Does Severity of Brain Injury on Magnetic Resonance Imaging Predict Short-Term Outcome in Neonates Who Received Therapeutic Hypothermia?

OBJECTIVE: The National Institute of Child Health and Human Development (NICHD) magnetic resonance imaging (MRI) pattern of brain injury is a known biomarker of childhood outcome following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). However, usefulness of this classification has not been evaluated to predict short-term outcomes. The study aimed to test the hypothesis that infants with NICHD MRI pattern of severe hypoxic-ischemic brain injury will be sicker with more severe asphyxia-induced multiorgan dysfunction resulting in prolonged length of stay (LOS) following therapeutic hypothermia. We also evaluated the role of other risk factors which may prolong LOS. STUDY DESIGN: We retrospectively reviewed the medical records of 71 consecutively cooled neonates to examine the ability of MRI patterns of brain injury to predict the LOS. A neuroradiologist masked to outcomes classified the patterns of brain injury on MRI as per NICHD. Pattern 2A (basal ganglia thalamic, internal capsule, or watershed infarction), 2B (2A with cerebral lesions), and 3 (hemispheric devastation) of brain injury was deemed "severe injury." RESULTS: Out of 71 infants, 59 surviving infants had both MRI and LOS data. LOS was higher for infants who had Apgar's score of ≤5 at 10 minutes, severe HIE, seizures, coagulopathy, or needed vasopressors or inhaled nitric oxide, or had persistent feeding difficulty, or remained intubated following cooling. However, median LOS did not differ between the infants with and without MRI pattern of severe injury (15 days, interquartile range [IQR]: 9-28 vs. 12 days, IQR: 10-20; p = 0.4294). On multivariate linear regression analysis, only persistent feeding difficulty (ß coefficient = 11, p = 0.001; or LOS = 11 days longer if had feeding difficulty) and ventilator days (ß coefficient 1.7, p < 0.001; or LOS increased 1.7 times for each day of ventilator support) but not the severity of brain injury predicted LOS. CONCLUSION: Unlike neurodevelopmental outcome, LOS is not related to severity of brain injury as defined by the NICHD. KEY POINTS: · The NICHD pattern of brain injury on MRI predicts neurodevelopmental outcome following hypothermia treatment for neonatal HIE.. · LOS did not differ between the infants with and without MRI patterns of severe injury.. · The severity of brain injury as defined by the NICHD was not predictive of the LOS following therapeutic hypothermia..

Clinical Outcomes of Acute Respiratory Failure Associated With Noninvasive and Invasive Ventilation in a Pediatric ICU.

BACKGROUND: It remains unknown if pediatric patients failing initial noninvasive ventilation (NIV) experience worse clinical outcomes than those successfully treated with NIV or those primarily intubated. METHODS: This was a single-center, retrospective review of patients admitted with acute respiratory failure to the University of Michigan pediatric intensive care or cardiothoracic ICUs and receiving NIV or invasive mechanical ventilation as first-line therapy. RESULTS: One hundred seventy subjects met inclusion criteria and were enrolled: 65 NIV success, 55 NIV failure, and 50 invasive mechanical ventilation alone. Of those failing NIV, median time to intubation was 1.8 (interquartile range [IQR] < 1-7) h. On multivariable regression, ICU-free days were significantly different between groups (NIV success: 22.9 ± 6.9 d; NIV failure: 13.0 ± 6.6 d; invasive ventilation: 12.5 ± 6.9 d; P < .001 across all groups). Multivariable regression revealed no difference in ventilator-free days between NIV failure and invasive ventilation groups (15.4 ± 10.1 d vs 15.9 ± 9.7 d, P = .71). Of 64 subjects (37.6%) meeting Pediatric Acute Lung Injury Consensus Conference pediatric ARDS criteria, only 14% were successfully treated with NIV. Ventilator-free days were similar between the NIV failure and invasive ventilation groups (11.6 vs 13.2 d, P = .47). On multivariable analysis, ICU-free days were significantly different across pediatric ARDS groups (P < .001): NIV success: 20.8 + 31.7 d; NIV failure: 8.3 + 23.8 d; invasive alone: 8.9 + 23.9 d, yet no significant difference in ventilator-free days between those with NIV failure versus invasive alone (11.6 vs 13.2 d, P = .47). CONCLUSIONS: We demonstrated that critically ill pediatric subjects unsuccessfully trialed on NIV did not experience increased ICU length of stay or fewer ventilator-free days when compared to those on invasive mechanical ventilation alone, including in the pediatric ARDS subgroup. Our findings are predicated on a median time to intubation of < 2 h in the NIV failure group and the provision of adequate monitoring while on NIV.

