Heart Rate Characteristics Index Research Articles

Targeting survival without morbidity: Heart rate characteristics for oxygen supplementation optimization in neonatal care

The preterm newborn is susceptible to many diseases related to oxidative stress, and supplemental oxygen therapy and its interaction with inflammatory processes may be a contributing factor to their underlying pathophysiology. Supplemental oxygen therapy can lead to over-oxygenation, and can complicate ischemia–reperfusion processes, which in turn can promote oxidative stress pathways. We hypothesize that the optimal dose of supplemental oxygen therapy likely varies for each preterm infant based on their unique and developing physiology, and may be adjusted through the assessment autonomic nervous function and pulmonary resilience by measuring heart rate variability. We present preliminary findings demonstrating that among extremely preterm infants with low-to-moderate heart rate characteristics index (HRCi) scores (indicating healthy ANS function) during the first six postnatal days, exposure to a low target oxygen saturation range was associated with decreased risk of the composite outcome of death by 36 weeks postmenstrual age (PMA), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and/or retinopathy of prematurity (ROP). This suggests a novel therapeutic approach to supplemental oxygen delivery in the neonatal intensive care unit (NICU) wherein the HRCi can be leveraged to guide the prescription of individualized target oxygen saturation ranges that are responsive to each infant’s unique and dynamic physiology, minimizing the risks of morbidity and mortality.

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

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. 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. 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. 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.

PP121 Assessment Of Heart Rate Characteristics Analysis

IntroductionThe heart rate characteristics (HRC) analysis is a technique for predicting and monitoring neonatal infectious diseases in infants with a risk for infectious disease, such as sepsis, using the HRC index based on the electrocardiogram (ECG) data transmitted from a HeRO® device connected to an ECG monitor.MethodsThe assessments were performed via a systematic review. Searching five databases (KoreaMed, Ovid-MEDLINE, Ovid-EMBASE, and Cochrane) yielded 284 related studies. Two reviewers independently assessed the quality of these studies, using the Scottish Intercollegiate Guidelines Network checklist and the assessment results were described based on the results of the quality appraisal and level of evidence.ResultsThe safety and effectiveness of the technique were assessed based on eight non-Korean studies (one randomized controlled trial (RCT), five cohort studies, one case-control study, one case series). The four studies that reported area under the curve (AUC) values, the timing of the analysis and AUC values (0.67– 0.75) were inconsistent among the studies. The elevation of the HRC index prior to the diagnosis of an infectious disease was not observed for meningitis or for multiple infectious diseases. In addition, although the group with additional monitoring using the technique had a significantly lower mortality rate, whether the HRC index had a direct impact on the infection prevention activities and the possibility of bias arising from the researchers’ precautionary treatment based on the clinical symptoms and other test results as well as the actual time of disease onset are unknown.ConclusionsTherefore, the committee presented the following recommendations based on the available evidence and expert opinion. HRC analysis is a safe technique for predicting and monitoring neonatal infectious diseases in infants with a risk for infectious disease, such as sepsis, using the HRC index based on the ECG data transmitted from a HeRO® device connected to an ECG monitor; however, further research is needed to determine its effectiveness (Level of evidence C, Technology category II-a).

Framework for Considering Abnormal Heart Rate Characteristics and Other Signs of Sepsis in Very Low Birth Weight Infants.

A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the neonatal intensive care unit (NICU). A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are needed. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants. We developed easy-recall acronyms for 10 signs of sepsis in VLBW infants. Over 12 months in a level IV NICU, neonatology fellows completed a brief survey after each shift to document changes prompting sepsis workups. We analyzed associations between survey data, hourly heart rate characteristic data, and the diagnosis of the workup, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures and <3 days antibiotics). We analyzed 93 sepsis workups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, and 38 SRO). The most frequently cited changes prompting the workups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0 to 12 hours before compared with 12to 72 hours prior the blood culture occurred in 31% of workups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO. The HeRO score can alert clinicians to VLBW infants at high or increasing risk of a sepsis-like illness, but heart rate characteristic patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis workups and the duration of antibiotics. · Abnormal heart rate characteristics can indicate sepsis or other pathologies in preterm infants.. · We developed a simple bedside tool to consider clinical signs potentially associated with sepsis.. · Considering vital sign trends together with clinical changes is a key to right-timing antibiotics..

