Dose-related cardiac outcomes in response to postnatal dexamethasone treatment in premature lambs.

Background: Postnatal corticosteroids are used in the critical care of preterm infants for the prevention and treatment of bronchopulmonary dysplasia. We aimed to investigate the effects of early postnatal dexamethasone therapy and dose on cardiac maturation and morphology in preterm lambs.

Methods: Lambs were delivered prematurely at ~128 days of gestational age and managed postnatally according to best clinical practice.

The impact of intrauterine growth restriction and prematurity on nephron endowment.

In humans born at term, maximal nephron number is reached by the time nephrogenesis is completed - at approximately 36 weeks' gestation. The number of nephrons does not increase further and subsequently remains stable until loss occurs through ageing or disease. Nephron endowment is key to the functional capacity of the kidney and its resilience to disease; hence, any processes that impair kidney development in the developing fetus can have lifelong adverse consequences for renal health and, consequently, for quality and length of life.

Preterm Birth With Neonatal Interventions Accelerates Collagen Deposition in the Left Ventricle of Lambs Without Affecting Cardiomyocyte Development.

Background: Adults born preterm (< 37 weeks' gestation) exhibit altered cardiac growth and are susceptible to cardiac dysfunction. Sheep studies have shown that moderate preterm birth results in maladaptive structural remodelling of the cardiac ventricles. The aim of this study was to examine ventricular structure in lambs born at a greater severity of preterm birth and ventilated postnatally.

Renal morphology and glomerular capillarisation in young adult sheep born moderately preterm.

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.

Microarchitecture of the hearts in term and former-preterm lambs using diffusion tensor imaging.

Diffusion tensor imaging (DTI) is an MRI technique that can be used to map cardiomyocyte tracts and estimate local cardiomyocyte and sheetlet orientation within the heart. DTI measures diffusion distances of water molecules within the myocardium, where water diffusion generally occurs more freely along the long axis of cardiomyocytes and within the extracellular matrix, but is restricted by cell membranes such that transverse diffusion is limited. DTI can be undertaken in fixed hearts and it allows the three-dimensional mapping of the cardiac microarchitecture, including cardiomyocyte organization, within the whole heart.

Induction of left ventricular hypoplasia by occluding the foramen ovale in the fetal lamb.

Disturbed fetal haemodynamics often affects cardiac development and leads to congenital cardiac defects. Reduced left ventricular (LV) preload in the fetus may result in hypoplastic LV, mitral and aortic valve, mimicking a moderate form of hypoplastic left heart complex. We aimed to induce LV hypoplasia by occluding the foramen ovale (FO) to reduce LV preload in the fetal sheep heart, using percutaneous trans-hepatic catheterisation.

A practical guide to the stereological assessment of glomerular number, size, and cellular composition.

The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli.

Normal foetal kidney volume in offspring of women treated for gestational diabetes.

Aims: The worldwide prevalence of gestational diabetes mellitus (GDM) is increasing. Studies in rodent models indicate that hyperglycaemia during pregnancy alters kidney development, yet few studies have examined if this is so in humans. The objective of this study was to evaluate the association of treated GDM with foetal kidney size.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants.

Impact of Intrauterine Growth Restriction on the Capillarization of the Early Postnatal Rat Heart.

Capillarization plays a key role in the growth of the developing heart. We therefore hypothesized that impaired heart development following intrauterine growth restriction (IUGR) may arise from inadequate myocardial capillary growth. The aims of the study were to examine the effect of IUGR on the growth and diffusion radius of intramyocardial capillaries in rats at postnatal day 1.

Morphology and Function of the Lamb Ileum following Preterm Birth.

Background: For infants born moderately/late preterm (32-37 weeks of gestation), immaturity of the intestine has the potential to impact both short- and long-term gastrointestinal function. The aim of this study conducted in sheep was to compare the morphology and smooth muscle contractility of the ileum in term and late preterm lambs.

Materials And Methods: Lambs delivered preterm (132 days gestation;  = 7) or term (147 days gestation;  = 9) were milk-fed after birth and euthanased at 2 days of age.

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants.

Background: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation.

Methods: Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth.

Impact of preterm birth on the developing myocardium of the neonate.

BackgroundGlobally, ∼10% of infants are born before full term. Preterm birth exposes the heart to the demands of postnatal cardiovascular function before cardiac development is complete. Our aim was to examine, in hearts collected from infants at autopsy, the effects of preterm birth on myocardial structure and on cardiomyocyte development.

The effect of sex and prematurity on the cardiovascular baroreflex response in sheep.

What is the central question of this study? Late preterm infants are often assumed to escape long-term morbidities known to impact earlier preterm offspring. Is this true for the cardiovascular system? What is the main finding and its importance? We show that late preterm birth is a risk factor for cardiovascular dysfunction in early adulthood and is influenced by sex. Early signs of cardiovascular dysfunction might predispose to heart disease in adulthood.

