Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012–2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies.

MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μs’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μs’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μs’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μs’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3− at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3− at the time of study were correlated with smaller μs’. Brain μs’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

BackgroundsEnvironmental factors during early life alter the hypothalamus-pituitary-adrenal (HPA) axis regulation and increase the risk of diseases in later life. However, adrenal function at each developmental stage has not fully been investigated in relation to pathological antenatal conditions. Cortisol levels of newborns with intrauterine growth restriction (IUGR) are elevated during the neonatal period; however, when studied during early childhood, cortisol levels are reduced compared with their peers, suggesting that the HPA axis regulation might be altered from activation to suppression, the timing of which remains uncertain.AimThe aim of this study was to assess the presence of an interaction between intrauterine growth and postnatal age on cortisol levels in newborns hospitalised at a neonatal intensive care unit.MethodsWe performed a secondary analysis using a dataset from saliva samples of 62 newborns collected between 30 and 40 weeks corrected age. Interactions between postnatal age and clinical variables with regard to cortisol levels were assessed.ResultsThe z-score of the birth weight and IUGR showed significant interactions with postnatal age on cortisol levels; cortisol levels were higher ≤5 days of birth and lower >14 days of birth than those in their peers without IUGR.ConclusionThe adrenal function of newborns with IUGR might be altered from activation to suppression within the first several weeks of life. Longitudinal studies need to address when/how IUGR alters adrenal functions, and how these responses are associated with diseases during adulthood.

Feeding-induced cortisol response was observed in newborns. The cortisol response was more prominent following oral feeding and was reduced with prolonged feeding. Future studies may investigate whether feeding-induced cortisol response plays a role in the acquisition of adrenal ultradian and diurnal rhythms.

If the brain structure is assessed at neonatal intensive care units, covert clinical events related with subtle brain injury might be identified. The reduced scattering coefficient of near-infrared light (μS’) obtained using time-resolved near-infrared spectroscopy from the forehead of infants is associated with gestational age, body weight and Apgar scores, presumably reflecting subtle changes of the brain related to foetal growth and birth transition. One hundred twenty-eight preterm and term infants were studied to test whether μS’ obtained from the head at term-equivalent age is associated with foetal growth, birth transition and nutritional status after birth, which are key independent variables of developmental outcomes. As potential independent variables of μS’, birth weight, Apgar scores, age at full enteral feeding and post-conceptional age at the study were assessed to represent foetal growth, birth transition and nutritional status after birth. Subsequently, higher μS’ values were associated with higher Apgar scores (p = 0.003) and earlier establishment of enteral feeding (p < 0.001). The scattering property of near-infrared light within the neonatal brain might reflect changes associated with birth transition and nutritional status thereafter, which might be used as a non-invasive biomarker to identify covert independent variables of brain injury in preterm infants.

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ObjectiveApgar scores of zero at 10 min strongly predict mortality and morbidity in infants. However, recent data reported improved outcomes among infants with Apgar scores of zero at 10 min. We aimed to review the mortality rate and neurodevelopmental outcomes of infants with Apgar scores of zero at 10 min in Japan.DesignObservational study.PatientsTwenty-eight of 768 infants registered in the Baby Cooling Registry of Japan between 2012 and 2016, at >34 weeks’ gestation, with Apgar scores of zero at 10 min who were treated with therapeutic hypothermia.InterventionsWe investigated the time of first heartbeat detection in infants with favourable outcomes and who had neurodevelopmental impairments or died.Main outcome measuresClinical characteristics, mortality rate and neurodevelopmental outcomes at 18–22 months of age were evaluated.ResultsNine (32%) of the 28 infants died before 18 months of age; 16 (57%) survived, but with severe disabilities and 3 (11%) survived without moderate-to-severe disabilities. At 20 min after birth, 14 of 27 infants (52%) did not have a first heartbeat, 13 of them died or had severe disabilities and one infant, who had the first heartbeat at 20 min, survived without disability.ConclusionOur study adds to the recent evidence that neurodevelopmental outcomes among infants with Apgar scores of zero at 10 min may not be uniformly poor. However, in our study, all infants with their first heartbeat after 20 min of age died or had severe disabilities.

There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full-term infants. It may therefore be preferable to modify the proposed immunization schedule.