Early Acute Kidney Injury in Preterm and Term Neonates: Incidence, Outcome, and Associated Clinical Features.

BACKGROUND: Critically ill neonates are at high risk of kidney injury, mainly in the first days of life. Acute kidney injury (AKI) may be underdiagnosed due to lack of a uniform definition. In addition, long-term renal follow-up is limited. OBJECTIVE: To describe incidence, etiology, and outcome of neonates developing AKI within the first week after birth in a cohort of NICU-admitted neonates between 2008 and 2018. Renal function at discharge in infants with early AKI was assessed. METHODS AND SUBJECTS: AKI was defined as an absolute serum Cr (sCr) value above 1.5 mg/dL (132 µmol/L) after the first 24 h or as stage 2-3 of the NIDDK neonatal definition. Clinical data and outcomes were collected from medical records and retrospectively analyzed. RESULTS: From January 2008 to December 2018, a total of 9,376 infants were admitted to the NICU of Wilhelmina Children's Hospital/UMC Utrecht, of whom 139 were diagnosed with AKI during the first week after birth. In 72 term infants, the most common etiology was perinatal asphyxia (72.2%), followed by congenital kidney and urinary tract malformations (CAKUT) (8.3%), congenital heart disease (6.9%), and sepsis (2.8%). Associated conditions in 67 preterm infants were medical treatment of a hemodynamic significant PDA (27.2%), -CAKUT (21%), and birth asphyxia (19.4%). Among preterm neonates and neonates with perinatal asphyxia, AKI was mainly diagnosed by the sCr >1.5 mg/dL criterion. Renal function at discharge improved in 76 neonates with AKI associated with acquired conditions. Neonates with stage 3 AKI showed increased sCr values at discharge. Half of these were caused by congenital kidney malformations and evolved into chronic kidney disease (CKD) later in life. Neurodevelopmental outcome (NDO) at 2 years was favorable in 93% of surviving neonates with detailed follow-up. CONCLUSION: During the first week after birth, AKI was seen in 1.5% of infants admitted to a level III NICU. Renal function at discharge had improved in most neonates with acquired AKI but not in infants diagnosed with stage 3 AKI. Long-term renal function needs further exploration, whereas NDO appears to be good.

The Effect of Head Positioning and Head Tilting on the Incidence of Intraventricular Hemorrhage in Very Preterm Infants: A Systematic Review.

BACKGROUND: Despite advances in neonatal intensive care, germinal matrix-intraventricular hemorrhage (GMH-IVH) remains a frequent, serious complication of premature birth. Neutral head position and head tilting have been suggested to reduce the risk of GMH-IVH in preterm infants during the first 72 h of life. OBJECTIVE: The aim of this study was to provide a systematic review of the effect of neutral head positioning and head tilting on the incidence of GMH-IVH in very preterm infants (gestational age ≤30 weeks). In addition, we reviewed their effect on cerebral hemodynamics and oxygenation. METHODS: Literature was searched (June 2016) in the following electronic databases: CINAHL, Embase, Medline, SCOPUS, and several trial registers. RESULTS: One underpowered trial studied the effect of head positioning on the incidence of GMH-IVH. This randomized controlled trial enrolled 48 preterm infants and found no effect on the occurrence of GMH-IVH. Three observational studies investigated the effect of head rotation and/or tilting on cerebral oxygenation in 68 preterm infants in total. Their results suggest that cerebral oxygenation is not significantly affected by changes in head positioning. The effect of head positioning and/or tilting on cerebral hemodynamics was described in 2 observational studies of 28 preterm infants and found no significant effect. CONCLUSIONS: There is insufficient evidence regarding the effect of head positioning and tilting on the incidence of GMH-IVH and cerebral hemodynamics and oxygenation in preterm infants. We recommend further research in this field, especially in extremely preterm and clinically unstable infants during the first postnatal days.

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

AIMS: The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. METHODS AND RESULTS: Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. CONCLUSION: Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

Persistent reduction in left ventricular strain using two-dimensional speckle-tracking echocardiography after balloon valvuloplasty in children with congenital valvular aortic stenosis.

