Study Design and Participants
death, hypothermia, HIE, disability, major life-threatening congenital malformations
SECONDARY
HELIX was an open-label randomized clinical trial (RCT) that recruited 408 neonates with moderate or severe HIE from 7 tertiary NICUs in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019,Neonates born at or after 36 weeks’ gestation with a birth weight of 1.8 kg or more who required continued resuscitation at age 5 minutes, had a 5-minute Apgar score less than 6, or both (or had lack of cry by age 5 minutes for home birth) were recruited if there was evidence of moderate or severe HIE on structured neurological examination performed between 1 and 6 hours after birth by a certified examiner. We excluded neonates who had no heart rate at age 10 minutes despite adequate resuscitation, those with major life-threatening congenital malformations, or those with parents who were unable to attend follow-up assessments. Neonates allocated to the hypothermia group had a controlled reduction of rectal temperatures to between 33.0 °C and 34.0 °C within 6 hours of birth that was continued for 72 hours followed by rewarming at 0.5 °C per hour using an neonate cooling and rewarming system (Tecotherm Neo; Inspiration Health Care [now International Biomedical]). The control group had rectal temperatures maintained between 36.0 °C and 37.0 °C. Neonates born at the participating tertiary NICUs with facilities for whole-body hypothermia were defined as inborn, and neonates born elsewhere (including other tertiary care centers, secondary care centers, primary care facilities, or at home) were defined as outborn. The primary outcome of the HELIX trial was death or moderate or severe disability assessed between 18 and 22 months by neurodevelopmental pediatricians masked to the allocation and neuroimaging data.