Mitral valve replacement in children: balancing durability and risk with mechanical and bioprosthetic valves.

OBJECTIVES: To investigate if there is still a place for bioprosthetic mitral valve replacement in children by comparing the prosthetic durability and transplant-free survival after bioprosthetic and mechanical mitral valve replacement. METHODS: We reviewed all mitral valve replacements in children between 1981 and 2020. Bioprosthetic mitral valve replacement cases were individually matched to mechanical mitral valve replacement cases. The incidence rate of a 2nd replacement was calculated using the cumulative incidence function that considered death or transplantation as a competing risk. RESULTS: The median age at implantation was 3.6 years (interquartile range 0.8-7.9) for the bioprosthetic valve cohort (n = 28) and 3 years (interquartile range 1.3-7.8) for the mechanical valve cohort (n = 28). Seven years after bioprosthetic mitral valve replacement, the cumulative incidence of death or transplantation was 17.9% [95% confidence interval (CI) 6.3-34.1] and the cumulative incidence of a 2nd replacement was 63.6% (95% CI 39.9-80.1). Seven years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 28.6% (95% CI 13.3-46) and the cumulative incidence of a 2nd replacement was 10.7% (95% CI 2.6-25.5). Fifteen years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 33.6% (95% CI 16.2-52.1) and the cumulative incidence of a 2nd replacement was 41.1% (95% CI 18.4-62.7). The cumulative incidence curves for bioprosthetic and mechanical mitral valve replacement were statistically different for a 2nd valve replacement (P < 0.001) but not for death or transplantation (P = 0.33). CONCLUSIONS: There is no difference in transplant-free survival after bioprosthetic and mechanical mitral valve replacement in children. The lifespan of bioprosthetic mitral valves remains limited in children because of structural valve failure due to calcification. After 15 years, 40% of mechanical valves were replaced, primarily because of patient-prosthesis mismatch related to somatic growth.

Organisation of paediatric echocardiography laboratories and governance of echocardiography services and training in Europe: current status, disparities, and potential solutions. A survey from the Association for European Paediatric and Congenital Cardiology (AEPC) imaging working group.

BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

Prospective assessment of inter-rater reliability of a neonatal adverse event severity scale.

Introduction: To ensure the quality of clinical trial safety data, universal data standards are required. In 2019 the International Neonatal Consortium (INC) published a neonatal adverse event severity scale (NAESS) to standardize the reporting of adverse event (AE) severity. In this study the reliability of AE severity grading with INC NAESS was prospectively assessed in a real-world setting. Methods: Severity of AEs was assessed by two independent observers at each of four centers across the world. In each center two series of 30 neonatal adverse events were assessed by both observers: in a first phase with a generic (Common Terminology Criteria for Adverse Events, CTCAE) severity scale not specific to neonates, and in a second phase with INC NAESS (after a structured training). Intraclass correlation coefficients (ICC) were calculated to express inter-rater agreement in both phases, and bootstrap sampling was used to compare them. Results: 120 AEs were included in each of both phases. The ICC with the use of INC NAESS in phase 2 was 0.69. This represents a significant but modest improvement in comparison to the initial ICC of 0.66 in phase 1 (confidence interval of ratio of ICC in phase 2 to phase 1 = 1.005-1.146; excludes 1). The ICC was higher for those AEs for which a diagnosis specific AE severity table was available in INC NAESS (ICC 0.80). Discussion: Good inter-rater reliability of the INC NAESS was demonstrated in four neonatal intensive care units (NICUs) across the globe. The ICC is comparable to what is reported for scales with similar purposes in different populations. There is a modest, but significant, improvement in inter-rater agreement in comparison to the naïve phase without INC NAESS. The better performance when reviewers use AE-specific NAESS tables highlights the need to expand the number of AEs that are covered by specific criteria in the current version of INC NAESS.

The QTc-Bazett Interval in Former Very Preterm Infants in Adolescence and Young Adulthood is Not Different from Term-Born Controls.

