Outcomes of neonatal hypoxic-ischaemic encephalopathy in centres with and without active therapeutic hypothermia: a nationwide propensity score-matched analysis

Abstract

ObjectiveTherapeutic hypothermia (TH) for neonatal hypoxic-ischaemic encephalopathy (HIE), delivered mainly in tertiary cooling centres (CCs), reduces mortality and neurodisability. It is unknown if birth in a non-cooling centre (non-CC), without active TH, impacts short-term outcomes.DesignRetrospective cohort study using National Neonatal Research Database and propensity score-matching.SettingUK neonatal units.PatientsInfants ≥36 weeks gestational age with moderate or severe HIE admitted 2011–2016.InterventionsBirth in non-CC compared with CC.Main outcome measuresPrimary outcome was survival to discharge without recorded seizures. Secondary outcomes were recorded seizures, mortality and temperature on arrival at CCs following transfer.Results5059 infants were included with 2364 (46.7%) born in non-CCs. Birth in a CC was associated with improved survival without seizures (35.1% vs 31.8%; OR 1.15, 95% CI 1.02 to 1.31; p=0.02), fewer seizures (60.7% vs 64.6%; OR 0.84, 95% CI 0.75 to 0.95, p=0.007) and similar mortality (15.8% vs 14.4%; OR 1.11, 95% CI 0.93 to 1.31, p=0.20) compared with birth in a non-CC. Matched infants from level 2 centres only had similar results, and birth in CCs was associated with greater seizure-free survival compared with non-CCs. Following transfer from a non-CC to a CC (n=2027), 1362 (67.1%) infants arrived with a recorded optimal therapeutic temperature but only 259 (12.7%) of these arrived within 6 hours of birth.ConclusionsAlmost half of UK infants with HIE were born in a non-CC, which was associated with suboptimal hypothermic treatment and reduced seizure-free survival. Provision of active TH in non-CC hospitals prior to upward transfer warrants consideration.

Organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort

“…Despite various criteria de ning optimal TH in the literature [16] (time to reach an optimal therapeutic temperature [12], or temperature at admission in therapeutic range [17]), and the extension of TH to less severe NE [18], our results of 70.2% of neonates reaching a rectal temperature within optimal range before 6 hr, is in line with data in the literature. In an early study from The Netherlands and Flanders, TH, indicated with "clear presence of perinatal asphyxia followed by neonatal encephalopathy", was started later than 6 hr after birth in 4.8% of infants [16].…”

“…In the United Kingdom, proportions of infants achieving optimal therapeutic temperatures at admission in a CC increased from 60.8% in 2011 to 76.0% in 2016 [12]. During the same period, 67.1% of UK neonates born in a non-CC arrived with a temperature between 33 and 34°C [17]. Data using the UK national neonatal research database have allowed to describe more precisely factors associated with delayed timing [17].…”

“…During the same period, 67.1% of UK neonates born in a non-CC arrived with a temperature between 33 and 34°C [17]. Data using the UK national neonatal research database have allowed to describe more precisely factors associated with delayed timing [17]. The higher proportion of adequate delay among neonates born in a CC versus a non-CC observed in our study (79.7% vs 63.8%) was also reported in the United Kingdom with a higher rate of neonates achieving optimal therapeutic temperatures at admission among those with access to immediate TH in CC versus infants born in a non-CC (83.5% vs 73.7%) [12].…”

Availability of active therapeutic hypothermia at birth for neonatal hypoxic ischaemic encephalopathy: a UK population study from 2011 to 2018

“…Animal studies support early TH (<3 hours of age) with less neuronal loss and better neuroprotection compared with late (3–6 hours) or delayed (>6 hours) treatment 17 18 20 40. This is supported by observational human data showing better motor development19 and less occurrence of seizures 41 42. Seizures associated with HIE can increase the long-term risk of a poor neurodevelopmental outcome 43–45.…”

Implications of the HELIX trial for treating infants with hypoxic-ischaemic encephalopathy in low-to-middle-income countries

“…Although there has never been a controlled clinical trial of the timing of initiation of therapeutic hypothermia, in a cohort of 76 infants recruited using the CoolCap/TOBY protocols, treatment before 3 hours of age was associated with improved psychomotor developmental index scores (Bayley Scales of Infant Development II) at 18 months compared with cooling from 3 to 6 hours 17. Moreover, there is evidence that infants with HIE born in a centre that offers therapeutic hypothermia onsite have improved seizure-free survival, presumptively due to earlier initiation of treatment 18. Hypothermia was initiated in HELIX at a median of 4.30 hours after birth (IQR 1.09–6.00), similar to previous trials.…”