Monitoring of heart rate characteristics to detect neonatal sepsis.

Monitoring of heart rate characteristics (HRC) index may improve outcomes of late-onset neonatal sepsis (LOS) through early detection. We aimed at describing the association between LOS and elevated HRC index. This single-center retrospective case-control study included neonates who presented with blood culture-proven hospital-acquired LOS. Controls were matched to cases (ratio 1:2) based on gestational age, postnatal age, and birthweight. We compared the highest HRC indexes in the 48 h preceding blood culture sampling in LOS cases to the highest HRC indexes at the same postnatal days in controls. In 59 LOS cases and 123 controls, an HRC index > 2 was associated with LOS (OR 7.1, 95% CI 2.6-19.0). Sensitivity and specificity of an HRC index > 2 to predict LOS were 53% (32/59) and 79% (98/123). Sensitivity increased from 25% in infants born > 32 weeks to 76% in infants born < 28 weeks. Specificity decreased from 97% in infants > 32 weeks to 63% in those born < 28 weeks. An increase of HRC index > 2 has a significant association with the diagnosis of LOS, supporting the use of HRC monitoring to assist early detection of LOS. Clinicians using HRC monitoring should be aware of its diagnostic accuracy and limitations in different gestational age groups. There is a paucity of data regarding the predictive value of heart rate characteristics (HRC) monitoring for early diagnosis of late-onset neonatal sepsis (LOS) in daily clinical practice. Monitoring of heart rate characteristics provides valuable information to assist the early diagnosis of LOS across all gestational age groups. However, the strong influence of gestational age on positive and negative predictive values adds complexity to the interpretation of HRC indexes.

Multivariable Predictive Models of Death or Neurodevelopmental Impairment Among Extremely Low Birth Weight Infants Using Heart Rate Characteristics

We hypothesized that a cumulative heart rate characteristics (HRC) index in real-time throughout the neonatal intensive care unit (NICU) hospitalization, alone or combined with birth demographics and clinical characteristics, can predict a composite outcome of death or neurodevelopmental impairment (NDI). We performed a retrospective analysis using data from extremely low birth weight infants who were monitored for HRC during neonatal intensive care. Surviving infants were assessed for NDI at 18-22months of age. Multivariable predictive modeling of subsequent death or NDI using logistic regression, cross-validation with repeats, and step-wise feature elimination was performed each postnatal day through day60. Among the 598 study participants, infants with the composite outcome of death or moderate-to-severe NDI had higher mean HRC scores during their stay in the NICU (3.1±1.8 vs 1.3±0.8; P<.001). Predictive models for subsequent death or NDI were consistently higher when the cumulative mean HRC score was included as a predictor variable. A parsimonious model including birth weight, sex, ventilatory status, and cumulative mean HRC score had a cross-validated receiver-operator characteristic curve as high as 0.84 on days 4, 5, 6, and 8 and as low as 0.78 on days 50-52 and 56-58 to predict subsequent death or NDI. In extremely low birth weight infants, higher mean HRC scores throughout their stay in the NICU were associated with a higher risk of the composite outcome of death or NDI. ClinicalTrials.gov: NCT00307333.

Sepsis and Mortality Prediction in Very Low Birth Weight Infants: Analysis of HeRO and nSOFA.

Scores to predict sepsis or define sepsis severity could improve care for very low birth weight (VLBW) infants. The heart rate characteristics (HRC) index (HeRO score) was developed as an early warning system for late-onset sepsis (LOS), and also rises before necrotizing enterocolitis (NEC). The neonatal sequential organ failure assessment (nSOFA) was developed to predict sepsis-associated mortality using respiratory, hemodynamic, and hematologic data. The aim of this study was to analyze the HRC index and nSOFA near blood cultures in VLBW infants relative to diagnosis and sepsis-associated mortality. Retrospective, single-center study of VLBW infants from 2011 to 2019. We analyzed HRC index and nSOFA around blood cultures diagnosed as LOS/NEC. In a subgroup of the cohort, we analyzed HRC and nSOFA near the first sepsis-like illness (SLI) or sepsis ruled-out (SRO) compared with LOS/NEC. We compared scores by diagnosis and mortality during treatment. We analyzed 179 LOS/NEC, 93 SLI, and 96 SRO blood culture events. In LOS/NEC, the HRC index increased before the blood culture, while nSOFA increased at the time of culture. Both scores were higher in nonsurvivors compared with survivors and in LOS/NEC compared with SRO. The nSOFA 12 hours after the time of blood culture predicted mortality during treatment better than any other time point analyzed (area under the curve 0.91). The HRC index provides earlier warning of imminent sepsis, whereas nSOFA after blood culture provides better prediction of mortality. · The HRC index and nSOFA provide complementary information on sepsis risk and sepsis-related mortality risk.. · This study adds to existing literature evaluating these risk scores independently by analyzing them together and in cases of not only proven but also suspected infections.. · The impact of combining risk models could be improved outcomes for premature infants..

Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. Describe the characteristics of UTI, including HRC, in VLBW infants. We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

Abnormal Heart Rate Characteristics Predict Urinary Tract Infections in VLBW Infants

Background: Urinary tract infection (UTI) is a common diagnosis in the neonatal intensive care unit (NICU). Approach to diagnosis and management of UTI is controversial in this population, but early detection may lead to improved outcomes. Abnormal heart rate characteristics (HRC) of decreased variability and repetitive transient decelerations are associated with late-onset neonatal sepsis. In an 8-center randomized clinical trial (RCT) of 3,003 VLBW infants, continuous HRC index (HeRO score) monitoring was associated with 22% lower all-cause mortality (Moorman, 2011) and 40% lower septicemia-associated mortality (Fairchild 2013). Urine culture results have …

Predicting extubation outcomes using the Heart Rate Characteristics index in preterm infants: a cohort study.

A strategy of early extubation to noninvasive respiratory support in preterm infants could be boosted by the availability of a decision support tool for clinicians. Using the Heart Rate Characteristics index (HRCi) with clinical parameters, we derived and validated predictive models for extubation readiness and success.Peri-extubation demographic, clinical and HRCi data for up to 96 h were collected from mechanically ventilated infants in the control arm of a randomised trial involving eight neonatal centres, where clinicians were blinded to the HRCi scores. The data were used to produce a multivariable regression model for the probability of subsequent re-intubation. Additionally, a survival model was produced to estimate the probability of re-intubation in the period after extubation.Of the 577 eligible infants, data from 397 infants (69%) were used to derive the pre-extubation model and 180 infants (31%) for validation. The model was also fitted and validated using all combinations of training (five centres) and test (three centres) centres. The estimated probability for the validation episodes showed discrimination with high statistical significance, with an area under the curve of 0.72 (95% CI 0.71-0.74; p<0.001). Data from all infants were used to derive models of the predictive instantaneous hazard of re-intubation adjusted for clinical parameters.Predictive models of extubation readiness and success in real-time can be derived using physiological and clinical variables. The models from our analyses can be accessed using an online tool available at www.heroscore.com/extubation, and have the potential to inform and supplement the confidence of the clinician considering extubation in preterm infants.

Trajectories of the heart rate characteristics index, a physiomarker of sepsis in premature infants, predict Neonatal ICU mortality.

ObjectiveTrajectories of physiomarkers over time can be useful to define phenotypes of disease progression and as predictors of clinical outcomes. The aim of this study was to identify phenotypes of the time course of late-onset sepsis in premature infants in Neonatal Intensive Care Units.MethodsWe examined the trajectories of a validated continuous physiomarker, abnormal heart rate characteristics, using functional data analysis and clustering techniques.ParticipantsWe analyzed continuous heart rate characteristics data from 2989 very low birth weight infants (<1500 grams) from nine NICUs from 2004–2010.ResultDespite the relative homogeneity of the patients, we found extreme variability in the physiomarker trajectories. We identified phenotypes that were indicative of seven and 30 day mortality beyond that predicted by individual heart rate characteristics values or baseline demographic information.ConclusionTime courses of a heart rate characteristics physiomarker reveal snapshots of illness patterns, some of which were more deadly than others.

Meningitis, urinary tract, and bloodstream infections in very low birth weight infants enrolled in a heart rate characteristics monitoring trial.

