Pulmonary Hypertension Of Newborn Research Articles

Modern engineering solutions for an original domestic nitric oxide generator (“Tianox”)

Nitric oxide (NO) is a biologically active molecule approved for the treatment of persistent pulmonary hypertension in newborns in the USA, Japan, and most European countries in 1999 – 2008. Inhaled NO is currently used to treat a spectrum of cardiopulmonary disorders, including pulmonary hypertension in children and adults. A commercially available NO delivery system uses pressurized cylinders as a source of NO. Current cylinder-based delivery systems are widely used around the world, but they are bulky, expensive and dependent on a reliable supply chain. The aim of the work was to present an original domestic generator for NO inhalation therapy. Over the past few years, to overcome the limitations of the balloon technology, specialists from the Federal State Unitary Enterprise “Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics” have developed a plasma-chemical NO generator that produces NO from ambient air using a nonequilibrium spark discharge plasma. In this case, a diffuse discharge mode is implemented, which ensures the most efficient synthesis of NO with the participation of excited nitrogen molecules (N2+) according to a chain mechanism similar to the Zeldovich – Semenov chain reaction. The result is a high-quality NO-containing gas mixture that does not contain toxic by-products (electrode material, ozone, etc.) usually formed in the known systems of this type. Conclusion. Based on the developed generator, the Federal State Unitary Enterprise “Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics” designed and created the world’s first commercially available device for inhalation therapy, “Tianox”. The device was approved for circulation on the territory of the Russian Federation by order of the Federal Service for Surveillance in Healthcare (2020) based on the results of technical and clinical tests. Serial production of “Tianox” meets the requirements of ISO 13485-2016 and GOST ISO 13485-2017.

Chronic Gestational Hypoxia Alters Plasma Exosomal miRNA Profile and Pulmonary Arterial Proteome and Metabolome in Fetal Lambs

Antenatal chronic hypoxia negatively impacts fetal development and increases the risk of cardio-pulmonary dysfunction after birth, including newborn pulmonary hypertension. Previously, we showed that fetal and newborn sheep exposed to chronic hypoxia during gestation exhibit a variety of cardio-pulmonary defects that parallel those of human infants including pulmonary vascular remodeling, heart dysfunction, and pulmonary hypertension. To explore the mechanisms involved in hypoxia-mediated newborn pulmonary hypertension, we test the hypothesis that antenatal chronic hypoxia impairs pathways critical to pulmonary vascular development that are coupled to abnormalities in lung structure and function through dysregulation in cell growth and proliferation. To address this hypothesis, we employed an animal model of pregnant sheep exposed to high altitude hypoxia at the White Mountain Research Station, which has an altitude of 3801 meters. Hypoxic pregnant sheep were housed at altitude during gestation for ~110 days out of 138-141 days of pregnancy while normoxic counterparts were kept at 700 meters. Animals were transferred to Loma Linda at 355 meters and fetal lambs studied at ~140 days of gestation. Fetal plasma samples were collected for exosomal miRNA analysis and pulmonary arteries were collected for proteomic and metabolomic analysis. Ingenuity pathway analysis and other bioinformatic tools were used to interrogate regulatory mechanisms and pathways and the web of molecular interactions affected by hypoxia. Antenatal hypoxic stress caused up and down regulation of a limited number of plasma exosomal miRNAs, pulmonary arterial metabolites and proteins, with discrete interconnections between the various analytes and molecules. There were marked changes in upstream regulators and markers that point to increased oxidative stress and inflammatory response along with pronounced downregulation of matrix proteins and phenotypic markers of vascular smooth muscle cell differentiation. Pathway analyses indicate antenatal chronic hypoxia dysregulates growth and proliferation of vascular cells and impinges on cell migration. While these data require additional study and verification, they provide new insights in the understanding of mechanisms underlying the development of pulmonary hypertension in the newborn following antenatal hypoxia. This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine, A pilot Project through the West Coast Metabolomics Center, the University of Redlands Summer Research Program, and the Walter E. Macpherson Society. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Bosentan in the treatment of persistent pulmonary hypertension in newborns: a systematic review and meta-analysis.

