Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness

Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for >7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p < 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness (p < 0.001). Continuous HRC monitoring is a generally valid and potentially useful noninvasive tool in the early diagnosis of neonatal sepsis and sepsis-like illness.     

Obstructive, mixed, and central apnea in the neonate: physiologic correlates.

In an attempt to determine physiologic responses to neonatal apnea, we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity. Of these episodes, 832 (39.9%) were central, 1032 (49.6%) were mixed, and 218 (10.5%) were obstructive. Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment, and the decrease in saturation was correlated with preapnea saturation. The baseline heart rate was similar for all apnea types. Infants receiving doxapram had a lower baseline heart rate (137.8 +/- 10.5 beats/min) than did infants receiving no therapy (142.8 +/- 16.6 beats/min) and infants receiving theophylline (149.7 +/- 15.0 beats/min) (p = < 0.001). A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events, and in infants who were not receiving therapy. Falls in heart rate were significantly less in infants receiving doxapram (27.8% +/- 18.0%) than in infants receiving theophylline (44.5% +/- 19.0%) or no therapy (48.4% +/- 18.3%) (p = < 0.001). The most common heart rate pattern overall was a gradual decrease interrupted by accelerations, whereas an initial heart rate acceleration was the most common pattern in obstructive apnea. We conclude that heart rate response to neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea.     

Adjustment of cardiac repolarization to changing cycle length in healthy infants

Summary This study describes the relation of cardiac repolarization (QT interval) to a changing heart rate (RR interval) in healthy infants, utilizing abbreviated electrocardiographic (ECG) recordings. A total of 105 limb lead ECG recordings were made in 53 infants of postconceptional age 30 to 52 weeks over a 5- to 15-minute period in order to obtain a heart rate variation of at least 20%. The QT and preceding RR intervals were measured during one cycle from each 3 second ECG segment (minimum 40 cycles) and the log QT-log RR relation was examined by linear regression statistics. Average RR was 387 ms (SD 42) and the average log QT/log RR slope 0.39 (SD 0.16). The slope correlated negatively with RR and was unassociated with age or sex. In 7 of the infants a single recording showed a QT-RR regression that failed to meet the 5% level of significance; 6 of these infants had additional tracings with a significant regression. When the log QT-log RR regression was studied in 20 continuous rhythm strips with spontaneous rate variation, the analysis of 9–32 consecutive cycles yielded an average slope of 0.13 (SD 0.07); in more than one-half of these strips the QT-RR relation in brief ECG recordings varies substantially in normal is concluded that: (1) the QT-RR relation in brief ECG recordings varies substantially in normal infants; (2) a substantial part of this variation may be due to nonrandomization of measurement error and to a statistical requirement for larger sample size when the slope calculation is based on measurement of fewer than 40 cycles; (3) normal infants occasionally manifest absence of QT adjustment to a changing RR; and (4) the adjustment of QT to a changing RR is not immediate, so consecutive cycle sampling during short periods of changing heart rate frequently fails to demonstrate a tracking of QT with RR.     

Oxidation of intravenous lipid in infants and children with systemic inflammatory response syndrome and sepsis

During sepsis in adults, fat becomes a preferred fuel; however, oxidation may be impaired relative to the circulating fatty acid levels. Little is known about the ability of infants and children to oxidize lipids during systemic inflammation (SIRS) and sepsis. The aim of this study was to examine the oxidation of exogenous lipid in these patients. Sixteen patients with SIRS/sepsis and eight controls with no evidence of sepsis were studied by indirect calorimetry during an i.v. lipid utilization test (1 h of 0.3 g/kg/h glucose followed by 3 h of 0.1 g/kg/h glucose plus 0.15 g/kg/h lipid). The respiratory quotient (RQ) (1.0 for carbohydrate utilization and 0.7 for fat utilization) was measured. Results were compared by repeated-measures analysis of variance (ANOVA), paired or unpaired t tests. There was no difference in baseline RQ between controls and patients with SIRS/sepsis (mean +/- SD; 0.82 +/- 0.08 versus 0.82 +/- 0.04). The RQ of controls dropped significantly to 0.78 +/- 0.08 at 240 min (p < 0.001). The RQ of patients with SIRS/sepsis also fell to 0.78 +/- 0.06 (p < 0.01). Infants and children with SIRS/sepsis are able to oxidize i.v. lipid.     

