Headline
Enteral feeding was associated with a lower risk of necrotising enterocolitis whereas parenteral nutrition gave a higher rate of late-onset infection but with lower mortality, and a randomised controlled trial is recommended.
Abstract
Background:
Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic–ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia.
Objectives:
To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection.
Design:
A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis.
Setting:
NHS neonatal units in England, Wales and Scotland.
Participants:
Babies born at ≥ 36 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment.
Interventions:
Enteral feeding analysis – babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis – babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control).
Outcome measures:
Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth.
Results:
A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising enterocolitis, and further comparative analyses were not conducted on this outcome. A total of 3236 babies were included in the matched enteral feeding analysis. Pragmatically defined necrotising enterocolitis was rare in both groups (0.5% vs. 1.1%) and was lower in babies who were fed during hypothermia (rate difference –0.5%, 95% confidence interval –1.0% to –0.1%; p = 0.03). Higher survival to discharge (96.0% vs. 90.8%, rate difference 5.2%, 95% confidence interval 3.9% to 6.6%; p < 0.001) and higher breastfeeding at discharge (54.6% vs. 46.7%, rate difference 8.0%, 95% confidence interval 5.1% to 10.8%; p < 0.001) rates were observed in enterally fed babies who also had a shorter neonatal stay (mean difference –2.2 days, 95% confidence interval –3.0 to –1.2 days). A total of 2480 babies were included in the matched parenteral nutrition analysis. Higher levels of late-onset bloodstream infection were seen in babies who received parenteral nutrition (0.3% vs. 0.9%, rate difference 0.6%, 95% confidence interval 0.1% to 1.2%; p = 0.03). Survival was lower in babies who did not receive parenteral nutrition (90.0% vs. 93.1%, rate difference 3.1%, 95% confidence interval 1.5% to 4.7%; p < 0.001).
Limitations:
Propensity score methodology can address imbalances in observed confounders only. Residual confounding by unmeasured or poorly recorded variables cannot be ruled out. We did not analyse by type or volume of enteral or parenteral nutrition.
Conclusions:
Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia, and the introduction of enteral feeding is associated with a lower risk of pragmatically defined necrotising enterocolitis and other beneficial outcomes, including rates of higher survival and breastfeeding at discharge. Receipt of parenteral nutrition during therapeutic hypothermia is associated with a higher rate of late-onset infection but lower mortality. These results support introduction of enteral feeding during therapeutic hypothermia.
Future work:
Randomised trials to assess parenteral nutrition during therapeutic hypothermia.
Trial registration:
Current Controlled Trials ISRCTN474042962.
Funding:
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 36. See the NIHR Journals Library website for further project information.
About the Series
Health Technology Assessment
ISSN (Print): 1366-5278
ISSN (Electronic): 2046-4924
Declared competing interests of authors: Chris Gale reports grants from the Medical Research Council (MRC) (London, UK) and the National Institute for Health Research (NIHR) during the conduct of the study, and grants from NIHR, Mason Medical Research Foundation (London, UK), Rosetrees Trust (Edgeware, UK) and from the Canadian Institute for Health Research (Ottawa, ON, Canada), outside the submitted work. He reports a grants from Chiesi Pharmaceuticals (Parma, Italy) outside the submitted work for a research study and a personal fee from Chiesi Pharmaceuticals to support attendance at an educational meeting. Chris Gale is vice chairperson of the NIHR Research for Patient Benefit London Regional Assessment Panel (2016–present). Chris Gale was an unremunerated member of the Neonatal Data Analysis Unit Steering Board that oversees the National Neonatal Research Database (2014–20). Cheryl Battersby reports personal fees from AbbVie Pharmaceuticals (Maidenhead, UK) and Chiesi Pharmaceuticals, outside the submitted work. Cheryl Battersby sits on the NIHR Health Technology Assessment (HTA) Prioritisation Panel for Maternal, Child and Mental Health Care (2019–present) Cheryl Battersby is an unremunerated member of the National Neonatal Research Database Steering Board (April 2020 to present). Shalini Ojha reports grants from the MRC and the Arts and Humanities Research Council (Swindon, UK), outside the work. Jon Dorling reports grants from Nutrinia Ltd (Ramat Gan, Israel), outside the submitted work. The grant from Nutrinia Ltd in 2018 was for part of his salary to work as an expert advisor on a trial. He was a member of the NIHR HTA General Board (2017–18) and the NIHR HTA, Newborn and Child Health Panel (2013–18). Nicholas Longford’s post is in part funded by the Healthcare Quality Improvement Programme (London, UK) as part of the National Neonatal Audit Programme (London, UK). Nicholas Longford reports grants from Chiesi Pharmaceuticals, outside the submitted work.
Last reviewed: December 2019; Accepted: June 2020.
