Lory Hage, Dusha Jeyakumaran, Cheryl Battersby, Jon Dorling, Shalini Ojha, Don Sharkey, Neena Modi, Nick Longford and Christopher Gale
Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London; IWK Health Centre, Halifax, Nova Scotia, Canada; School of Medicine, University of Nottingham.
Hypoxic ischaemic encephalopathy (HIE) is a leading cause of long-term disability. Standard of care for moderate to severe HIE is therapeutic hypothermia. Therapeutic hypothermia is increasingly used in infants with mild HIE in other parts of the world, despite limited evidence of benefit in mild HIE. Receipt of therapeutic hypothermia is used for surveillance purposes as an indicator of brain injury in the UK1, therefore any change in the population receiving this treatment has the potential to influence national surveillance programs. The aim of this study is to describe the clinical characteristics of babies diagnosed with HIE who received therapeutic hypothermia in the UK between 2010 to 2017. We tested the hypothesis that there has not been a change of the illness characteristics of babies receiving therapeutic hypothermia for HIE.
A retrospective, descriptive, study using deidentified, routinely recorded clinical data held in the National
Neonatal Research Database (NNRD). Infants born between 1st January 2010 and 31st December 2017 admitted into a neonatal unit in England, Scotland and Wales, were eligible for inclusion in the study if; (i) they had a recorded gestational age of ≥36+0 weeks+days at birth, (ii) were recorded as having received therapeutic hypothermia for 3 days or died during therapeutic hypothermia and (iii) had a diagnosis of HIE as “primary clinical reason for admission” or “principal diagnosis at discharge”. Clinical characteristics to describe severity of hypoxia ischaemia were selected a-priori: condition at birth, resuscitation characteristics, and condition at admission in the neonatal unit. Continuous variables were analysed using a linear regression analysis and Spearman’s rank correlation to eliminate the normality assumption. Ordinal variables were tested using Spearman’s rank correlation and binary data was assessed with a Chi-squared test for trend. Research Ethics Committee approval was obtained (17/EM/0307).
In the study period 6031 babies received therapeutic hypothermia for 3 consecutive days or died during cooling, of which 5201 had a diagnosis of HIE. The number of babies diagnosed for HIE who have received therapeutic hypothermia increased from 2010 to 2017. The clinical characteristics of the babies treated for HIE changed over the study period with a decreasing proportion of infants with clinical characteristics of severe hypoxia. These trends were statistically significant and consistent across multiple markers of severity (Figure 1 and 2).
Over the study period, more infants with less severe clinical markers of hypoxia were treated with therapeutic hypothermia for HIE in the UK. Study strengths include population coverage, limitations include missing data and variation in data entry between medical professionals for data items such as seizures. These data highlight the need to investigate the benefit of therapeutic hypothermia in mild HIE and its use as a marker for brain injuries.
Gale, C et al. Neonatal brain injuries in England: population-based incidence derived from routinely recorded clinical data held in the National Neonatal Research Database. ADCFN 103,4 (2018): F301-F306.
Figure 1. Line charts of the umbilical cord pH at birth from 2010 to 2017. The pH values were categorized; over 7.0 (>7.0), between 6.9 and 7.0 ([6.9;7.0]) and under 6.9 (<6.9). Statistical significance of the pH of babies from 2010 to 2017 (linear regression analysis p=0.0003 and Spearman correlation test p≤0.0001).
Figure 2. Line chart of the percentage of resuscitation characteristics and the condition on the first day of admission of babies from 2010 to 2017. Statistical significance for the three resuscitation interventions (chi-squared test for trend p≤0.0001). Significant difference in the proportion of babies where seizures, inotropes and invasive ventilation were recorded (chi-squared test for trend p≤0.0001, p≤0.0001 and p=0.0016, respectively).