Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. METHODS: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. RESULTS: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. CONCLUSIONS: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.

Impact of Congenital Heart Disease on the Outcomes of Very Low Birth Weight Infants.

OBJECTIVE: To investigate the association of congenital heart disease (CHD) with morbidity and mortality of very low birth weight (VLBW) infants. STUDY DESIGN: This matched case-control study included VLBW infants born at a single institution between 2001 and 2015. The primary outcome was mortality. Secondary outcomes included necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity, and intraventricular hemorrhage. These outcomes were assessed by comparing VLBW-CHDs with control VLBW infants matched by gestational age within a week, birth weight within 500 g, sex, and birth date within a year using conditional logistic regression. Multivariable logistic regression analyzed differences in outcomes in the VLBW-CHD group between two birth periods (2001-2008 and 2009-2015) to account for changes in practice. RESULTS: In a cohort of 44 CHD infants matched with 88 controls, the mortality rate was 27% in infants with CHD and 1% in controls (p < 0.0001). The VLBW-CHDs had increased BPD; (odds ratio [OR]: 7.70, 95% confidence interval [CI]: 1.96-30.29) and sepsis (OR: 10.59, 95% CI: 2.99-37.57) compared with the control VLBWs. When adjusted for preoperative ventilator use, the VLBW-CHDs still had significantly higher odds of BPD (OR: 6.97, 95% CI: 1.73-28.04). VLBW-CHDs also had significantly higher odds of both presumed and culture-positive sepsis as well as late-onset sepsis than their matched controls. There were no significant differences in outcomes between the two birth periods. CONCLUSION: VLBW-CHDs showed higher odds of BPD, sepsis, and mortality than VLBW infants without CHD. Future research should focus on the increased mortality and specific complications encountered by VLBW infants with CHD and implement targeted strategies to address these risks. KEY POINTS: · Incidence of CHD is higher in preterm infants than in term infants but the incidence of their morbidities is not well described.. · VLBW infants with CHD have higher odds of mortality, bronchopulmonary dysplasia, and sepsis.. · Future research is needed to implement targeted preventive responses..

Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Reducing Variability in Practice through a Collaborative Telemedicine Initiative.

OBJECTIVE: This study aimed to assess the viability of implementing a tele-educational training program in neurocritical care for newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia (TH), with the goal of reducing practice variation. STUDY DESIGN: Prospective study including newborns with HIE treated with TH from 12 neonatal intensive care units in Brazil conducted from February 2021 to February 2022. An educational intervention consisting of 12 biweekly, 1-hour, live videoconferences was implemented during a 6-month period in all centers. Half of the centers had the assistance of a remote neuromonitoring team. The primary outcome was the rate of deviations from TH protocol, and it was evaluated during a 3-month period before and after the intervention. Logistic regression via generalized estimating equations was performed to compare the primary and secondary outcomes. Protocol deviations were defined as practices not in compliance with the TH protocol provided. A subanalysis evaluated the differences in protocol deviations and clinical variables between centers with and without neuromonitoring. RESULTS: Sixty-six (39.5%) newborns with HIE were treated with TH during the preintervention period, 69 (41.3%) during the intervention period and 32 (19.1%) after intervention. There was not a significant reduction in protocol deviations between the pre- and postintervention periods (37.8 vs. 25%, p = 0.23); however, a decrease in the rates of missing Sarnat examinations within 6 hours after birth was seen between the preintervention (n = 5, 7.6%) and postintervention (n = 2, 6.3%) periods (adjusted odds ratio [aOR]: 0.36 [0.25-0.52], p < 0.001). Centers with remote neuromonitoring support had significantly lower rates of seizures (27.6 vs. 57.5%; aOR: 0.26 [0.12-0.55], p < 0.001) and significant less seizure medication (27.6 vs. 68.7%; aOR: 0.17 [0.07-0.4], p < 0.001). CONCLUSION: This study shows that implementing a tele-educational program in neonatal neurocritical care is feasible and may decrease variability in the delivery of care to patients with HIE treated with TH. KEY POINTS: · Neurocritical care strategies vary widely in low- and middle-income countries.. · Heterogeneity of care may lead to suboptimal efficacy of neuroprotective strategies.. · Tele-education and international collaboration can decrease the variability of neurocritical care provided to infants with HIE..

