Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal–Wallis analysis were performed using SAS version 9.4. Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values.

Introduction Congenital diaphragmatic hernia is a complex disease associated with pulmonary hypoplasia and hypertension. Fetoscopic endoluminal tracheal occlusion (FETO) has been shown to improve survival and pulmonary hypertension, however, is associated with tracheomegaly. We aim to describe neonatal tracheomegaly, airway management, and outcomes following FETO. Methods A single-center retrospective cohort review was performed for congenital diaphragmatic hernia patients who received FETO at our institution (4/12-6/22). Those with fetal demise, death at delivery, and those awaiting delivery were excluded. Demographics and perinatal outcomes were collected. Tracheal measurements were collected from initial postnatal chest x-ray by a single radiologist. Data were analyzed with descriptive analysis. Results 34 patients underwent FETO with a median gestational age at a diagnosis of 23 wk [IQR 20-26] and at delivery of 36 wk [IQR 34-37]. Tracheomegaly was noted in 24 patients. The median maximum tracheal diameter was 9.9 mm [IQR 8.7-10.5]. All patients were intubated at birth. Ten (29%) eventually received a cuffed endotracheal tube (ETT), with 7/10 switched from an uncuffed ETT due to clinical concerns (i.e., large air leak) and 3/10 initially intubated with cuffed ETT. Nine (26%) patients underwent airway endoscopy, with two initially intubated with cuffed ETT compared to 7 with uncuffed ETT. A maximum of five endoscopies were performed on a single patient initially intubated with an uncuffed ETT, compared to 2 with cuffed ETT. Conclusions Given the need for multiple reintubations and use of airway endoscopies following FETO in patients with and without tracheomegaly, the placement of larger or cuffed ETT may be considered in initial resuscitation of FETO patients.

OBJECTIVE:To develop a consensus guideline to meet nutritional challenges faced by infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN:The CDH Focus Group utilized a modified Delphi method to develop these clinical consensus guidelines (CCG). Topic leaders drafted recommendations after literature review and group discussion. Each recommendation was sent to focus group members via a REDCap survey tool, and members scored on a Likert scale of 0-100. A score of > 85 with no more than 25% outliers was designated a priori as demonstrating consensus among the group. RESULTS:In the first survey 24/25 recommendations received a median score > 90 and after discussion and second round of surveys all 25 recommendations received a median score of 100. CONCLUSIONS:We present a consensus evidence-based framework for managing parenteral and enteral nutrition, somatic growth, gastroesophageal reflux disease, chylothorax, and long-term follow-up of infants with CDH.

Introduction Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of fetoscopic endoluminal tracheal occlusion (FETO) has added further complexity. While FETO has been shown to improve survival outcomes, there are risks of prematurity and potential surfactant deficiency. We aim to evaluate the characteristics and outcomes of surfactant administration for CDH infants and elucidate potential benefits or risks in this unique population. Methods A single-center retrospective cohort review of patients with unilateral CDH from September 2015 to July 2022 was performed. Demographics, prognostic perinatal imaging features, and outcomes were collected. Patients were stratified by surfactant administration and history of FETO. Data were analyzed with descriptive statistics, two-sample t-tests, chi-squared analyses, and logistic regression. Results Of 105 included patients, 19 (18%) underwent FETO and 25 (24%) received surfactant. Overall, surfactant recipients were born at earlier gestational ages and lower birthweights regardless of FETO history. Surfactant recipients possessed significantly worse prenatal prognostic features such as observed to expected total fetal lung volume, observed to expected lung to head ratio, and percent liver herniation. In CDH patients without FETO history, surfactant recipients demonstrated worse outcomes than nonrecipients. This association is notably absent in the FETO population, where surfactant recipients have more favorable survival and comparable outcomes. When controlling for defect severity or surfactant usage, as a proxy for respiratory status, surfactant recipients that underwent FETO trended toward improved survival and decreased ECMO use. Conclusions Surfactant administration is not associated with increased morbidity and mortality and may be beneficial in CDH patients that have undergone FETO.

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values.