Background:Displaying heart rate characteristics (HRC) scores was associated with lower sepsis-associated mortality in very low birth weight (VLBW) infants in a multicenter randomized controlled trial (HeRO trial).Objective:To test whether HRC indices rise before diagnosis of urinary tract infection (UTI) or meningitis, with and without concomitant BSI.Design/Methods:Blood, urine and cerebrospinal fluid (CSF) culture data after 3 days of age and within 120 days of study enrollment were analyzed from 2,989 VLBW infants. The HRC index was analyzed 12h prior to positive cultures compared to 36h prior, using paired signed rank tests.Results:UTI, meningitis, and BSI was diagnosed in 10%, 2%, and 24% of infants respectively. The mean hourly HRC index was significantly higher 12h prior to diagnosis of UTI and BSI compared to 36h prior (UTI 2.07 versus 1.81; BSI 2.62 versus 2.25, both p<0.0001). The baseline HRC index was higher for meningitis, compared to UTI or BSI, but without a statistically significant rise in the day prior to meningitis diagnosis.Conclusions:In a large cohort of VLBW infants enrolled in the HeRO trial, the HRC index increased in the 24h period prior to diagnosis of UTI and BSI, but not meningitis.

Predicting Extubation Outcomes—A Model Incorporating Heart Rate Characteristics Index

To test the hypothesis that in neonates on mechanical ventilation, heart rate characteristics index (HRCi) can be combined with a clinical model for predicting extubation outcomes in neonates. HRCi and clinical data for all intended intubation-extubation events (episodes) were retrospectively analyzed between June 2014 and January 2015. Each episode started 6 hours pre-extubation or at the time of primary intubation if ventilation duration was shorter than 6 hours (baseline). The episodes ended at 72 hours postextubation for successful extubations or at reintubation for failed extubations. Mean of 6 hourly epoch HRCi-scores (baseline) or fold-changes (postextubation) were analyzed. Results are expressed as medians (IQR) for continuous data and proportions for categorical data. Multivariable logistic regression mixed model was used for statistical analysis. Sixty-six infants contributed to 96 episodes (18 failed extubations, 78 successful extubations) in the study. Failed extubations had significantly longer duration of ventilation (65.3 hours, 19.94-158.2 vs 38.4, 16.5-71.3) and more culture positive sepsis (33.3% vs 3.8%) than successful extubations. Baseline HRCi scores (1.68, 1.29-2.45 vs 0.95, 0.54-1.86) and postextubation epoch-1 fold changes (1.25, 0.94-1.55 vs 0.94, 0.82-1.11) were higher in failed extubations compared with successful extubations. Multivariable linear mixed-effects regression was used to create prediction models for success of extubation, using relevant variables. The baseline and postextubation HRCi were significantly higher in neonates with extubation failure compared with those who succeeded. Models using HRCi and clinical variables to predict extubation success may add to the confidence of clinicians considering extubation.

Dexamethasone effect on heart rate variability in preterm infants on mechanical ventilation.

Dexamethasone is administered to some preterm infants with chronic lung disease to facilitate weaning from mechanical ventilation. Heart rate characteristics (HRC), including heart rate variability (HRV), may be impacted by glucocorticoids and may predict extubation readiness. A commercially available monitor developed for sepsis detection continuously calculates HRV and an HRC index, which are inversely related. Determine the impact of dexamethasone on HRV and the HRC index, in relation to extubation success. We identified 109 preterm infants who received dexamethasone while on mechanical ventilation and had HRC index monitoring data available. Average hourly HRV and HRC index were compared the day before and the day after initiation of dexamethasone in three groups: infants who remained on mechanical ventilation, those who were successfully extubated, and those who were extubated and required reintubation in < 3 days. There was a significant increase in HRV and decrease in the HRC index the day after dexamethasone was started (HRV 16.2±0.5 vs 27.6±1.1 ms; HRC index 1.51±0.11 vs. 0.79±0.06 mean SE, p < 0.001). The 63 infants who were extubated within a day of starting dexamethasone had significantly higher HRV compared to those who remained on mechanical ventilation. There was no difference in HRV or its change with dexamethasone in the 45 infants who remained successfully extubated compared to the 18 infants who required reintubation within 3 days. Dexamethasone improves HRV and lowers the HRC index in preterm infants with chronic lung disease on mechanical ventilation.

