Autism risk in neonatal intensive care unit patients associated with novel heart rate patterns

Background Neonatal intensive care unit (NICU) patients are at increased risk for autism spectrum disorder (ASD). Autonomic nervous system aberrancy has been described in children with ASD, and we aimed to identify heart rate (HR) patterns in NICU patients associated with eventual ASD diagnosis. Methods This retrospective cohort study included NICU patients from 2009 to 2016 with archived HR data and follow-up beyond age 3 years. Medical records provided clinical variables and ASD diagnosis. HR data were compared in infants with and without ASD. Results Of the 2371 patients, 88 had ASD, and 689,016 h of data were analyzed. HR skewness (HRskw) was significantly different between ASD and control infants. Preterm infants at early postmenstrual ages (PMAs) had negative HRskw reflecting decelerations, which increased with maturation. From 34 to 42 weeks PMA, positive HRskw toward accelerations was higher in males with ASD. In 931 males with at least 4 days of HR data, overall ASD prevalence was 5%, whereas 11% in the top 5th HRskw percentile had ASD. Conclusion High HRskw in NICU males, perhaps representing autonomic imbalance, was associated with increased ASD risk. Further study is needed to determine whether HR analysis identifies highest-risk infants who might benefit from earlier screening and therapies. Impact In a large retrospective single-center cohort of NICU patients, we found that high positive skewness of heart rate toward more accelerations was significantly associated with increased risk of eventual autism spectrum disorder diagnosis in male infants but not in females. Existing literature describes differences in heart rate characteristics in children, adolescents, and adults with autism spectrum disorders, but the finding from our study in NICU infants is novel. Heart rate analysis during the NICU stay might identify, among an inherently high-risk population, those infants with especially high risk of ASD who might benefit from earlier screening and therapies.