Search

Purpose We aimed to evaluate the implementation and use of a high quality innovative bubble continuous positive airway pressure (bCPAP) System into a neonatal unit in Belgium. Methods A prospective observational study of neonates who met criteria for non-invasive respiratory support was conducted. All medical and nursing staff completed an on-line Thinkific course, followed by a live demonstration and practice of device application. Clinical indicator and device settings were recorded for every neonate. Staff surveys were administered after the training, after treatment of a neonate with a Vayu bCPAP System, and eight months after device introduction. Results Seven neonates were treated with Vayu bCPAP Systems. Their mean birth weight was 3170g with a median duration of treatment with bCPAP of 19 hours (IQR 2h–6d). Four term neonates had transient tachypnea of the newborn (TTN, n=4). One preterm and one term baby suffered from respiratory distress syndrome (RDS, n=2) and one baby had meconium aspiration syndrome (MAS, n=1). Six of the seven neonates improved their respiratory status and were weaned off the bCPAP System. One neonate needed more extensive ventilatory support and was transferred to a higher level neonatal intensive care unit (NICU). Staff surveys demonstrated that the devices were easy to use and satisfaction rates were high. Conclusions It was feasible to use Vayu bCPAP Systems to provide neonates with non-invasive respiratory support in our neonatal unit. Since implementation of this device there is less hesitancy among the medical staff to start babies on CPAP.

Introduction: Extremely low birth weight (ELBW) survivors have microvascular structural differences already described in kidney and retina, suggesting changes in endothelial integrity. A biomarker of endothelial integrity is perfused boundary region (PBR), which measures glycocalycal thickness. The endothelial glycocalyx is a complex, highly versatile structure with essential roles in vascular integrity and function. We explored PBR patterns together with other microvascular markers in healthy controls and former ELBW children. Methods: In the PREMATCH cohort (87 healthy controls, 93 ELBW survivors), we assessed endothelial integrity by calculating PBR (sidestream dark-field imaging), several microvascular markers (blood pressure, estimated glomerular filtration rate (eGFR cysC)), and retinal imaging in early adolescence. We explored differences between both groups, and searched for perinatal determinants of PBR and correlations between different microvascular markers. Results: We provided reference values for PBR (average 1.90 µm, SD 0.30) in children. PBR was not different from ELBW survivors during early adolescence, despite their higher blood pressure, lower eGFR cysC, and different retinal vessel width and tortuosity. Conclusions: We generated reference values for PBR in early adolescence. Despite some correlations between microvascular parameters, there seem to be numerous confounders to propose PBR as a marker for endothelial integrity in ELBW survivors. Impact: The endothelial glycocalyx is a complex and versatile structure. Changes in blood pressure and retinal and renal vascularization suggest a disturbance of its integrity in extremely low birth weight (ELBW) survivors. Its thickness can be measured by calculating perfused boundary region (PBR) using sidestream dark-field imaging, with a higher PBR indicating a thinner glycocalyx.We generated reference values for PBR in healthy adolescents. These values were not different in former ELBW children.Despite some correlations of PBR with other microvascular biomarkers, these are not strong enough to describe endothelial integrity and its covariates in former ELBW children.

Background: Whether preterm birth is associated with cardiac conduction or repolarization abnormalities in later life is still poorly explored, with conflicting data on QTc prolongation in former extreme low birth weight (ELBW