Early Heart Rate Characteristics Predict Death and Morbidities in Preterm Infants

To determine whether an early heart rate characteristics (HRC) index (HeRO score), measured in the first day and week after birth predicts death and morbidities compared with established illness severity scores. For all very low birth weight infants in a single neonatal intensive care unit from 2004-2014, the average first day HRC index was calculated within 24hours of birth (aHRC-24h) and the average first week HRC index within 7days of birth (aHRC-7d). The Score for Neonatal Acute Physiology (SNAP-II) and Clinical Risk Indicator for Babies (CRIB-II) were calculated when data were available. The aHRC was compared with the SNAP-II and CRIB-II for predicting death, late-onset septicemia, necrotizing enterocolitis, bronchopulmonary dysplasia, severe intraventricular hemorrhage, or severe retinopathy of prematurity. All 4 scores were associated with death and severe intraventricular hemorrhage (P<.01). The OR and 95% CI for every 1-point increase in aHRC for predicting mortality, adjusted for gestational age, was 1.59 (1.25-2.00) for aHRC-24h and 2.61 (1.58-4.33) for aHRC-7d. High aHRC-7d, SNAP-II, and CRIB-II were associated with bronchopulmonary dysplasia (P<.001). High aHRC-7d was associated with late-onset septicemia (P<.05). None of the scores predicted necrotizing enterocolitis or severe retinopathy of prematurity. HRC assessed in the first day or first week after birth compares favorably to established risk scores to predict death and morbidities in very low birth weight infants.

PS-046 First Day Heart Rate Characteristics Predict Death And Adverse Events In Preterm Infants: Abstract PS-046 Table 1

Purpose Abnormal heart rate characteristics (HRC) of decreased variability and decelerations occur in preterm infants with sepsis and other pathologic conditions. We sought to determine whether an HRC index (HeRO score) in the first day after birth predicts death and morbidities and to compare it to an established risk index, the Score for Neonatal Acute Physiology (SNAP-II). Methods The HRC index was analysed within 24 h of birth in 163 extremely low birth weight infants, and SNAP-II was calculated when data were available. Associations between the maximum HRC index (HRC-1), SNAP-II, and death and major morbidities were analysed using logistic regression to correct for gestational age. Results HRC-1 was significantly associated with death, severe head ultrasound abnormalities (sHUS = grade 3–4 intraventricular haemorrhage or cystic periventricular leukomalacia), and late-onset septicemia (LOS) (Table). SNAP-II could be calculated in 122 cases (75%) and was correlated with HRC-1 (r = 0.50, p Conclusion The HRC index in the first day after birth predicts death and multiple morbidities in ELBW infants and is strongly correlated with SNAP-II, an established illness severity score.

PS-380 Heart Rate Characteristics Index Predicts Extubation Failure In Preterm Infants: Abstract PS-380 Table 1

Background Determining extubation readiness in preterm infants is often difficult, and infants who have respiratory failure and require reintubation incur additional morbidities. A heart rate characteristics index (HRC index or HeRO Score) developed for sepsis detection in VLBW infants has been shown to be associated with other adverse events including respiratory decompensation (Sullivan, J. Paediatrics 2014). Objective Test the hypothesis that the HRC index predicts extubation failure in VLBW infants. Methods We analysed all extubations within 3 weeks of birth for VLBW infants enrolled in a multicenter trial of HRC index monitoring (HeRO trial) randomised to the control arm (HeRO scores not displayed to caregivers). Results There were 427 extubations in 365 VLBW infants. Excluding 20 infants who died within 3 days, 98 (24%) infants failed extubation, requiring reintubation within 72 h. Infants who failed extubation had significantly lower postmenstrual age (mean PMA 27.2 vs 28.6 weeks) and higher HRC index (2.2 vs. 1.5). Relative risk of extubation failure if PMA was 1.0 were 2.3 and 2.2, respectively. HRC index added to PMA in predicting extubation failure, and infants 1.0 had 55% failure rate (Table). Conclusion The HRC index adds to PMA for prediction of extubation failure in VLBW infants. View this table: Abstract PS-380 Table 1

Abnormal heart rate characteristics are associated with abnormal neuroimaging and outcomes in extremely low birth weight infants.

