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Optimising Nutrition During Neonatal Therapeutic Hypothermia In The United Kingdom: An Observational Study Using Propensity Score Matching

Dusha Jeyakumaran1; Cheryl Battersby1, Kayleigh Ougham1; Jon Dorling2; Shalini Ojha3; Nicholas T Longford1; Chris Gale1 
Institution
1. Imperial College London, London, UK; 2. Dalhousie University, Halifax, Nova Scotia, Canada; 3. School of Medicine, University of Nottingham, United Kingdom 
Introduction (include hypothesis) 
There is limited evidence to inform provision of nutrition during therapeutic hypothermia in infants with hypoxic ischemic encephalopathy (HIE)1 and enteral feeding is often withheld for fear of necrotising enterocolitis (NEC). Study aims were to compare the rates of outcomes including NEC and survival in a matched group of babies treated with therapeutic hypothermia who were and were not provided milk in the first 3 days. 
Methods (include source of funding and ethical approval if required) 
A retrospective cohort study using data from UK National Neonatal Research Database (NNRD). Babies born ≥36 weeks gestational age (GA) between 1 Jan 2010 and 31 Dec 2017 who received therapeutic hypothermia for 72 hours or died during treatment were included. Propensity model building proceeded using a stepwise approach with maternal, delivery and birth characteristics included initially. 1:1 matching was implemented; matching quality assessed using balance plots. Mean rates of outcomes were compared in the matched groups. The study was pre-registered ISRCTN474042962; Research Ethics Committee approval 17/EM/0307. 
Results 
6031 babies met the inclusion criteria for the study. Mean (SD) GA and birthweight were 39.4 (1.6) weeks and 3370 (627) grams. 55.2% were males and 45.5% were delivered by caesarean section. 3405 babies (56.5%) received enteral nutrition during therapeutic hypothermia. Incidence of NEC was low; 20 cases (0.3%) meeting UKNC definition of severe NEC, 68 cases (1.1%) meeting a broader definition; 90.3% of babies survived until discharge. Matching reduced the sample size to 1599 pairs (3198 babies). There was no evidence of a difference between rates of severe NEC in those that were and were not fed (rate% (95% CI), enteral feeds: 0.4% (0.1-0.7%); no enteral feeds: 0.2% (0.0-0.5%); OR, 1.5 (95% CI, 0.0-15.3); p=0.314). Higher rates of survival to discharge were seen in those that were fed during therapeutic hypothermia (rate% (95% CI): enteral feeds, 96.1% (95.1-97.1%); no enteral feeds: 91.6% (89.8-93.4%); OR, 2.2 (95% CI, 1.6-3.2); p<0.001). 
Conclusions 
NEC in babies treated with therapeutic hypothermia is rare. Provision of enteral feeds during therapeutic hypothermia appears safe and we find no evidence of an association between enteral feeds and NEC in this population. 
References (include acknowledgement here if appropriate) 
1. Ojha S, Dorling J, Battersby C, et al. Optimising nutrition during therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed 2018.  2. Battersby C, Longford N, Patel M, et al. Study Protocol: Optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: Observational study of routinely collected data using propensity matching. BMJ Open. 2018 

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