Aniko Deierl

Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes

BACKGROUNDnIn the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits.nnnMETHODSnWe randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher.nnnRESULTSnA total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of childrens health status and in results on 10 of 11 psychometric tests.nnnCONCLUSIONSnModerate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. Funding UK Medical Research Council.

The efficacy of inhaled nitric oxide treatment in premature infants with acute pulmonary hypertension

BACKGROUNDnAlthough inhaled nitric oxide (iNO) therapy in term infants with pulmonary hypertension (PHT) has demonstrated definite benefit, the use of iNO in preterm infants remains inconclusive.nnnAIMSnTo evaluate the impact of iNO treatment in premature infants with acute PHT.nnnSTUDY DESIGNnRetrospective cohort.nnnSUBJECTSnInfantsu202f<u202f34u202fweeks gestational age, admitted during 2010-2016 to two neonatal units, having treated with iNO for confirmed PHT. A positive response was defined by FiO2 reduction ≥20% within 3-h post iNO initiation. Early PHT was defined when developed within the first 72u202fh of age.nnnOUTCOME MEASURESnThe primary outcome was the evaluation of the acute response to iNO administration. Secondary outcomes included the comparison of neonatal characteristics and outcomes between positive and negative responders, and early or late PHT infants.nnnRESULTSnOf the 55 infants of our cohort, 39 (71%) had a positive response to iNO administration. No differences noted regarding bronchopulmonary dysplasia, intraventricular haemorrhage or other morbidities; however, positive responders had significantly higher survival rate in overall (77 vs 21%, pu202f=u202f0.001) and within early PHT subgroup (74 vs 33%, pu202f=u202f0.044). Regression analysis revealed that oligohydramnios (OR 2.834, 95%CI 1.652-6.070) and early PHT (OR 1.953, 95%CI 1.377-2.930) were significantly related with a positive response.nnnCONCLUSIONSnPreterm infants with confirmed acute PHT respond in significant proportion to the iNO administration, especially in the background of oligohydramnios or the development of early PHT.