Hypothermia for moderate or severe neonatal encephalopathy in low and middle-income countries (HELIX): a randomised control trial in India, Sri Lanka and Bangladesh
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low- and middle-income countries (LMICs) remains unclear. We examined if therapeutic hypothermia alongside optimal supportive intensive care reduces death or disability after neonatal encephalopathy in South Asia. Methods: We conducted a multi-country open label randomised controlled trial involving seven tertiary neonatal intensive care units in India, Sri Lanka and Bangladesh, between August 2015 and September 2020. We allocated infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy into whole body hypothermia (33·5 0 C) for 72 hours using a servo-controlled cooling device, or usual care (control group), within six hours of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support and access to 3 Telsa magnetic resonance imaging and spectroscopy. The primary outcome was a combined end point of death or moderate or severe disability at 18 to 22 months of age, assessed by Bayley scales of infant development (Version III).Findings: Of 576 eligible infants, we assigned 202 to hypothermia and 206 to control group. Primary outcome data were available for 394 (96·5%) infants, and occurred in 98(50·3%) of the hypothermia and 94 (47·2%) of the control group (Risk Ratio (RR) 1·06;95% confidence intervals (CI) 0·87 to 1·30 (p = 0·55). Eighty-four infants (42·4%) in the hypothermia group and 63 (31·3%) (p = 0·02) infants in the control group died, of whom 72 (35·6%) and 49 (23·8%) (p = 0·009) died during neonatal hospitalisation. Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at18 months after neonatal encephalopathy in LMICs, but significantly increased mortality. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in LMICs even when tertiary neonatal intensive care facilities are available.
Date Issued
2021-09
Date Acceptance
2021-05-27
Citation
The Lancet Global Health, 2021, 9 (9), pp.e1273-e1285
ISSN
2214-109X
Publisher
Elsevier
Start Page
e1273
End Page
e1285
Journal / Book Title
The Lancet Global Health
Volume
9
Issue
9
Copyright Statement
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
License URL
Sponsor
Medical Research Council (MRC)
National Institute for Health Research
National Institute for Health Research
National Institute for Health Research
Identifier
https://www.sciencedirect.com/science/article/pii/S2214109X21002643?via%3Dihub
Grant Number
MR/R001375/1
NIHR200144
NIHR300118
NIHR301082
Subjects
Bangladesh
Brain Diseases
Developing Countries
Female
Humans
Hypothermia, Induced
India
Infant, Newborn
Intensive Care, Neonatal
Male
Severity of Illness Index
Sri Lanka
Treatment Outcome
HELIX consortium
Humans
Brain Diseases
Treatment Outcome
Intensive Care, Neonatal
Hypothermia, Induced
Severity of Illness Index
Developing Countries
Infant, Newborn
Bangladesh
India
Sri Lanka
Female
Male
0605 Microbiology
1117 Public Health and Health Services
Publication Status
Published
Date Publish Online
2021-08-03