Delayed Umbilical Cord Clamping is Not Associated with Acute Kidney Injury in Very Low Birth Weight Neonates.

OBJECTIVE: This study aimed to determine if delayed cord clamping (DCC) is associated with a reduction in neonatal acute kidney injury (AKI). STUDY DESIGN: A retrospective single-center cohort study of 278 very low birth weight (VLBW) neonates was performed to compare the incidence of AKI in the following groups: immediate cord clamping (ICC), DCC, and umbilical cord milking. AKI was diagnosed by the modified neonatal Kidney Diseases and Improving Global Outcomes (KDIGO) definition. RESULTS: The incidence of AKI in the first week was 20.1% with no difference between groups (p = 0.78). After adjustment for potential confounders, the odds of developing AKI, following DCC, compared with ICC was 0.93 (confidence interval [CI]: 0.46-1.86) with no reduction in the stage of AKI between groups. CONCLUSION: In this study, DCC was not associated with a reduced rate of AKI in VLBW neonates. However, the data suggest that DCC is also not harmful to the kidneys, further supporting the safety of DCC in VLBW neonates.

The effect of congenital diaphragmatic hernia on the development of left-sided heart structures.

INTRODUCTION: Patients with congenital diaphragmatic hernias often have concomitant congenital heart disease (CHD), with small left-sided cardiac structures as a frequent finding. The goal of this study is to evaluate which left-sided heart structures are affected in neonates with congenital diaphragmatic hernias. METHODS: Retrospective review of neonates between May 2007 and April 2015 with a diagnosis of a congenital diaphragmatic hernia was performed. Clinical and echocardiographic data were extracted from the electronic medical record and indexed to body surface area and compared to normative values. Univariable regression models assessed for associations between different variables and length of stay. RESULTS: Data of 52 patients showed decreased mean z scores for the LVIDd (-3.16), LVIDs (-3.05), aortic annulus (-1.68), aortic sinuses (-2.11), transverse arch (-3.11), and sinotubular junction (-1.47) with preservation of the aorta at the diaphragm compared to age-matched normative data with similar body surface areas. Regression analysis showed a percent reduction in length of stay per 1 mm size increase for LVIDd (8%), aortic annulus (27%), aortic sinuses (18%), sinotubular junctions (20%), and transverse arches (25%). CONCLUSIONS: Patients with congenital diaphragmatic hernias have significantly smaller left-sided heart structures compared to age-matched normative data. Aortic preservation at the diaphragm provides evidence for a mass effect aetiology with increased right-to-left shunting at the fetal ductus resulting in decreased size. Additionally, length of stay appears to be prolonged with decreasing size of several of these structures. These data provide quantitative evidence of smaller left-sided heart structures in patients with congenital diaphragmatic hernias.

Depressed heart rate variability is associated with abnormal EEG, MRI, and death in neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: Asphyxia can lead to autonomic nervous system dysfunction, including depressed heart rate variability (HRV). We tested the hypothesis that low HRV is associated with adverse short-term outcomes of abnormalities on electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) and death in neonates with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Neonates undergoing hypothermia therapy for HIE underwent monitoring of HRV. HRV in the first day after birth and after hypothermia and rewarming (days 4-7) were analyzed in relation to death and severity of abnormal findings on EEG and MRI. RESULTS: A total of 37 neonates had data available in the first 24 hour after birth and 67 had data days 2 to 7. Depressed HRV was significantly associated with adverse outcomes of death or moderate-to-severe abnormalities on EEG or MRI. In the first 24 hours, the odds ratio (OR) of one or more adverse outcomes for every 10-millisecond decrease in HRV was 3.19 (95% CI, 1.3-7.8; p = 0.01). HRV improved over time but low HRV remained significantly associated with adverse outcomes days 4 to 7 (OR, 2.72; CI, 1.32-5.61; p < 0.01). CONCLUSIONS: Monitoring HRV, which is reflected in the heart rate characteristic index, may provide useful adjunct information on the severity of brain injury in infants with HIE.