Background: Premature infants are born with immature cerebral autoregulation function and are vulnerable to pressure passive cerebral circulation and subsequent brain injury. Measurements derived from near-infrared spectroscopy (NIRS) have enabled continuous assessment of cerebral vasoreactivity. Although NIRS has enabled a growing field of research, the lack of clear standardization in the field remains problematic. A major limitation of current literature is the absence of a comparative analysis of the different methodologies. Objectives: To determine the relationship between NIRS-derived continuous indices of cerebral autoregulation in a cohort of extremely low birth weight (ELBW) infants. Methods: Premature infants of birth weight 401–1000 g were studied during the first 72 h of life. The cerebral oximetry index (COx), hemoglobin volume index (HVx), and tissue oxygenation heart rate reactivity index (TOHRx) were simultaneously calculated. The relationship between each of the indices was assessed with Pearson correlation. Results: Fifty-eight infants with a median gestational age of 25.8 weeks and a median birth weight of 738 g were included. Intraventricular hemorrhage (IVH) was detected in 33% of individuals. COx and HVx demonstrated the highest degree of correlation, although the relationship was moderate at best (r = 0.543, p < 0.001). No correlation was found either between COx and TOHRx (r = 0.318, p < 0.015) or between HVx and TOHRx (r = 0.287, p < 0.029). No significant differences in these relationships were found with respect to IVH and no IVH in subgroup analysis. Conclusions: COx, HVx, and TOHRx are not numerically equivalent. Caution must be applied when interpreting or comparing results based on different methodologies for measuring cerebral autoregulation. Uniformity regarding data acquisition and analytical methodology are needed to firmly establish a gold standard for neonatal cerebral autoregulation monitoring.

Introduction: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH). Methods: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity. Results: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a <10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO <10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008–0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01–0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31–47.04; p = 0.024). Conclusion: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders.

La hernia diafragmática congénita es una afección rara pero potencialmente mortal en la que los órganos abdominales se hernian en la cavidad torácica, lo que conduce a la hipoplasia pulmonar y la dificultad respiratoria. Existe variabilidad inter-institucional para el manejo, y en este documento presenta las recomendaciones, basadas en evidencia, respecto al manejo en sala de partos, soportes respiratorio, hemodinámico y nutricional, sedación, y acceso vascular. Un adecuado manejo preoperatorio es fundamental para estabilizar a estos neonatos antes de la corrección quirúrgica, con el objetivo de mejorar la función pulmonar y el bienestar neonatal en general. En este documento, se detalla el enfoque preoperatorio empleado por el Texas Children's Hospital para el manejo de la hernia diafragmática congénita.

Cerebrovascular reactivity defines the ability of the cerebral vasculature to regulate its resistance in response to both local and systemic factors to ensure an adequate cerebral blood flow to meet the metabolic demands of the brain. The increasing adoption of near-infrared spectroscopy (NIRS) for non-invasive monitoring of cerebral oxygenation and perfusion allowed investigation of the mechanisms underlying cerebrovascular reactivity in the neonatal population, confirming important associations with pathological conditions including the development of brain injury and adverse neurodevelopmental outcomes. However, the current literature on neonatal cerebrovascular reactivity is mainly still based on small, observational studies and is characterised by methodological heterogeneity; this has hindered the routine application of NIRS-based monitoring of cerebrovascular reactivity to identify infants most at risk of brain injury. This review aims (1) to provide an updated review on neonatal cerebrovascular reactivity, assessed using NIRS; (2) to identify critical points that need to be addressed with targeted research; and (3) to propose feasibility trials in order to fill the current knowledge gaps and to possibly develop a preventive or curative approach for preterm brain injury.ImpactNIRS monitoring has been largely applied in neonatal research to assess cerebrovascular reactivity in response to blood pressure, PaCO2 and other biochemical or metabolic factors, providing novel insights into the pathophysiological mechanisms underlying cerebral blood flow regulation. Despite these insights, the current literature shows important pitfalls that would benefit to be addressed in a series of targeted trials, proposed in the present review, in order to translate the assessment of cerebrovascular reactivity into routine monitoring in neonatal clinical practice.

The critical closing pressure (CrCP) of the cerebral vasculature is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. Because the ABP of preterm infants is low and close to the CrCP, there is often no CBF during diastole. Thus, estimation of CrCP may become clinically relevant in preterm neonates. Transcranial Doppler (TCD) ultrasound has been used to estimate CrCP in preterm infants. Diffuse correlation spectroscopy (DCS) is a continuous, noninvasive optical technique that measures microvascular CBF. Our objective was to compare and validate CrCP measured by DCS versus TCD ultrasound. Hemorrhagic shock was induced in 13 neonatal piglets, and CBF was measured continuously by both modalities. CrCP was calculated using a model of cerebrovascular impedance, and CrCP determined by the two modalities showed good correlation by linear regression, median r 2 = 0.8 (interquartile range (IQR) 0.71-0.87), and Bland-Altman analysis showed a median bias of -3.5 (IQR -4.6 to -0.28). This is the first comparison of CrCP determined by DCS versus TCD ultrasound in a neonatal piglet model of hemorrhagic shock. The difference in CrCP between the two modalities may be due to differences in vasomotor tone within the microvasculature of the cerebral arterioles versus the macrovasculature of a major cerebral artery.