Brainstem hypoxic-ischemic lesions on MRI in infants treated with therapeutic cooling: effects on the length of stay and mortality.

OBJECTIVE: To test the hypothesis that brainstem hypoxic-ischemic injury on magnetic resonance imaging (MRI) would be independently associated with short-term outcomes in cooled asphyxiated infants. METHODS: A total of 90 consecutively cooled asphyxiated infants who survived to have brain MRI were reviewed. A neuroradiologist who was masked to outcomes evaluated MRI images for brainstem involvement. Outcomes were mortality and length of stay. RESULTS: Brainstem lesions were present on post-cooling brain MRI in 20 of the 90 infants (22%). Overall, four infants died before discharge, and all four had brainstem involvement. The infants with brainstem involvement had longer hospital stay (29 days, IQR 20-47 versus 16 days, IQR 10-26; P = 0.0001), compared to infants without brainstem lesions (n = 70); and upon multivariate analysis, brainstem involvement remained independently associated with prolonged hospital stay (ß = 12.4, P = 0.001). CONCLUSION: This study demonstrates the importance of recognizing brainstem injury for the prediction of short-term outcomes in cooled asphyxiated infants.

Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique.

BACKGROUND: Several indirect calorimetry (IC) instruments are commercially available, but comparative validity and reliability data are lacking. Existing data are limited by inconsistencies in protocols, subject characteristics, or single-instrument validation comparisons. The aim of this study was to compare accuracy and reliability of metabolic carts using methanol combustion as the cross-laboratory criterion. METHODS: Eight 20-minute methanol burn trials were completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O2 and CO2 recovery were calculated. RESULTS: For accuracy, 1 Omnical, Cosmed Quark CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3 variables within 2% of the true value; both DeltaTracs and the Vmax Encore System (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking best (coefficient of variation [CV] < 1.26%). Both Cosmeds, Parvos, DeltaTracs, 1 Jaeger Oxycon Pro (Oxycon), Max-II Metabolic Systems (Max-II), and Vmax were reliable for at least 1 variable (CV ≤ 3%). For multiple regression, humidity and amount of combusted methanol were significant predictors of RER (R2 = 0.33, P < .001). Temperature and amount of burned methanol were significant predictors of O2 recovery (R2 = 0.18, P < .001); only humidity was a predictor for CO2 recovery (R2 = 0.15, P < .001). CONCLUSIONS: Omnical, Parvo, Cosmed, and DeltaTrac had greater accuracy and reliability. The small number of instruments tested and expected differences in gas calibration variability limits the generalizability of conclusions. Finally, humidity and temperature could be modified in the laboratory to optimize IC conditions.

Predicting the need for home gavage or g-tube feeds in asphyxiated neonates treated with therapeutic hypothermia.