INTRODUCTION: Although relevant for precision pharmacovigilance, there are conflicting data on whether former preterm birth is associated with QTc-Bazett prolongation in later life. METHODS: To explore QTc-Bazett interval differences between former preterm and/or extremely low birth weight (ELBW) cases and term-born controls in adolescence and young adulthood, we analyzed pooled individual data after a structured search on published cohorts. To test the absence of a QTc-Bazett difference, a non-inferiority approach was applied (one-sided, upper limit of the 95% confidence interval [CI] mean QTc-Bazett difference, 5 and 10 ms). We also investigated the impact of characteristics, either perinatal or at assessment, on QTc-Bazett in the full dataset (cases and controls). Data were reported as median and range. RESULTS: The pooled dataset contained 164 former preterm and/or ELBW (cases) and 140 controls born full-term from three studies. The median QTc-Bazett intervals were 409 (335-490) and 410 (318-480) ms in cases and controls. The mean QTc-Bazett difference was 1 ms, with an upper 95% CI of 6 ms (p > 0.05 and p < 0.01 for 5 and 10 ms, respectively). In the full dataset, females had a significantly longer QTc-Bazett than males (415 vs. 401 ms; p < 0.0001). CONCLUSIONS: QTc-Bazett intervals are not significantly different between former preterm and/or ELBW cases and term-born controls, and we rejected a potential prolongation > 10 ms in cases. When prescribing QTc-prolonging drugs, pharmacovigilance practices in this subpopulation should be similar to the general public (NCT05243537).

Location-specific pathology analysis of the monopodial pulmonary vasculature in a rabbit model of bronchopulmonary dysplasia-A pilot study.

The mammalian pulmonary vasculature consists of functionally and morphologically heterogeneous compartments. When comparing sets of lungs, for example, in disease models or therapeutic interventions, local changes may be masked by the overall heterogeneity of the organ structure. Therefore, alterations taking place only in a sub-compartment may not be detectable by global analysis. In the monopodial lung, the characterization of distinct vessel groups is difficult, due to the asymmetrical branching pattern. In this pilot study, a previously established method to classify segments of the monopodial pulmonary arterial tree into homogeneous groups was employed. To test its suitability for experimental settings, the method was applied to a hyperoxia (HYX, ≥95% oxygen) rabbit model of bronchopulmonary dysplasia and a normoxic control group (NOX, 21% oxygen). The method allowed the identification of morphological differences between the HYX and the NOX groups. Globally visible differences in lumen diameter were pinpointed to specific lung regions. Furthermore, local changes of wall dimension and cell layers in single compartments, that would not have been identifiable in an unfocused analysis of the whole dataset, were found. In conclusion, the described method achieves a higher precision in morphological studies of lung disease models, compared to a common, global analysis approach.

Prematurity and Hyperoxia Have Different Effects on Alveolar and Microvascular Lung Development in the Rabbit.

Bronchopulmonary dysplasia (BPD) is a developmental disorder of infants born prematurely, characterized by disrupted alveolarization and microvascular maturation. However, the sequence of alveolar and vascular alterations is currently not fully understood. Therefore, we used a rabbit model to evaluate alveolar and vascular development under preterm birth and hyperoxia, respectively. Pups were born by cesarean section 3 days before term and exposed for 7 days to hyperoxia (95% O2) or normoxia (21% O2). In addition, term-born rabbits were exposed to normoxia for 4 days. Rabbit lungs were fixed by vascular perfusion and prepared for stereological analysis. Normoxic preterm rabbits had a significantly lower number of alveoli than term rabbits. The number of septal capillaries was lower in preterm rabbits but less pronounced than the alveolar reduction. In hyperoxic preterm rabbits, the number of alveoli was similar to that in normoxic preterm animals; however, hyperoxia had a severe additional negative effect on the capillary number. In conclusion, preterm birth had a strong effect on alveolar development, and hyperoxia had a more pronounced effect on capillary development. The data provide a complex picture of the vascular hypothesis of BPD which rather seems to reflect the ambient oxygen concentration than the effect of premature birth.

