Humidity in Incubators for Tiny Infants (HumidITI) Trial

About This Grant

PROJECT SUMMARY/ABSTRACT One in 500 births occurs at 22-24 weeks' gestation. Infants of 22-24 weeks' gestation make up one-fifth of all U.S. infant deaths (~3500 deaths/year) and many survivors have major morbidity. Birth hospitalization costs exceed $500,000/survivor (>$2 billion/year). Despite universal use of heated, humidified incubators in neonatal intensive care units (NICUs) for these patients, no evidence exists to guide basic clinical management, including the optimal humidity. There is strong physiologic rationale that suboptimal humidity could contribute to mortality, morbidity, and healthcare costs in infants <25 weeks; however, this question has never been studied. Current practices vary dramatically, with incubator humidity ranging from 60% to >95% across hospitals. The Humidity in Incubators for Tiny Infants (HumidITI) Trial addresses this critical knowledge gap through an innovative multicenter point-of-care randomized controlled trial (RCT) that overcomes historic barriers to conducting research in this patient group. The study will be conducted in an established network of institutions, the Tiny Baby Collaborative, that supports evidence collation, investigation, and dissemination. In the first large RCT in infants <25 weeks' gestation, we will enroll 600 infants at 8 U.S. hospitals to compare higher (90%) versus lower (70%) humidity during the first two postnatal weeks. Specific Aim 1 will evaluate whether 90% versus 70% humidity improves the probability of survival with fewer morbidities, using an ordinal outcome comprising mortality and six major morbidities (grade III-IV intraventricular hemorrhage, surgical necrotizing enterocolitis/intestinal perforation, grade III bronchopulmonary dysplasia, treated retinopathy of prematurity, patent ductus arteriosus surgery, and culture-proven late-onset sepsis) identified as important to patients and families. Specific Aim 2 will evaluate physiologic measures (weight loss, serum sodium, fluid intake volume, infant temperature) that may be affected by humidity and may explain the effect of humidity on clinical outcomes. Specific Aim 3 will compare the effects of 90% versus 70% humidity on birth hospitalization healthcare costs from a health system perspective, providing economic data to support implementation. Exploratory observational data and preliminary data from a pilot RCT of 77 infants at 4 sites strongly support the need for this trial. The HumidITI Trial will provide the first high-quality evidence to guide clinical practice for the increasing number of infants <25 weeks' gestation admitted to the NICU. The study design and collaboration with parents and nurses will serve as a foundation for future RCTs in this difficult-to-study patient group, advancing evidence-based medical care and improving outcomes for infants at highest risk of death and lifelong disability.