Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study
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Author(s)
Type
Journal Article
Abstract
Background:
Therapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.
Methods:
We did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.
Findings:
6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2–0·9] in the fed group vs 1·1% [0·7–1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference −11·6% [95% CI −14·0 to −9·3]; p<0·0001), higher survival to discharge (5·2% [3·9–6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1–10·8]; p<0·0001), and shorter neonatal unit stays (−2·2 [–3·0 to −1·2] days; p<0·0001) compared with the unfed group.
Interpretation:
Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia.
Funding:
UK National Institute for Health Research Health Technology Assessment programme 16/79/13.
Therapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.
Methods:
We did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.
Findings:
6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2–0·9] in the fed group vs 1·1% [0·7–1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference −11·6% [95% CI −14·0 to −9·3]; p<0·0001), higher survival to discharge (5·2% [3·9–6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1–10·8]; p<0·0001), and shorter neonatal unit stays (−2·2 [–3·0 to −1·2] days; p<0·0001) compared with the unfed group.
Interpretation:
Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia.
Funding:
UK National Institute for Health Research Health Technology Assessment programme 16/79/13.
Date Issued
2021-06-01
Date Acceptance
2021-01-26
Citation
The Lancet Child and Adolescent Health, 2021, 5 (6), pp.408-416
ISSN
2352-4642
Publisher
Elsevier
Start Page
408
End Page
416
Journal / Book Title
The Lancet Child and Adolescent Health
Volume
5
Issue
6
Copyright Statement
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY 4.0 license (https://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000653480600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Pediatrics
ENCEPHALOPATHY
Publication Status
Published
Date Publish Online
2021-04-21