Effect of Therapeutic Hypothermia on DNA Damage and Neurodevelopmental Outcome among Term Neonates with Perinatal Asphyxia: A Randomized Controlled Trial

Abstract

TH reduces oxidative stress-induced DNA damage and improves neurodevelopmental outcome. <Trial registration No: CTRI/2011/10/002094>

Therapeutic Hypothermia for Perinatal Asphyxia in Low-Resource Settings

“…The study sites chosen may have access to 3 Tesla MRI scanners and spectroscopy but that does not imply that their care for the study participants would match the standard of care and experience available in centers which are routinely cooling babies. Contrary to the results of a systematic review [5,6] and studies reported from various sites in India [7][8][9][10][11][12][13][14][15][16], higher mortality and morbidity in the HELIX trial need to be explored. In the HELIX trial, chronic hypoxic changes in MRI were recorded.…”

“…The authors have self-proclaimed that HELIX is the only phase III clinical trial in LMIC belittling all the research work done in LMIC including that in CMC, Vellore and Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry in this area [7][8][9][10][11][12][13][14][15][16]. It is mentioned in the review that between 2012 and 2020, six randomized controlled trials (RCTs) were reported from JIP-MER, Puducherry.…”

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial

“…Trials from LMICs, however, have not consistently demonstrated benefits of cooling,4–6 and two recent reviews concluded that evidence for the safety or efficacy of TH as a neuroprotectant for HIE in LMICs is lacking and that TH in this setting is experimental 4 7. There are only three RCTs from LMICs (China and India) reporting neurodevelopmental outcomes beyond 12 months of age, and all concluded with a beneficial effect of TH 8–10. Population characteristics with higher incidence of fetal growth restriction and different comorbidities (eg, higher incidences of sepsis and meconium aspiration), facility characteristics with limited staffing with limited training and unavailability of expensive servo-controlled cooling equipment have been suggested as reasons for why TH can still not be recommended as standard of care for moderate to severe HIE in low-resource settings.…”

Neonatal Ogg1/Mutyh knockout mice have altered inflammatory gene response compared to wildtype mice in the brain and lung after hypoxia-reoxygenation

“…Mice deficient in repair of 8-oxoG have increased frequencies of germline mutations [2]. Hypoxiareoxygenation injury after neonatal asphyxia leads to oxidative stress and oxidative DNA damage [3], and hyperoxic reoxygenation increases the oxidative stress [4]. Epidemiological studies have found an association between resuscitation with oxygen at birth and later increased risk of childhood cancer [5,6].…”