Risk of mortality associated with neonatal hypothermia in southern Nepal

Objective: To quantify the neonatal mortality/hypothermia relationship and develop evidence-based cutoffs for global definitions of neonatal hypothermia. Design: Cohort study. Field workers recorded neonatal axillary temperature at home and recorded vital status at 28 days. Setting: Rural Nepal. Participants: Twenty-three thousand two hundred forty infants in Sarlahi, Nepal. Main Exposure: Hypothermia. Outcome Measures: Mortality risk was estimated using binomial regression models. Infants were classified using (1) World Health Organization (WHO) cutoffs for mild, moderate, and severe hypothermia; (2) quarter-degree intervals from 32.0°C to 36.5°C; and (3) continuous temperatures. Estimates were adjusted for age, ambient temperature, and other potential confounders. Results: Mortality increased among mild (relative risk [RR], 1.70; 95% confidence interval [CI], 1.23-2.35]), moderate (RR, 4.66; 95% CI, 3.47-6.24]), and severe (RR, 23.36; 95% CI, 4.31-126.70]) hypothermia cases. Within the WHO's moderate classification, risk relative to normothermic infants ranged from 2 to 30 times. Adjusted mortality risk increased 80% (95% CI, 63%-100%) for each degree decrease, was strongly associated with temperatures below 35.0°C (RR, 6.11; 95% CI, 3.98-9.38), and was substantially higher among preterm infants (RR, 12.02; 95% CI, 6.23-23.18]) compared with full-term infants (RR, 3.12; 95% CI, 1.75-5.57). Relative risk was highest in the first 7 days, but remained elevated through 28 days. Conclusions: A new hypothermia classification system should be considered by the WHO for global guidelines. We recommend that grade 1 be equivalent to the current mild category (36.0°C), restricting and splitting the moderate category into grades 2 (35.0°C-36.0°C) and 3 (34.0°C-35.0°C), and expanding severe hypothermia to less than 34.0°C (grade 4). Reducing hypothermia may dramatically decrease the global neonatal mortality burden.