Abstract
SummaryBackgroundTherapeutic 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.MethodsWe 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.Findings6030 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.InterpretationNecrotising 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.FundingUK National Institute for Health Research Health Technology Assessment programme 16/79/13.
Highlights
Therapeutic hypothermia is standard of care in highincome countries for babies born at or after 36 weeks of gestational age with signs of hypoxic ischaemic encephalopathy.1 Optimal nutritional support for babies receiving therapeutic hypothermia is uncertain; previ ously published trials either did not specify nutritional management2 or stipulated that milk feeds should be withheld.3 In the absence of high-quality evidence, pro vision of enteral nutrition to infants during hypothermia is variable;4 withholding enteral feeds during therapeutic hypothermia is almost universal in some settings,5 whereas in other settings milk feeding is routine.6Milk feeds are withheld during therapeutic hypothermia partly to reduce the risk of necrotising enterocolitis
Between Jan 1, 2010, and Dec 31, 2017, 703 907 babies were admitted to National Health Service (NHS) neonatal units in England, Scotland, or Wales; 6030 were at least 36 weeks of gestational age and treated with therapeutic hypothermia for 3 days or died during treatment. 1873 (31·1%) of 6030 received enteral feeds during therapeutic hypothermia; this proportion changed only slightly between 2010 and 2017
In the total study cohort of babies, and before matching, seven (0·1%) of 6030 babies that received therapeutic hypothermia were diagnosed with severe necrotising enterocolitis, and 68 (1·1%) of 6030 were classified as having necrotising enterocolitis using the pragmatic definition. 30 (0·5%) of 6030 babies had a pure growth of a recognised pathogen in a blood culture after day 3
Summary
Therapeutic hypothermia is standard of care in highincome countries for babies born at or after 36 weeks of gestational age with signs of hypoxic ischaemic encephalopathy. Optimal nutritional support for babies receiving therapeutic hypothermia is uncertain; previ ously published trials either did not specify nutritional management or stipulated that milk feeds should be withheld. In the absence of high-quality evidence, pro vision of enteral nutrition to infants during hypothermia is variable; withholding enteral feeds during therapeutic hypothermia is almost universal in some settings, whereas in other settings milk feeding is routine.6Milk feeds are withheld during therapeutic hypothermia partly to reduce the risk of necrotising enterocolitis. Therapeutic hypothermia is standard of care in highincome countries for babies born at or after 36 weeks of gestational age with signs of hypoxic ischaemic encephalopathy.. Optimal nutritional support for babies receiving therapeutic hypothermia is uncertain; previ ously published trials either did not specify nutritional management or stipulated that milk feeds should be withheld.. In the absence of high-quality evidence, pro vision of enteral nutrition to infants during hypothermia is variable; withholding enteral feeds during therapeutic hypothermia is almost universal in some settings, whereas in other settings milk feeding is routine.. Milk feeds are withheld during therapeutic hypothermia partly to reduce the risk of necrotising enterocolitis. The incidence of necrotising enterocolitis in term and near term infants with neonatal encephalopathy is poorly reported but is thought to be low.. The incidence of necrotising enterocolitis in term and near term infants with neonatal encephalopathy is poorly reported but is thought to be low. some data suggest beneficial effects of enteral feeding after perinatal ischaemia.
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