Postnatal Nephrogenesis in Preterm Infants: The Need to Safeguard Kidney Development After Birth.
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ABSTRACT:
SUBMITTER: Nakatsugawa AC
PROVIDER: S-EPMC10851061 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Postnatal Nephrogenesis in Preterm Infants: The Need to Safeguard Kidney Development After Birth.
Nakatsugawa Antonia C AC Sampogna Rosemary V RV
Kidney international reports 20231223 2
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Project description:IntroductionHuman nephrogenesis is typically completed by 36 weeks gestation; however, it is impacted by preterm birth. Early studies suggested that nephrogenesis persisted for ≤40 postnatal days in preterm infants. However, the postmenstrual age (PMA) of the preterm infants who survived >40 days was uncertain. In this study, we sought to reexamine postnatal kidney development in preterm infants surviving >40 days.MethodsHuman kidney samples were obtained from an institutional biobank. Samples were considered controls if survival was ≤4 days after birth with PMA of 30 to ≤36 weeks. Kidneys from preterm neonates with postnatal survival >40 days and PMA of 30 to ≤36 weeks were compared to controls. We counted glomerular generations, measured nephrogenic zone widths (NZW), and performed immunofluorescence (IF) with SIX1 and RET. We compared kidney weights and quantified the cross-sectional area of proximal (lotus tetragonolobus lectin [LTL], SL22A2), distal (SLC12A3, KCNJ10), and glomerular (nephrin) markers using IF.ResultsSeven preterm infants surviving >40 days and 8 controls were analyzed. Four of 7 preterm infants had histologic and molecular evidence of nephrogenesis. Cessation of nephrogenesis in preterm infants occurred 2 weeks earlier than PMA-matched controls with attenuated expression of both SIX1 and RET. We found increased kidney weight-to-body weight ratio, increased distal tubular cross-sectional staining in the superficial nephrons, and distal tubular hypertrophy and hyperplasia in the preterm infant kidneys.ConclusionOur study supports that nephrogenesis in preterm infants persists longer than previously thought with evidence of early nephron stress, placing importance on the neonatal environment.
| S-EPMC10851065 | biostudies-literature
Project description:BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.
| S-EPMC5511508 | biostudies-literature
Project description:BackgroundBronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits.MethodsPups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms.ResultsPreterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences.ConclusionsPreterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.
| S-EPMC7035772 | biostudies-literature
Project description:Preterm birth, defined as birth before the gestational age of 37 weeks, affects 11% of the newborns worldwide. While extensive research has focused on the immediate complications associated with prematurity, emerging evidence suggests a link between prematurity and the development of kidney disease later in life. It has been demonstrated that the normal course of kidney development is interrupted in infants born prematurely, causing an overall decrease in functional nephrons. Yet, the pathogenesis leading to the alterations in kidney development and the subsequent pathophysiological consequences causing kidney disease on the long-term are incompletely understood. In the present review, we discuss the current knowledge on nephrogenesis and how this process is affected in prematurity. We further discuss the epidemiological evidence and experimental data demonstrating the increased risk of kidney disease in these individuals and highlight important knowledge gaps. Importantly, understanding the intricate interplay between prematurity, abnormal kidney development, and the long-term risk of kidney disease is crucial for implementing effective preventive and therapeutic strategies.
| S-EPMC11004308 | biostudies-literature
Project description:Inflammation often accompanies preterm birth and contributes to poor neurodevelopment in preterm infants. The purpose of this study was to describe postnatal cytokine trajectories among non-infected very preterm infants during the first weeks of life. Blood samples for cytokine analysis were collected weekly from infants born between 28 and 31 weeks post-menstrual age. We used linear mixed models to calculate slopes for each cytokine and allowed the slopes to differ by infant biological sex and post-menstrual age at birth. Levels of interleukin-6, interleukin-8, and interleukin-1 receptor antagonist decreased, on average, during the neonatal period. Monocyte chemoattractant protein-1 levels increased over time, and tumor necrosis factor-alpha levels were stable. Interleukin-6 and interleukin-8 slopes differed by post-menstrual age at birth but were unaffected by infant sex. Knowledge of average cytokine trajectories may be useful in identifying infants with unresolving inflammation that increases their risk for poor neurodevelopment.