Serum amyloid A protein is a useful inflammatory marker during late-onset sepsis in preterm infants

BACKGROUND: Few studies demonstrated that serum amyloid A (SAA), a non-specific acute-phase reactant, could be used as a reliable early marker for the diagnosis of late-onset sepsis (LOS). OBJECTIVES: To evaluate the diagnostic value and the dynamics of SAA levels during the course of LOS and to compare it to those of other inflammatory markers. METHODS: Levels of SAA, C-reactive protein (CRP) and IL-6 together with clinical variables, biochemical parameters and cultures retrieved from all preterm infants suspected of LOS were checked at the first suspicion of sepsis and after 8, 24, 48 and 72 h. Results were compared to healthy, matched infants. RESULTS: One hundred and sixteen infants were included in the study, 38 in the sepsis and 78 in the non-sepsis group. High levels of SAA were observed at sepsis onset, with a gradual decline thereafter, while CRP levels increased only at 24 h after sepsis onset. In the sepsis group, levels of SAA returned faster to baseline than CRP levels. Receiver-operating characteristic analysis values revealed that SAA at 10 mug/ml had the highest sensitivity at 0, 8 and 24 h after sepsis onset (95, 100 and 97%, respectively) and a negative predictive value (97, 100 and 98%, respectively). CONCLUSIONS: SAA is an accurate acute-phase protein during LOS in preterm infants. Quick and reliable SAA kits can make this marker a useful tool in LOS in preterm infants.     

SIRS and group-B streptococcal sepsis in newborns: pathogenesis and perspectives in adjunctive therapy

Clinical signs of systemic inflammation and suspected systemic infection are common in neonatal medicine. Yet, causative infectious organisms can only infrequently be isolated. In previously healthy infants at low risk of sepsis, group B streptococcus (GBS) is the most common isolate. In vitro and in vivo data suggest that immune cells from newborn infants have impaired antimicrobial properties against GBS. In contrast large amounts of inflammatory mediators are formed upon GBS challenge and Toll-like receptors (TLR) are critical host molecules in this context. Thus, the immune balance tilts towards inflammation, SIRS and sepsis. Adjunctive therapy of neonatal sepsis needs to adjust the inflammatory response without further impairing bacterial clearance. This article summarises the pathophysiological events leading to sepsis and suggests molecular targets for adjunctive therapy.     

Clinician observation of physiological trend monitoring to identify late-onset sepsis in preterm infants

AIM: To determine whether trends in routinely collected physiological variables can be used retrospectively to classify infants according to the presence or absence of late-onset neonatal sepsis. METHODS: Case control study. Thirty infants born < or =32 weeks of gestation who developed late-onset sepsis were matched with 30 controls for gestational and postnatal age but remained sepsis free. For each infant, 25 clinicians inspected 48 h of routine monitoring of heart rate, respiratory rate and oxygen saturation. Clinicians were asked to determine whether the recording was obtained from an infant who did or did not develop sepsis and also indicate how confident they were in their judgement. Clinicians were stratified into three groups by professional role. RESULTS: The median correct assignment of infant's recordings was 67% (IQR 62-72). When very confident, this improved to 82% (IQR 67-88). Overall sensitivity was 53% (IQR 43-63) and specificity 80% (IQR 67-87). Advanced neonatal nurse practitioners consistently assigned babies to the correct group more often than other professional groups. CONCLUSION: The simple observation physiological trend graphs can classify infants according to the presence or absence of late-onset neonatal sepsis. The accuracy of this method is good to strong but varies with experience of neonatal intensive care.     