BACKGROUND: Asphyxiated infants treated with therapeutic cooling can have persistent oral feeding difficulty because of involvement of neural pathways in the brainstem, cortex, and basal ganglia. The goal is to predict the composite adverse outcome of death or persistent oral feeding difficulty using precooling/cooling attributes, and the severity and distribution of hypoxic-ischemic lesions, especially brainstem lesions on post-cooling brain magnetic resonance imaging (MRI). METHODS: Retrospective review of 86 asphyxiated infants cooled from January 2006 to August 2014. Persistent feeding difficulty was defined as needing feeding support (gastrostomy tube (g-tube) or home gavage feeds) after discharge. Clinical and laboratory risk factors, and the brain MRI abnormalities including the presence of brainstem lesions were compared between infants with and without adverse outcome using univariate analysis. Significant variables were then analyzed in a stepwise logistic regression (LR) model. RESULTS: Infants with adverse outcome (n = 31, 4 died pre-discharge) had longer hospital stay (26 days, interquartile range (IQR) 19-43 vs. 13 days, IQR 9-20; p < 0.01) and reached goal enteral feeds (oral/gavage) later (11 days vs. 8 days, p < 0.01) compared to 55 infants discharged on full oral feeds. The former infants were more likely to have cord pH ≤ 7.15, severely abnormal neurological examination, bleeding diathesis, continued need for ventilation, and positive MRI findings including brainstem lesions. In LR analysis, brainstem lesions on MRI (p = 0.00, odds ratio 19, 95% confidence interval 4-85) was independently associated with the adverse outcome. CONCLUSIONS: Brainstem involvement on post-cooling brain MRI was predictive of adverse outcome. Early identification of these infants may facilitate discussion of home feeding plans between clinicians and parents earlier, thereby potentially reducing the length of hospital stay.

Safety and efficacy of perflubron-induced lung growth in neonates with congenital diaphragmatic hernia: Results of a prospective randomized trial.

BACKGROUND: Mechanical transduction has been shown to promote fetal lung growth. We examined the safety and efficacy of perflubron-induced lung growth (PILG) in neonates with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO). METHODS: Infants with left-sided CDH requiring ECMO were eligible. Exclusion criteria included active air leak, intracranial hemorrhage, major congenital anomalies, and oxygenation index >25 for 24hours. Perflubron was instilled endotracheally and continuous positive airway pressure was applied without ventilation. Survival to discharge was the primary outcome. Daily chest radiographs were used to quantify lung size (the secondary outcome). Midway through the study our institutional practice shifted toward earlier repair of CDH. RESULTS: Eight infants were randomized to each arm. In the conventional-ventilation arm, six survived to discharge (75%). In the perflubron arm, four survived (50%); the others succumbed to suprasystemic pulmonary hypertension. No adverse events related to perflubron occurred. Within the perflubron group, 4/8 patients had "late repair" (15-19days of life [DOL]) and 4 had "early repair" (2-3 DOL). "Early repair" patients had similar total lung growth, but accelerated growth and shorter ECMO runs. CONCLUSION: PILG is safe in CDH and doubles the total lung size on average (accelerated with early repair). Despite amelioration of pulmonary hypoplasia with PILG, pulmonary hypertension persists.

Assessment of association between rapid fluctuations in serum sodium and intraventricular hemorrhage in hypernatremic preterm infants.

AIM: This study aims to determine the association between the rapid fluctuations in serum sodium and intraventricular hemorrhage (IVH) or death in hypernatremic preterm infants. STUDY DESIGN: Single center observational study including 216 infants < 1,000 g birth weight and <29 weeks gestational age, who had serum sodium levels monitored at least every 12 hours. Logistic regression analyses were used to identify which of the commonly cited risk factors for IVH, including the rapid (to the extent of ≥10 and ≥15 mmol/L/d) rise or fall in serum sodium, was associated with the primary outcome of any IVH, or the secondary composite outcome of severe IVH or death during the first 10 days of life in hypernatremic infants. RESULTS: Of 216 infants, 126 (58%) studied developed hypernatremia (serum sodium ≥ 150 mmol/L). IVH was more frequent in hypernatremic infants (p = 0.01). Presence of hypernatremia was an independent risk factor for IVH on logistic regression analysis (p = 0.022, odds ratio 2.0, 95% confidence interval: 1.1-3.8). Rapid (≥ 10 and ≥ 15 mmol/L/d) rise or fall in serum sodium in hypernatremic infants was not associated with the outcomes. CONCLUSION: Hypernatremia per se, but not the rapid fluctuations (not exceeding 10-15 mmol/L/d) in serum sodium was independently associated with IVH.

Validation of the V(max) metabolic cart in a simulated pediatric model.