| S-EPMC8898980 | biostudies-literature
Project description:BackgroundPreterm infants are at high risk for growth failure and childhood weight problems due to the disruption of normal intrauterine growth and nutrition. Early nutritional support and microbiome acquisition can play an important role in childhood growth.ObjectiveOur study examined potential postnatal indicators, including gut bacterial compositions, macronutrients, and catch-up growth, of growth pattern from infancy into early childhood.MethodsThis is a retrospective study of preterm infants born < 35 weeks who were followed up in the university complex care clinic from 2012-2018. Weight and length z-scores at birth, 1, 2, 4, 6, 12 and 15 months, and body mass index (BMI) and length z-scores from 2 to 5 years of age were collected. Catch-up growths were calculated by changes in z-scores and divided into early (birth-4 months) and late (4-18 months). Postnatal nutritional data and fecal samples were collected. Fecal microbiome data obtained from 16S RNA V4 sequencing was analyzed against clinical and growth data using a regression model.Results160 infants included in the final analysis had birth weight and gestational age of 1,149 ± 496 grams and 28 ± 3 weeks. Early weight gain positively correlated with length z-scores but not with BMI at 2 years of age. BMI at 2 years of age strongly correlated with BMI at 3, 4, and 5 years of age. Postnatal abundance of Gammaproteobacteria was negatively associated with early growth while Bacteroides and Lactobacillus were positively associated with childhood BMI.ConclusionOur findings suggest that optimal postnatal nutrition promoted early catch-up growth in weight as well as improved linear growth without influence on childhood BMI. Postnatal gut microbial colonization, which is a modifiable factor, was associated with childhood growth in preterm infants.
| S-EPMC9395978 | biostudies-literature
Project description:BackgroundThere is no consensus with regard to which charts are most suitable for monitoring the postnatal growth of preterm infants.ObjectiveWe aimed to assess the strategies used to develop existing postnatal growth charts for preterm infants and their methodologic quality.DesignA systematic review of observational longitudinal studies, having as their primary objective the creation of postnatal growth charts for preterm infants, was conducted. Thirty-eight items distributed in 3 methodologic domains ("study design," "statistical methods," and "reporting methods") were assessed in each study. Each item was scored as a "low" or "high" risk of bias. Two reviewers independently selected the studies, assessed the risk of bias, and extracted data. A total quality score [(number of "low risk" of bias marks/total number of items assessed) × 100%] was calculated for each study. Median (range, IQR) quality scores for each methodologic domain and for all included studies were computed.ResultsSixty-one studies met the inclusion criteria. Twenty-seven (44.3%) of the 61 studies scored ≥50%, of which 10 scored >60% and only 1 scored >66%. The median (range, IQR) quality score for the 61 included studies was 47% (26-75%, 34-56%). The scores for the domains study design, statistical methods, and reporting methods were 44% (19-67%, 33-52%), 25% (0-88%, 13-38%), and 33% (0-100%, 0-33%), respectively. The most common shortcomings were observed in items related to anthropometric measures (the main variable of interest), gestational age estimation, follow-up duration, reporting of postnatal care and morbidities, assessment of outliers, covariates, and chart presentation.ConclusionsThe overall methodologic quality of existing longitudinal studies was fair to low. To overcome these problems, the Preterm Postnatal Follow-up Study, 1 of the 3 main components of The International Fetal and Newborn Growth Consortium for the 21st Century Project, was designed to construct preterm postnatal growth standards from a prospective cohort of "healthy" pregnancies and preterm newborns without evidence of fetal growth restriction.
