin prevents complement activation in vitro and in vivo in a rat model of acute inflammation. Blood. 1999;93(3):942–51.PubMed
10.
Oesser S, Schulze C, Seifert J. Protective capacity of a IgM/IgA-enriched polyclonal immunoglobulin-G preparation in endotoxemia. Res Exp Med (Berl). 1999;198(6):325–39.CrossRef
11.
Khassawneh M, Hayajneh WA, Kofahi H, Khader Y, Amarin Z, Daoud A. Diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6 and immunoglobulin M. Scand J Immunol. 2007;65(2):171–5.CrossRef
12.
Liu J, Zhu H, Qian J, Xiong E, Zhang L, Wang YQ, Chu Y, Kubagawa H, Tsubata T, Wang JY. Fcμ Receptor Promotes the Survival and Activation of Marginal Zone B Cells and Protects Mice against Bacterial Sepsis. Front Immunol. 2018;5;9:160.
13.
Dale DC, Liles WC, Summer WR, Nelson S. Review: granulocyte colony-stimulating factor--role and relationships in infectious diseases. J Infect Dis. 1995;172(4):1061–75.CrossRef
14.
Iguchi K, Inoue S, Kumar A. Effect of recombinant human granulocyte colony-stimulating factor administration in normal and experimentally infected newborn rats. Exp Hematol. 1991;19(5):352–8.PubMed
15.
Mathias B, Szpila BE, Moore FA, Efron PA, Moldawer LL. A Review of GM-CSF Therapy in Sepsis. Medicine (Baltimore). 2015;94(50):e2044.CrossRef
16.
Carr R, Modi N, Doré CJ, El-Rifai R, Lindo D. A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation. Pediatrics. 1999;103:796–802.CrossRef
17.
INIS Collaborative Group, Brocklehurst P, Farrell B, King A, et al. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med. 2011;365(13):1201–11.CrossRef
18.
Gathwala G, Walia M, Bala H, Singh S. Recombinant human granulocyte colony-stimulating factor in pretermneonates with sepsis and relative neutropenia: a randomized, single-blind, non-placebo-controlled trial. J Trop Pediatr. 2012;58(1):12–8.CrossRef
19.
Kreymann KG, de Heer G, Nierhaus A, Kluge S. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med. 2007;35(12):2677–85.PubMed
20.
Franco AC, Torrico AC, Moreira FT, Sá FP, D'Elia HV, Bernardo WM. Adjuvant use of intravenous immunoglobulin in the treatment of neonatal sepsis: a systematic review with a meta-analysis. J Pediatr. 2012;88(5):377–83.
21.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.CrossRef
22.
Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin N Am. 2004;51:939–59 viii–ix.CrossRef
23.
Benitz WE. Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis. Clin Perinatol. 2010;37:421–38.CrossRef
24.
Cantey JB, Wozniak PS, Sanchez PJ. Prospective surveillance of antibiotic use in the neonatal intensive care unit: results from the SCOUT study. Pediatr Infect Dis J. 2015;34:267–72.CrossRef
25.
Hornik CP, Fort P, Clark RH, et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev. 2012;88(Suppl 2):S69–74.CrossRef
26.
Adhikari M, Coovadia HM, Gaffin SL, Brock-Utne JG, Marivate M, Pudifin DJ. Septicaemic low birthweight neonates treated with human antibodies to endotoxin. Arch Dis Child. 1985;60(4):382–4.CrossRef
27.
Ahmad A, Laborada G, Bussel J, Nesin M. Comparison of recombinant granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor and placebo for treatment of septic preterm infants. Pediatr Infect Dis J. 2002;21(11):1061–5.CrossRef
28.
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(3):97–104.CrossRef
29.
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. Am J Perinatol. 2014;31(10):905–12.CrossRef
30.
Aktaş D, Demirel B, Gürsoy T, Ovalı F. A randomized case-controlled study of recombinant human granulocyte colonystimulating factor for the treatment of sepsis in preterm neutropenic infants. Pediatr Neonatol. 2015;56(3):171–5.CrossRef
31.
Bedford Russell AR, Emmerson AJ, Wilkinson N, Chant T, Sweet DG, Halliday HL, Holland B, Davies EG. A trial of recombinant human granulocyte colony stimulating factor for thetreatment of very low birthweight infants with presumed sepsis andneutropenia. Arch Dis Child Fetal Neonatal Ed. 2001;84(3):F172–6.CrossRef
32.
Bilgin K, Yaramiş A, Haspolat K, Taş MA, Günbey S, Derman O. A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia. Pediatrics. 2001;107(1):36–41.CrossRef
33.
Borjianyazdi L, Froomandi M, Noori Shadkam M, Hashemi A, Fallah R. The effect of granulocyte colony stimulating factor administration on preterminfant with neutropeniaand clinical sepsis: a randomized clinical trial. Iran J Ped Hematol Oncol. 2013;3(2):64–8.PubMedPubMedCentral
34.
Chaudhuri J, Mitra S, Mukhopadhyay D, Chakraborty S, Chatterjee S. Granulocyte Colony-stimulating factor for Preterms with Sepsis and neutropenia: a randomized controlled trial. J Clin Neonatol. 2012;1(4):202–6.CrossRef