Accurate automated apnea analysis in preterm infants.

OBJECTIVE: In 2006 the apnea of prematurity (AOP) consensus group identified inaccurate counting of apnea episodes as a major barrier to progress in AOP research. We compare nursing records of AOP to events detected by a clinically validated computer algorithm that detects apnea from standard bedside monitors. STUDY DESIGN: Waveform, vital sign, and alarm data were collected continuously from all very low-birth-weight infants admitted over a 25-month period, analyzed for central apnea, bradycardia, and desaturation (ABD) events, and compared with nursing documentation collected from charts. Our algorithm defined apnea as > 10 seconds if accompanied by bradycardia and desaturation. RESULTS: Of the 3,019 nurse-recorded events, only 68% had any algorithm-detected ABD event. Of the 5,275 algorithm-detected prolonged apnea events > 30 seconds, only 26% had nurse-recorded documentation within 1 hour. Monitor alarms sounded in only 74% of events of algorithm-detected prolonged apnea events > 10 seconds. There were 8,190,418 monitor alarms of any description throughout the neonatal intensive care unit during the 747 days analyzed, or one alarm every 2 to 3 minutes per nurse. CONCLUSION: An automated computer algorithm for continuous ABD quantitation is a far more reliable tool than the medical record to address the important research questions identified by the 2006 AOP consensus group.

Predictive monitoring for respiratory decompensation leading to urgent unplanned intubation in the neonatal intensive care unit.

BACKGROUND: Infants admitted to the neonatal intensive care unit (NICU), and especially those born with very low birth weight (VLBW; <1,500 g), are at risk for respiratory decompensation requiring endotracheal intubation and mechanical ventilation. Intubation and mechanical ventilation are associated with increased morbidity, particularly in urgent unplanned cases. METHODS: We tested the hypothesis that the systemic response associated with respiratory decompensation can be detected from physiological monitoring and that statistical models of bedside monitoring data can identify infants at increased risk of urgent unplanned intubation. We studied 287 VLBW infants consecutively admitted to our NICU and found 96 events in 51 patients, excluding intubations occurring within 12 h of a previous extubation. RESULTS: In order of importance in a multivariable statistical model, we found that the characteristics of reduced O(2) saturation, especially as heart rate was falling; increased heart rate correlation with respiratory rate; and the amount of apnea were all significant independent predictors. The predictive model, validated internally by bootstrap, had a receiver-operating characteristic area of 0.84 ± 0.04. CONCLUSION: We propose that predictive monitoring in the NICU for urgent unplanned intubation may improve outcomes by allowing clinicians to intervene noninvasively before intubation is required.

Transcatheter Occlusion of Left-To-Right Shunts in Premature Infants with Bronchopulmonary Dysplasia.

INTRODUCTION: Patent ductus arteriosus (PDA) and atrial septal defects (ASDs) cause pulmonary overcirculation, potentially worsening bronchopulmonary dysplasia (BPD) in premature infants. Transcatheter device occlusion of these defects is feasible and safe, though no case-controlled studies have assessed respiratory outcomes in infants with BPD. We hypothesized infants with BPD and ASDs or PDAs would experience improved respiratory outcomes following device occlusion of these lesions as compared to those who did not. METHODS: We conducted a single-center, retrospective case-control study of premature infants diagnosed with BPD and either a small to large ASD or a small to moderate PDA from 2015 to 2021. The intervention group underwent transcatheter device occlusion of their defects and the control group did not. We compared changes in BPD severity over time between these two groups. RESULTS: The control and intervention groups demonstrated comparable baseline demographics. Of the 15 patients in the intervention group, 9 underwent PDA device occlusion and 6 underwent ASD device occlusion at median postmenstrual age of 42 weeks (IQR 41-45 weeks). Despite having higher severity BPD at baseline, there was a more pronounced improvement in BPD severity in the intervention group as compared to the control group. DISCUSSION: Premature infants with BPD and an ASD or PDA who underwent transcatheter occlusion of their lesion demonstrated a faster rate of improvement of their BPD severity as compared to a control cohort with similar lesions who did not undergo device occlusion of their lesion.

