Summary Background Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. Methods We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , NCT02387385 . Findings We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. Interpretatio...

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection. Neonatal encephalopathy (NE) related to perinatal asphyxia is the most common cause of death and neurodisability in term babies with an incidence of 2 to 3 per 1,000 live births in high-income countries, and 10 to 20 per 1,000 livebirths in low and middle-income countries 1,2. In high income countries, therapeutic hypothermia partially improves outcomes, although adverse outcomes still occur in up to 30% of the cooled infants 3. As the underlying brain injury evolves over hours and days after birth, early identification of at-risk encephalopathic infants is challenging and often inaccurate, particularly in cooled infants 4. Furthermore, NE is heterogenous condition resulting from a multitude of aetiologies including acute or sub-acute perinatal hypoxia,

not available DOI: http://dx.doi.org/10.3329/bjch.v38i3.22823 Bangladesh J Child Health 2014; VOL 38 (3) :142-150

Background: Oropharyngeal administration of colostrum has found to play a role in preventing the Necrotizing Enterocolitis (NEC), thus reducing mortality and morbidity in preterm infants. We aimed to determine whether early oropharyngeal administration of mother’s own colostrum can reduce the rates of NEC and/or mortality in preterm infants. Methods: We conducted a randomized, placebo controlled, intervention study in Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Dhaka from 2019 to 2021. Total 92 infants were enrolled, 52 were randomized to oropharyngeal administration of colostrum group and 40 to placebo group. Oropharyngeal administration of colostrum group received maternal colostrum (0.2 ml), after 24 hours of postnatal life and were given every 3 hour for the next 3 days. Serum IgA was measured at 24 hrs and 7th day of postnatal age. Clinical data during hospitalization were collected. SPSS version 21 was used for statistical analysis. Results: Baseline characteristics were comparable and almost similar between the two groups. There was significant reduction in the incidence of NEC stage 2, 16 (30.7%) vs. 26, (65%); p = 0.001). There was significant reduction of age of achieving full enteral feeding (12.1±4.5 vs 19.5±7.5; p = 0.001), disseminated intravascular coagulation (DIC) 12 (23%) vs. 22 (55%); p=0.002, use of mechanical ventilators, 11 (21.1%) vs. 22 (55%); p = 0.001 and number of inotropes (1.2±0.3 vs. 1.61±0.4975; p = 0.002), duration of inotropes (19.7±14.2 vs. 36.5±17.5; p=0.002) in OAC group. However, there was no significant difference in probable sepsis, culture proven sepsis, survival rate and serum IgA level at 1st and 7th day in OAC group, compared to placebo. Conclusions: There was a positive effect in decreasing the incidence of NEC, but no significant effect was observed on survival rate. This intervention facilitates faster achievement of full enteral feeding, reducing the risk of DIC in preterm infants.

Abstract