Basics of Functional Echocardiography in Children and Neonates.

Functional echocardiography has become an invaluable tool in the pediatric and neonatal intensive care unit. "Point-of-care," "target," or "focus" echocardiography allows bedside cardiac ultrasound evaluation of the hemodynamic status of the patient, helps in directing treatment, thus improves patients care. In order to be able to perform functional echocardiography, it is essential to understand the principles of ultrasound, to know the echocardiographic equipment and settings necessary to acquire the images. This article focuses therefore on the basics of cardiac ultrasound. It is meant to give an overview of two-dimensional echocardiographic views, M-mode imaging and Doppler echocardiography for neonatologists and pediatric intensivists. It is richly illustrated for better understanding with some examples of clinical applications of functional echocardiography in the intensive care setting

FGF Signaling Pathway in the Developing Chick Lung: Expression and Inhibition Studies

Background: Fibroblast growth factors (FGF) are essential key players during embryonic development. Through their specific cognate receptors (FGFR) they activate intracellular cascades, finely regulated by modulators such as Sprouty. Several FGF ligands (FGF1, 2, 7, 9, 10 and 18) signaling through the four known FGFRs, have been implicated in lung morphogenesis. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies. Methodology/Principal Findings: In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patterns in early stages of chick lung development by in situ hybridization and observe that they are expressed similarly to their mammalian counterparts. Furthermore, aiming to determine a role for FGF signaling in chick lung development, in vitro FGFR inhibition studies were performed. Lung explants treated with an FGF receptor antagonist (SU5402) presented an impairment of secondary branch formation after 48 h of culture; moreover, abnormal lung growth with a cystic appearance of secondary bronchi and reduction of the mesenchymal tissue was observed. Branching and morphometric analysis of lung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. Conclusions/Significance: This work demonstrates that FGFRs are essential for the epithelial-mesenchymal interactions tha

Partial pulmonary embolization disrupts alveolarization in fetal sheep

BACKGROUND: Although bronchopulmonary dysplasia is closely associated with an arrest of alveolar development and pulmonary capillary dysplasia, it is unknown whether these two features are causally related. To investigate the relationship between pulmonary capillaries and alveolar formation, we partially embolized the pulmonary capillary bed. METHODS: Partial pulmonary embolization (PPE) was induced in chronically catheterized fetal sheep by injection of microspheres into the left pulmonary artery for 1 day (1d PPE; 115d gestational age; GA) or 5 days (5d PPE; 110-115d GA). Control fetuses received vehicle injections. Lung morphology, secondary septal crests, elastin, collagen, myofibroblast, PECAM1 and HIF1 alpha abundance and localization were determined histologically. VEGF-A, Flk-1, PDGF-A and PDGF-R alpha mRNA levels were measured using real-time PCR. RESULTS: At 130d GA (term approximately 147d), in embolized regions of the lung the percentage of lung occupied by tissue was increased from 29 +/- 1% in controls to 35 +/- 1% in 1d PPE and 44 +/- 1% in 5d PPE fetuses (p < 0.001). Secondary septal crest density was reduced from 8 +/- 0% in controls to 5 +/- 0% in 1d PPE and 4 +/- 0% in 5d PPE fetuses (p < 0.05), indicating impaired alveolar formation. The deposition of differentiated myofibroblasts (23 +/- 1% vs 28 +/- 1%; p < 0.001) and elastin fibres (3 +/- 0% vs 4 +/- 0%; p < 0.05) were also impaired in embolized lung regions of PPE fetuses compared to controls. PPE did not alter the deposition of collagen or PECAM1. At 116d GA in 5d PPE fetuses, markers of hypoxia indicated that a small and transient hypoxic event had occurred (hypoxia in 6.7 +/- 1.4% of the tissue within embolized regions of 5d PPE fetuses at 116d compared to 0.8 +/- 0.2% of tissue in control regions). There was no change in the proportion of tissue labelled with HIF1 alpha. There was no change in mRNA levels of the angiogenic factors VEGF and Flk-1, although a small increase in PDGF-R alpha expression at 116d GA, from 1.00 +/- 0.12 in control fetuses to 1.61 +/- 0.18 in 5d PPE fetuses may account for impaired differentiation of alveolar myofibroblasts and alveolar development. CONCLUSIONS: PPE impairs alveolarization without adverse systemic effects and is a novel model for investigating the role of pulmonary capillaries and alveolar myofibroblasts in alveolar formation