Anemia, apnea of prematurity, and blood transfusions.

OBJECTIVE: To compare the frequency and severity of apneic events in very low birth weight (VLBW) infants before and after blood transfusions using continuous electronic waveform analysis. STUDY DESIGN: We continuously collected waveform, heart rate, and oxygen saturation data from patients in all 45 neonatal intensive care unit beds at the University of Virginia for 120 weeks. Central apneas were detected using continuous computer processing of chest impedance, electrocardiographic, and oximetry signals. Apnea was defined as respiratory pauses of >10, >20, and >30 seconds when accompanied by bradycardia (<100 beats per minute) and hypoxemia (<80% oxyhemoglobin saturation as detected by pulse oximetry). Times of packed red blood cell transfusions were determined from bedside charts. Two cohorts were analyzed. In the transfusion cohort, waveforms were analyzed for 3 days before and after the transfusion for all VLBW infants who received a blood transfusion while also breathing spontaneously. Mean apnea rates for the previous 12 hours were quantified and differences for 12 hours before and after transfusion were compared. In the hematocrit cohort, 1453 hematocrit values from all VLBW infants admitted and breathing spontaneously during the time period were retrieved, and the association of hematocrit and apnea in the next 12 hours was tested using logistic regression. RESULTS: Sixty-seven infants had 110 blood transfusions during times when complete monitoring data were available. Transfusion was associated with fewer computer-detected apneic events (P < .01). Probability of future apnea occurring within 12 hours increased with decreasing hematocrit values (P < .001). CONCLUSIONS: Blood transfusions are associated with decreased apnea in VLBW infants, and apneas are less frequent at higher hematocrits.

Pausing TPN to Decrease Abnormal Newborn Screens: A NICU Quality Initiative.

Detection of metabolic and genetic disorders via the newborn screen (NBS) remains a great diagnostic achievement in medicine. Unfortunately, many false positives for neonates due to acute illness lead to repeat testing. For example, the rate of abnormal NBS in very low birth weight (VLBW) neonates at the University of Virginia was 66%, with 23% due to total parenteral nutrition (TPN) on the amino acid profile. Methods: This study describes a quality improvement (QI) initiative completed in the NICU at a quaternary care center. The primary and secondary outcomes were the percentage of abnormal NBSs in VLBWs and all admissions. The intervention required a pause in TPN, and a dextrose-containing fluid ran for 4 hours before collecting the NBS. During PDSA cycle 1, the TPN pause occurred at 1400, and the collection of the NBS occurred at 1800. During PDSA cycle 2, we aimed to decrease the number of blood draws per neonate and, thus, paused the TPN at 0000 to enable NBS collection at 0400 with routine morning laboratory work. Results: The rate of abnormal screens in VLBWs decreased from 66% to 49%; P < 0.006; 95% CI, 0.04-0.27, and the rate of abnormal screens in all admissions dropped from 45.2% to 28.8%; P < 0.0001; 95% CI, 0.06-0.51. Hospital costs decreased from $244.79 to $170.86 per patient in the cost of the NBS cards alone. Conclusion: By pausing TPN for 4 hours before drawing the NBS, we decreased the number of abnormal NBS in all admissions while also decreasing hospital costs.

Safety and efficacy of a home nasogastric monitoring program for premature infants.

