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...

BackgroundTherapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18–22 months after neonatal encephalopathy, in LMICs.MethodsWe will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1–2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months.DiscussionUpon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection.Trial registrationClinicalTrials.gov, NCT02387385. Registered on 27 February 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2165-3) contains supplementary material, which is available to authorized users.

BackgroundSick newborns in neonatal units who are unable to breastfeed are fed expressed breast milk. In Sri Lanka, most mothers stay in hospital throughout baby’s stay to provide this milk freshly. In other countries mothers go home, express breast milk at home and bring it to hospital. There are concerns about the safety of transported expressed milk if used in a tropical middle-income country. The aim of this paper is to compare and contrast advice offered by different hospitals and organizations on how to express, store and transport breast milk safely.MethodsWe assessed guidelines used by hospital staff of the four Level 3 neonatal units in Melbourne, Australia, National Health Service UK, guidelines and training manuals of the Human Milk Banking Association of North America, the World Health Organization and an information leaflet from Family Health Bureau, Sri Lanka. Information on breast milk expression, storage and transport provided by the guidelines were tabulated under seven topics: general information; container for milk collection; hand expression; using a pump for expression; storage; thawing / warming; and transport of expressed breast milk. The AGREE II tool was used to assess the guidelines written for hospital staff.ResultsThere was considerable agreement on most recommendations provided by these sources, but no single source covered all topics in full. Most recommend hand expression as the initial method for expressing of breast milk, followed by breast pump use, except the Sri Lankan recommendations which strongly discourages the use of breast pumps. Durations of storage under various conditions are generally similar in the different recommendations. Most guidelines recommend a ‘cool box’ or container with ice or freezer packs for transportation of milk.ConclusionA single document containing recommendations on all aspects of expressing, storing and transporting breast milk should be available for each unit, with the same basic information for mothers and the healthcare staff and further technical details for staff if required. The Sri Lankan recommendations need to be updated based on current worldwide practices and further studies are needed to establish a safe method of transport of expressed breast milk in Sri Lanka.Electronic supplementary materialThe online version of this article (10.1186/s12887-018-1244-2) contains supplementary material, which is available to authorized users.

Sri Lankan family members should be educated further about normal patterns of milk production during the postpartum period. The authors recommend that PIM be included in screening tools for postpartum depression in Sri Lanka.