Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study

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.

10.1016/S2352-4642(21)00026-2

2352-4650

408-416

Gale, Chris

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Longford, Nicholas T.

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Jeyakumaran, Dusha

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Ougham, Kayleigh

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Battersby, Cheryl

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Ojha, Shalini

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Dorling, Jon

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18 May 2021

Gale, Chris

210b7c81-9a39-460a-9ab3-54fe92a69f8e

Longford, Nicholas T.

2f3303da-6aa2-49e7-bb14-df151389aee2

Jeyakumaran, Dusha

4af51f70-a8d5-42db-a5c9-5dfbf703a274

Ougham, Kayleigh

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Battersby, Cheryl

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Ojha, Shalini

adc62cc2-df92-446f-8ad2-4c0cf006d689

Dorling, Jon

e55dcb9a-a798-41a1-8753-9e9ff8aab630

Gale, Chris, Longford, Nicholas T., Jeyakumaran, Dusha, Ougham, Kayleigh, Battersby, Cheryl, Ojha, Shalini and Dorling, Jon (2021) Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study. The Lancet Child and Adolescent Health, 5 (6), 408-416. (doi:10.1016/S2352-4642(21)00026-2).

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e-pub ahead of print date: 21 April 2021

Published date: 18 May 2021

Additional Information: Funding Information: This study was funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment programme (16/79/13). The funder had no role in designing the study, the collection, analysis, or interpretation of the data, or in the writing of this Article. Electronic patient data recorded at participating neonatal units that collectively form the UK Neonatal Collaborative are transmitted to the UK Neonatal Data Analysis Unit (NDAU) to form the NNRD; UK Neonatal Collaborative leads are listed in the appendix (pp 15–17 ). We thank the families that agreed to the inclusion of their infants' data in the NNRD, the health professionals who recorded the data, and Richard Colquhoun and Surbhi Shah at the NDAU for data extraction and administrative support. CG is supported by grants from the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) and UK Medical Research Council (MRC), and is vice chair of NIHR Research for Patient Benefit London Panel. CB is supported by grants from the NIHR and is deputy chair of the NIHR HTA Prioritisation Committee: Hospital Based Care. SO was supported by grants from NIHR and MRC during the study. JD is supported by grants from the NIHR HTA during the study. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care. This research was funded by the NIHR HTA programme 16/79/13.