The neonatal adverse event severity scale: current status, a stakeholders' assessment, and future perspectives.

To support informed decisions on drug registration and prescription, clinical trials need tools to assess the efficacy and safety signals related to a given therapeutic intervention. Standardized assessment facilitates reproducibility of results. Furthermore, it enables weighted comparison between different interventions, instrumental to facilitate shared decisions. When focused on adverse events in clinical trials, tools are needed to assess seriousness, causality and severity. As part of such a toolbox, the international Neonatal Consortium (INC) developed a first version of the neonatal adverse event severity scale (NAESS). This version underwent subsequent validation in retro-and prospective trials to assess its applicability and impact on the inter-observer variability. Regulators, sponsors and academic researchers also reported on the use of the NAESS in regulatory documents, trial protocols and study reports. In this paper, we aim to report on the trajectory, current status and impact of the NAESS score, on how stakeholders within INC assess its relevance, and on perspectives to further develop this tool.

Stent expansion of restrictive Fontan conduits to nominal diameter and beyond.

BACKGROUND: Mechanical factors may cause bottlenecks in a Fontan circuit. Extracardiac conduits (ECC) are placed at a young age, but the materials do not allow growth. Restriction in ECC dimensions may deteriorate the function of the circuit. AIMS: This study aimed to evaluate the feasibility and safety of stent expansion of an ECC to the nominal dimension at the time of implant and, if possible, beyond nominal. METHODS: Retrospective, single-center observational review of all ECC Fontan patients who received a stent to expand a previously placed surgical conduit. RESULTS: A total of 44 restrictive conduits were stented over a 14-year study period with a median of 11.8 (interquartile ranges [IQR]: 9.1-13.8) years after ECC placement. Cross-sectional areas were a median of 30% (IQR: 21-42) smaller than the originally placed ECC; there was no gradient in 23/44 patients and in 21/44, a minimal gradient of 1.3 ± 0.5 (range 1-3 mmHg). All conduits could be enlarged with a significant (p < 0.0001) increase in diameter from 13.6 ± 1.8 to 19.2 ± 1.2 mm, corresponding to a median cross-sectional area increase of 171% (IQR: 153-220). In three patients where the conduits were not contracted, expansion of between 127% and 165% was obtained. There were no conduit ruptures and only one minor complication. CONCLUSIONS: ECC in some Fontan patients become smaller than nominal over time, usually without overt symptoms. The dimensions of ECC's can be safely and significantly increased to nominal or even beyond employing stenting. It allows adjustment of ECC dimensions to compensate for somatic growth.

QTc Interval Reference Values and Their (Non)-Maturational Factors in Neonates and Infants: A Systematic Review.

QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, the interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neonates. Further research in this age category is needed to improve primary screening practices and QTcthresholds, earlier detection of risk factors and precision pharmacovigilance.

Late Fontan Circulatory Failure. What Drives Systemic Venous Congestion and Low Cardiac Output in Adult Fontan Patients?

The Fontan circulation provides definite palliation for children born with a single anatomical or functional ventricle by diverting systemic venous blood directly to the pulmonary arteries, effectively rendering systemic venous return into portal vessels to the lung. Although this restores pulmonary blood flow and avoids the mixture of oxygenated and deoxygenated blood, it also results in elevated systemic venous pressures and low cardiac output. These are the two hallmarks of any Fontan circulation and the cause of Fontan circulatory failure later in life. We highlight the determinants of systemic venous return, its changed relationship with the pulmonary circulation, how it affects preload, and the changed role of the heart (myocardium, valves, and heart rate). By critically evaluating the components of the Fontan circulation, we hope to give some clues in how to optimize the Fontan circulation and avenues for future research.

Persistent Markers of Kidney Injury in Children Who Developed Acute Kidney Injury After Pediatric Cardiac Surgery: A Prospective Cohort Study.