连续性血液透析滤过治疗肠穿孔腹膜炎SIRS幼猪疗效观察

目的：全身炎症反应综合征（SIRS）是各种原因引起多脏器功能障碍综合征的共同通路,目前临床缺乏有效的治疗措施。该研究旨在对肠穿孔腹膜炎诱导的SIRS幼猪行早期连续性血液透析滤过,观察SIRS动物的体温、心率、呼吸、血压、血气分析和外周血细胞计数,为临床治疗提供实验依据。方法：12只上海种小白猪,体重7~9 kg,雌雄不限。随机分为2组：对照组（n=6）;治疗组（n=6,连续性血液透析滤过,CVVHDF）。以盲肠穿孔术诱导SIRS,造模成功后治疗组行CVVHDF 6 h,血流速度20 mL/min,透析液速度600 mL/h,置换液速度300 mL/h,零平衡。于动物基础状态、成模时、成模后2,4,6 h分别记录两组动物的心率、呼吸、血压、体温、外周血细胞计数和血气分析结果。结果：所有动物经造模后均出现心率、呼吸频率上升,血压、动脉血氧分压、白细胞计数下降。成模时对照组动物心率和呼吸增快在6 h内持续保持较高水平;治疗组动物成模2 h后心率下降,6 h后呼吸频率下降与对照组相比差异有显著性,P<0.05。对照组动物成模4 h后平均动脉压下降,与治疗组比较差异有显著性,P<0.05。两组动物成模后动脉血氧分压均较基础状态降低,6 h内对照组动物保持低水平,治疗组动物动脉血氧分压有上升趋势,但组间差异无显著性。实验中动物体温及外周血细胞计数变化组间比较差异无显著性。结论：早期CVVHDF可稳定肠穿孔腹膜炎诱导的SIRS幼猪血流动力学,改善血氧分压,可能对改善疾病预后有益。［中国当代儿科杂志,2007,9（3）：237-240］     

Developmental patterns of heart rate and variability in prematurely-born infants with apnea of prematurity

At equivalent post-conceptional ages, prematurely-born infants have higher heart rates and reduced heart rate variability, relative to full-term neonates. Premature birth might exert long-lasting effects on central and peripheral mechanisms that control cardiovascular activity. We assessed development of heart rate and heart rate variability in symptomatic preterm infants up to 6 months of age. Fifty 6.5-h evening recordings of EKG and breathing were obtained from prematurely-born infants (gestational ages: 24–35 weeks). Cardiac R-R intervals were captured with a resolution of ±0.5 msec. One-min epochs were selected from three periods of regular respiration in recordings from premature infants and 72 recordings of full-term infants at comparable post-conceptional ages. Mean heart rate and heart rate variability were determined for each recording. At 40 weeks post-conception, prematurely-born infants with apnea of prematurity showed higher heart rates and reduced heart rate variability than did full-term neonates. These differences between premature and full-term infants persisted throughout the next 6 months in those infants born prior to 30 weeks gestation, and in those infants born at 30–35 weeks who experienced respiratory distress syndrome (RDS) during the neonatal period. The findings suggest that premature delivery, or complications thereof, exerts long-lasting effects on cardiac control.     

Standardized oculocardiac reflex in ex-premature near full term (93 cases)]

The aim of the study was to present data investigating vagal reactivity in a population of premature infants reaching term, using the oculo-cardiac reflex. PATIENTS AND METHODS: Ninety three premature infants, free of any disease, near full term at the moment of testing, were prospectively investigated at a time close to discharge from neonatal unit. After an all-night polygraphic recording, a standardized oculo-cardiac reflex test was performed during quiet sleep. Data were classified in relation to both chronological and postconceptional ages. Simple liner regression analyses were performed on the selected variables. RESULTS: The results showed heterogeneity of the vagal response in this population: longest asystole (1049 ms +/- 540; 95th percentile = 1894 ms); maximal percentage of deviation between two successive RR intervals (88% +/- 90; 95th percentile = 200%); and duration between the beginning of decrease in heart rate and return to mean heart rate (14 s +/- 10; 95th percentile = 30 s). CONCLUSION: Our healthy premature infants at time of discharge exhibited a wider range of vagal reactivity than previously reported for the full term newborns. Considering our findings, we recommend caution before proceeding with treatment of vagal bradycardia in a similar premature infant population.     