BACKGROUND: The aim of this study was to investige serial changes of myocardial deformation using two-dimensional speckle-tracking echocardiographic (2DSTE) imaging in children undergoing balloon valvuloplasty for congenital valvular aortic stenosis (VAS). METHODS: Thirty-seven children with isolated congenital VAS were enrolled in this study prospectively. Patients underwent echocardiographic evaluation at three instances: before balloon valvuloplasty, 6 months after intervention, and 3 years after intervention. Longitudinal, circumferential, and radial peak systolic strain values were determined, as well as systolic strain rate and the time to peak global systolic strain. Linear mixed statistical models were used to assess changes in 2DSTE parameters after balloon intervention. Using one-way analysis of variance, 2DSTE results at 3-year follow-up were compared with 2DSTE measurements in 74 healthy age-matched children and 76 children with uncorrected VAS whose severity of stenosis corresponded to residual stenosis of study subjects at 3-year follow-up. RESULTS: Global peak strain and strain rate measurements in all three directions were decreased before intervention compared with healthy children. Global peak strain and strain rate measurements increased significantly (P < .001) several months after balloon valvuloplasty and continued to increase at 3-year follow-up. However, at 3-year follow-up, global peak strain and strain rate in the longitudinal and circumferential directions were significantly lower (P < .001) compared with both control groups. Measurements of time to peak global systolic strain were significantly shorter at early follow-up compared with measurements before intervention (P < .05). CONCLUSIONS: Shortly after balloon valvuloplasty for severe congenital VAS, there is an improvement in systolic myocardial deformation. However, 2DSTE parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation.

Synchronicity of systolic deformation in healthy pediatric and young adult subjects: a two-dimensional strain echocardiography study.

Two-dimensional speckle tracking echocardiography (2DSTE) offers valuable information in the echocardiographic assessment of ventricular myocardial function. It enables the quantification and timing of systolic ventricular myocardial deformation. In addition, 2DSTE can be used to identify mechanical dyssynchrony, which is an important parameter in predicting the response to cardiac resynchronization therapy for heart failure. Detailed knowledge of normal timing of systolic deformation and its degree of synchronicity in children is lacking. We aimed to establish the normal timing of left ventricular myocardial systolic deformation using 2DSTE in a large cohort of healthy children and young adults. Transthoracic echocardiograms were acquired in 195 healthy subjects (139 children and 56 young adult <40 yr of age) and were retrospectively analyzed. Time to peak systolic longitudinal, circumferential, and radial strain was determined by means of speckle tracking. Strong, statistically significant relations between age as well as various anthropometric variables (e.g., heart rate) and timing of systolic deformation (P < 0.0001) were present. The extent of dyssynchronous deformation increased with age. This is the first report that establishes reference values per cardiac segment for time to peak systolic myocardial strain values in all three directions assessed with 2DSTE in a large pediatric and young adult cohort. We emphasize the need for using age-specific reference values as well as heart rate correction for the adequate interpretation of 2DSTE measurements.

Cardiac evaluation in children with Prader-Willi syndrome.

AIM: To assess cardiac anatomy and myocardial systolic function in children with Prader-Willi syndrome (PWS). METHODS: Physical examination, electrocardiographic (ECG) recordings and transthoracic echocardiograms including two-dimensional speckle tracking echocardiography (2DSTE) were performed and evaluated in the Radboud University Hospital Nijmegen, the Netherlands. In total, 19 children diagnosed with PWS and 38 age-matched control subjects underwent cardiac evaluation. RESULTS: Abnormal ECG findings were detected in nine PWS patients. Echocardiography revealed mild structural cardiac abnormalities in two patients. Conventional echocardiographic findings did not indicate systolic left ventricular dysfunction, in contrast to 2DSTE examination. Global peak systolic strain (rate) measurements, in all three directions of contraction, were significantly lower in children with PWS (p < 0.001) compared with healthy age-matched children. In two-thirds of the patients, 2DSTE revealed abnormal systolic deformation (peak systolic strain as well as strain rate). T2P values in PWS patients were similar to control subject. Systolic myocardial function appears more affected in case of maternal uniparental disomy. CONCLUSION: Cardiac evaluation, including 2DSTE, detects frequent alterations in myocardial systolic function in children diagnosed with PWS, whose conventional echocardiographic findings did not indicate ventricular systolic dysfunction. Because cardiovascular morbidity and mortality is substantial in PWS, especially adults, we emphasize the need for cardiac assessment in PWS.

Reference values for myocardial two-dimensional strain echocardiography in a healthy pediatric and young adult cohort.