Left Ventricular Strain, Arch Angulation, and Velocity-Time Integral Ratio Improve Performance of a Clinical Pathway for Fetal Diagnosis of Neonatal Coarctation of the Aorta.

INTRODUCTION: Neonatal presentation of coarctation of the aorta (CoA) is a potentially life-threatening condition that is difficult to diagnose in fetal life. We therefore sought to validate and compare novel metrics that may add diagnostic value for fetal CoA, including the diastolic to systolic aortic isthmus VTI ratio (VTId:VTIs), ascending aorta to descending aorta angle (AAo-DAo), transverse aorta to descending aorta angle (TAo-DAo), and LV longitudinal strain (LVS), then to evaluate whether these novel metrics improve specificity to identify fetuses at the highest risk for postnatal CoA without compromising sensitivity. METHODS: Retrospective cohort study of fetuses followed a prospective clinical pathway and previously classified as mild, moderate, or high-risk for CoA based on standard fetal echo metrics. Novel metrics were retrospectively measured in a blinded manner. RESULTS: Among fetuses with prenatal concern for CoA, VTId:VTIs, AAo-DAo angle, TAo-DAo angle, and LVS were significantly different between surgical and non-surgical cases (p < 0.01 for all variables). In the subgroup of moderate- and high-risk fetuses, the standard high-risk criteria (flow reversal at the foramen ovale or aortic arch) did not discriminate effectively between surgical and non-surgical cases. VTId:VTIs, AAo-Dao angle, Tao-DAo angle, and LVS all demonstrated greater discrimination than standard high-risk criteria, with specificity of 100% and PPV (positive predictive value) of 78-100%. CONCLUSIONS: The incorporation of novel metrics added diagnostic value to our clinical pathway for fetal CoA with higher specificity than the previous high-risk criteria. The incorporation of these metrics into the evaluation of fetuses at moderate- or high-risk for surgical CoA may improve prenatal counseling, allow for more consistent surgical planning, and ultimately optimize hospital resource allocation.

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia.

BACKGROUND: Inhaled nitric oxide (iNO) is widely used for the management of infants with congenital diaphragmatic hernia (CDH); however, evidence of benefit is limited. METHODS: This is a multicenter cohort study using data from the Congenital Diaphragmatic Hernia Study Group between 2015 and 2020. The impact of early iNO use in the first 3 days of life prior to ECLS use on mortality or ECLS use was explored using multivariate logistic regression models and subgroup analyses. RESULTS: Of the 1777 infants, 863 (48.6%) infants received early iNO treatment. Infants receiving iNO had lower birth weight, larger defect size, more severe pulmonary hypertension, and abnormal ventricular size and function. After controlling for these factors, early iNO use was associated with increased mortality (aOR 2.06, 95% CI 1.05-4.03, P = 0.03) and increased ECLS use (aOR 3.44, 95% CI 2.11-5.60, P < 0.001). Subgroup analyses after stratification by echocardiographic characteristics and defect size revealed no subgroup with a reduction in mortality or ECLS use. CONCLUSIONS: Use of iNO in the first 3 days of life prior to ECLS was not associated with a reduction in mortality or ECLS use in either the regression models or the subgroup analyses. The widespread use of iNO in this vulnerable population requires reconsideration. IMPACT: Evidence to support widespread use of iNO for infants with congenital diaphragmatic hernia is limited. The use of iNO in the first 3 days of life was associated with significantly increased mortality and ECLS use. Stratification by echocardiographic characteristics and defect size did not reveal a subgroup that benefited from iNO. Even the subset of patients with R-to-L shunts at both ductal and atrial levels, a surrogate for elevated pulmonary arterial pressures in the absence of significantly decreased LV compliance, did not benefit from early iNO use. Early iNO therapy was of no benefit in the management of acute pulmonary hypertension in infants with congenital diaphragmatic hernia, supporting reconsideration of its use in this population.