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 called for innovation in addressing age-related disabilities. Our study aimed to identify and validate a urinary peptidomic profile (UPP) differentiating healthy from unhealthy ageing in the general population, to test the UPP predictor in independent patient cohorts, and to search for targetable molecular pathways underlying age-related chronic diseases. METHODS: In this prospective population study, we used data from participants in the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), done in northern Belgium from 1985 to 2019, and invited participants to a follow-up examination in 2005-10. Participants were eligible if their address was within 15 km of the examination centre and if they had not withdrawn consent in any of the previous examination cycles (1985-2004). All participants (2005-10) were also invited to an additional follow-up examination in 2009-13. Participants who took part in both the 2005-10 follow-up examination and in the additional 2009-13 follow-up visit constituted the derivation dataset, which included their 2005-10 data, and the time-shifted internal validation dataset, which included their 2009-13 data. The remaining participants who only had 2005-10 data constituted the synchronous internal validation dataset. Participants were excluded from analyses if they were incapacitated, had not undergone UPP, or had either missing or outlying (three SDs greater than the mean of all consenting participants) values of body-mass index, plasma glucose, or serum creatinine. The UPP was assessed by capillary electrophoresis coupled with mass spectrometry. The multidimensional UPP signature reflecting ageing was generated from the derivation dataset and validated in the time-shifted internal validation dataset and the synchronous validation dataset. It was further validated in patients with diabetes, COVID-19, or chronic kidney disease (CKD). In FLEMENGHO, the mortality endpoints were all-cause, cardiovascular, and non-cardiovascular mortality; other endpoints were fatal or non-fatal cancer and musculoskeletal disorders. Molecular pathway exploration was done using the Reactome and Kyoto Encyclopedia of Genes and Genomes databases. FINDINGS: 778 individuals (395 [51%] women and 383 [49%] men; aged 16·2-82·1 years; mean age 50·9 years [SD 15·8]) from the FLEMENGHO cohort had a follow-up examination between 2005 and 2010, of whom 559 participants had a further follow-up from Oct 28, 2009, to March 19, 2013, and made up the derivation (2005-10) and time-shifted internal validation (2009-13) datasets. 219 were examined once and constituted the synchronous internal validation dataset (2005-10). With correction for multiple testing and multivariable adjustment, chronological age was associated with 210 sequenced peptides mainly showing downregulation of collagen fragments. The trained model relating chronological age to UPP, derived by elastic net regression, included 54 peptides from 17 proteins. The UPP-age prediction model explained 76·3% (r=0·87) of chronological age in the derivation dataset, 54·4% (r=0·74) in the time-shifted validation dataset, and 65·3% (r=0·81) in the synchronous internal validation dataset. Compared with chronological age, the predicted UPP-age was greater in patients with diabetes (chronological age 50·8 years [SE 0·37] vs UPP-age 56·9 years [0·30]), COVID‑19 (53·2 years [1·80] vs 58·5 years [1·67]), or CKD (54·6 years [0·97] vs 62·3 years [0·85]; all p

Background. Dolichocolon is an inborn anatomic variant of the colon with redundancies often causing constipation and/or volvulus presenting in childhood, adolescence, or adulthood. To the best of our knowledge, this is the first case of dolichocolon presenting in infancy with constipation and bilateral hydronephrosis. Case Presentation. A nineteen-day-old neonate presented to the emergency department with severe constipation and discomfort. During his admission, he developed pyelonephritis, and subsequent ultrasound of the kidneys and bladder showed bilateral hydroureteronephrosis. A barium enema was performed and it showed a dolichocolon. Enemas and lactulose were initiated with good effect on both the constipation as well as the hydronephrosis. Conclusions. Dolichocolon in a neonate can cause severe constipation which could also lead to an obstructive nephropathy if untreated. Monitoring of urine flow might be indicated when a neonate presents with severe constipation.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-β4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-β4 abundance was confirmed with ELISA. Knockout of thymosin-β4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin β4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable. ispartof: KIDNEY INTERNATIONAL vol:99 issue:3 pages:737-749 ispartof: location:United States status: published

IntroductionIbuprofen exposure results in acute transient renal dysfunction in preterm neonates, but we are unaware of data on long-term renal safety.MethodsIn a previously studied cohort of extreme low birth weight (ELBW, cysC) at the age of 11 years. This data set in 93 ELBW cases may also generate data on long-term drug safety on ibuprofen. In this post hoc analysis, we linked markers of renal function in young adolescence in ELBW cases with their perinatal (prenatal maternal, setting at birth, treatment modalities including drug prescription during neonatal stay, neonatal creatinine values, postdischarge growth) characteristics, including but not limited to ibuprofen exposure during neonatal stay.ResultsIbuprofen exposure was not associated with significant differences in renal length or eGFRcysC. Moreover, we were unable to identify any other risk factor (perinatal characteristics, postnatal creatinine trends, postdischarge growth) on renal outcome in this cohort.ConclusionsNeonatal exposure to ibuprofen did not affect renal function. Larger studies are needed to explore the confounders of variability in renal function in former ELBW cases. This matters since ELBW relates to risk for hypertension, cardiovascular events and renal disease in later life and identification of risk factors holds the promise of secondary prevention.Trial registration numberNCT02147457.