| S-EPMC6443302 | biostudies-literature
Project description:Preterm birth survivors are at a higher risk of growth and developmental disabilities compared to their term counterparts. Development of strategies to lower the complications of preterm birth forms the rising need of the hour. Appropriate nutrition is essential for the growth and development of preterm infants. Early administration of optimal nutrition to preterm birth survivors lowers the risk of adverse health outcomes and improves cognition in adulthood. A group of neonatologists, pediatricians, and nutrition experts convened to discuss and frame evidence-based recommendations for optimizing nutrition in preterm low birth weight (LBW) infants. The following were the primary recommendations of the panel: (1) enteral feeding is safe and may be preferred to parenteral nutrition due to the complications associated with the latter; however, parenteral nutrition may be a useful adjunct to enteral feeding in some critical cases; (2) early, fast, or continuous enteral feeding yields better outcomes compared to late, slow, or intermittent feeding, respectively; (3) routine use of nasogastric tubes is not advisable; (4) preterm infants can be fed while on ventilator or continuous positive airway pressure; (5) routine evaluation of gastric residuals and abdominal girth should be avoided; (6) expressed breast milk (EBM) is the first choice for feeding preterm infants due to its beneficial effects on cardiovascular, neurological, bone health, and growth outcomes; the second choice is donor pasteurized human milk; (7) EBM or donor milk may be fortified with human milk fortifiers, without increasing the osmolality of the milk, to meet the high protein requirements of preterm infants; (8) standard fortification is effective and safe but does not fulfill the high protein needs; (9) use of targeted and adjustable fortification, where possible, helps provide optimal nutrition; (10) optimizing weight gain in preterm infants prevents long-term cardiovascular complications; (11) checking for optimal weight and sucking/swallowing ability is essential prior to discharge of preterm infants; and (12) appropriate counseling and regular follow-up and monitoring after discharge will help achieve better long-term health outcomes. This consensus summary serves as a useful guide to clinicians in addressing the challenges and providing optimal nutrition to preterm LBW infants.
| S-EPMC5445116 | biostudies-other
Project description:Weight shapes the intestinal microbiome in preterm infants: results of a prospective observational study
| PRJEB44936 | ENA
Project description:Congenital reduction in nephron number (renal hypoplasia) is a predisposing factor for chronic kidney disease and hypertension. Despite identification of specific genes and pathways in nephrogenesis, determinants of final nephron endowment are poorly understood. Here, we report that mice with germ-line p53 deletion (p53(-/-)) manifest renal hypoplasia; the phenotype can be recapitulated by conditional deletion of p53 from renal progenitors in the cap mesenchyme (CM(p53-/-)). Mice or humans with germ-line heterozygous mutations in Pax2 exhibit renal hypoplasia. Since both transcription factors are developmentally expressed in the metanephros, we tested the hypothesis that p53 and Pax2 cooperate in nephrogenesis. In this study, we provide evidence for the presence of genetic epistasis between p53 and Pax2: a) p53(-/-) and CM(p53-/-)embryos express lower Pax2 mRNA and protein in nephron progenitors than their wild-type littermates; b) ChIP-Seq identified peaks of p53 occupancy in chromatin regions of the Pax2 promoter and gene in embryonic kidneys; c) p53 binding to Pax2 gene is significantly more enriched in Pax2 -expressing than non-expressing metanephric mesenchyme cells; d) in transient transfection assays, Pax2 promoter activity is stimulated by wild-type p53 and inhibited by a dominant negative mutant p53; e) p53 knockdown in cultured metanephric mesenchyme cells down-regulates endogenous Pax2 expression; f) reduction of p53 gene dosage worsens the renal hypoplasia in Pax2(+/-) mice. Bioinformatics identified a set of developmental renal genes likely to be co-regulated by p53 and Pax2. We propose that the cross-talk between p53 and Pax2 provides a transcriptional platform that promotes nephrogenesis, thus contributing to nephron endowment.
| S-EPMC3440354 | biostudies-literature