Background Acute kidney injury (AKI) after pediatric cardiac surgery is common. Longer-term outcomes and the incidence of chronic kidney disease after AKI are not well-known. Methods and Results All eligible children (aged <16 years) who had developed AKI following cardiac surgery at our tertiary referral hospital were prospectively invited for a formal kidney assessment ≈5 years after AKI, including measurements of estimated glomerular filtration rate, proteinuria, α1-microglobulin, blood pressure, and kidney ultrasound. Longer-term follow-up data on kidney function were collected at the latest available visit. Among 571 patients who underwent surgery, AKI occurred in 113 (19.7%) over a 4-year period. Fifteen of these (13.3%) died at a median of 31 days (interquartile range [IQR], 9-57) after surgery. A total of 66 patients participated in the kidney assessment at a median of 4.8 years (IQR, 3.9-5.7) after the index AKI episode. Thirty-nine patients (59.1%) had at least 1 marker of kidney injury, including estimated glomerular filtration rate <90 mL/min per 1.73 m2 in 9 (13.6%), proteinuria in 27 (40.9%), α1-microglobinuria in 5 (7.6%), hypertension in 13 (19.7%), and abnormalities on kidney ultrasound in 9 (13.6%). Stages 1 to 5 chronic kidney disease were present in 18 (27.3%) patients. Patients with CKD were more likely to have an associated syndrome (55.6% versus 20.8%, P=0.015). At 13.1 years (IQR, 11.2-14.0) follow-up, estimated glomerular filtration rate <90 mL/min per 1.73 m² was present in 18 of 49 patients (36.7%), suggesting an average estimated glomerular filtration rate decline rate of -1.81 mL/min per 1.73 m² per year. Conclusions Children who developed AKI after pediatric cardiac surgery showed persistent markers of kidney injury. As chronic kidney disease is a risk factor for cardiovascular comorbidity, long-term kidney follow-up in this population is warranted.

QTc intervals are not prolonged in former ELBW infants at pre-adolescent age.

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, <1000 g) infants. METHODS: Twelve lead electrocardiograms (ECG) at rest, collected in the PREMATurity as predictor of children's Cardiovascular-renal Health (PREMATCH) study in former ELBW cases and term controls during pre-adolescence (8-14 years) were analyzed on corrected QT time (QTc, Bazett) and QT dispersion (QTd). ECG findings were compared between groups (Mann-Whitney), and associations with clinical and biochemical findings were explored (Spearman). In ELBW cases, associations between QTc and perinatal characteristics (at birth, neonatal stay) were explored (Mann-Whitney, Spearman). RESULTS: QTc and QTd were similar between 93 ELBW cases and 87 controls [409 (range 360-465) versus 409 (337-460); 40 (0-100) versus 39 (0-110)] ms. Age, height, weight, or body mass index were not associated with the QTc interval, while female sex (median difference 11.4 ms) and lower potassium (r = -0.26) were associated with longer QTc interval. We could not observe any significant association between QTc interval and perinatal characteristics. CONCLUSIONS: There were no differences in QTc or QTd between ELBW and term controls in ECGs at rest in pre-adolescents. IMPACT: This study aimed to assess the differences in QTc and QTd intervals between extreme low birth weight infants (ELBW) and term controls in electrocardiographic measurements at rest during pre-adolescence. This analysis confirmed the absence of significant differences in QTc or QTd findings between ELBW cases and term controls, while female sex and lower potassium were associated with a prolonged QTc interval. These data suggest that QTc screening strategies-including for pharmacovigilance-should not differentiate between former ELBW cases and term controls. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02147457.

Neurocognitive sequelae of antenatal corticosteroids in a late preterm rabbit model.

