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As the approach to the patent ductus arteriosus (PDA) in the preterm infant remains controversial, the potential consequences of a significant ductal shunt on the brain should be evaluated. In this population at high risk of adverse outcomes, including intraventricular haemorrhage and white matter injury, as well as longer-term neurodevelopmental impairment, it is challenging to attribute sequelae to the PDA. Moreover, individual patient characteristics including gestational age and timing of PDA intervention factor into risks of brain injury. Haemodynamic assessment of the ductus combined with bedside neuromonitoring techniques improve our understanding of the role of the PDA in neurological injury. Effects of various PDA management strategies on the brain can similarly be investigated. This review incorporates current understanding of how the PDA impacts the developing brain of preterm infants and examines modalities to measure these effects.

ispartof: NEONATOLOGY vol:119 issue:6 pages:792-794 ispartof: location:Switzerland status: published

Brain injury is one of the most consequential problems facing neonates, with many preterm and term infants at risk for cerebral hypoxia and ischemia. To develop effective neuroprotective strategies, the mechanistic basis for brain injury must be understood. The fragile state of neonates presents unique research challenges; invasive measures of cerebral blood flow and oxygenation assessment exceed tolerable risk profiles. Near-infrared spectroscopy (NIRS) can safely and non-invasively estimate cerebral oxygenation, a correlate of cerebral perfusion, offering insight into brain injury-related mechanisms. Unfortunately, lack of standardization in device application, recording methods, and error/artifact correction have left the field fractured. In this article, we provide a framework for neonatal NIRS research. Our goal is to provide a rational basis for NIRS data capture and processing that may result in better comparability between studies. It is also intended to serve as a primer for new NIRS researchers and assist with investigation initiation.

Prematurity is a common risk factor in children, affecting approximately 10% of live births, globally. It is more common in children with critical congenital heart disease (CCHD) and carries important implications in this group of patients. While outcomes have been improving over the years, even late preterm birth is associated with worse outcomes in children born with critical congenital heart disease compared to those without. Infants with both prematurity and CCHD are at particularly high risk for important comorbidities, including: necrotizing enterocolitis, intraventricular hemorrhage, white matter injury, neurodevelopmental anomalies and retinopathy of prematurity. Lesion-specific intensive care management of these infants, interventional and peri-operative management specifically tailored to their needs, and multidisciplinary care all have the potential to improve outcomes in this challenging group.

Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

BACKGROUND Theophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies. METHODS A population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5 mg/kg intravenous (i.v.) load then 1.8 mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10 mg/L) associated with clinical response was examined. RESULTS Birth weight was a significant predictor of theophylline clearance and volume of distribution (p

BACKGROUND Neonates with hypoxic-ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied. METHODS A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline. RESULTS Sixteen neonates cooled for HIE received aminophylline starting at 25 ± 14 h of life. Within 12 h of starting aminophylline, UOP increased by 2.6 ± 1.9 mL/kg/h. SCr declined by 0.4 ± 0.2 mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group (p

To determine the association between prenatal ultrasound (US) and magnetic resonance imaging (MRI) characteristics in right congenital diaphragmatic hernia (RCDH) with postnatal outcome.CDH Study Group data were reviewed for all RCDH infants (n = 156) born between 2015 and 2019. Prenatal US and MRI lung size measurements were correlated with survival, extracorporeal life support (ECLS), and defect size.Overall survival was 64.1%. ECLS was required in 40.4%. US and MRI-based prenatal assessment of pulmonary hypoplasia does not predict survival. Prenatal measurement of lung size using either US or MRI correlates with ECLS use. Only MRI-based measures of lung size are associated with defect size.Image-based prenatal predictors of survival, ECLS, and defect size are of limited value in RCDH. Extrapolation of prenatal survival and morbidity indicators from left to right-sided CDH is not appropriate. There is an urgent need to develop RCDH prenatal prediction models.