Brain injury in preterm infants may lead to an inflammatory response and central nervous system dysfunction reflected by abnormal heart rate characteristics (HRC). We hypothesized that a continuously monitored HRC index reflecting reduced HR variability and decelerations correlates with abnormal neuroimaging and outcomes in extremely low birth weight infants (ELBW). We analyzed the average HRC index within 28 days after birth (aHRC28) and head ultrasound (HUS) in 384 ELBW infants. In 50 infants with brain magnetic resonance imaging (MRI) and 70 infants with Bayley neurodevelopmental testing at 1 year of age, we analyzed the relationship between aHRC28, MRI abnormalities and low Bayley scores. aHRC28 was higher in infants with severe HUS abnormalities (2.65±1.27 for Grade III-IV intraventricular hemorrhage (IVH) or cystic periventricular leukomalacia (cPVL) versus 1.72±0.95 for normal or Grade I-II IVH, P<0.001). Higher aHRC28 was also associated with white matter damage on MRI and death or Bayley motor or mental developmental index <70. Associations persisted after adjusting for gestational age, birth weight and septicemia. For every one point increase in aHRC28, the odds ratio of death or Bayley score <70 was 2.45 (95% CI 1.46, 4.05, P<0.001). A continuously monitored HRC index provides an objective, noninvasive measure associated with abnormal brain imaging and adverse neurologic outcomes in ELBW infants.

Infection and Other Clinical Correlates of Abnormal Heart Rate Characteristics in Preterm Infants

To identify clinical conditions associated with a large increase (spike) in the heart rate characteristics index in very low birth weight (VLBW) infants. Retrospective medical record review within a day of all large heart rate characteristics index spikes (increase of ≥3 from the previous 5-day average) in VLBW infants at a single center enrolled from 2007 to 2010 in a multicenter trial of heart rate characteristics monitoring. In the trial, infants were randomized to having their heart rate characteristics index displayed to clinicians or not displayed. Of 274 eligible infants, 224 large heart rate characteristics spikes occurred in 105 infants. Thirty-three spikes were associated with surgery or procedures requiring anesthetic or anticholinergic medications, and infection-related conditions were the most common clinical association with the other spikes. Of the first spikes in 47 infants randomized to conventional monitoring (heart rate characteristics index not displayed to clinicians), 53% were associated with suspected or proven infection. Respiratory deterioration without suspected infection occurred with 34%, and no association was identified in 13%. Infants randomized to having their heart rate characteristics index displayed were more likely to have antibiotics initiated around the time of a large heart rate characteristics index spike. Sepsis, other infectious or systemic inflammatory conditions, respiratory deterioration, and surgical procedures are the most common clinical associations with a large increase in the heart rate characteristics index in VLBW infants. This information may improve use of heart rate characteristics monitors in patients in the neonatal intensive care unit.

Complex signals bioinformatics: evaluation of heart rate characteristics monitoring as a novel risk marker for neonatal sepsis

Heart rate characteristics monitoring for early detection of late-onset neonatal sepsis was first described in 2003. This technique, which uses mathematical methods to report the fold-increase in the risk of imminent neonatal sepsis, adds independent information to laboratory tests and clinical findings, and, in a large randomized trial, reduced NICU mortality of very low birth weight infants. Through re-analysis and new secondary analyses of published studies, we have systematically evaluated the utility of this new risk marker for screening the growing population of premature infants. We followed the guidelines proposed by Hlatky et al. (Circulation, 119:2408-2416, 2009), reviewed past works, and re-analyzed data from 1,489 patients receiving conventional monitoring alone, 348 of whom had 488 episodes of proven sepsis, in the large randomized trial. Heart rate characteristics monitoring passed all phases of risk marker development from proof of concept to improvement of clinical outcomes. The predictiveness curve affirmed good calibration, and addition of the heart rate characteristics index to predictive models using standard risk factors favorably impacted the receiver operating characteristic curve area (increase of 0.030), continuous net reclassification index (0.389) and the integrated discrimination index (0.008), and compares well to other modern risk factors. Heart rate characteristics monitoring is a validated risk marker for sepsis in the NICU.