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case‐control study, we enrolled 55 children aged 11 years weighing P P =0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, P P =0.011]) and forward (−2.57 µm; CI, −4.81 to −0.32 µm [ P =0.026]) and backward (−3.20 µm; CI, −5.47 to −0.94 µm [ P =0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, P =0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov . Unique Identifier: NCT02147457.

Objective To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Methods 74 SFK fetuses (unilateral renal agenesis (12), multicystic dysplastic kidney (36) and severe renal dysplasia (26)) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), Pulsatility Index (PI ) and Resistance Index (RI) of the renal artery (RA) were measured; 2- and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Results Compared with the control group, the PSV RA was significantly lower in non-functioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared to healthy kidneys. All but four children had GFR above 70 ml/min/1.73 m2 and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between pre-and postnatal SFK volume and GFR at 2 years was demonstrated. Conclusion Low PSV RA might have a predictive value for diagnosing a non-functioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared to healthy kidneys.

The diameters of the retinal microvasculature reflect intermediate target organ damage and predict adverse health outcomes. In view of the pulsatility of the cerebral blood flow and refinement of software used for off-line analysis, we assessed the repeatability of retinal microvascular diameters in ECG-gated vs. non-gated images using nonmydriatic retinal photographs (Canon Cr-DGi visualization system) postprocessed by IVAN (Vasculomatic ala Nicola, version 1.1) or SIVA (Singapore I Vessel Assessment, version 3.6). Using these algorithms, we determined the central retinal arteriolar (CRAE) and venular (CRVE) equivalents and their ratio (arteriole-to-venule ratio (AVR)). The estimates of CRAE (mean, 158.5 μm), CRVE (222.5 μm) and AVR (0.71) in 10 volunteers were unaffected (P⩾0.059) by ECG gating. We assessed intragrader repeatability by the Bland and Altman approach in 30 participants with non-gated images and 30 with ECG-gated photographs. Repeatability, which was expressed as the percentage of near maximal variability (4-s.d. range), did not improve with ECG gating. Using SIVA, CRAE and CRVE were systematically larger (P⩽0.031), and the AVR estimates were similar (P⩾0.15) compared with IVAN. The differences (IVAN-SIVA) averaged -5.4 μm for CRAE, -3.9 μm for CRVE and -0.012 for AVR in the non-gated images and -3.3 μm, -6.9 μm and 0.006, respectively, in the ECG-gated photographs. In conclusion, ECG gating does not affect estimates of the retinal microvascular diameters or improve intragrader repeatability. SIVA yields slightly but significantly larger estimates of the retinal arteriolar and venular diameters. Combining historical readings analyzed by IVAN with more recent readings by SIVA is possible only for AVR and is not recommended for either CRAE or CRVE. ispartof: Hypertension Research vol:39 issue:12 pages:886-892 ispartof: location:England status: published

Background: A number of studies examined the association between preterm delivery and kidney size and function later in life. However, the number of cases in published cohort studies is low. This study was aimed at performing a multicenter collaboration to pool data to obtain more accurate results to quantify the extent of renal impairment in former extremely low birth weight (ELBW; Methodology: We performed a subject-level meta-analysis to pool data from Cracow (64 cases/34 controls) and Leuven (93 cases/87 controls). We assessed and analyzed cystatin C, estimated glomerular filtration rate (eGFR), ultrasound kidney length, and blood pressure (BP) in 11-year-old ELBW children compared with controls born at term. The prevalence of hypertension (HT) and prehypertension (preHT) in both groups was also analyzed. Results: The study group comprised 157 former ELBW children (gestational age 23–33 weeks and birth weight 430–1,000 g) and 123 children born at term. Former ELBW children had lower mean eGFR (100.62 ± 16.53 vs. 111.89 ± 15.26 mL/min/1.73 m2; p < 0.001), smaller absolute kidney length (8.56 ± 0.78 vs. 9.008 ± 0.73 cm; p = 0.01) and diastolic (68.6 ± 6.8 vs. 66.3 ± 7.7 mm Hg; p = 0.03) BP. Smaller renal size in former ELBW children was positively associated with lower birth weight, shorter gestational age, and severity of perinatal complications (intraventricular hemorrhage, length of stay, mechanical ventilation, and oxygen therapy). Conclusion: ELBW is associated with lower eGFR and a high frequency of preHT and HT.