Persistent pulmonary hypertension of the newborn is a life-threatening condition that affects about 1-2 per 1,000 live births worldwide. Bosentan is an oral dual endothelin receptor antagonist that may have a beneficial effect on persistent pulmonary hypertension of the newborn by reducing pulmonary vascular resistance and improving oxygenation. However, its role in persistent pulmonary hypertension of the newborn remains unclear. To systematically evaluate the efficacy and safety of bosentan as an adjuvant therapy for persistent pulmonary hypertension of the newborn in newborns. We searched six English and two Chinese databases from their inception to 1 January 2023 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomised controlled trials and retrospective studies that compared bosentan with placebo or other drugs for persistent pulmonary hypertension of the newborn in newborns. We performed a meta-analysis using random-effects models and assessed the risk of bias and heterogeneity in the included studies. We included 10 studies with a total of 550 participants. Bosentan significantly reduced the treatment failure rate (relative risk = 0.25, P < 0.001), pulmonary artery pressure (mean difference = -11.79, P < 0.001), and length of hospital stay (mean difference = -1.04, P = 0.003), and increased the partial pressure of oxygen (mean difference = 10.02, P < 0.001) and blood oxygen saturation (SpO2) (mean difference = 8.24, P < 0.001) compared with a placebo or other drugs. The occurrence of adverse reactions was not significantly different between bosentan and a placebo or other drugs. Bosentan is effective in the treatment of persistent pulmonary hypertension of the newborn but adverse reactions such as abnormal liver function should be observed when using it.

Deep Learning Based Prediction of Pulmonary Hypertension in Newborns Using Echocardiograms

Pulmonary hypertension (PH) in newborns and infants is a complex condition associated with several pulmonary, cardiac, and systemic diseases contributing to morbidity and mortality. Thus, accurate and early detection of PH and the classification of its severity is crucial for appropriate and successful management. Using echocardiography, the primary diagnostic tool in pediatrics, human assessment is both time-consuming and expertise-demanding, raising the need for an automated approach. Little effort has been directed towards automatic assessment of PH using echocardiography, and the few proposed methods only focus on binary PH classification on the adult population. In this work, we present an explainable multi-view video-based deep learning approach to predict and classify the severity of PH for a cohort of 270 newborns using echocardiograms. We use spatio-temporal convolutional architectures for the prediction of PH from each view, and aggregate the predictions of the different views using majority voting. Our results show a mean F1-score of 0.84 for severity prediction and 0.92 for binary detection using 10-fold cross-validation and 0.63 for severity prediction and 0.78 for binary detection on the held-out test set. We complement our predictions with saliency maps and show that the learned model focuses on clinically relevant cardiac structures, motivating its usage in clinical practice. To the best of our knowledge, this is the first work for an automated assessment of PH in newborns using echocardiograms.

The Role of Reactive Oxygen Species in the Regulation of Blood Vessel Tone in Perinatal and Early Postnatal Ontogenesis

Reactive oxygen species (ROS) have been considered for many years as negative regulators in the cardiovascular system. Indeed, excessive production of ROS characterizes many cardiovascular diseases. The damaging effect of ROS can be especially pronounced in a newborn organism, since during this period their contractile effect in pulmonary arteries remains as high as in the pre-term fetus arteries and the antioxidant systems have not yet formed. Therefore, in the first hours and days of independent life, pulmonary arteries tend to contract, primarily due to the low bioavailability of endothelial NO, which increases the risk of developing pulmonary hypertension in newborns. At the same time, during the perinatal period, ROS play an important role in the adaptive reactions of the circulatory system. ROS provide occlusion of the ductus arteriosus and separation of the pulmonary and systemic circulations soon after birth, and also contribute to the contraction of peripheral vessels during hypoxia, which often accompanies the delivery, and therefore provide priority blood supply to the brain in these conditions. The vasomotor effect of ROS is also pronounced in early postnatal ontogenesis, but it has a different character. In the first weeks of life, the action of ROS serves as one of the mechanisms for increasing endothelium-dependent relaxation of pulmonary vessels. In addition, during early postnatal ontogeny, ROS may play an important role in the regulation of systemic vascular tone. This review outlines the current understanding of the vasomotor role of ROS in the vessels of the pulmonary and systemic circulation and considers the mechanisms of ROS effects on the functioning of vascular endothelial and smooth muscle cells in the perinatal and early postnatal periods.

A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension.

