Heart Rate Characteristics Predict Risk of Mortality in Preterm Infants in Low and High Target Oxygen Saturation Ranges

Abstract

The Neonatal Oxygenation Prospective Meta-analysis found that in infants <28 weeks gestational age, targeting an oxygen saturation (SpO2) range of 85–89%versus91–95% resulted in lower rates of retinopathy of prematurity (ROP) but increased mortality. We aimed to assess the accuracy of the heart rate characteristics index (HRCi) to assess the dynamic risk of mortality among infants managed with low and high target SpO2ranges.The SUPPORT and HRCi datasets from one center where both RCTs overlapped were linked. We examined the maximum daily HRCi (MaxHRCi24) to predict death among patients randomized to the lower and higher SpO2groups by generating predictiveness curves and calculating model performance metrics, including AUROC at prediction windows from 1–60 days. Cox proportional hazards models tested whether MaxHRCi24 was an independent predictor of death. We also conducted a moderation analysis.There were 84 infants in the merged dataset. MaxHRCi24 predicted death in subjects randomized to lower target SpO2, with area under the receiver operating characteristic curve (AUROCs 0.79–0.89) depending upon the prediction window, and higher target SpO2(AUROCs 0.82–0.91). MaxHRCi24 was an important additional predictor of death in multivariable modeling. In moderation analysis, in a model that also included demographic predictor variables, the individual terms and the interaction term between MaxHRCi24 and target SpO2range all predicted death.Associations between HRCi and mortality, at low and high SpO2target ranges, suggest that future research may find HRCi metrics helpful to individually optimize target oxygen saturation ranges for hospitalized preterm infants.