BACKGROUND: The ability to accurately measure resting energy expenditure (REE) using indirect calorimetry, often referred to as the "gold standard" in nutrition needs assessment, is important given the well-established positive correlation between patient outcome and proportion of the nutrition goal met. While many studies have been done to compare various metabolic carts with one another, the literature lacks a large simulator-based validation of any metabolic cart system. MATERIALS AND METHODS: In the present study, 8 specifically trained staff members independently conducted 10 simulation trials each using the V(max) Encore metabolic analyzer in conjunction with a metabolic calibration system, which simulates patient metabolic activity, to validate the accuracy of the V(max) Encore across a wide range of simulated metabolic conditions. Testing conditions consisted of incremental adjustments in calibrated gas infusion with a consistently set tidal volume and respiratory rate. RESULTS: There was a strong, statistically significant correlation between the predicted and actual VO2 and VCO2 data (VO2, R (2) = 0.998; VCO2, R (2) = 0.997). In addition, we observed no significant difference between individuals performing these trials (VO2, P = 1.000, F = 0.021, df = 79; VCO2, P = 1.000, F = 0.030, df = 79). CONCLUSIONS: This study is the first to report on such a wide spectrum of metabolic activity (50-2000 kcal REE) using a calibrated bench model and validates the accuracy, reproducibility, and use of the V(max) Encore metabolic cart.

Replacement of anesthesia machines improves intraoperative ventilation parameters associated with the development of acute respiratory distress syndrome.

BACKGROUND: The impact of anesthetic equipment on clinical practice parameters associated with development of acute respiratory distress syndrome (ARDS) has not been extensively studied. We hypothesized a change in anesthesia machines would be associated with parameters associated with lower rates of ARDS. METHODS: We performed a retrospective cohort study on a subset of data used to evaluate intraoperative ventilation. Patients included adults receiving a non-cardiac, non-thoracic, non-transplant, non-trauma, general anesthetic between 2/1/05, and 3/31/09 at the University of Michigan. Existing anesthesia machines (Narkomed IIb, Drager) were exchanged for new equipment (Aisys, General Electric). The initial subset compared the characteristics of patients anesthetized between 12/1/06 and 1/31/07 (pre) with those between 4/1/07 and 5/30/07 (post). An extended subset examined cases two years pre and post exchange. Using the standard predicted body weight (PBW), we calculated and compared the tidal volume (total Vt and mL/kg PBW) as well as positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), Delta P (PIP-PEEP), and FiO2. RESULTS: A total of 1,414 patients were included in the 2-month pre group and 1,635 patients included in the post group. Comparison of ventilation characteristics found statistically significant differences in median (pre v post): PIP (26 ± 6 v 21 ± 6 cmH2O, p < .001), Delta P (24 ± 6 v 19 ± 6 cmH2O, p < .001), Vt (588 ± 139 v 562 ± 121 ml, p < 0.001; 9.3 ± 2.2 v 9.0 ± 1.9 ml/kg predicted body weight, p < .001), FiO2 (0.57 ± 0.17 v 0.52 ± 0.18, p < .001). Groups did not differ in age, ASA category, PBW, or BMI. The two year subgroup had similar parameters. Risk adjustment resulted in minimal differences in the analysis. New anesthesia machines were associated with a non-statistically significant reduction in postoperative ARDS. CONCLUSIONS: In this study, a change in ventilator management was associated with an anesthesia machine exchange. The smaller Vt and lower PIP noted in the post group may imply a lower risk of volutrauma and barotrauma, which may be significant in at-risk populations. However, there was not a statistically significant reduction in the incidence of post-operative ARDS.

Evaluation of the oxygenation index in adult respiratory failure.

BACKGROUND: The oxygenation index (mean airway pressure × FIO2 divided by PaO2) was originally devised to measure severity of illness and predict outcome in neonatal respiratory failure. We evaluated the discrimination of a modified oxygenation index (modified with age) for predicting 28-day mortality in adults with respiratory failure (adult respiratory distress syndrome [ARDS]) using the ALVEOLI section of the ARDSNet database and validated the results in the full ARDSNet database. METHODS: We compared age-adjusted oxygenation index (AOI) on ventilator Days 1 to 4 with 28-day mortality. RESULTS: AOI correlated positively with mortality (area under the receiver operating characteristic curve, 0.70-0.74, for ARDS Days 1-4). Following initial development, AOI related to mortality was validated in two other ARDSNet databases producing similar results (area under the receiver operating characteristic curve, 0.70-0.78). CONCLUSION: The observed sensitivity and specificity analysis demonstrated that AOI is equivalent to or better than other mortality prediction systems used for ARDS. LEVEL OF EVIDENCE: Prognostic, level III.