Objective The objective of this article was to correlate hypotension and cerebral saturation from near-infrared spectroscopy (cNIRS) in neonates on dopamine. Study Design Retrospective review of neonates receiving dopamine between August 2018 and 2019 was performed. Hypotension thresholds included mean arterial pressure (MAP) of postmenstrual age (PMA) ± 5 and 30 mm Hg and gestational age (GA) ± 5 mm Hg. Time below threshold MAP was compared with time with cerebral hypoxia (cNIRS Results Hypotension occurred 6 to 33% of the time on dopamine in 59 cases. Hypotension did not correlate with abnormal cNIRS overall, within PMA subgroups or by outcomes. Hypotensive periods with MAP Conclusion cNIRS may be a more clinically relevant measure than MAP for the assessment of neonatal hypotension. Key Points

To evaluate multi-organ dysfunction (MOD) in newborns treated with therapeutic hypothermia (TH) for hypoxic ischemic encephalopathy (HIE), and to compare MOD in those with normal/mild magnetic resonance imaging (MRI) findings to those with moderate to severe MRI findings or death.Retrospective single-center observational study of infants treated with TH. A total of 16 parameters across 7 organ systems were analyzed. Primary outcome was death or moderate to severe brain injury on MRI.Of 157 infants treated with TH, 77% had ≥2 organ systems with dysfunction. The number of organ systems with dysfunction was strongly associated with death or moderate-to-severe brain injury (p 0.0001). Hematologic (68%) and hepatic (65%) dysfunction were most common. Neurologic and renal dysfunction were most strongly associated with the primary outcome (OR 13.5 [6.1-29.8] and 11.2 [4.1-30.3], respectively), while pulmonary hypertension was not.MOD is prevalent in infants undergoing TH for HIE, and the association between MOD and adverse outcomes may impact clinical care and counseling.

OBJECTIVE: To describe renal regional saturation of oxygen (RrSO(2)) values during the first week of life for preterm neonates born at

Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p 0.001).Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population.Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

Objective Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE). Study design Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions. Results A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p = 0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p = 0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p = 0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction. Conclusion Newborns who died or had moderate-to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities. Key points · Newborns with HIE with functional LV/RV dysfunction are at risk for death or brain injury.. · All neonates with HIE had elevated pulmonary pressure, but neonates with poor outcome had RV dysfunction.. · When evaluating newborns with HIE by echocardiography, beyond estimation of pulmonary pressure, it is important to assess biventricular function..

Background Understanding factors that impact tissue oxygen extraction may guide red blood cell (RBC) transfusion decision making in preterm infants. Our objective was to assess the influence of enteral feeding and anemia on cerebral and mesenteric oxygen saturation (Csat and Msat) and fractional tissue oxygen extraction (cFTOE and mFTOE) over the entire time course of RBC transfusion. Study design and methods Preterm, very low-birth-weight infants receiving RBC transfusions at a single center were enrolled. Near-infrared spectroscopy sensors measured Csat and Msat levels from an hour before transfusion to 24 hours after. During this period, changes in Csat, Msat, cFTOE, and mFTOE were described, and their association with enteral feeding status and pretransfusion degree of anemia were assessed using generalized estimating equations. Results RBC transfusion data from 31 preterm infants were included. Infants receiving enteral feeds exhibited lower pretransfusion Msat. Infants with pretransfusion hematocrit greater than 30% exhibited higher pretransfusion Csat and lower pretransfusion cFTOE. Such differences in baseline measurements persisted through 24 hours after transfusion. However, no statistically significant differences in oxygenation measures over time by enteral feeding or anemia status were identified. Conclusion Compared to NPO, enteral feeding was associated with lower Msat; anemia (hematocrit ≤30%) was associated with lower Csat and higher cFTOE. Over the time course of RBC transfusion, trajectories of Csat, Msat, cFTOE and mFTOE did not differ by enteral feeding or anemia status.

To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases. Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed. Out of 63 fetal cases, 33 were live-born, > 50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach to omphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3–422), p = 0.006). Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

We assessed the utility of near-infrared spectroscopy to evaluate neonates with mitochondrial disorders. We observed abnormally high cerebral oxygen saturation levels indicating insufficient tissue oxygen utilization. We propose that near-infrared spectroscopy may be an additional tool in the diagnostic evaluation of a suspected mitochondrial disorder.

The Induced Hypothermia (IH) and Optimizing Cooling (OC) trials for hypoxic–ischemic encephalopathy (HIE) had similar inclusion criteria. The rate of death/moderate–severe disability differed for the subgroups treated with therapeutic hypothermia (TH) at 33.5 °C for 72 h (44% vs. 29%, unadjusted p = 0.03). We aimed to evaluate differences in patient characteristics and care practices between the trials. We compared pre/post-randomization characteristics and care practices between IH and OC. There were 208 patients in the IH trial, 102 cooled, and 364 in the OC trial, 95 cooled to 33.5 °C for 72 h. In OC, neonates were less ill, fewer had severe HIE, and the majority were cooled prior to randomization. Differences between IH and OC were observed in the adjusted difference in the lowest PCO2 (+3.08 mmHg, p = 0.005) and highest PO2 (−82.7 mmHg, p