UNLABELLED: Limiting the number of days until achievement of full enteral feeding in extremely low birth weight neonates (ELBW

Background and aims Serum creatinine is traditionally used as a marker of renal function in neonates and relates to gestational age and disease severity in extremely low birth weight (ELBW) infants. Creatinine is commonly used as a biomarker for early morbidity, but we aim to compare postnatal creatinemia trends as a biomarker for subsequent cognitive outcome. We hypothesize that impaired microcirculation not only in the kidney, but also in general (i.e. brain development) can explain this possible link. Study design and outcome measures A cohort of ELBW infants was analyzed by Bayley Scales of Infant Development (BSID-II) at the corrected age of 2 years old. Besides other perinatal indicators, neonatal creatinemia trends of survivors (n = 140) and BSID scores (n = 96) are compared and analyzed using optimal matching analysis. Hierarchical clustering analysis is applied to identify createnimia trends. Results Four different creatinemia trends were identified (persistently high, normal, low, high but normalizing). A low creatinemia trend is significantly associated with the lowest percentages of postnatal corticosteroids, NSAIDS and intraventricular hemorrhage (p = 0.005, p = 0.013 and p = 0.041 respectively) compared to a normal or persistently high creatinemia trend and associated with the best cognitive outcome (+ 13 points compared to the mean creatinemia trend and + 23 points compared to a persistently high creatinemia trend). Conclusions Creatinemia trends after birth are not only useful to predict renal function, but are also associated with cognitive outcome in extremely low birth weight infants. Neonates who have low creatinemia trends after birth, have the highest BSID scores at the age of two years old.

Background Retinal microvessels can be visualized non-invasively and mirror the status of the cerebral microvasculature. Aims To investigate whether in young children born prematurely or at term cognitive performance is related to retinal microvascular traits. Study design, subjects In 93 prematurely born infants (birth weight, Highlights • Head circumference, IQ, spatial span and matrix reasoning decrease with smaller retinal arteriolar diameter. • These associations with retinal arteriolar diameters persisted after adjustment for risk factors of cognitive impairment. • Cognitive impairment in prematurely born children might be caused by microvascular maldevelopment in the perinatal period.

Background: The retinal microvasculature can be visualized noninvasively and mirrors the status of the cerebral vasculature. We therefore investigated in 93 prematurely born infants (birth weight < 1000 g) and 87 controls born at term whether neurocognitive performance at ∼11 years is associated with the diameter of retinal microvessels. Methods: We post-processed retinal photographs by a semi-automated software (Singapore I Vessel Assessment, version 3.6) and administered the Wechsler Non-Verbal test, Dutch version (Pearson, The Netherlands) to estimate the intelligence quotient (IQ) by combining matrix reasoning and spatial span. Results: Compared with the controls, cases had lower IQ (92.5 vs. 108.7; P < 0.001), smaller central retinal arteriolar (CRAE; 162.7 vs. 174.0 mm; P < 0.001) and venular (CRVE; 234.7 vs. 242.7 mm; P = 0.003) diameters and CRAE/CRVE ratio (AVR; 0.70 vs. 0.72; P = 0.002) and lower body mass index (17.0 vs. 17.7 kg/m2; P = 0.044), but higher mean arterial pressure (82.7 vs. 77.7 mmHg; P < 0.001). In all children, the effect sizes associated with a 1-SD increase in CRAE were +3.87 (P < 0.001), +1.80 (P = 0.004) and +2.26 (P = 0.003) for total IQ, matrix reasoning, and spatial span, respectively. In models adjusted for body mass index and mean arterial pressure, these estimates were +3.21 (P = 0.009), +1.57 (P = 0.020), and +1.84 (P = 0.024), respectively. The associations of IQ and matrix reasoning with AVR also attained significance (P ≤ 0.031). Conclusions: In conclusion, our findings suggest that underdevelopment of the microcirculation in prematurely born children might have lasting effects on their cognitive performance.