BACKGROUND: Late preterm birth is associated with short-term respiratory and adaptive problems. Although antenatal corticosteroids seem to reduce the respiratory burden, this may come at the cost of adverse neuropsychological outcomes later in life. This impact has not been investigated. OBJECTIVE: Herein, we investigate what the short- and long-term neurodevelopmental effects of a single course of betamethasone in simulated late preterm birth. STUDY DESIGN: Time-mated pregnant does received 0.1 mg/kg betamethasone (n=8) or 1 mL saline intramuscular (n=6) at the postconceptional ages of 28 and 29 days. The antenatal corticosteroid dose and scheme were based on previous studies and were comparable with routine clinical use. Cesarean delivery was done on postconceptional age 30 days (term=31 days), and new-born rabbits were foster-cared for 28 days and were thereafter cared for in group housing. Neonatal lung function testing and short-term neurobehavioral testing was done. Open field, spontaneous alternation, and novel object recognition tests were subsequently performed at 4 and 8 weeks of age. On postnatal day 1 and at 8 weeks, a subgroup was euthanized and transcardially perfuse fixated. Ex vivo high-resolution Magnetic Resonance Imaging was used to calculate the Diffusion Tensor Imaging-derived fractional anisotropy and mean diffusivity. Fixated brains underwent processing and were serial sectioned, and a set of 3 coronal sections underwent anti-NeuN, Ki67, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. RESULTS: Antenatal corticosteroid exposure was associated with improved neonatal lung function, yet resulted in a long-term growth deficit that coincided with a persistent neurobehavioral deficit. We demonstrated lower neonatal motor scores; a persistent anxious behavior in the open field test with more displacements, running, and self-grooming episodes; persistent lower alternation scores in the T-Maze test; and lower discriminatory indexes in the novel object recognition. On neuropathological assessment, antenatal corticosteroid exposure was observed to result in a persistent lower neuron density and fewer Ki67+ cells, particularly in the hippocampus and the corpus callosum. This coincided with lower diffusion tensor imaging-derived fractional anisotropy scores in the same key regions. CONCLUSION: Clinical equivalent antenatal corticosteroid exposure in this late preterm rabbit model resulted in improved neonatal lung function. However, it compromised neonatal and long-term neurocognition.

QTc Intervals Are Prolonged in Late Preterm and Term Neonates during Therapeutic Hypothermia but Normalize Afterwards.

BACKGROUND: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker for pharmacovigilance during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. METHODS: A structured search and literature assessment (PubMed, Embase, and Google Scholar) with 'Newborn/Infant, QT and hypothermia' was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1-7). RESULTS: We retrieved 94 QTc intervals (during TH (n = 50, until day 3) or subsequent normothermia (n = 44, day 4-7)) in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430-678), and 410 (317-540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. CONCLUSIONS: We highlighted a relevant non-maturational covariate (°C dependent TH) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Inter-rater reliability of the neonatal adverse event severity scale using real-world Neonatal clinical trial data.

OBJECTIVE: The Neonatal Adverse Event Severity Scale (NAESS) was developed to improve scoring of neonatal adverse events (AEs) and accelerate neonatal drug development. This is the first validation study of the novel tool. STUDY DESIGN: Retrospective validation study assessing the inter-rater reliability (IRR) of the NAESS. Reviewers used real-world AE data from a neonatal trial. Intra-class correlation (ICC) statistical analysis was performed. RESULT: Sixty AEs were randomly assigned to twelve reviewers for a total of 240 severity scores. Generic and AE-specific NAESS tables were assessed. The ICC was 0.63 (95% confidence interval 0.51 to 0.73). Percent variation due to reviewer and residual error was 0.03 and 0.34, respectively. CONCLUSION: In this first study of the NAESS tool, an ICC of 0.63 indicates moderate reliability. Results highlight the need for improved data collection on neonatal AE forms, augmented training on the NAESS tool, and will inform the prospective validation studies.

Combination of µCT and light microscopy for generation-specific stereological analysis of pulmonary arterial branches: a proof-of-concept study.