Kidney dysfunction and acute kidney injury (AKI) frequently accompanies neonatal encephalopathy and contributes to neonatal morbidity and mortality. While there are currently no proven therapies for the treatment of AKI, understanding the pathophysiology along with early recognition and treatment of alterations in fluid, electrolyte and metabolic homeostasis that accompany AKI offer opportunity to reduce associated morbidity. Promising new tests and technologies, including urine and serum biomarkers and renal near-infrared spectroscopy offer opportunities to improve diagnosis and monitoring of neonates at risk for kidney injury. Furthermore, recent advances in neonatal kidney supportive therapies such as hemofiltration and hemodialysis may further improve outcomes in this population. This chapter provides an overview of disorders of fluid balance, electrolyte homeostasis and kidney function associated with neonatal encephalopathy and therapeutic hypothermia. Recommendations for fluid and electrolyte management based upon published literature and authors' opinions are provided.

Background Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO. Methods Newborns Results Forty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3 ± 3.8 weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE. Conclusions NIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.

Objective To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. Study design We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. Results AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. Conclusions Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

BACKGROUND Near-infrared spectroscopy measures cerebral saturation (Csat), although correlation with cerebral blood flow remains unclear in premature newborns at risk for intraventricular hemorrhage (IVH). OBJECTIVES Compare Doppler markers of anterior cerebral artery (ACA) flow with Csat obtained during head ultrasound (HUS). METHOD Newborns

Background: Previous studies describe a short-term decrease in cerebral oxygen saturation (StO2) after intraventricular hemorrhage (IVH) in premature infants; little is known about long-term implications. Methods: Infants born

The American Academy of Pediatrics classifies neonatal intensive care units (NICUs) from level I to IV based on the acuity of care each unit can provide. Birth in a higher level center is associated with lower morbidity and mortality in high-risk populations. Congenital heart disease accounts for 25-50% of infant mortality related to birth defects in the U.S., but recent data are lacking on where infants with critical congenital heart disease (CCHD) are born. We used a linked dataset from the Office of Statewide Health Planning and Development to access ICD-9 diagnosis codes for all infants born in California from 2008 to 2012. We compared infants with CCHD to the general population, identified where infants with CCHD were born based on NICU level of care, and predicted level IV birth among infants with CCHD using logistic regression techniques. From 2008 to 2012, 6325 infants with CCHD were born in California, with 23.7% of infants with CCHD born at a level IV NICU compared to 8.4% of the general population. Level IV birth for infants with CCHD was associated with lower gestational age, higher maternal age and education, the presence of other congenital anomalies, and the diagnosis of a single ventricle lesion. More infants with CCHD are born in a level IV NICU compared to the general population. Future studies are needed to determine if birth in a lower level of care center impacts outcomes for infants with CCHD.

Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM). Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children’s Hospital Stanford 1/1/2009–6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated. A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related. Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.

Objective Many critically ill neonates have an existing brain injury or are at risk of neurologic injury. We developed a “NeuroNICU” (neurologic neonatal intensive care unit) to better provide neurologically focused intensive care. Study Design Demographic and clinical variables, services delivered, and patient outcomes were recorded in a prospective database for all neonates admitted to the NeuroNICU between April 23, 2013, and June 25, 2015. Results In total, 546 neonates were admitted to the NeuroNICU representing 32% of all NICU admissions. The most common admission diagnoses were congenital heart disease (30%), extreme prematurity (18%), seizures (10%), and hypoxic–ischemic encephalopathy (9%). Neuromonitoring was common, with near-infrared spectroscopy used in 69%, amplitude-integrated electroencephalography (EEG) in 45%, and continuous video EEG in 35%. Overall, 43% received neurology or neurosurgery consultation. Death prior to hospital discharge occurred in 11%. Among survivors, 87% were referred for developmental follow-up, and among those with a primary neurologic diagnosis 57% were referred for neurology or neurosurgical follow-up. Conclusion The NeuroNICU-admitted newborns with or at risk of brain injury comprise a high percentage of NICU volume; 38% had primary neurologic diagnoses, whereas 62% had medical diagnoses. We found many opportunities to provide brain focused intensive care, impacting a substantial proportion of newborns in our NICU.