A novel technique was used to calculate pulse pressure variation. The algorithm reliably predicted fluid responsiveness to transfusion, with a receiver operating characteristic area under the curve of 0.89. This technique may assist clinicians in the management of fluids and vasoactive medications for premature infants.

Introduction: Although patent ductus arteriosus (PDA) has been implicated to play a role in the development of cerebral ischemia and intraventricular hemorrhage (IVH) through a cerebral steal phenomenon, there is conflicting data on the impact of PDA size on cerebral blood flow (CBF). Cerebral autoregulation is the brain’s innate protective mechanism to maintain constant CBF despite changes in blood pressure, and it is unclear if it is influenced by PDA hemodynamics. Objective: To delineate the relationship between PDA size and CBF velocity (CBFv) in premature infants. Methods: 113 premature infants born at 23–29 weeks’ gestation had echocardiograms performed during the first week after birth to evaluate for PDA. The infants were divided into 3 groups according to PDA size: none-to-small, moderate, or large. All infants had continuous recordings of umbilical artery blood pressure (ABP) and CBFv during the first week after birth. Critical closing pressure (CrCP) was calculated from ABP and CBFv tracings. Diastolic closing margin (DCM), defined as diastolic blood pressure minus CrCP, was calculated as a marker for the risk of developing IVH. Results: Infants with a large PDA (n = 16) had the lowest ABP across all phases of the cardiac cycle (systole [p = 0.003], mean [p = 0.005], and diastole [p = 0.012]) compared to infants with a moderate (n = 19) or none-to-small PDA (n = 78). Despite blood pressure being different, systolic, mean, and diastolic CBFv were not different across groups. Cerebral autoregulation, as measured during systole, was intact regardless of the PDA size. CrCP and DCM were also not different across groups. Conclusions: In this cohort, CBFv and cerebral autoregulation during systole were not influenced by PDA size. Intact cerebral autoregulation may play a role in maintaining CBFv regardless of PDA size and differences in ABP.

Background Creatinine values are unreliable within the first weeks of life; however, creatinine is used most commonly to assess kidney function. Controversy remains surrounding the time required for neonates to clear maternal creatinine. Methods Eligible infants had multiple creatinine lab values and were admitted to the neonatal intensive care unit (NICU). A mathematical model was fit to the lab data to estimate the filtration onset delay, creatinine filtration half-life, and steady-state creatinine concentration for each subject. Infants were grouped by gestational age (GA) [(1) 22–27, (2) >27–32, (3) >32–37, and (4) >37–42 weeks]. Results A total of 4808 neonates with a mean GA of 34.4 ± 5 weeks and birth weight of 2.34 ± 1.1 kg were enrolled. Median (95% confidence interval) filtration onset delay for Group 1 was 4.3 (3.71, 4.89) days and was significantly different than all other groups ( p < 0.001). Creatinine filtration half-life of Groups 1, 2, and 3 were significantly different from each other ( p < 0.001). There was no difference in steady-state creatinine concentration among the groups. Conclusions We quantified the observed kidney behavior in a large NICU population as a function of day of life and GA using creatinine lab results. These results can be used to interpret individual creatinine labs for infants to detect those most at risk for acute kidney injury. Impact One of the largest cohorts of premature infants to describe the evolution of kidney development and function over their entire hospitalization. New concept introduced of the kidney filtration onset delay, the time needed for the kidney to begin clearance of creatinine, and that it can be used as an early indicator of kidney function. The smallest premature infants from 22 to 27 weeks gestation took the longest time to begin and complete maternal creatinine clearance. Clinicians can easily compare the creatinine level of their patient to the normative curves to improve understanding of kidney function at the bedside

Cruz, Stephanie MD; Lau, Patricio E. MD; Rusin, Craig PhD; Style, Candace MD; Ocampo, Elena MD; Rhee, Christopher MD; Brady, Kenneth M. MD; Andropoulos, Dean B. MD; Olutoye, Oluyinka O. MBChB, PhD, FACS Author Information

Background Cerebrovascular critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow ceases. Preterm ABP is low and close to CrCP. The diastolic closing margin (diastolic ABP minus CrCP) has been associated with intraventricular hemorrhage in preterm infants. CrCP is estimated from middle cerebral artery cerebral blood flow velocity (CBFV) and ABP waveforms. However, these estimations have not been validated due to a lack of gold standard. Direct observation of the CrCP in preterm infants with hypotension is an opportunity to validate synchronously estimated CrCP. Methods ABP and CBFV tracings were obtained from 24 extremely low birth weight infants. Recordings where diastolic CBFV was zero were identified. The gold standard CrCP was delineated using piecewise regression of ABP and CBFV values paired by rank ordering and then estimated using a published formula. The measured and estimated values were compared using linear regression and Bland–Altman analysis. Results Linear regression showed a high degree of correlation between measured and calculated CrCP ( r 2 = 0.93). Conclusions This is the first study to validate a calculated CrCP by comparing it to direct measurements of CrCP from preterm infants when ABP is lower than CrCP.

