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The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis

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Abstract

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61–0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate–high risk of bias was largely due to inadequate sample sizes and follow-up durations.

Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate–high risk of bias and heterogeneity.

Trial registration: PROSPERO (CRD42020176629) (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629)

What is Known:

• Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis.

What is New:

• The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

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Abbreviations

AMR:

Antimicrobial resistance

CCF:

Congestive cardiac failure

CI:

Confidence intervals

CSF:

Cerebrospinal fluid

DVET:

Double volume exchange transfusion

ET:

Exchange Transfusion

GBS:

Group B streptococci

G-CSF:

Granulocyte colony stimulating factor

GM-CSF:

Granulocyte monocyte colony stimulation factor

HMD:

Hyaline membrane disease

NHLBI:

National Heart, Lung and Blood Institute

NOS:

Newcastle-Ottawa Scale

PDA:

Patent ductus arteriosus

RCT:

Randomized controlled trial

RR:

Risk ratio

SMD:

Standardized mean difference

SVET:

Single volume exchange transfusion

TRALI:

Transfusion-related acute lung injury

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Acknowledgements

Thank you to Dr. Nishad Plakkal (Associate Professor, Neonatology, JIPMER) for reviewing our manuscript and providing invaluable insight and suggestions.

Author information

Author notes

  1. Carl Britto, Suman Rao are joint senior authors on this paper.

Authors and Affiliations

  1. St. John’s Medical College, St. John’s National Academy of Health Sciences, Bangalore, India

    Sitarah Mathias, Bharathi Balachander, Ashish Bosco & Suman Rao

  2. Department of Neonatology, St. John’s Medical College and Hospital, St. John’s National Academy of Health Sciences, Bangalore, 560034, India

    Bharathi Balachander & Suman Rao

  3. Department of Infectious Disease, St. John’s Research Institute, Bangalore, India

    Carl Britto

  4. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK

    Carl Britto

  5. Boston Children’s Hospital, Boston, USA

    Carl Britto

  6. Consultant, Division of Department of Maternal, Newborn and Adolescent Health, World Health Organisation, Geneva, Switzerland

    Suman Rao

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  1. Sitarah Mathias
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Contributions

Prof. S. Rao conceptualized the study and critically reviewed the manuscript for intellectual content, Dr. Britto designed the study, carried out the meta-analysis, assessment of publication bias and graphical representation of data; drafted the initial manuscript; and reviewed and revised the final manuscript, Drs. Balachander and Bosco conducted the search for articles and reviewed the manuscript. Dr Balachander was also involved in analysis and critically reviewed the manuscript for intellectual content, Dr. Mathias conducted the search for articles, designed the data collection instruments and extracted relevant data from the articles; carried out the descriptive analysis, assessment of study quality and risk of bias; drafted the initial manuscript; and reviewed and revised the final manuscript.

Corresponding author

Correspondence to Bharathi Balachander.

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Ethics approval

Since it is a meta-analysis, ethics approval was not sought.

Consent for participation

No human subjects were enrolled as part of the study. A meta-analysis was done.

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All authors have scrutinized the manuscript and consent to publish.

Conflict of interest

The authors declare no competing interests.

Table of contents summary

The role of exchange transfusion is unclear in neonatal sepsis. Based on this meta-analysis exchange transfusion is not directly recommended for neonatal sepsis given the heterogeneity and high risk of bias. Exchange transfusion may be considered on a case-basis in centres with adequate monitoring facilities.

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Communicated by Daniele De Luca

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Mathias, S., Balachander, B., Bosco, A. et al. The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis. Eur J Pediatr 181, 369–381 (2022). https://doi.org/10.1007/s00431-021-04194-w

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  • DOI: https://doi.org/10.1007/s00431-021-04194-w

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