Cerebral oxygen saturation in neonates: a bedside comparison between neonatal and adult NIRS sensors.

BACKGROUND: The majority of neonatal NIRS literature recommends target ranges for cerebral saturation (rScO2) based on data using adult sensors. Neonatal sensors are now commonly used in the neonatal intensive care unit (NICU). However, there is limited clinical data correlating these two measurements of cerebral oxygenation. METHODS: A prospective observational study was conducted in two NICUs between November 2019 and May 2021. An adult sensor was placed on infants undergoing routine cerebral NIRS monitoring with a neonatal sensor. Time-synchronized rScO2 measurements from both sensors, heart rate, and systemic oxygen saturation values were collected over 6 h under varying clinical conditions and compared. RESULTS: Time-series data from 44 infants demonstrated higher rScO2 measurements with neonatal sensors than with adult sensors; however, the magnitude of the difference varied depending on the absolute value of rScO2 (Adult = 0.63 × Neonatal + 18.2). While there was an approximately 10% difference when adult sensors read 85%, readings were similar when adult sensors read 55%. CONCLUSION: rScO2 measured by neonatal sensors is typically higher than measured by adult sensors, but the difference is not fixed and is less at the threshold indicative of cerebral hypoxia. Assuming fixed differences between adult and neonatal sensors may lead to overdiagnosis of cerebral hypoxia. IMPACT: In comparison to adult sensors, neonatal sensors rScO2 readings are consistently higher, but the magnitude of the difference varies depending on the absolute value of rScO2. Marked variability during high and low rScO2 readings was noted, with approximately 10% difference when adult sensors read 85%, but nearly similar (58.8%) readings when adult sensors read 55%. Estimating fixed differences of approximately 10% between adult and neonatal probes may lead to an inaccurate diagnosis of cerebral hypoxia and result in subsequent unnecessary interventions.

Renal oximetry for early acute kidney injury detection in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). METHODS: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 - Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. RESULTS: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48-84 HOL (AUC 0.71-0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42-66 HOL (AUC 0.8-0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). CONCLUSIONS: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Renal Oxygen Saturations and Acute Kidney Injury in the Preterm Infant with Patent Ductus Arteriosus.

OBJECTIVE: Decreased near-infrared spectroscopy (NIRS) measures of renal oxygen saturation (Rsat) have identified preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA). NIRS may further identify infants at risk for acute kidney injury (AKI) in a population with concern for hsPDA. STUDY DESIGN: Review of infants ≤29 weeks' gestation undergoing NIRS and echocardiography due to concern for hsPDA. The hsPDA was defined by two of the following: moderate-large size, left to right shunt, aortic flow reversal, left atrial enlargement. AKI was defined by neonatal modified Kidney Disease Improving Global Outcomes (KDIGO). Rsat and cerebral saturation (Csat), averaged over 1 hour, were evaluated for the 24-hour period around echocardiography. RESULTS: Among 77 infants, 29 (38%) had AKI by neonatal modified KDIGO criteria. hsPDA was found on echocardiography in 59 (77%). There were no differences in hsPDA in infants with and without AKI (p = 0.1). Rsat was not associated with AKI (p = 0.3). Infants on dopamine had less Rsat variability (p < 0.01). CONCLUSION: Rsat prior to echocardiography did not discriminate AKI in this cohort of preterm infants at risk for hsPDA; however, data may not capture optimal timing of Rsat measurement before AKI. KEY POINTS: · No Rsat value was found to be associated with the development of AKI.. · The optimal timing of Rsat measurement should be evaluated in infants at risk for hsPDA.. · NIRS bedside monitoring of Csat and Rsat measures may be useful in trending perfusion patterns.. · Identification of those at high risk for AKI may allow for more careful kidney function monitoring..

In-Hospital Morbidities for Neonates with Congenital Diaphragmatic Hernia: The Impact of Defect Size and Laterality.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.

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.