Early enteral nutrition is associated with lower mortality in critically ill children.

BACKGROUND: The purpose of this study was to examine the association of early enteral nutrition (EEN), defined as the provision of 25% of goal calories enterally over the first 48 hours of admission, with mortality and morbidity in critically ill children. METHODS: We conducted a multicenter retrospective study of patients in 12 pediatric intensive care units (PICUs). We included patients aged 1 month to 18 years who had a PICU length of stay (LOS) of ≥96 hours for the years 2007-2008. We obtained patients' demographics, weight, Pediatric Index of Mortality-2 (PIM2) score, LOS, duration of mechanical ventilation (MV), mortality data, and nutrition intake data in the first 4 days after admission. RESULTS: We identified 5105 patients (53.8% male; median age, 2.4 years). Mortality was 5.3%. EEN was achieved by 27.1% of patients. Children receiving EEN were less likely to die than those who did not (odds ratio, 0.51; 95% confidence interval, 0.34-0.76; P = .001 [adjusted for propensity score, PIM2 score, age, and center]). Comparing those who received EEN to those who did not, adjusted for PIM2 score, age, and center, LOS did not differ (P = .59), and the duration of MV for those receiving EEN tended to be longer than for those who did not, but the difference was not significant (P = .058). CONCLUSIONS: EEN is strongly associated with lower mortality in patients with PICU LOS of ≥96 hours. LOS and duration of MV are slightly longer in patients receiving EEN, but the differences are not statistically significant.

Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia.

BACKGROUND: We hypothesized that acute kidney injury (AKI) in asphyxiated neonates treated with therapeutic hypothermia would be associated with hypoxic-ischemic lesions on brain magnetic resonance imaging (MRI). METHODS: Medical records of 88 cooled neonates who had had brain MRI were reviewed. All neonates had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h through cooling; and then on day 5 or 7 of life. A neonatal modification of the Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI. MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of interest was abnormal brain MRI at 7-10 d of life. RESULTS: AKI was found in 34 (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and 3, respectively. Brain MRI abnormalities related to hypoxia-ischemia were present in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.3-8.2). Multivariate analysis identified AKI (OR = 2.9; 95% CI = 1.1-7.6) to be independently associated with the primary outcome. CONCLUSION: AKI is independently associated with the presence of hypoxic-ischemic lesions on postcooling brain MRI.

Preoperative and intraoperative predictors of postoperative acute respiratory distress syndrome in a general surgical population.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a devastating condition with an estimated mortality exceeding 30%. There are data suggesting risk factors for ARDS development in high-risk populations, but few data are available in lower incidence populations. Using risk-matched analysis and a combination of clinical and research data sets, we determined the incidence and risk factors for the development of ARDS in this general surgical population. METHODS: We conducted a review of common adult surgical procedures completed between June 1, 2004 and May 31, 2009 using an anesthesia information system. This data set was merged with an ARDS registry and an institutional death registry. Preoperative variables were subjected to multivariate analysis. Matching and multivariate regression was used to determine intraoperative factors associated with ARDS development. RESULTS: In total, 50,367 separate patient admissions were identified, and 93 (0.2%) of these patients developed ARDS. Preoperative risk factors for ARDS development included American Society of Anesthesiologist status 3-5 (odds ratio [OR] 18.96), emergent surgery (OR 9.34), renal failure (OR 2.19), chronic obstructive pulmonary disease (OR 2.16), number of anesthetics during the admission (OR 1.37), and male sex (OR 1.65). After matching, intraoperative risk factors included drive pressure (OR 1.17), fraction inspired oxygen (OR 1.02), crystalloid administration in liters (1.43), and erythrocyte transfusion (OR 5.36). CONCLUSIONS: ARDS is a rare condition postoperatively in the general surgical population and is exceptionally uncommon in low American Society of Anesthesiologists status patients undergoing scheduled surgery. Analysis after matching suggests that ARDS development is associated with median drive pressure, fraction inspired oxygen, crystalloid volume, and transfusion.