Serotonin (5-HT) is a bioamine that has been implicated in the pathogenesis of pulmonary hypertension (PH). The lung serves as an important site of 5-HT synthesis, uptake, and metabolism with signaling primarily regulated by tryptophan hydroxylase (TPH), the 5-HT transporter (SERT), and numerous unique 5-HT receptors. The 5-HT hypothesis of PH was first proposed in the 1960s and, since that time, preclinical and clinical studies have worked to elucidate the role of 5-HT in adult PH. Over the past several decades, accumulating evidence from both clinical and preclinical studies has suggested that the 5-HT signaling pathway may play an important role in neonatal cardiopulmonary transition and the development of PH in newborns. The expression of TPH, SERT, and the 5-HT receptors is developmentally regulated, with alterations resulting in pulmonary vasoconstriction and pulmonary vascular remodeling. However, much remains unknown about the role of 5-HT in the developing and newborn lung. The purpose of this review is to discuss the implications of 5-HT on fetal and neonatal pulmonary circulation and summarize the existing preclinical and clinical literature on 5-HT in neonatal PH.

Inhaled iloprost is an effective alternative therapy for persistent pulmonary hypertension in newborns.

Persistent pulmonary hypertension of the newborn(PPHN) is one of the diseases of the neonate with severe potential morbidity and mortality. Inhaled iloprost, a stable prostacyclin analog, has been suggested as an alternative treatment for inhaled nitric oxide (iNO). However, more data on neonates' dosing, setting, and effectiveness still needs to be solved. This study suggests using inhaled iloprost as rescue therapy for PPHN based on our experience. This was a retrospective study. The data from medical records of six newborns diagnosed with PPHN and had received inhaled iloprost from December 2019 to April 2022 were collected. Demographic and clinical features, dosing regimen, changes in oxygenation index, echocardiographic findings, and mortality were evaluated. The inhalation dose was 2-4 mcg/dose, and 3-48 inhalations per day were applied over 2-7 days. Inhaled iloprost was effective in all patients. No side effects were attributable to inhaled iloprost, and no mortality was recorded. Our experience suggests that inhaled iloprost can be used as a first-line therapy in newborn infants with PPHN when iNO is unavailable. However, there are large fluctuations in the oxygenation index due to the setting.

Caffeine Is a Stimulant

Caffeine is a stimulant compound belonging to the xanthine chemical category that is found in coffee, tea, and cocoa or chocolate (lower diploma), and is protected in many light fluids, as well as in large amounts of energy fluids. Caffeine is a methyl xanthine-type drug used for various purposes, including high-quality breathing in premature babies, pain relief, and combating sleepiness. Caffeine is similar to theophylline and theobromine. Caffeine is used in various cosmetic products and can be administered topically, orally, by inhalation, or by injection. The FDA first approved caffeine citrate injection for apnea of prematurity in 1999. According to a 2017 article, more than 15 million babies worldwide are born prematurely. This corresponds to approximately one to ten births. Early initiation can lead to apnea and pulmonary bronchial dysplasia, a condition that impairs lung development and ultimately causes bronchial allergies or early-onset emphysema in premature infants. Caffeine citrate injections are used to treat apnea of prematurity owing to their effectiveness, safety, and low cost. Caffeine citrate injections are also used to treat postoperative apnea as well as other conditions such as severe hypoxemia, congenital heart defects, obstructive sleep apnea syndrome, and respiratory distress syndrome. Caffeine citrate injections are also used to treat persistent pulmonary hypertension in newborns and seizures due to post-anoxia encephalopathy. Caffeine citrate injections are well tolerated in newborns and infants with few side effects. Common adverse effects include gastrointestinal upset, palpitations, tachycardia, increased blood pressure, restlessness, irritability, and insomnia. In addition, caffeine citrate injections can cause adverse effects such as hyperglycemia, hypocalcemia, hypokalemia, hypomagnesemia, and hypophosphatemia.

Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled β2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial).