BACKGROUND: A novel home monitoring program, in which premature infants are cared for at home with a nasogastric tube in place prior to achievement of full oral feeding, was evaluated. The program combines a digital, fully EMR-integrated, virtual daily rounding platform with direct provider video and telephone contact. METHODS: A case-control study was performed evaluating infants < 34 weeks' gestation who were followed in our program. A historical control group, was created by matching 2 : 1 based on gestational age±6 days, retroactively. RESULT: 15 patients discharged in the program were compared with 30 controls. The home cohort gained an average of 30 g/day compared with the in-hospital group at 27g/day (p = 0.325). The home group required a mean of 5.9±2.9 days to full oral feeding once discharged, not different from the control group at 5.4±3.7 days (p = 0.606). The percentage of oral feeds for the home cohort, however, increased at a rate of 12.2%before discharge compared to rising 57%at home (p < 0.001). The control group spent an additional 8.1±3.9 days in the hospital after reaching criteria. There were no reported adverse events or readmissions. CONCLUSION: Premature infants can safely advance oral feeds using a home monitoring program. While at home, infants gained weight similarly to their inpatient controls, yet gained full oral skills at a significantly faster rate compared to when they were in the hospital.

Time to regain birth weight predicts neonatal growth velocity: A single-center experience.

BACKGROUND: Failure to Thrive (FTT) describes the development of an inappropriate pattern of growth, generally secondary to inadequate nutritional intake, and is associated with several negative outcomes. We describe key features among neonates with FTT as well as the variables that predicted their growth after birth at a Neonatal Intensive Care Unit. METHODS: A retrospective single center study of 340 patients grouped into FTT (n = 100) and non-FTT (n = 240) was conducted. FTT was defined as having a weight <10th percentile on the Fenton 2013 curve at the time of discharge. For analyzing growth velocity, 204 patients were grouped into 4 quartiles based on their calculated growth velocity (grams/kilograms/day [g/kg/day]; 4th quartile had the highest velocity). Multivariate regression models were used to identify predictors of growth velocity. RESULTS: When comparing FTT vs. non-FTT patients, lower birth weights (1897.9 ± 561.4 vs. 2445.9 ± 783.0 g, t(255.1) = -7.2, p < 0.001) and higher growth velocities (9.2 ± 3.9 vs. 8.0 ± 4.1 g/kg/day, t(153.6) = 2.2, p = 0.03) were noted. Among patients with higher growth velocities, birth weights were lower (1st to 4th quartiles: 2474.0 ± 677.0, 2000.0 ± 297.0, 1715.0 ± 285.0, 1533.0 ± 332.0 g, F(3, 200) = 46.5, p < 0.001, adjusted R2 = 0.4). Days to regain birth weight was the most consistent predictor of growth velocity in our overall patient sample (ß [SE] = -0.3 [0.03], p < 0.001) and in the lowest growth velocity quartile subgroup (ß [SE] = -0.3 [0.04], p < 0.001). CONCLUSIONS: Days to regain birth weight was consistently the strongest predictor of neonatal growth velocity along with difference in gender positive predicting growth velocity in the total sample. This highlights the importance of the first week of life in growth pattern establishment.

Cholestasis affects enteral tolerance and prospective weight gain in the NICU.

BACKGROUND: Intestinal Failure-Associated Liver Disease is characterized by cholestasis and hepatic dysfunction due to parenteral nutrition (PN) therapy. We described key features of cholestatic infants receiving PN to assess overall outcomes in this population at our institution. METHODS: This is a retrospective single center study of 163 neonates grouped into cholestatic (n = 63) and non-cholestatic (n = 100) as defined by peak conjugated bilirubin of ≥2.0 mg/dL or < 0.8 mg/dL, respectively. Univariate and multiple regression models were used to study associations between variables and outcomes of interest. RESULTS: Lower Apgar scores (4 ± 3 vs. 6 ± 3, p-value = <0.005 at 1 min; 6 ± 2 vs. 7 ± 2, p < 0.005 at 5 min) and lower birth weight (adj ß [SE] = 0.62 [0.27], p-value = 0.024) were risk factors for developing cholestasis. Cholestatic infants were more likely to have had gastrointestinal surgery (31 [49%] vs. 15 [15%], p-value <0.005), received PN for a longer duration (40 ± 39 days vs. 11 ± 7 days, p-value <0.005), and started enteral feeds later in life (86 ± 23 days vs. 79 ± 20 days, p-value <0.005) when compared to non-cholestatic infants. Weight percentiles in cholestatic infants were lower both at hospital discharge (14 ± 19 vs. 24 ± 22, p-value <0.005) and at 6 months of age (24 ± 28 vs. 36 ± 31, p-value = 0.05). CONCLUSIONS: Cholestasis in the NICU is a multifactorial process, but it has a long lasting effect on prospective weight gain in infants who receive PN in the NICU. This finding highlights the importance of follow-up for adequate growth and the potential benefit from aggressive nutritional support.