35.
Chen JY. Intravenous immunoglobulin in the treatment of full-term and premature newborns with sepsis. J Formos Med Assoc. 1996;95(11):839–44.PubMed
36.
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(4 Pt 1):606–14.CrossRef
37.
Drossou-Agakidou V, Kanakoudi-Tsakalidou F, Sarafidis K, Taparkou A, Tzimouli V, Tsandali H, et al. Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression. Results of a randomized controlled trial. Eur J Pediatr. 1998;157(7):583–8.CrossRef
38.
Drossou-Agakidou V, Kanakoudi-Tsakalidou F, Sarafidis K, Tzimouli V, Taparkou A, Kremenopoulos G, et al. In vivo effect of rhGM-CSF and rhG-CSF on monocyte HLA-DR expression of septic neonates. Cytokine. 2002;18(5):260–5.CrossRef
39.
El-Ganzoury MM, El-Farrash RA, Saad AA, Mohamed AG, El-Sherbini IG. In vivo effect of recombinant human granulocyte colony-stimulating factor onneutrophilic expression of CD11b in septic neonates: a randomized controlledtrial. Pediatr Hematol Oncol. 2012;29(3):272–84.CrossRef
40.
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(4):277–81.PubMed
41.
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(1):39–42.CrossRef
42.
Haque KN, Zaidi MH, Bahakim H. IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis. Am J Dis Child. 1988;142(12):1293–6.PubMed
43.
Haque KN, Remo C, Bahakim H. Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis. Clin Exp Immunol. 1995;101(2):328–33.CrossRef
44.
Kücüködük S, Sezer T, Yildiran A, Albayrak D. Randomized, double-blinded, placebo-controlled trial of early administration ofrecombinant human granulocyte colony-stimulating factor to non-neutropenicpreterm newborns between 33 and 36 weeks with presumed sepsis. Scand J Infect Dis. 2002;34(12):893–7.CrossRef
45.
Mancilla-Ramirez J, Gonzalez-Yunes R, Castellanos-Cruz C, Garcia-Roca P, Santos-Preciado JI. Intravenous immunoglobulin in the treatment of neonatal septicemia. Bol Med Hosp Infant Mex. 1992;49(1):4–11.PubMed
46.
Miura E, Procianoy RS, Bittar C, Miura CS, Melo C, Miura MS. Assessing the efficacy of the recombinant human granulocyte colony-stimulating factor "rhG-CSF" in the treatment of early neonatal sepsis in premature neonates. J Pediatr. 2000;76(3):193–9.CrossRef
47.
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.
48.
Schibler KR, Osborne KA, Leung LY, Le TV, Baker SI, Thompson DD. A randomized, placebo-controlled trial of granulocyte colony-stimulating factoradministration to newborn infants with neutropenia and clinical signs of early-onset sepsis. Pediatrics. 1998;102(1 Pt 1):6–13.CrossRef
49.
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 Pediatr. 1999;36(11):1113–8.PubMed
50.
Sidiropoulos D, Bohme U, von Muralt G, Morell A, Barandun S. Immunoglobulin substitution in the treatment of neonatal septicemia. Schweiz Med Wochenschr. 1981;111(44):1649–55.PubMed
51.
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(3):434–43.CrossRef
52.
Ohlsson A, Lacy J. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev. 2010;17(3):CD001239.
53.
54.
55.
Bernstein HM, Pollock BH, Calhoun DA, Christensen RD. Administration of recombinant granulocyte colony-stimulating factor to neonates with septicemia: a meta-analysis. J Pediatr. 2001;138(6):917–20.CrossRef
56.
Busani S, Damiani E, Cavazzuti I, Donati A, Girardis M. Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness. Minerva Anestesiol. 2016;82(5):559–72.PubMed
Metadata
Title
Effects of immunotherapy on mortality in neonates with suspected or proven sepsis: a systematic review and network meta-analysis
Authors
Yuhang Li
Shulong Yang
Guiyue Wang
Miao Liu
Zhaodi Zhang
Haitao Liu
Kaijiang Yu
Changsong Wang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2019
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-019-1609-1

Other articles of this Issue 1/2019

BMC Pediatrics 1/2019 Go to the issue

Research article

Prevalence, risk factors and outcome of congenital anomalies among neonatal admissions in OGBOMOSO, Nigeria

Research article

Intravenous versus intravenous/oral antibiotics for perforated appendicitis in pediatric patients: a systematic review and meta-analysis

Research article

Prenatal and neonatal factors involved in the development of childhood allergic diseases in Guangzhou primary and middle school students

Correction

Correction to: Digenic inheritance of SLC12A3 and CLCNKB genes in a Chinese girl with Gitelman syndrome

Research article

ICU admission following an unscheduled return visit to the pediatric emergency department within 72 hours

Research article

Macronutrient content of pooled donor human milk before and after Holder pasteurization