Transient tachypnea of the newborn (TTN), which results from inadequate absorption of fetal lung fluid, is the most common cause of neonatal respiratory distress. Stimulation of β-adrenergic receptors enhances alveolar fluid absorption. Therefore, the β2-adrenergic receptor agonist salbutamol has been proposed as a treatment for TTN. This study aims to evaluate the efficacy and safety of salbutamol as supportive pharmacotherapy together with non-invasive nasal continuous positive airway pressure (NIV/nCPAP) for the prevention of persistent pulmonary hypertension of the newborn (PPHN) in infants with TTN. This multicenter, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks who are affected by respiratory disorders and treated in eight neonatal intensive care units in Poland. A total of 608 infants within 24 h after birth will be enrolled and randomly assigned (1:1) to receive nebulized salbutamol with NIV or placebo (nebulized 0.9% NaCl) with NIV. The primary outcome is the percentage of infants with TTN who develop PPHN. The secondary outcomes are the severity of respiratory distress (assessed with the modified TTN Silverman score), frequency of need for intubation, duration of NIV and hospitalization, acid-base balance (blood pH, partial pressure of O2 and CO2, and base excess), and blood serum ionogram for Na+, K+, and Ca2+. The Respiratory Failure with Salbutamol (REFSAL) study will be the first clinical trial to evaluate the efficacy and safety of salbutamol in the prevention of persistent pulmonary hypertension in newborns with tachypnea, and will improve short term outcomes. If successful, the study will demonstrate the feasibility of early intervention with NIV/nCPAP together with nebulized salbutamol in the management of TTN. The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland on November 16, 2020 (decision number KB/190/2020). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. It is registered at ClinicalTrials.gov NCT05527704, EudraCT 2020-003913-36; Protocol version 5.0 from 04/01/2022.

Effects of inhaled nitric oxide (iNO) in pulmonary hypertension secondary to arteriovenous malformations: a retrospective cohort study from the European iNO registry

This study aims to assess the effects of inhaled nitric oxide (iNO) on oxygenation in the management of pulmonary hypertension (PH) secondary to arteriovenous malformations (AVMs) in neonates. This is a matched retrospective cohort study from January 1, 2013, to December 31, 2017. The European inhaled nitric oxide registry from 43 neonatal and pediatric ICUs in 13 countries across Europe was used to extract data. The target population was neonates treated with iNO for the management of PH. The cases (PH secondary to AVMs treated with iNO) were matched (1:4 ratio) to controls (PH without AVMs treated with iNO). The main outcome measure was the absolute change of oxygenation index (OI) from baseline to 60 min after starting iNO in cases and controls. The primary outcome of our study was that the mean absolute change in OI from baseline to after 60 min was higher among cases 10.7 (14), than in controls 6 (22.5), and was not statistically different between the groups. The secondary outcome variable — death before discharge — was found to be significantly higher in cases (55%) than in controls (8%). All the other variables for secondary outcome measures remained statistically insignificant. Conclusion: Infants with PH secondary to AVMs treated with iNO did not respond differently compared to those presented with PH without AVMs treated with iNO. Right ventricular dysfunction on echocardiography was higher in cases than controls (cases: 66.7% and controls: 28.6%) but was not statistically significant.What is Known:• Arterioenous malformation (AVM) is a well-known cause of persistent pulmonary hypertension in newborns. Inhaled nitric oxide (iNO) is most commonly used as first-line therapy for pulmonary hypertension in newborns.• Around 40–50% of vein of Galen malformations (VOGMs) are found to have congestive heart failure in the neonatal period.What is New:• Neonates may present with an isolated PH of the newborn as the main feature of the VOGMs. A large proportion of cases with AVMs have been associated with right ventricular cardiac dysfunction. • Results from one of the largest database registries in the world for iNO have been used to answer our research question.

Implementation of an Inhaled Nitric Oxide Weaning Protocol and Stewardship in a Level 4 NICU to Decrease Inappropriate Use.

Inhaled nitric oxide (iNO) is an effective but expensive treatment of pulmonary hypertension in newborns, with limited data regarding weaning. Our institution implemented a multidisciplinary iNO weaning protocol and stewardship to reduce inappropriate use of iNO. The objective of this study was to evaluate our institutional iNO usage before and after implementation. Single-center study comparing a retrospective control group to a prospective cohort after implementation of an iNO weaning protocol. All infants in the neonatal intensive care unit (NICU) who received iNO during the study timeframe were included. The primary outcome was duration of iNO per course. A total of 47 courses of iNO occurred during the pre-protocol timeframe compared with 37 courses in the post-protocol timeframe. Median iNO usage per course was 149 hours (IQR, 63-243) in the pre-protocol group versus 59 hours (IQR, 37-122) in the post-protocol group (p = 0.008). Length of stay was significantly longer in the pre-protocol group (p = 0.02), likely related to significantly longer ventilator days in the pre-protocol group (p = 0.02). Compliance with initiation of weaning when recommended per the protocol was 72%, and the incidence of successful weaning was 74%. The implementation of an iNO weaning protocol in the NICU significantly decreased iNO usage by approximately 60% with no notable negative effects.

