Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh.

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. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

Facility readiness in low and middle-income countries to address care of high risk/ small and sick newborns.

BACKGROUND: The successful promotion of facility births in low and middle-income countries has not always resulted in improved neonatal outcome. We evaluated key signal functions pertinent to Level II neonatal care to determine facility readiness to care for high risk/ small and sick newborns. METHOD: Facility readiness for care of high risk/ small and sick babies was determined through self-evaluation using a pre-designed checklist to determine key signal functions pertinent to Level II neonatal care in selected referral hospitals in Uganda (10), Indonesia (4) and India (2) with focus on the Sub-Saharan country with greater challenges. RESULTS: Most facilities reported having continuous water supply, resources for hand hygiene and waste disposal. Delivery rooms had newborn corners for basic neonatal resuscitation, but few practiced proper reprocessing of resuscitation equipment. Birth weight records were not consistently maintained in the Ugandan hospitals. In facilities with records of birth weights, more than half (51.7%) of newborns admitted to the neonatal units weighed 2500 g or more. Neonatal mortality rates ranged from 1.5 to 22.5%. Evaluation of stillbirths and numbers of babies discharged against medical advice gave a more comprehensive idea of outcome. Kangaroo Mother Care was practiced to varying extents. Incubators were more common in Africa while radiant warmers were preferred in Indian hospitals. Tube feeding was practiced in all and cup feeding in most, with use of human milk at all sites. There were proportionately more certified pediatricians and nurses in Indonesia and India. There was considerable shortage of nursing staff, (worst nurse -bed ratio ranging from 1 to 15 in the day shift, and 1 to 30 at night). There was significant variability in facility readiness, as in data maintenance, availability of commodities such as linen, air -oxygen blenders and infusion pumps and of infection prevention practices. CONCLUSIONS: Referral neonatal units in LMIC have challenges in meeting even the basic level II requirements, with significant variability in equipment, staffing and selected care practices. Facility readiness has to improve in concert with increased facility births of high risk newborns in order to have an impact on neonatal outcome, and on achieving Sustainable Development Goals 3.2.2.