Hypoxic–ischemic encephalopathy (HIE) remains a significant cause of mortality and neurodevelopmental impairment despite treatment with therapeutic hypothermia. Magnetic resonance H1-spectroscopy measures concentrations of cerebral metabolites to detect derangements in aerobic metabolism. We assessed MR spectroscopy in neonates with HIE within 18–24 h of initiating therapeutic hypothermia and at 5–6 days post therapeutic hypothermia. Eleven neonates with HIE underwent MR spectroscopy of the basal ganglia and white matter. We compared metabolite concentrations during therapeutic hypothermia and post-therapeutic hypothermia and between moderate and severe HIE. During therapeutic hypothermia, neonates with severe HIE had decreased basal ganglia N-acetylaspartate (NAA; 0.62±0.08 vs. 0.72±0.05; P=0.02), NAA + N-acetylaspartylglutamate (NAAG; 0.66±0.11 vs. 0.77±0.06; P=0.05), glycerophosphorylcholine + phosphatidylcholine (GPC+PCh; 0.28±0.05 vs. 0.38±0.06; P=0.02) and decreased white matter GPC+PCh (0.35±0.13 vs. 0.48±0.04; P=0.02) compared to neonates with moderate HIE. For all subjects, basal ganglia NAA decreased (−0.08±0.07; P=0.01), whereas white matter GPC+PCh increased (0.03±0.04; P=0.04) from therapeutic hypothermia MRI to post-therapeutic-hypothermia MRI. All metabolite values are expressed in mmol/L. Decreased NAA and GPC+PCh were associated with greater HIE severity and could distinguish neonates who might benefit most from targeted additional neuroprotective therapies.

Objective This study aimed to evaluate the association between acute kidney injury (AKI) and lung outcomes in infants born >= 32 weeks of gestational age (GA). Study Design Secondary analysis of infants >= 32 weeks of GA in the assessment of worldwide acute kidney injury epidemiology in neonates (AWAKEN) retrospective cohort ( n = 1,348). We used logistic regression to assess association between AKI and a composite outcome of chronic lung disease (CLD) or death at 28 days of age and linear regression to evaluate association between AKI and duration of respiratory support. Results CLD occurred in 82/1,348 (6.1%) infants, while death occurred in 22/1,348 (1.6%); the composite of CLD/death occurred in 104/1,348 (7.7%). Infants with AKI had an almost five-fold increased odds of CLD/death, which remained after controlling for GA, maternal polyhydramnios, multiple gestations, 5-minute Apgar's score, intubation, and hypoxic-ischemic encephalopathy (adjusted odds ratio [OR] = 4.9, 95% confidence interval [CI]: 3.2-7.4; p < 0.0001). Infants with AKI required longer duration of respiratory support (count ratio = 1.59, 95% CI: 1.14-2.23, p = 0.003) and oxygen (count ratio = 1.43, 95% CI: 1.22-1.68, p < 0.0001) compared with those without AKI. Conclusion AKI is associated with CLD/death and longer duration of respiratory support in infants born at >= 32 weeks of GA. Further prospective studies are needed to elucidate the pathophysiologic relationship.

Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes.

Background Most studies of neonatal acute kidney injury (AKI) have focused on the first week following birth. Here, we determined the outcomes and risk factors for late AKI (>7d). Methods The international AWAKEN study examined AKI in neonates admitted to an intensive care unit. Late AKI was defined as occurring >7 days after birth according to the KDIGO criteria. Models were constructed to assess the association between late AKI and death or length of stay. Unadjusted and adjusted odds for late AKI were calculated for each perinatal factor. Results Late AKI occurred in 202/2152 (9%) of enrolled neonates. After adjustment, infants with late AKI had higher odds of death (aOR:2.1, p = 0.02) and longer length of stay (parameter estimate: 21.9, p < 0.001). Risk factors included intubation, oligo- and polyhydramnios, mild-moderate renal anomalies, admission diagnoses of congenital heart disease, necrotizing enterocolitis, surgical need, exposure to diuretics, vasopressors, and NSAIDs, discharge diagnoses of patent ductus arteriosus, necrotizing enterocolitis, sepsis, and urinary tract infection. Conclusions Late AKI is common, independently associated with poor short-term outcomes and associated with unique risk factors. These should guide the development of protocols to screen for AKI and research to improve prevention strategies to mitigate the consequences of late AKI.