Heart rate variability in infants with apparent life-threatening events

Heart rate variability (HRV) is often used as an index of sympatho-vagal balance. A decreased HRV has been observed in patients with central hypoventilation and in infants who have later succumbed to sudden infant death syndrome (SIDS). The aim of the present study was to investigate whether HRV is altered in infants with apparent life-threatening events (ALTE), a group with an increased risk of SIDS. Fifty infants with ALTE were compared with 50 age- and sex-matched controls. ECG was recorded overnight in all infants. Two sequences of RR intervals free of artefacts were selected from each sleep state and spectral analysis of RR variability was performed. The mean and SD of RR and the low (LFPow) and high (HFPow) frequency power were analysed. In active sleep (AS) the LF/HF ratio was lower in ALTE infants, but no differences were seen in either the LFPow or the HFPow. In quiet sleep (QS), however, ALTE infants had higher SD-RR (p = 0.006), greater HFPow (p = 0.02) and VLFPow (very low frequency power, p = 0.02) than the control infants. The same results were seen when the two sleep states were combined for analysis, ALTE infants had higher SD-RR (p = 0.004), HFPow (p = 0.006) and VLFPow (p = 0.04). Conclusion: The different HRV pattern in ALTE infants compared to healthy controls suggests an altered autonomic control.     

Postural differences in cardiac dynamics during quiet and active sleep in low birthweight infants

To study the effects of body position (supine versus prone) on changes in cardiac inter-beat interval during quiet and active sleep, 6-h continuous electrocardiographic recordings and simultaneous minute-by-minute behavioural activity state assignments were made in 61 healthy, growing, low birthweight infants. The infants weighed 795-1600 g at birth and ranged between 30-38 wk in postconceptual age. Infants were randomly assigned to the supine or prone position for the first 3 h of each study; the position was reversed for the second 3 h. Higher heart rates and lower time and frequency domain measures of inter-beat interval variability were observed in the prone position as compared to the supine position, during both quiet and active sleep. In addition, an analysis of consecutive increases and decreases in the instantaneous heart rate revealed a lower incidence of sustained accelerations or decelerations in the prone position. Although consistent findings concerning inter-beat interval variability and sleeping position were obtained from all analytic techniques, the differences derived from analysis of consecutive inter-beat changes were the most robust. These differences in multiple measures of cardiac rate and rhythm between prone and supine positions suggest that autonomic control of the heart is altered by body position, the net effect on heart rate being increased sympathetic dominance.     

Maternal antibiotics and decreased periventricular leukomalacia in very low-birth-weight infants

OBJECTIVE: To investigate the effect of maternal antibiotics, given in the predelivery period, on neonatal outcomes. DESIGN: Retrospective cohort study. SETTING: A single level 3 neonatal intensive care unit. PATIENTS: All infants with birth weights 1500 g or less cared for from July 1994 to July 2000 (n = 834) were included in the study. Mothers were classified as receiving antibiotics if they received any parenteral antibiotics in the predelivery period. Infants whose mothers received antibiotics were compared with infants whose mothers received no antibiotics. MAIN OUTCOME MEASURES: The main outcome variables studied included intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), sepsis, and mortality. RESULTS: Of 834 mothers, 374 (45%) received antibiotics prior to delivery. On univariate analysis, there were no differences in the relative risk (RR) of mortality (1.26; 95% confidence interval [CI], 0.86-1.79) or grades 3 to 4 IVH (RR, 1.39; 95% CI, 0.82-1.90) between the antibiotics and no-antibiotics groups. Infants born to mothers receiving antibiotics had an increased risk of culture-proven sepsis (RR, 1.4; 95% CI, 1.02-1.64) and a decreased risk of cystic PVL (RR, 0.26; 95% CI, 0.09-0.79) compared with infants whose mothers did not receive antibiotics. After controlling for confounding variables, maternal antibiotics were not associated with a decrease in the risk of mortality (adjusted risk [AR], 1.0; 95% CI, 0.5-2.1), grades 3 to 4 IVH (AR, 1.0; 95% CI, 0.5-1.9), or sepsis (AR, 0.9; 95% CI, 0.7-1.4). However, the use of maternal antibiotics was associated with a decreased risk of developing cystic PVL (AR, 0.09; 95% CI, 0.02-0.5). CONCLUSIONS: In our population of very low-birth-weight infants, maternal antibiotics were associated with a decreased risk of cystic PVL. Maternal antibiotics do not change the risk of mortality, sepsis, or severe IVH.     