Background Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. Objective To illustrate the feasibility of developing an in vitro model for neonatal proximal tubule epithelial cells (nPTECs) to study renal drug disposition at this age. Method nPTECs were isolated from urine samples of neonates of different gestational ages and were conditionally immortalized using a temperature sensitive SV40T antigen and human telomerase hTERT. Cell clones were characterized on gene expression level for PTEC markers such as P-glycoprotein (ABCB1), aquaporin1 (AQP1), and organic cation transport protein 2 (SLC22A2), and for kidney progenitor cell and podocyte markers. In addition, protein expression and functional assessment were performed for P-gp and OCT2. Results We established 101 clonal cell lines of conditionally immortalized nPTECs derived from neonatal urines. Characterization of primary cells lines showed expression of genes from different cell types such as progenitors, PTECs and podocytes, however the developed conditionally immortalized nPTECs only expressed proximal tubule markers. Quantitative PCR analysis confirmed the expression of proximal tubule markers in nPTECs similar to the adult control PTECs. P-gp was expressed in nPTECs derived from the different gestational ages with a similar functionality compared with adult derived PTECs. In contrast, OCT2 functionality was significantly lower in nPTEC cell lines compared with adult PTECs. Conclusion We demonstrate the feasibility of culturing proximal tubule epithelial cells with high efficiency from urine of neonates. These cells expressed PTEC-specific genes and functional drug transporters. The cell model presented is a valuable tool to study proximal tubule physiology and pharmacology in newborns. In addition, we demonstrate the physiological differences between the neonatal and adult kidney, which emphasizes the importance of studying drug disposition in neonatal models instead of extrapolating from adult data.

Low birth weight and prematurity are risk factors for hypertension in adulthood. Few studies in preterm or full-term born children reported on plasma renin activity (PRA). We tested the hypothesis that renin might modulate the incidence of hypertension associated with prematurity. We enrolled 93 prematurely born children with birth weight 2 (6.4–16.6) lower in cases, whereas their systolic/diastolic blood pressure (BP) was 7.5 mm Hg (4.8–10.3)/4.0 mm Hg (2.1–5.8) higher ( P P P =0.002). Twenty-four hours of urinary sodium excretion was similar in cases and controls (102.1 versus 106.8 mmol; P =0.47). Sodium load per nephron was estimated as sodium excretion divided by kidney length (mmol/cm). PRA was 0.54 ng/mL per hour (0.23–0.85; P =0.001) lower in cases. PRA, systolic BP, and sodium load were available in 43 cases and 56 controls. PRA decreased with systolic BP (slope −0.022 ng/mL per hour/ − mm Hg ; P =0.048), but was unrelated to sodium load (slope +0.13 mmol/cm − mm Hg ; P =0.54). The slope of PRA on systolic BP was similar ( P =0.17) in cases and controls. In conclusion, extremely low birth weight predisposes young adolescents to low-renin hypertension, but does not affect the inverse association between PRA and BP. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02147457.

In psychiatry, the social zeitgeber theory argues that social life provides important social cues that entrain circadian rhythms. Disturbance of these social cues might lead do dis-entrainment of circadian rhythms and evoke somatic symptoms that increase the risk of mood disorders. In preventing and treating patients with bipolar disorders, the Interpersonal and Social Rhythm Therapy (IPSRT) relies on the Social Rhythm Metric (SRM) to (re)establish patients’ social cues and an re-entrain circadian rhythms. Since the SRM quantifies social rhythms that are derived from a patient’s interaction with a social environment, this contribution (a) calculates the SRM of the social environment of a representative healthy population study (n = 1249), (b) evaluates the robustness of the SRM as a quantifier of social rhythms by matching the scores of the pilot study, revealing the near absence of variance across population characteristics and investigation months—circadian rhythms need to be entrained for every month and for everyone—and (c) examines its use in IPSRT by relating high SRM-scores to lower psychological distress (p = 0.004) and low SRM-scores to higher social and emotional dysfunction (p = 0.018).

Irrespective of presence of growth restriction at birth, preterm infants are vulnerable to extra-uterine growth restriction (EUGR) during neonatal stay and after discharge, related to cumulative protein and energy deficits.[...]