Various lung diseases, including pulmonary hypertension, chronic obstructive pulmonary disease or bronchopulmonary dysplasia, are associated with structural and architectural alterations of the pulmonary vasculature. The light microscopic (LM) analysis of the blood vessels is limited by the fact that it is impossible to identify which generation of the arterial tree an arterial profile within a LM microscopic section belongs to. Therefore, we established a workflow that allows for the generation-specific quantitative (stereological) analysis of pulmonary blood vessels. A whole left rabbit lung was fixed by vascular perfusion, embedded in glycol methacrylate and imaged by micro-computed tomography (µCT). The lung was then exhaustively sectioned and 20 consecutive sections were collected every 100 µm to obtain a systematic uniform random sample of the whole lung. The digital processing involved segmentation of the arterial tree, generation analysis, registration of LM sections with the µCT data as well as registration of the segmentation and the LM images. The present study demonstrates that it is feasible to identify arterial profiles according to their generation based on a generation-specific color code. Stereological analysis for the first three arterial generations of the monopodial branching of the vasculature included volume fraction, total volume, lumen-to-wall ratio and wall thickness for each arterial generation. In conclusion, the correlative image analysis of µCT and LM-based datasets is an innovative method to assess the pulmonary vasculature quantitatively.

A Systematic Review of the Influence of Continuous Positive Airway Pressure on Fetal and Newborn Animal Models: Suggestions to Improve Neonatal Respiratory Care.

INTRODUCTION: Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the risk of bronchopulmonary dysplasia. Continuous positive airway pressure (CPAP), a form of noninvasive ventilation, is commonly used in modern neonatology. Limited clinical data are available on the acute and long-term effect of neonatal exposure to CPAP on the lung. Given the restricted clinical data, newborn animal models have been used to study the influence of CPAP on lung structure and function. The findings of animal studies can guide neonatal care and improve the use of CPAP. METHODS: A systematic review of electronic databases (Medline, Embase, and Cinahl) was performed using the medical subject heading terms, "CPAP" or "continuous positive airway pressure" and "animals" and "newborn." Abstracts were screened for inclusion using predetermined eligibility criteria. RESULTS: In total, 235 abstracts were identified and screened for inclusion. Of these, 21 papers were included. Large (N = 18) and small (N = 3) animal models investigated the effects of CPAP. Pulmonary outcomes included gas exchange, lung structure and function, surfactant metabolism, lung inflammation and injury, and the effect of intrapulmonary therapy. Compared to mechanical ventilation, CPAP improves lung function, evokes less lung injury, and does not disrupt alveolar development. Surfactant administration combined with CPAP further improves respiratory outcomes. Of concern are findings that CPAP may increase airway reactivity. DISCUSSION/CONCLUSION: CPAP offers numerous advantages over mechanical ventilation for the immature lung. The combination of CPAP and exogenous surfactant administration offers further pulmonary benefit.

Glomerular developmental delay and proteinuria in the preterm neonatal rabbit.

Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to transient and permanent problems in these fragile patients. Premature birth (<36 gestational weeks) occurs during critical renal development and maturation. Some consequences have been observed but the exact pathophysiology is still not entirely known. This experimental animal study aims to investigate the effect of premature birth on postnatal nephrogenesis in premature neonatal rabbits compared to term rabbits of the same corrected age. We analyzed renal morphology, glomerular maturity and functional parameters (proteinuria and protein/creatinine ratio) in three cohorts of rabbit pups: preterm (G28), preterm at day 7 of life (G28+7) and term at day 4 of life (G31+4). We found no significant differences in kidney volume and weight, and relative kidney volume between the cohorts. Nephrogenic zone width increased significantly over time when comparing G31 + 4 to G28. The renal corpuscle surface area, in the inner cortex and outer cortex, tended to decrease significantly after birth in both preterm and term groups. With regard to glomerular maturity, we found that the kidneys in the preterm cohorts were still in an immature state (presence of vesicles and capillary loop stage). Importantly, significant differences in proteinuria and protein/creatinine ratio were found. G28 + 7 showed increased proteinuria (p = 0.019) and an increased protein/creatinine ratio (p = 0.023) in comparison to G31 +4. In conclusion, these results suggest that the preterm rabbit kidney tends to linger in the immature glomerular stages and shows signs of a reduced renal functionality compared to the kidney born at term, which could in time lead to short- and long-term health consequences.