Esophageal and rectal temperatures as estimates of core temperature during therapeutic whole-body hypothermia.

We monitored whole-body cooling concurrently by both esophageal and rectal probes. Esophageal temperature was significantly higher compared with simultaneous rectal temperature during cooling, with a temperature gradient ranging from 0.46 to 1.03°C (median, 0.8°C; IQR, 0.6-0.8°C). During rewarming, this temperature difference disappeared.

Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia.

OBJECTIVE: To test the hypothesis that acute kidney injury (AKI) would be independently associated with increased morbidity and mortality. STUDY DESIGN: A total of 96 consecutively cooled infants were reviewed retrospectively. Modified Acute Kidney Injury Network criteria were used to classify AKI based on absolute rise in serum creatinine (SCr) level from a previous trough (stage I, rise in SCr of 0.3 mg/dL or SCr 150-<200%; stage II, rise in SCr of 200-<300%; stage III, rise in SCr of ≥300%, SCr 2.5 mg/dL, or dialysis). Outcomes were mortality, duration of neonatal intensive care unit (NICU) stay, and duration of mechanical ventilation. RESULTS: AKI occurred in 36 of 96 infants (38%). Overall mortality was 7% and was higher for those with AKI, with the difference approaching statistical significance (14% vs 3% in those without AKI; P = .099). Patients with AKI stayed longer in the NICU (mean, 15.4 ± 9.3 days vs 11 ± 5.9 days; P = .014) and required prolonged mechanical ventilation (mean, 9.7 ± 5.9 days vs 4.8 ± 3.7 days; P < .001). On multivariate analysis, AKI remained predictive of prolonged duration of mechanical ventilation and prolonged NICU stay. CONCLUSION: We used the Acute Kidney Injury Network definition for AKI in asphyxiated newborns undergoing therapeutic hypothermia to demonstrate that the incidence of AKI remains high, but lower than rates published before the advent of therapeutic hypothermia. We highlight the importance of recognizing AKI in asphyxiated newborns undergoing therapeutic hypothermia, along with the potential benefits of early recognition.

Current knowledge of acute lung injury and acute respiratory distress syndrome.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) continues to be a major cause of mortality in adult and pediatric critical care medicine. This article discusses the pulmonary sequelae associated with ALI and ARDS, the support of ARDS with mechanical ventilation, available adjunctive therapies, and experimental therapies currently being tested. It is hoped that further understanding of the fundamental biology, improved identification of the patient's inflammatory state, and application of therapies directed at multiple sites of action may ultimately prove beneficial for patients suffering from ALI/ARDS.

The effect of late preterm birth on mortality of infants with hypoplastic left heart syndrome.

OBJECTIVES: We evaluated the effect of late preterm (34 to 36 weeks' gestation) delivery on hospital mortality of infants with hypoplastic left heart syndrome (HLHS). STUDY DESIGN: Retrospective review of records of infants born at or after 34 weeks with no other lethal anomalies, cared for in a single tertiary perinatal center between 2002 and 2009. Factors associated with death prior to discharge from the hospital were ascertained using univariate and multivariate analyses. RESULTS: Of the 243 infants with HLHS, 35 were late preterm and 208 were ≥37 weeks (term). Using logistic regression analysis, late preterm delivery (odds ratio [OR] 2.95; 95% confidence interval [CI] 1.35 to 6.45), the presence of other major cardiac defects (OR 3.76; 95% CI 1.31 to 10.81), and the presence of noncardiac congenital anomalies (OR 6.13; 95% CI 1.43 to 26.22) were independently associated with hospital death. CONCLUSION: Late preterm birth of infants with HLHS was independently associated with an increased risk of hospital death compared with those delivered at term.