Therapeutic hypothermia is now the standard of care treatment for neonatal encephalopathy in high-income countries [1]. Although all major cooling trials so far have been conducted in such settings, anecdotal evidence suggests that therapeutic hypothermia is increasingly used in many low- and middle-income countries (LMIC), despite a lack of adequate safety and efficacy data [2]. The dangers of clinical adoption without robust local evidence have been recently highlighted with several therapeutic interventions such as antenatal corticosteroids [3, 4], and fluid bolus for septic shock, where a standard of care therapy in high-income countries was shown to be harmful in LMIC settings [4]. We wanted to examine if therapeutic hypothermia was being offered as a standard of care in Indian neonatal units, and if so, whether the established cooling protocols from high-income countries were being adhered to.

We identified potential participants using the online listing of all level 2 (a and b) and 3 neonatal intensive care units in hospitals across India on the National Neonatology Forum database [5]. We formulated a 10-part questionnaire using multiple choice or dichotomous questions (www.surveymonkey.com), and e-mailed an individualized link to the survey to the lead clinicians of the eligible centers, in May 2015. We contacted the lead clinician over telephone if there was no response to multiple e-mail reminders. We exported the responses to Microsoft Excel, and calculated the frequencies and percentages for all categorical responses. We clarified any data queries over telephone with the participants.

We contacted a total of 120 neonatal units, of which 93 (78%) responded. The majority (91%) of respondents were of consultant grade. Of those who responded, 68 (73%) units were in the private or semi-private sector (where patients had to pay full or partial treatment costs), and 25 (27%) were in the public sector (offering free health care to patients). Annual median neonatal encephalopathy admissions in public and private sector hospitals were 250 and 31, respectively.

Forty-seven (51%) units offered cooling therapy in clinical practice, and all of these units were located in areas of low infant mortality (Web Fig. 1). A further 41 (44%) hospitals wanted to offer cooling therapy, but were unable to, due to a lack of cooling devices and trained staff. Although five (5.4%) wanted to see more rigorous research data from clinical trials before routine clinical use, none of the responders felt that cooling therapy was unsafe or ineffective (Table I).

TABLE I	Practice of Cooling Therapy in Selected Tertiary and Secondary Care Indian Neonatal Units

Our survey suggests that despite a lack of local evidence [2], cooling therapy is now widely used both in public and private sector hospitals in all major Indian cities. However, the cooling practices varied widely from high-income country guidelines [1], particularly in private sector hospitals. As with any survey, the data presented here is subject to recall bias of the respondents as there are no prospective cooling registries in India. Hence, we made no attempt to collect mortality or morbidity data.

Many of these current cooling practices (lack of sedation, delayed cooling therapy beyond 6 hours of age), and locally improvised cooling methods without reliable core temperature control, may be ineffective, and potentially harmful [4]. Extreme cooling methods using ice and frozen gel packs may result in marked fluctuations in core temperature without close nursing monitoring. On the other hand, milder cooling methods using phase change materials, fans, water bottles, or air-conditioning may not result in adequate hypothermia [4]. Furthermore, lower thresholds of inclusion criteria may unnecessarily expose babies without encephalopathy or with mild encephalopathy to cooling therapy.

Deviation from the evidence base established by rigorous randomized controlled trials is not uncommon when a new therapy is introduced into clinical practice, with clinicians becoming increasingly comfortable with the new therapy. A recent Australian survey reported almost half of the cooling in babies in New South Wales deviated from accepted protocols [6]. However, clinicians in LMIC need to recognize that the evidence base for the routine use of cooling therapy in these settings is not yet available, and further research is required to establish this. The success of the cooling story appears to be so overwhelming that none of the neonatal centers in India expressed concerns about safety or ineffectiveness, despite a lack of any published long-term outcome studies of cooling therapy from low- and middle-income countries.

Whilst more research data are awaited from rigorous randomized controlled trials of cooling therapy in LMIC, it may be prudent to develop national guidelines and training programs on cooling therapy for routine clinical practice in these countries.

Acknowledgements: Professor Kumutha Kumaraswami (Saveetha Medical College, Tamil Nadu) for contacting neonatal units and encouraging them to participate in the survey, and Subhadeep Paul (Department of Statistics, University　of Illinois, USA) for generating the heat map of infants mortality rates.

Contributors: MC designed the study, collected and analysed the data along with RS and prepared the initial draft of the manuscript. SS and SR interpreted the data and developed the manuscript. ST conceived the idea, designed the study, interpreted the data and developed the manuscript. All authors approved the final version of manuscript for submission.

Funding: This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Competing interests: None stated.

1. National Institute for Health and Care Excellence. Therapeutic Hypothermia With Intracorporeal Temperature Monitoring for Hypoxic Perinatal Brain Injury. Available from: https://www.nice.org.uk/guidance/ipg347. Accessed April 17, 2017.

2. 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.

3. Althabe F, Belizán JM, McClure EM, Hemingway-Foday J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial. Lancet. 2015;385:629-39.

4. 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.

5. National Neonatology Forum Accredited Centres. Available from: http://www.nnfi.org/images/pdf/accreditation/NNFAccreditationAssessmentUndertakenas perRevisedLevelIIGuidelines.pdf. Accessed April 17, 2017.

6. Mehta S, Joshi A, Bajuk B, Badawi N, McIntyre S, Lui K, et al. Eligibility criteria for therapeutic hypothermia: From trials to clinical practice. J Pediatr Child Health. 2017;53:295-300.