Impact of Kangaroo mother care on autonomic cardiovascular control in foetal-growth-restricted preterm infants.

Background: Kangaroo mother care (KMC) is WHO-recommended for low-birth-weight infants, yet its impact on autonomic cardiovascular control in preterm foetal growth-restricted (FGR) infants remains unclear. We hypothesised that KMC would promote autonomic cardiovascular control, benefiting preterm FGR infants with reduced baseline autonomic function compared to appropriate for gestational age (AGA) infants.

Methods: Autonomic control was assessed via heart rate variability (HRV) in low frequency (LF) and high frequency (HF) bands using spectral analysis.

Therapeutic potential of extracellular vesicles derived from human amniotic epithelial cells for perinatal cerebral and pulmonary injury.

Lung and brain injury that occurs during the perinatal period leads to lifelong disability and is often driven and/or exacerbated by inflammation. Human amniotic epithelial cells (hAEC), which demonstrate immunomodulatory, anti-fibrotic, and regenerative capabilities, are being explored as a therapeutic candidate for perinatal injury. However, limitations regarding scalable manufacturing, storage, transport, and dose-related toxicity have impeded clinical translation.

Phenotype of early-onset fetal growth restriction in sheep.

Introduction: Fetal growth restriction (FGR) is a common pregnancy complication, caused by placental insufficiency, with serious adverse consequences for development and postnatal wellbeing. There are no antenatal treatments to improve growth or organ development in FGR, and animal models are essential to mimic the physiological adaptations in FGR and to assess potential interventions. This study aimed to identify the temporal nature of reduced developmental trajectory in fetuses with FGR, and to examine the effects of common factors that may mediate differential growth such as glucocorticoid treatment.

Implications of maternal-fetal health on perinatal stem cell banking.

Cell based therapies are being assessed for their therapeutic potential across a variety of diseases. Gestational tissues are attractive sources for cell therapy. The large number of births worldwide ensures sufficient access to gestational tissues, however, limited information has been reported around the impact of birth trends, delivery methods and pregnancy conditions on perinatal stem cell banking.

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs is enhanced following sildenafil and inhaled nitric oxide administration.

Neurovascular coupling (NVC) leads to an increase in local cerebral blood flow and oxygenation in response to increased neural activity and metabolic demand. Impaired or immature NVC reported in the preterm brain, potentially reduces cerebral oxygenation following increased neural activity, predisposing to cerebral tissue hypoxia. Endogenous nitric oxide (NO) is a potent vasodilator and a major mediator of NVC and the cerebral haemodynamic response.

The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced following intrauterine inflammation and dopamine infusion.

Background: Neurovascular coupling leads to an increase in local cerebral blood flow and oxygenation in response to increased neural activity. Reduced cerebral functional responses may predispose to tissue hypoxia when neural activity is increased. Intrauterine inflammation, identified clinically as chorioamnionitis, is a major contributor to the neuropathology arising after preterm birth.

Effect of 2D and 3D Culture Microenvironments on Mesenchymal Stem Cell-Derived Extracellular Vesicles Potencies.

Therapeutic benefits of mesenchymal stem cells (MSCs) are now widely believed to come from their paracrine signalling, i.e. secreted factors such as cytokines, chemokines, and extracellular vesicles (EVs).

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7-10-day old lambs born at term: Direct synchrotron microangiography assessment.

Neurovascular coupling has been well-defined in the adult brain, but variable and inconsistent responses have been observed in the neonatal brain. The mechanisms that underlie functional haemodynamic responses in the developing brain are unknown. Synchrotron radiation (SR) microangiography enables high-resolution imaging of the cerebral vasculature.

The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced with dopamine or dobutamine infusion.

Background: In the adult brain, increases in neural activity lead to increases in local blood flow. However, in the preterm neonate, studies of cerebral functional haemodynamics have yielded inconsistent results, including negative responses suggesting decreased perfusion and localised tissue hypoxia, probably due to immature neurovascular coupling. Furthermore, the impact of vasoactive medications, such as dopamine and dobutamine used as inotropic therapies in preterm neonates, on cerebrovascular responses to somatosensory input is unknown.

Increased peak end-expiratory pressure in ventilated preterm lambs changes cerebral microvascular perfusion: direct synchrotron microangiography assessment.

Positive end-expiratory pressure (PEEP) improves oxygenation in mechanically ventilated preterm neonates by preventing lung collapse. However, high PEEP may alter cerebral blood flow secondarily to the increased intrathoracic pressure, predisposing to brain injury. The precise effects of high PEEP on cerebral hemodynamics in the preterm brain are unknown.

Maternal sildenafil impairs the cardiovascular adaptations to chronic hypoxaemia in fetal sheep.

Key Points: Fetal growth restriction induces a haemodynamic response that aims to maintain blood flow to vital organs such as the brain, in the face of chronic hypoxaemia Maternal sildenafil treatment impairs the hypoxaemia-driven haemodynamic response and potentially compromises fetal development.

Abstract: Inadequate substrate delivery to a fetus results in hypoxaemia and fetal growth restriction (FGR). In response, fetal cardiovascular adaptations redirect cardiac output to essential organs to maintain oxygen delivery and sustain development.

Effects of Maternal Sildenafil Treatment on Vascular Function in Growth-Restricted Fetal Sheep.

Objective- The objective of this study was to investigate the effect of intravenous maternal sildenafil citrate (SC) administration on vascular function in growth-restricted fetal sheep. Approach and Results- Fetal growth restriction (FGR) results in cardiovascular adaptations that redistribute cardiac output to optimize suboptimal intrauterine conditions. These adaptations result in structural and functional cardiovascular changes, which may underlie postnatal neurological and cardiovascular sequelae.

Dose-dependent exacerbation of ventilation-induced lung injury by erythropoietin in preterm newborn lambs.

Erythropoietin (EPO) is being trialled in preterm infants to reduce brain injury, but high doses increase lung injury in ventilated preterm lambs. We aimed to determine whether early administration of lower doses of EPO could reduce ventilation-induced lung injury and systemic inflammation in preterm lambs. Ventilation was initiated in anaesthetized preterm lambs [125 ± 1 (SD) days gestation] using an injurious strategy for the first 15 min.

Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition.

Objective: Umbilical cord milking (UCM) at birth may benefit preterm infants, but the physiological effects of UCM are unknown. We compared the physiological effects of two UCM strategies with immediate umbilical cord clamping (UCC) and physiological-based cord clamping (PBCC) in preterm lambs.

Methods: At 126 days' gestational age, fetal lambs were exteriorised, intubated and instrumented to measure umbilical, pulmonary and cerebral blood flows and arterial pressures.

Exacerbation of Ventilation-Induced Lung Injury and Inflammation in Preterm Lambs by High-Dose Nanoparticles.

Mechanical ventilation of preterm neonates causes lung inflammation and injury, with potential life-long consequences. Inert 50-nm polystyrene nanoparticles (PS50G) reduce allergic inflammation in the lungs of adult mice. We aimed to confirm the anti-inflammatory effects of PS50G in a sheep asthma model, and investigate the effects of prophylactic administration of PS50G on ventilation-induced lung injury (VILI) in preterm lambs.

Lung ultrasound accurately detects pneumothorax in a preterm newborn lamb model.

Aim: Pneumothorax is a common emergency affecting extremely preterm. In adult studies, lung ultrasound has performed better than chest x-ray in the diagnosis of pneumothorax. The purpose of this study was to determine the efficacy of lung ultrasound (LUS) examination to detect pneumothorax using a preterm animal model.