Respiratory failure secondary to congenital pulmonary arterial thrombus with lung dysplasia.

Respiratory failure requiring extracorporeal membranous oxygenation in the newborn is commonly seen secondary to severe pathology such as congenital diaphragmatic hernia, meconium aspiration syndrome, pulmonary hypertension and pulmonary hypoplasia. However, atypical causes of respiratory failure, such as pulmonary arterial thrombi, are often refractory to traditional management and require careful multidisciplinary evaluation. We report a case of respiratory failure secondary to congenital pulmonary arterial thrombosis of unknown aetiology in an otherwise healthy neonate. We discuss the abnormal anatomy and pathophysiology that presented in our patient secondary to this condition and discuss our diagnostic process, management and outcomes. Additionally, we review the literature for reported cases and discuss current hypotheses on the development of congenital pulmonary arterial thrombi. Given the rare occurrence of this event, we hope to contribute to the understanding of future similar cases and emphasise the importance of keeping pulmonary arterial thrombi in the clinical differential.

Tough Decisions for Premature Triplets.

When infants are born at the borderline of viability, doctors and parents have to make tough decisions about whether to institute intensive care or provide only palliative care. Often, these decisions are made in moments of profound emotional turmoil, and parents receive different information from different health professionals. Communication can become garbled. It may be difficult to tell when and whether the patient's clinical condition has changed enough so that certain choices that had once been permissible become impermissible. In this "Ethics Rounds," we present a case of triplets born at the borderline of viability. We sought comments from the triplets' parents, the doctors and ethicist who were caring for the infants, and a bioethicist/neonatologist from another hospital.

NASCAR pit-stop model improves delivery room and admission efficiency and outcomes for infants <27 weeks' gestation.

AIM: To evaluate a new process based on teamwork in a manner similar to the race car pit stop on organization and efficiency during the "Golden Hours" for extremely preterm infants. METHODS: A team designed an improved process focused on checklists, preparation, assigning roles, and best practices, for the care of infants <27 weeks' gestation in the delivery room (DR) through admission to the neonatal intensive care unit (NICU). Clinical outcomes 2 years before and after implementation were analyzed. A survey was administered to NICU staff prior to and 14 months after implementation. The survey assessed organization and efficiency in the DR and during the admission process of the target population. RESULTS: There were 62 inborn infants prior to and 90 infants after implementation with overall survival of 90.3% and 86.6%, respectively (p = 0.61). Infants were more stable on admission with a mean arterial blood pressure equal to or greater than their gestational age in the post intervention group compared to the pre-cohort (76% vs 57%, p = 0.02) and discharged home at a lower mean postmenstrual age (39.0 ± 2.2 vs 40.1 ± 3.5 weeks, p = 0.04) The survey demonstrated improvement in assessment of roles being clearly defined in the DR and in the organization and the efficiency both in the DR and during the NICU admission (p < 0.05). CONCLUSIONS: A systematic approach to the care of the <27 weeks' gestation neonate increased staff perception of improved organization and efficiency in the DR through admission processes and improved outcomes.

Very long apnea events in preterm infants.

