Authors
Odd D, Sabir H, Jones S A, Gale C, Chakkarapani E.

Institution(s)
1.Translational Health Sciences, University of Bristol, Bristol, United Kingdom. 2. Universitäts-Kinderklinik Bonn, Bonn, Germany. 3. Cardiff University, Cardiff, United Kingdom.4. Medicine, Imperial College London, London, United Kingdom.

Introduction
Pre-clinical studies1 and small single center studies2 report conflicting degrees of neuroprotection with therapeutic hypothermia (TH) following inflammation prior to hypoxia-ischemic encephalopathy (inflammation-sensitized HIE). Therefore, we aimed to determine the independent effect of inflammation-sensitization on death and nasogastric (NG) tube feeding at discharge, and its association with major organ dysfunction, length of stay and time to full oral feeds in cooled HIE infants from the larger UK national neonatal research database (NNRD).

Methods
Retrospective cohort study utilizing NNRD between Jan 2008 and Feb 2018. Population: infants ≥36wks gestation with HIE undergoing TH. Exposure: inflammation-sensitization defined as 1/more of: rupture of membranes >18hrs, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or intrapartum antibiotics. Primary outcome: death and or NG feeds/nil by mouth at discharge. Secondary outcomes: major organ dysfunction; length of stay; intraventricular haemorrhage; days &no. of anticonvulsants. We used a multilevel regression model (by birth year) and adjusted for demographics and intrapartum factors.

Results
Of 7265 eligible infants, 998 (13.7%) had evidence of antenatal inflammation-sensitization. Inflammation-sensitized group were heavier, mature, differed in mode of delivery, had higher cord pH and a lesser proportion of grade 3 HIE. Primary outcome occurred in 20.3% of inflammation-sensitized group and 23.1% in non-exposed group (p=0.05). Death occurred in 13% of inflammation-sensitized and 14% of non-exposed group (p=0.321). Multivariable association showed results compatible with the univariable analysis (OR 0.87 (0.71-1.08)). There was no difference in the secondary outcomes of major organ dysfunction, length of stay and intraventricular haemorrhage. Inflammation-sensitization group compared to non-exposed group were more likely to achieve full oral feeds earlier (means (95% CI): 7.1 (6.8-7.5) vs 7.8 (7.6-8.0), p<0.001), and received fewer anticonvulsants (1.36 (1.31-1.41) vs 1.43 (1.41-1.45, p=0.008) for fewer days (2.8 (2.6-3.0) vs 3.2 (3.1-3.3), p=0.006).

Conclusions
Infants developing HIE after inflammation-sensitization did not have increased risk of death or NG feeding at discharge than other HIE infants, and in some domains have better outcomes. Objective measurement of inflammation-sensitization may identify the role of antenatal inflammation on developmental outcomes in HIE.

References: Falck M, et al. Dev Neurosci 2017;39 (1-4):238-247, Hakobyan et al., Neonatology. 2019;115(2):127-133.