To determine in-hospital morbidities for neonates with right-sided congenital diaphragmatic hernia (R-CDH) compared with those with left-sided defects (L-CDH) and to examine the differential effect of laterality and defect size on morbidities.This retrospective, multicenter, cohort study from the international Congenital Diaphragmatic Hernia Study Group registry collected data from neonates with CDH surviving until hospital discharge from 90 neonatal intensive care units between January 1, 2007, and July 31, 2020. Major pulmonary, cardiac, neurologic, and gastrointestinal morbidities were compared between neonates with L-CDH and R-CDH, adjusted for prenatal and postnatal factors using logistic regression.Of 4123 survivors with CDH, those with R-CDH (n = 598 [15%]) compared with those with L-CDH (n = 3525 [85%]) had an increased odds of pulmonary (1.7; 95% CI, 1.4-2.2, P .0001), cardiac (1.4; 95% CI, 1.1-1.8; P = .01), gastrointestinal (1.3; 95% CI, 1.1-1.6; P = .01), and multiple (1.6; 95% CI, 1.2-2.0; P .001) in-hospital morbidities, with a greater likelihood of morbidity with increasing defect size. There was no difference in neurologic morbidities between the groups.Neonates with R-CDH and a larger defect size are at an increased risk for in-hospital morbidities. Counseling and clinical strategies should incorporate knowledge of these risks, and approach to neonatal R-CDH should be distinct from current practices targeted to L-CDH.

Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome. Simultaneous use of these monitoring modalities may improve our ability to provide meaningful prognostic information regarding ongoing treatments. Evidence will be summarized in this review for each of these modalities, by describing (1) the methods, (2) the clinical evidence in context of NE both before and with hypothermia, and (3) the research and future directions.

Objective To evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress. Method Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as: Intubation and mechanical ventilation at birth, surgery before discharge, or ECMO. The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation (CPAM) volume ratio (CVR) by US and MRI was analyzed. Results 47 fetal lung mass cases were included; of those, 8 (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 + 5.6 vs. 22.3 + 3 weeks, p = 0.09); however, those with respiratory distress had higher CVR at that time (1.0 vs. 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume >24.0 cm3 by MRI (100% sensitivity, 91% specificity, 60% PPV, 100% NPV), and maximal volume >34.0 cm3 by US, (100% sensitivity, 85% specificity, 54% PPV, 100% NPV). Conclusion US and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value.

Importance Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration clinicaltrials.gov Identifier:NCT00614744

To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P .001) and pervasive developmental problems (P .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values .05).BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking versus delayed cord clamping among infants

Objective To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. Study design Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. Results Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. Conclusions MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia–ischemia. Trial registration Clinicaltrials.gov: NCT00614744 .

The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD.

To determine if decreased cerebral oxygenation or altered cerebral autoregulation as measured by near-infrared spectroscopy (NIRS) in the first 96 postnatal hours is associated with an increased risk of death or severe neuroradiographic abnormalities in very preterm infants.The Early NIRS prospective, multicenter study enrolled very preterm infants with a birth weight of1250 g from 6 tertiary neonatal intensive care units. Mean arterial blood pressure and cerebral oxygen saturation (Csat) were continuously monitored using a neonatal sensor until 96 hours of age. Moving window correlations between Csat and mean arterial blood pressure determined time periods with altered cerebral autoregulation, and percentiles of correlation were compared between infants with and without the adverse outcome of mortality or severe neuroradiographic abnormalities by early cranial ultrasound.Of 103 subjects with mean gestational age of 26 weeks, 21 (20%) died or had severe neuroradiographic abnormalities. Infants with adverse outcomes had a lower mean Csat (67 ± 9%) compared with those without adverse outcomes (72 ± 7%; P = .02). A Csat of50% was identified as a cut-point for identifying infants with adverse outcome (area under the curve, 0.76). Infants with adverse outcomes were more likely to have significant positive or negative correlations between Csat and mean arterial blood pressure, indicating impaired cerebral autoregulation (P = .006).Early NIRS monitoring may detect periods of lower cerebral oxygenation and altered cerebral autoregulation, identifying preterm infants at risk for mortality or neuroradiographic injury. An improved understanding of the relationship between altered hemodynamics and cerebral oxygenation may inform future strategies to prevent brain injury.

Near-infrared spectroscopy (NIRS) monitoring provides a noninvasive, bedside measure of cerebral and somatic oxygenation in neonates at risk for hemodynamic instability and brain injury. This technology has been increasingly utilized in the neonatal intensive care unit, however, clinicians perceive a lack of evidence for the added value of NIRS monitoring. We present six clinical scenarios illustrating the value of NIRS monitoring for the diagnosis and management of critically ill newborns.