Renal oxygenation measured by near-infrared spectroscopy in preterm neonates in the first week.

OBJECTIVE: To describe renal regional saturation of oxygen (RrSO2) values during the first week of life for preterm neonates born at <32 weeks gestational age (GA). METHODS: RrSO2 values recorded over the first week of life using near-infrared spectroscopy were retrospectively analyzed in this two-center cohort study of preterm infants without known congenital anomalies of the kidney. RESULTS: A cohort of 109 neonates with a median GA of 26.9 weeks and a median of 120 (IQR: 87-141) hours of continuous RrSO2 monitoring were included. Separately fitted trends in RrSO2 did not differ (p = 0.52) between sites and demonstrated a consistent decrease in RrSO2 by 20 points (95% CI: 9.6-30.1) during the first 60 h of life, followed by a stabilization of RrSO2 thereafter. RrSO2 baseline trends increased by 2.1 (95% CI: 0.8-3.3) percentage points for each additional week GA between 24 and 32 weeks GA. CONCLUSIONS: Despite differences in adjusted RrSO2 values between sites, profiles over time are consistent, allowing for the determination of RrSO2 trajectories in preterm infants. This expected pattern of RrSO2 changes in the first week may help guide future investigations and interventions to identify and reduce kidney injury in the preterm neonate. IMPACT: Renal regional saturation of oxygen (RrSO2) slowly decreases during the first 60 h of age in <32-week preterm neonates. While site differences were identified with respect to absolute values, RrSO2 trends from two different centers were not different. Lower gestational age neonates have lower RrSO2 levels during the first week.

Early brain and abdominal oxygenation in extremely low birth weight infants.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. IMPACT: 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.

Blood Pressure Goals: Is Cerebral Saturation the New Mean Arterial Pressure?

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 <55%). 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 < GA had fewer corresponding percent time with abnormal cNIRS events (3.7 ± 1.3%) compared with MAP < PMA (11.9 ± 4.9%, p < 0.003) or 30 mm Hg thresholds (12.2 ± 4.7%, p < 0.0001). In most premature infants, mean cNIRS values during hypotension were still within normal range (57 ± 6%). CONCLUSION: cNIRS may be a more clinically relevant measure than MAP for the assessment of neonatal hypotension. KEY POINTS: · 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.. · MAP. · We found no cNIRS difference between IVH grades, mortality, average Hct, lactates, or urine output.. · cNIRS may be a more clinically relevant measure than MAP for the assessment of neonatal hypotension..

Near-Infrared Spectroscopy as a Hemodynamic Monitoring Tool during Neonatal Extracorporeal Life Support: A Case Series.

Near-infrared spectroscopy (NIRS) is a non-invasive clinical tool allowing for real-time, continuous measurement of regional tissue oxygenation (rSO2); though predominantly used for neuromonitoring, it also has the potential for early detection of hemodynamic compromise in the patients on extracorporeal life support (ECLS). The authors present two cases of neonates for whom continuous monitoring of multisite rSO2 with NIRS provided the first indication of a significant compromise in hemodynamic status from catastrophic hemorrhagic complications while on ECLS ahead of conventional ECLS monitoring parameters. Routine NIRS monitoring of neonates on ECLS has utility for ongoing assessment of hemodynamic status and can be used for early detection of complications leading to impaired tissue perfusion.

Aminophylline for renal protection in neonatal hypoxic-ischemic encephalopathy in the era of therapeutic hypothermia.

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 < 0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group. CONCLUSIONS: Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline. IMPACT: The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia. Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline. Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.

End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn - an observational cohort study.

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 < 29 weeks' gestation (2013-2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers. 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.

Cerebral Oxygenation and Autoregulation in Preterm Infants (Early NIRS Study).

OBJECTIVE: 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. STUDY DESIGN: The Early NIRS prospective, multicenter study enrolled very preterm infants with a birth weight of <1250 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. RESULTS: 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 of <50% 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). CONCLUSIONS: 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.

Influence of enteral feeding and anemia on tissue oxygen extraction after red blood cell transfusion in preterm infants.

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.