 Firstly, all high-income country clinical trials to date have provided cooling therapy along side optimal tertiary neonatal intensive care and cardiorespiratory support. Such tertiary care includes 1:1 expert nursing care, continuous clinical monitoring of vital physiological parameters, close attention to acid base and electrolyte balance, optimal ventilatory and inotropic support, parenteral nutrition, nitric oxide and cerebral function monitoring. These centres also have access to extra-corporeal membrane oxygenation ECMO facilities for infants with persistent pulmonary hypertension and meconium aspiration that may be adversely affected by cooling. The safety and efficacy of cooling therapy without optimal tertiary neonatal intensive care is unknown. Even the best resourced public sector tertiary neonatal units in India and other low and middle-income countries do not have the facilities and expertise that are comparable to the neonatal units where the high-income cooling trials were originally performed. The dangers of extrapolating the safety and efficacy data from high income country intensive care units to low and middle-income countries is well known, and has been recently re-emphasised by the increased mortality seen after fluid boluses in children with septic shock in Africa FEAST trial. The HELIX trial will examine the safety of cooling therapy in under resourced public sector neonatal units in India, who do not have the above-mentioned facilities for providing optimal tertiary intensive care, alongside cooling therapy. Secondly, there are significant population differences in babies who suffer from encephalopathy in high-income countries and those in low and middle-income countries with a higher incidence of perinatal infection and meconium aspiration. Antenatal care is often poor, and intra uterine growth restriction and delayed hospital admission in obstructed labour are extremely common. 