Neurodevelopmental evaluation of very low birth weight infants with sepsis at 18 to 24 months’ corrected age

In this cohort study, neurodevelopmental outcome of 20 of 24 surviving very low birth weight infants with sepsis followed-up between 2008 and 2009 was compared with 20 control (uninfected infants). We found that plasma interleukin-6 and C-reactive protein values were negatively correlated with mental developmental index scores (r= ?0.33, P= 0.03 and r= ?0.40, P= 0.01, respectively) at 18 to 24 months’ corrected age. The results of this study indicate that sepsis experienced in the neonatal period seems to be related to low mental developmental index scores at 18 to 24 months’ corrected age.     

IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis

Despite the development of newer generation of antibiotics, mortality from neonatal sepsis remains high. In a prospective, randomized study, we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis. Two groups of 30 infants each (matched for gestational age, sex, weight, and other variables) were randomly allocated to receive either antibiotics alone (control group) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously (immunotherapy group). Mortality from sepsis in the control group was 20% (6/30), while in the immunotherapy group it was 3.3% (1/30). We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis.     

Factors affecting heart rate variability and heart rate responses to tilting in infants aged 1 and 3 months

Heart rate variability (HRV) and heart rate (HR) responses following a 60 degree head-up tilt were measured in 60 infants at 1 and 3 mo of age to investigate the effects on these of age, sleep state, sleep position, and mother's smoking status. HRV was determined from Poincaré plots of 500 sequential RR intervals to measure overall variability derived from the SDRR of this plot, and instantaneous variability derived from the SDdeltaRR. HR responses to the tilt were measured as changes in RR interval length from rest to immediately following the tilt and again once a stable pattern was reached. SDRR and SDdeltaRR increased 20 and 40%, respectively, with age (p < 0.0001), SDRR was higher in active sleep (AS) than quiet sleep (QS, +72%, p < 0.0001) but both measures of variability (SDRR and SDdeltaRR) were lower in the prone position compared with supine (-18%, p < 0.0001). However, several findings were dependent on the basal RR interval, thus the age effect disappeared once RR interval was taken into account, sleep state remained an important factor and the lower variability when prone now became a difference of -3% (p = 0.034). The tilt generally provoked a reflex tachycardia followed by a bradycardia and settling to a stable HR level below, at, or above baseline within 30 s. The more unusual responses were no HR change, sustained tachycardia or sustained bradycardia (15% of total). These were more likely to occur in younger infants (p = 0.008) and in AS (p < 0.0001). No changes were seen in any of the cardiac indices related to maternal smoking status. The findings confirm several reports indicating that prone sleeping damps some physiologic responses. The data emphasize the need to consider basal heart rate, and sleep position as well as sleep state in autonomic function testing during infant sleep.     

Systemic inflammatory response syndrome

Despite advances in perinatal care in the past decade, sepsis and its complications continue to present problems for the neonate, remaining a major cause of neonatal morbidity and mortality. Sepsis research is focusing on how the neonate (host) responds to bacteria. The newborn may develop a systemic reaction to bacteria that induces the release of substances known as inflammatory mediators. Termed the systemic inflammatory response syndrome (SIRS), this reaction is believed to be responsible for the signs and symptoms of sepsis. This article introduces the neonatal nurse to SIRS, providing an overview of various inflammatory mediators and cytokines, their clinical consequences, and potential new therapies in the management of SIRS.     