BACKGROUND: The accurate evaluation of intrinsic myocardial contractility in children with or without congenital heart disease (CHD) has turned out to be a challenge. Two-dimensional strain echocardiographic (2DSTE) imaging or two-dimensional speckle-tracking echocardiographic imaging appears to hold significant promise as a tool to improve the assessment of ventricular myocardial function. The aim of this study was to estimate left ventricular myocardial systolic function using 2DSTE imaging in a large cohort consisting of healthy children and young adults to establish reference strain values. METHODS: Transthoracic echocardiograms were acquired in 195 healthy subjects (139 children, 56 young adults) and were retrospectively analyzed. Longitudinal, circumferential, and radial peak systolic strain values were determined by means of speckle tracking. Nonlinear regression analysis was performed to assess the effect of aging on these 2DSTE parameters. RESULTS: There was a strong, statistically significant second-order polynomial relation (P < .001) between global peak systolic strain parameters and age. Global peak systolic strain values were lowest in the youngest and oldest age groups. CONCLUSION: This is the first report to establish age-dependent reference values per cardiac segment for myocardial strain in all three directions assessed using 2DSTE imaging in a large pediatric and young adult cohort. There is a need to use age-specific reference values for the adequate interpretation of 2DSTE measurements.

Early detection of myocardial dysfunction in children with mitochondrial disease: An ultrasound and two-dimensional strain echocardiography study.

BACKGROUND: Myocardial dysfunction in children diagnosed with mitochondrial disease is an ominous sign and has been associated with substantial increased mortality rates. Early detection of cardiac involvement would therefore be desirable. Two dimensional strain echocardiography (2DSTE) has proven to be more sensitive than conventional echocardiography for the detection of early myocardial dysfunction in various (cardiac) conditions. AIMS: To determine left ventricular systolic function in children with mitochondrial disorders by means of physical examination, electrocardiography (ECG), conventional echocardiography and 2DSTE. METHODS: A total of 27 children with established mitochondrial disease and 54 age-matched control subjects underwent cardiac evaluation. Longitudinal, circumferential and radial peak systolic strain (S) values were determined as well as peak systolic strain rate (Sr) and the time to peak global systolic strain (T2P). One Way analysis of Variance was performed to assess the influence of the presence of mitochondrial disease on conventional echocardiographic and 2DSTE outcomes. RESULTS: Conventional echocardiographic findings did not indicate systolic left ventricular dysfunction. Global peak S, Sr and T2P measurements in all three directions were significantly lower in children with mitochondrial disease (P<0.001) when compared to controls. CONCLUSION: 2DSTE detects alterations in myocardial systolic function in children diagnosed with mitochondrial disease, whose conventional echocardiographic findings did not indicate ventricular systolic dysfunction.

Myocardial strain and strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of childhood cancer.

We studied the role of global myocardial strain and strain rate in monitoring subclinical heart failure in a large group of asymptomatic long-term survivors of childhood cancer. Global strain (rate) parameters of survivors were compared with those in healthy controls and were related to conventional echocardiographic parameters, N-terminal-pro-natriuretic peptide (NT-pro-BNP) levels and clinical parameters. Two-dimensional (2-D) echocardiography was performed in 111 survivors and 107 healthy controls. Blood samples were taken from survivors to determine NT-pro-BNP levels. We showed that global myocardial strain, strain rate and time to peak systolic strain in asymptomatic survivors of childhood cancer were significantly lower compared with healthy controls (p values <0.0001) and were significantly related to several systolic and diastolic left ventricular parameters. Whether myocardial strain and strain rate are superior to conventional echocardiography in the early detection of subclinical heart failure needs to be explored in further longitudinal prospective studies.

A case of juvenile bullous pemphigoid--successful treatment with diaminodiphenylsulfone and prednisone.

Blistering skin diseases can be difficult to diagnose, particularly in children. Because of the wide variety of bullous disorders and the considerable clinical overlap between them, it is difficult to differentiate one from the other on clinical features alone. Appropriate additional investigations are required to confirm the diagnosis. These include routine histologic examination of the skin, in addition to immunohistochemical staining and immune serology. Here, we present a rare case of juvenile bullous pemphigoid, which we will use to illustrate the difficulties encountered in the diagnostic process and to show how acquired blistering disorders of childhood should be approached.