Therapeutic hypothermia in infants <36 weeks gestation: proceed with caution

Therapeutic hypothermia (TH) reduces the rate of death or disability in term and near-term infants with hypoxic-ischemic encephalopathy (HIE). 1 Although studies in preterm animals suggested neuroprotection with TH, 2 , 3 the initial human trials included limited numbers of infants at 35 weeks gestation and none at less than 35 weeks. 4 , 5 Over time, more preterm infants have been treated with TH, 6 despite sparse evidence of safety and efficacy of TH in this population. A large international survey found that 60% of sites use 35 weeks as the minimum gestational age for TH. 7 Recently, a landmark trial by Faix et al enrolled 168 infants between 33 0/7 to 35 6/7 weeks gestation, randomized to TH versus normothermia, and found no benefit of TH on death or moderate or severe disability and a possible increase in mortality with TH. 8 Faix and colleagues included 48 infants at 35 weeks gestation (of whom 28 were treated with TH). Although this is the largest randomized TH trial for preterm infants to date, it was not powered for subgroup analysis at different gestations, 8 and there is still controversy, particularly around the impact on infants of 35 weeks gestation. 9