Neurodevelopmental outcome of neonates treated with nitric oxide for persistent pulmonary hypertension

Persistent pulmonary hypertension of the newborn (PPHN) is a life threatening condition associated with an increased risk of neurodevelopmental impairment. The recommended treatment for this condition is inhaled nitric oxide (iNO) and has been used in our Neonatal Intensive Care Unit since 1998. We prospectively offered neurodevelopmental follow-up to children treated with iNO for PPHN, including extensive neurological evaluation, developmental/cognitive evaluation at 18 months and 3.5-5 years old, and evaluated the rate of severe and moderate handicap and normal neurodevelopmental outcome, compared to a control group and the literature. Population consisted of 29 patients treated only with iNO, born between 01.01.1999 and 31.12.2005 (study group), and 32 healthy term infants born in 1998 in our maternity (control group). During those seven years, 65 infants were admitted in our Unit with PPHN, of whom 40 were treated with iNO alone. 34 children survived (85%) and were offered neurodevelopmental follow-up, 7 children were lost to follow-up due to various reasons. 22 children were examined at the age of 18 months (76%) with a rate of moderate handicap of 22% (2 with expressive language delay, 2 with difficult behavior, and 1 child with moderate hearing loss), and a rate of major handicap of 4.5% (1 child with cerebral palsy due to perinatal stroke, and moderate hearing loss). At preschool age, 17 (50%) were examined, the rate of moderate handicap was 22% (4 borderline intelligence, 1 hearing loss), and the rate of major handicap was 4.5% (one child with cerebral palsy and hearing loss), compared to 26.9% and 0% in the control group. Mean developmental quotient at 18 months was 100.3 ± 8.7 (control group 118.3), and at preschool age mean cognitive indices were within normal limits for the 2 tests performed at 3.5 or 5 years (108 ± 21, 94.4 ± 17). Most of the children with a less favorable neurodevelopmental outcome suffered from birth asphyxia (ruptured uterus, placental abruption, maternal hypotension, diabetic cardiomyopathy), and notably, the 2 children with sensorineural hearing loss both suffered from severe hypoxic-ischemic enkelopathy. Treatment with iNO was not the direct cause of the neurodevelopmental impairments observed in children treated for PPHN

Neurodevelopmental follow-up of neonates treated with magnesium sulfate for persistent pulmonary hypertension

Persistent pulmonary hypertension of the newborn (PPHN) is a life threatening condition associated with an increased risk of neurological impairment. Magnesium sulfate (MgSO_{4}) is an alternative and low cost treatment for PPHN. Despite more appropriate and available therapies MgSO_{4} is still widely used, especially in developing countries, but long-term follow-up is unknown. In a retrospective controlled study we evaluated whether MgSO_{4} therapy for PPHN was associated with increased neuro-developmental impairments at follow-up, as compared to a control group. Population consisted of 33 infants treated for PPHN with MgSO_{4}only (study group) and 32 healthy term infants (control group). Extensive neuro-developmental follow-up examination was performed at 18 months and 5 years of age. Rate of major impairments and minor impairments were evaluated and compared to the literature. The rates of major impairments in the study group at 18 months and 5 years were 6% and 11.4%, respectively, and 0% at both ages in the control group. The rates of minor impairments at the same ages were 3% and 26.9% for the study group, and 0% and 26.1% for the control group. Mean developmental quotients at 18 months were 106.6 (SD 1.6) in the study group and 118.3 (SD 1.0) in the control group (p&lt;0.001). General intellectual index at preschool age was not significantly different between the two groups. Treatment with MgSO_{4} does not increase the rate of disability, as compared to other treatments for PPHN

Die Unterstützung der Adaptation und Reanimation des Neugeborenen: revidierte Empfehlungen der Schweizerischen Gesellschaft für Neonatologie (2017)

