We agree with the authors that there is insufficient evidence to support the use of therapeutic hypothermia in low- and middle-income countries [1], and randomized controlled trials are urgently required. We also agree that the profile of mothers and infants with encephalopathy due to hypoxia-ischemia may be different in high resource countries from those in LMIC [2]. The aim of our survey was merely to highlight the therapeutic creep of cooling therapy in Indian neonatal units, despite lack of such evidence [3]. Given the recall bias and subjectivity of web-based surveys, collection of specific details is unlikely to be accurate, and hence we did not attempt to collect data on eligibility criteria for cooling, morbidity and mortality and outcome of infants.

While blood gas based criteria may be useful, it may not be available round the clock in most Indian neonatal units. However, it is essential that a structured neurological examination is performed to ensure babies have moderate or severe encephalopathy, and not mild encephalopathy, before offering cooling therapy. The NICHD neurological examination has been validated in Indian settings, and if performed accurately, will identify these infants. Long term follow-up rates are extremely poor in routine clinical settings in India to provide meaningful outcome data.

The concerns raised by the authors regarding lack of safety of cooling methods used in the Neonatal units in India and lack of data on safety and efficacy of cooling when initiated after 6 hours of age have been addressed in our manuscript [3]. The NICHD Neonatal Research Network data from high-income countries on cooling for neonatal encephalopathy between 6 and 24 hours of age was recently published [4].

A large phase III randomized controlled trial of whole body cooling is currently ongoing in several public sector tertiary neonatal units in India, Bangladesh and Sri Lanka [5]. All recruited babies are having detailed neuro-developmental follow up at 18 months using Bayley III Infant and Toddler Assessment. Once completed, this would be the largest ever cooling trial and should provide the definitive answer for safety and efficacy of cooling therapy in these settings. We agree, until these data are available, cooling therapy in Indian neonatal units should be considered as experimental, and it may be prudent to obtain informed parental consent after discussing the risk benefits.

1. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: A systematic review and meta-analysis. PLoS One. 2013;8:e58834.

2. Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil S. Cooling in a low-resource environment: lost in translation. Semin Fetal Neonatal Med. 2015;20:72-9.

3. Chandrasekaran M, Swamy R, Ramji S, Shankaran S, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in Indian neonatal units: A survey of national practices. Indian Pediatr. 2017;54:969-70.

4. Shankaran S, Laptook AR, Pappas A, McDonald SA,　Das A,　Tyson JE, et al. Effect of depth and duration of cooling on death or disability at age 18 months among neonates with hypoxic-ischemic encephalopathy: A randomized clinical trial. JAMA. 2017;318:57-67.