新生儿寒冷损伤与全身炎症反应综合征关系的临床研究

目的　探讨新生儿寒冷损伤与全身炎症反应综合征 (SIRS)发生的关系。方法　对 6 0例以寒冷损伤综合征为原发病并排除合并感染的新生儿 ,根据SIRS的发生与否分SIRS组及非SIRS组 ,比较两组入院时体温、复温时间 (低温持续时间 ) ,复温速度及其多器官功能障碍综合征 (MODS)发生率、病死率 ;并比较不同体温患儿SIRS和MODS发生率、病死率 ;比较SIRS组中符合SIRS项目数与存活率的关系 ;以及两组发生MODS的具体脏器分布的差异。结果　SIRS组复温时间较非SIRS组长 (P <0 0 5 ) ,复温速度比非SIRS组慢 (P <0 0 5 ) ,MODS发生率SIRS组比非SIRS组明显升高 (P <0 0 5 ) ,病死率比较无显著性差异。不同体温组中SIRS及MODS发生率、病死率比较差异具有显著性意义 ,体温越低 ,SIRS及MODS发生率、病死率越高。发生 3个以上器官损害患儿的病死率较 2个器官损害患儿的病死率高。结论　在新生儿寒冷损伤综合征中 ,SIRS及MODS的发生、发展与低体温严重程度及持续时间密切相关。     

新生儿败血症病原菌及耐药性10年回顾性分析

目的 分析新生儿败血症病原菌分布随时间的变化规律及抗生素耐药情况。方法 收集2010年1月至2019年12月中南大学湘雅二医院10年来确诊的新生儿败血症的相关资料,分析新生儿败血症的发生率、病原菌分布情况及抗生素耐药特点。结果 新生儿败血症的发生率为4.02%(447/11 111)。排名前4位的菌株依次为凝固酶阴性葡萄球菌(coagulase-negative staphylococci,CoNS)、肺炎克雷伯菌、大肠埃希菌和念珠菌属。败血症发生率和病原菌占比分布随时间无明显变化趋势。肺炎克雷伯菌在早产儿(33.9%)、极低出生体重儿(29.5%)、小于胎龄儿(42.5%)中均为检出比例最高的菌株。CoNS、肺炎克雷伯菌和大肠埃希菌对青霉素类抗生素和第三代头孢菌素的耐药率均较高。结论 新生儿败血症的发生率较高,病原菌以CoNS为主,对青霉素类抗生素和第三代头孢菌素的耐药率较高。应加强新生儿感染防控和病原菌监测,进一步规范抗生素的合理运用。[中国当代儿科杂志,2022,24 (10):1111-1116]     

Abnormal heart rate characteristics are associated with neonatal mortality

Estimating the risk of in-hospital mortality in the newborn intensive care unit can provide important information for health-care providers, and illness severity scores have been devised to provide mortality risk estimates. Calculation of illness severity scores is time-consuming, and the information used to predict mortality is collected only for the first 12 to 24 h of life. A noninvasive continuous measure that uses information collected throughout the hospitalization and that requires no data entry could be less costly and more informative. We have previously shown that the abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations accompany neonatal illness such as late-onset sepsis. We hypothesized that more frequent and severe abnormal HRC are associated with an increased risk of death. We tested this hypothesis in two ways. Using data on infants older than 7 d of age, we first determined the association of the HRC index with death in the next week. Second, we devised a cumulative HRC score and determined its association with in-hospital death. There were 37 deaths in the 685 patients. The major findings were 1) the HRC index showed highly significant association with death in the succeeding 7 d (receiver-operating characteristic area > 0.7, p < 0.001), and 2) the cumulative HRC was highly significantly associated with neonatal in-hospital mortality (receiver-operating characteristic area > 0.80, p < 0.001). In both analyses, HRC added information to birth weight, gestational age, and postnatal age (p < 0.01). The HRC index provides independent information about the risk of neonatal death in the upcoming 7 d, and the cumulative HRC is an estimate of the risk of in-hospital neonatal mortality.