Effects of preterm birth and ventilation on glomerular capillary growth in the neonatal lamb kidney.

Objectives: Preterm birth is linked to the development of hypertension later in life. This may relate to impaired glomerular capillary growth following preterm birth. The aim of this study was to determine the effects of preterm birth, and/or ventilation, on glomerular capillary growth in the neonatal lamb kidney.

Three-dimensional direct measurement of cardiomyocyte volume, nuclearity, and ploidy in thick histological sections.

Quantitative assessment of myocardial development and disease requires accurate measurement of cardiomyocyte volume, nuclearity (nuclei per cell), and ploidy (genome copies per cell). Current methods require enzymatically isolating cells, which excludes the use of archived tissue, or serial sectioning. We describe a method of analysis that permits the direct simultaneous measurement of cardiomyocyte volume, nuclearity, and ploidy in thick histological sections.

The effects of preterm birth and its antecedents on the cardiovascular system.

Introduction: Preterm birth occurs in approximately 10% of all births worldwide. It prematurely exposes the developing cardiovascular system to the hemodynamic transition that occurs at birth and to the subsequent functional demands of life ex utero. This review describes the current knowledge of the effects of preterm birth, and some of its common antecedents (chorioamnionitis, intra-uterine growth restriction, and maternal antenatal corticosteroid administration), on the structure of the myocardium.

Calibrated integrated backscatter and myocardial fibrosis in patients undergoing cardiac surgery.

Objective: The reported association between calibrated integrated backscatter (cIB) and myocardial fibrosis is based on study of patients with dilated or hypertrophic cardiomyopathy and extensive (mean 15-34%) fibrosis. Its association with lesser degrees of fibrosis is unknown. We examined the relationship between cIB and myocardial fibrosis in patients with coronary artery disease.

Impaired myocardial development resulting in neonatal cardiac hypoplasia alters postnatal growth and stress response in the heart.

Aims: Foetal growth has been proposed to influence cardiovascular health in adulthood, a process referred to as foetal programming. Indeed, intrauterine growth restriction in animal models alters heart size and cardiomyocyte number in the perinatal period, yet the consequences for the adult or challenged heart are largely unknown. The aim of this study was to elucidate postnatal myocardial growth pattern, left ventricular function, and stress response in the adult heart after neonatal cardiac hypoplasia in mice.

Transgenerational left ventricular hypertrophy and hypertension in offspring after uteroplacental insufficiency in male rats.

Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar-Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively.

Low-dose maternal alcohol consumption: effects in the hearts of offspring in early life and adulthood.

High alcohol consumption during pregnancy leads to deleterious effects on fetal cardiac structure and it also affects cardiomyocyte growth and maturation. This study aimed to determine whether low levels of maternal alcohol consumption are also detrimental to cardiomyocyte and cardiac growth in the early life of offspring and whether cardiac structure and function in adulthood is affected. Pregnant Sprague-Dawley rat dams were fed a control or 6% (volume/volume) liquid-based ethanol supplemented (isocaloric) diet throughout gestation.

Obesity is associated with lower coronary microvascular density.

Background: Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure.

Methods: We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy.

Vitamin D deficiency in early life and the potential programming of cardiovascular disease in adulthood.

Vitamin D deficiency is a major worldwide public health problem affecting people of all ages, from infants to the elderly. Of particular concern is the high incidence of vitamin D deficiency in women during pregnancy and lactation, leading to the exposure of the growing fetus/infant to inadequate levels of vitamin D, which is essential for normal development. Vitamin D deficiency in adulthood is linked to the etiology of hypertension and to a multitude of adverse cardiovascular outcomes.

Chronic intrauterine exposure to endotoxin does not alter fetal nephron number or glomerular size.

A reduced nephron endowment early in life adversely impacts on long-term functional reserve in the kidney. A recent study has shown that acute exposure to chorioamnionitis during late gestation can adversely impact on nephrogenesis. The present study aimed to examine the effects of chronic, low-dose endotoxin exposure in utero, during the period of nephrogenesis, on nephron number and glomerular size in preterm lambs.

When birth comes early: effects on nephrogenesis.

Preterm birth (birth prior to 37 completed weeks of gestation) may occur at a time when the infant kidney is very immature and nephrogenesis is often ongoing. In autopsied preterm human kidneys and in a baboon model of preterm birth it has been shown that nephrogenesis continues after preterm birth, with a significant increase in the number of glomerular generations and number of nephrons formed within the kidney after birth. Of concern, however, morphologically abnormal glomeruli (with a cystic Bowman's space) are often observed; the abnormal glomeruli are only located in the outer renal cortex, suggesting that it is the recently formed glomeruli (perhaps those formed in the extra-uterine environment) that are affected.