Heart rate characteristics predict risk of mortality in preterm infants in low and high target oxygen saturation ranges

Background The Neonatal Oxygenation Prospective Meta-analysis found that in infants <28 weeks gestational age, targeting an oxygen saturation (S-pO2) range of 85-89% versus 91-95% resulted in lower rates of retinopathy of prematurity but increased mortality. We aimed to evaluate the accuracy of the heart rate characteristics index (HRCi) in assessing the dynamic risk of mortality among infants managed with low and high target S-pO2 ranges. Methods We linked the SUPPORT and HRCi datasets from one centre in which the randomised controlled trials overlapped. We examined the maximum daily HRCi (MaxHRCi24) to predict mortality among patients randomised to the lower and higher target S-pO2 groups by generating predictiveness curves and calculating model performance metrics, including area under the receiver operating characteristics curve (AUROC) at prediction windows from 1-60 days. Cox proportional hazards models tested whether MaxHRCi24 was an independent predictor of mortality. We also conducted a moderation analysis. Results There were 84 infants in the merged dataset. MaxHRCi24 predicted mortality in infants randomised to the lower target S-pO2 (AUROC of 0.79-0.89 depending upon the prediction window) and higher target S-pO2 (AUROC 0.82-0.91). MaxHRCi24 was an important additional predictor of mortality in multivariable modelling. In moderation analysis, in a model that also included demographic predictor variables, the individual terms and the interaction term between MaxHRCi24 and target S-pO2 range all predicted mortality. Conclusions Associations between HRCi and mortality, at low and high S-pO2 target ranges, suggest that future research may find HRCi metrics helpful to individually optimise target oxygen saturation ranges for hospitalised preterm infants.