Einführung Entstehung und Anwendung dieser Empfehlungen Eine Arbeitsgruppe der Schweizerischen Gesellschaft für Neonatologie (SGN) hat erstmals im Jahr 2000 Empfehlungen zur Betreuung und Reanimation von Neugeborenen für die Schweiz ausgearbeitet. Diese Empfehlungen werden nun nach zwei Revisionen (2007/2012) erneut angepasst, basierend auf den Evidenzen aus einer kritischen Evaluation der aktuell zur Verfügung stehenden wissenschaftlichen Publikationen1), 2) sowie Revisionen internationaler Empfehlungen2)-4). Mit berücksichtigt wurden publizierte Reflektionen zu diesen revidierten internationalen Empfehlungen (insbesondere ERC und ILCOR) 5)-7) sowie die 2016 von einer interdisziplinären Gruppe schweizerischer Fachgesellschaften publizierten Empfehlungen zur Organisation der neonatalen Erstversorgung8). Diese Leitlinien sollen als Empfehlungen verstanden werden, die im individuellen Fall angepasst werden können und sollen

Muscarinic receptor M1 and phosphodiesterase 1 are key determinants in pulmonary vascular dysfunction following perinatal hypoxia in mice.

Perinatal adverse events such as limitation of nutrients or oxygen supply are associated with the occurrence of diseases in adulthood, like cardiovascular diseases and diabetes. We investigated the long-term effects of perinatal hypoxia on the lung circulation, with particular attention to the nitric oxide (NO)/cGMP pathway. Mice were placed under hypoxia in utero 5 days before delivery and for 5 days after birth. Pups were then bred in normoxia until adulthood. Adults born in hypoxia displayed an altered regulation of pulmonary vascular tone with higher right ventricular pressure in normoxia and increased sensitivity to acute hypoxia compared with controls. Perinatal hypoxia dramatically decreased endothelium-dependent relaxation induced by ACh in adult pulmonary arteries (PAs) but did not influence NO-mediated endothelium-independent relaxation. The M(3) muscarinic receptor was implicated in the relaxing action of ACh and M(1) muscarinic receptor (M(1)AChR) in its vasoconstrictive effects. Pirenzepine or telenzepine, two preferential inhibitors of M(1)AChR, abolished the adverse effects of perinatal hypoxia on ACh-induced relaxation. M(1)AChR mRNA expression was increased in lungs and PAs of mice born in hypoxia. The phosphodiesterase 1 (PDE1) inhibitor vinpocetine also reversed the decrease in ACh-induced relaxation following perinatal hypoxia, suggesting that M(1)AChR-mediated alteration of ACh-induced relaxation is due to the activation of calcium-dependent PDE1. Therefore, perinatal hypoxia leads to an altered pulmonary circulation in adulthood with vascular dysfunction characterized by impaired endothelium-dependent relaxation and M(1)AChR plays a predominant role. This raises the possibility that muscarinic receptors could be key determinants in pulmonary vascular diseases in relation to "perinatal imprinting.

Perinatal arterial ischemic stroke related to carotid artery occlusion.

BACKGROUND: The aetiology of perinatal arterial ischemic stroke remains speculative. It is however widely accepted that the aetiology is multifactorial, involving various maternal, placental, foetal and neonatal risk factors. A resulting thromboembolic process is hypothesized and the placenta identified as the most plausible source. An arteriopathy, as observed in a significant proportion of childhood ischemic stroke, is thought to be rare. METHODS: We report here five cases of perinatal stroke that differ from the vast majority by documented carotid occlusion, and add eleven other similar cases from the literature. RESULTS: In the majority, an intraluminal thrombus of placental origin is the most probable hypothesis, while in the remaining ones, one can reasonably presume a direct vessel wall injury related to a traumatic delivery, yet generally unproven by imaging. CONCLUSION: We hypothesize that most of these cases share similar pathophysiology with the more common perinatal arterial ischemic stroke but differ by a persistent identified thrombus in the carotid artery at the time of first imaging, leading to a more severe and extended ischemic damage responsible for an adverse neurological outcome