Apnea is nearly universal among very low birth weight (VLBW) infants, and the associated bradycardia and desaturation may have detrimental consequences. We describe here very long (>60 s) central apnea events (VLAs) with bradycardia and desaturation, discovered using a computerized detection system applied to our database of over 100 infant years of electronic signals. Eighty-six VLAs occurred in 29 out of 335 VLBW infants. Eighteen of the 29 infants had a clinical event or condition possibly related to the VLA. Most VLAs occurred while infants were on nasal continuous positive airway pressure, supplemental oxygen, and caffeine. Apnea alarms on the bedside monitor activated in 66% of events, on average 28 s after cessation of breathing. Bradycardia alarms activated late, on average 64 s after cessation of breathing. Before VLAs oxygen saturation was unusually high, and during VLAs oxygen saturation and heart rate fell unusually slowly. We give measures of the relative severity of VLAs and theoretical calculations that describe the rate of decrease of oxygen saturation. A clinical conclusion is that very long apnea (VLA) events with bradycardia and desaturation are not rare. Apnea alarms failed to activate for about one-third of VLAs. It appears that neonatal intensive care unit (NICU) personnel respond quickly to bradycardia alarms but not consistently to apnea alarms. We speculate that more reliable apnea detection systems would improve patient safety in the NICU. A physiological conclusion is that the slow decrease of oxygen saturation is consistent with a physiological model based on assumed high values of initial oxygen saturation.

Breath-by-breath analysis of cardiorespiratory interaction for quantifying developmental maturity in premature infants.

In healthy neonates, connections between the heart and lungs through brain stem chemosensory pathways and the autonomic nervous system result in cardiorespiratory synchronization. This interdependence between cardiac and respiratory dynamics can be difficult to measure because of intermittent signal quality in intensive care settings and variability of heart and breathing rates. We employed a phase-based measure suggested by Schäfer and coworkers (Schäfer C, Rosenblum MG, Kurths J, Abel HH. Nature 392: 239-240, 1998) to obtain a breath-by-breath analysis of cardiorespiratory interaction. This measure of cardiorespiratory interaction does not distinguish between cardiac control of respiration associated with cardioventilatory coupling and respiratory influences on the heart rate associated with respiratory sinus arrhythmia. We calculated, in sliding 4-min windows, the probability density of heartbeats as a function of the concurrent phase of the respiratory cycle. Probability density functions whose Shannon entropy had a <0.1% chance of occurring from random numbers were classified as exhibiting interaction. In this way, we analyzed 18 infant-years of data from 1,202 patients in the Neonatal Intensive Care Unit at University of Virginia. We found evidence of interaction in 3.3 patient-years of data (18%). Cardiorespiratory interaction increased several-fold with postnatal development, but, surprisingly, the rate of increase was not affected by gestational age at birth. We find evidence for moderate correspondence between this measure of cardiorespiratory interaction and cardioventilatory coupling and no evidence for respiratory sinus arrhythmia, leading to the need for further investigation of the underlying mechanism. Such continuous measures of physiological interaction may serve to gauge developmental maturity in neonatal intensive care patients and prove useful in decisions about incipient illness and about hospital discharge.

A new algorithm for detecting central apnea in neonates.

Apnea of prematurity is an important and common clinical problem, and is often the rate-limiting process in NICU discharge. Accurate detection of episodes of clinically important neonatal apnea using existing chest impedance (CI) monitoring is a clinical imperative. The technique relies on changes in impedance as the lungs fill with air, a high impedance substance. A potential confounder, however, is blood coursing through the heart. Thus, the cardiac signal during apnea might be mistaken for breathing. We report here a new filter to remove the cardiac signal from the CI that employs a novel resampling technique optimally suited to remove the heart rate signal, allowing improved apnea detection. We also develop an apnea detection method that employs the CI after cardiac filtering. The method has been applied to a large database of physiological signals, and we prove that, compared to the presently used monitors, the new method gives substantial improvement in apnea detection.