Right ventricular (RV) function as assessed by deformation has been evaluated prenatally and after palliation in hypoplastic left heart syndrome (HLHS). However, limited data exist about the immediate postnatal cardiac adaptation and RV function in HLHS. We compared echocardiographic measures of cardiac performance in HLHS versus controls in their first week of life. As a secondary objective, we evaluated if markers at the first echocardiogram were associated with mid- and long-term outcomes. Clinical and echocardiographic data of patients with HLHS between 2013 and 2016 were reviewed. The study population was matched with controls whose echocardiograms were obtained due to murmur or rule out coarctation. Speckle-tracking echocardiography was used to assess deformation. Thirty-four patients with HLHS and 28 controls were analyzed. Age at echocardiogram was similar between HLHS and controls. The RV of HLHS was compared to both RV and left ventricle (LV) of controls. HLHS deformation parameters [RV peak global longitudinal strain (GLS), global longitudinal strain rate (GLSR)] and tricuspid annular plane systolic excursion (TAPSE) were decreased compared to RV of controls. The LV-fractional area change, peak GLS, GLSR, circumferential strain, and strain rate of controls were higher than the RV of HLHS. Calculated cardiac output (CO) was higher in the HLHS group (592 vs. 183 mL/kg/min, p = 0.0001) but similar to the combined LV and RV output of controls. Later mortality or cardiac transplantation was associated with the RV CO and RV stroke distance at initial echocardiogram. Cox proportional hazard regression determined that restriction at atrial septum, decreased initial RV stroke distance and decreased TAPSE had a higher risk of death or cardiac transplantation. TAPSE and RV stroke distance by velocity time integral had adequate inter-reader variability by Bland–Altman plot and Pearson’s correlation. Our study found that the HLHS RV deformation is decreased in the early postnatal period when compared to both LV and RV of controls, but deformation was not associated with mid- and long-term outcomes. Later mortality or cardiac transplantation was associated with decreased initial stroke distance and cardiac output. Early evaluation of patients with HLHS should include an assessment of stroke distance and future research should evaluate its implication in management strategies.

A successful fetal center provides a complete continuum of care for complex fetal patients, expectant mothers, and families. Ongoing communication among community obstetricians, pediatricians, maternal-fetal medicine physicians, neonatologists, and other pediatric specialists is critical to provide comprehensive prenatal counseling and establish a supportive care team for families before and after the birth of their child. This case reveals the role of a fetal center in planning for the delivery and resuscitation of conjoined twins and their subsequent postnatal care.

To investigate the range of renal near-infrared spectroscopy (NIRS) measures in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) and to determine the association between renal NIRS measures and the development of acute kidney injury (AKI).A retrospective chart review was conducted of neonates with moderate to severe HIE who received therapeutic hypothermia at a tertiary care center from 2014 to 2016. Neonates had routine continuous NIRS monitoring of cerebral and renal saturation (Rsat) as part of their clinical care for 72 hours of cooling and until 24 hours after rewarming. The outcome of AKI was defined by an abnormal rate of decline of serum creatinine over the first 5 days of life. Mixed effects models determined the association between renal NIRS measures and AKI over time.Of 38 neonates with HIE undergoing cooling, 15 (39%) developed AKI. Rsat was lower than cerebral saturation during cooling (P .01), but Rsat increased over time after rewarming, while renal oxygen extraction levels decreased (P .0001). Neonates with AKI had higher Rsat levels (P .01) compared with those without AKI after 24 hours of life. Using receiver operating characteristic curves, Rsat75% by 24-48 hours predicted AKI with a sensitivity of 79% and specificity of 82% (area under the receiver operating characteristic curve = 0.76).Throughout cooling, neonates with AKI had higher Rsat measures than those without AKI. These differences may reflect lower oxygen extraction by the injured kidney. NIRS monitoring of Rsat may identify neonates with HIE at risk of developing AKI.

Advances in prenatal imaging and genetic testing have increased the ability to diagnose fetal anomalies earlier in pregnancy and with greater accuracy and detail. These advances prompted the development of fetal interventions aimed at reducing mortality or significant long-term morbidity, thus ushering in a new era of fetal medicine and the creation of fetal centers. Despite these innovations, infants with congenital anomalies often require intensive care from the moment they are born, have lengthy initial hospitalizations, and require substantial continued care and services after discharge. The complexity and variety of fetal diagnoses underscore the importance of a multidisciplinary team approach beginning in fetal life, and the neonatologist is central to this collaborative effort. With a background in general pediatrics and neonatal-perinatal medicine, the neonatologist is uniquely positioned to contribute to the clinical operations of a fetal center, from counseling the expectant mother to directing a complex delivery room resuscitation, providing continuing care through the neonatal period, and preparing families for transitioning care through childhood.