Prostacyclins and pulmonary arterial hypertension in children.

Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and treatment options are limited and ineffective. Drugs to treat pulmonary hypertension include endothelin antagonists, phosphodiesterase type 5 inhibitors and prostacyclin, which is the most widely used to treat pediatric pulmonary hypertension. The main aim of this study was to provide a comprehensive overview of the advantages and disadvantages of prostacyclin and its analogs for treating pulmonary hypertension in children. To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (Prostacyclins) or (Epoprostenol) or (Iloprost) or (Treprostinil) or (Beraprost), (children) and (pulmonary arterial hypertension). The time limits used for the search were December 1983 to May 2021. The search retrieved a total of 238 articles. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included. Epoprostenol can be effective against severe pulmonary hypertension. Iloprost can treat severe persistent pulmonary hypertension in newborns and inhaled iloprost can be used in pulmonary vasoreactivity testing. Treprostinil is a long-acting prostacyclin analog, and it shows the highest antiproliferative activity among prostacyclins. Beraprost may be effective in premature infants, but available evidence comes from only one patient, so more clinical testing is needed.

Oxidative Stress and Respiratory Diseases in Preterm Newborns.

Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.

A maChine and deep Learning Approach to predict pulmoNary hyperteNsIon in newbornS with congenital diaphragmatic Hernia (CLANNISH): Protocol for a retrospective study.

IntroductionOutcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses.Methods and analyticsPatients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns’ and mothers’ clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed.Ethics and disseminationThis retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study.RegistrationThe study was registered at ClinicalTrials.gov with the identifier NCT04609163.

Pulmonary hypertension in late onset neonatal sepsis using functional echocardiography: a prospective study.

Pulmonary hypertension (PH) in the newborn period is associated with significant morbidity and mortality. Sepsis has been identified as an independent risk factor for PH in newborns. Data on the proportion and severity of PH in association with neonatal sepsis are scarce. This study was aimed to measure the pulmonary artery systolic pressure (PASP) in neonates with late onset sepsis (LOS) and to estimate the proportion of PH in neonatal sepsis using functional echocardiography (FnECHO). This prospective observational study was conducted at a tertiary neonatal intensive care unit (NICU). All neonates admitted in the NICU with suspected LOS underwent FnECHO within 6 hours of onset of clinical signs and PASP was recorded. Pulmonary hypertension was defined as PASP of > 35mmHg. PASP of neonates with positive culture results (proven LOS) was compared with that of gestational age-matched stable controls without sepsis. Thirty three neonates with proven LOS were analysed (study group). Sixteen neonates (49%) in the study group had PH. Mean PASP of the study group was significantly higher than that of the control group (35.3 ± 10.13mmHg and 12.58 ± 3.92mmHg, respectively; P < 0.0001). None of the neonates in the control group had PH. Pulmonary artery pressure was higher in neonates with late onset neonatal sepsis as compared to that of stable babies without sepsis. Pulmonary hypertension was seen in nearly half of term as well as preterm neonates with late onset sepsis.

Safety and Efficacy of Sildenafil Citrate to Reduce Operative Birth for Intrapartum Fetal Compromise at Term: A Phase 2 Randomized Controlled Trial

(Am J Obstet Gynecol. 2020;222:401–414) Intrapartum fetal compromise, or fetal distress, is a major cause of perinatal death and hypoxic-ischemic encephalopathy in low- to middle-income countries, and causes 1 in 5 cases of cerebral palsy in high-income countries. The only proven interventions for intrapartum fetal compromise are emergency cesarean delivery or emergency delivery by instrumental vaginal birth, both of which carry significant risks. Sildenafil citrate increases fetal and uteroplacental blood flow and is an effective treatment for adult and newborn pulmonary hypertension. This study evaluated the efficacy and safety of sildenafil citrate in reducing the rate of emergency cesarean delivery or instrumental vaginal birth for intrapartum fetal distress.

A retrospective study of predisposing factors and outcome of persistant pulmonary hypertension among newborns at rural tertiary care centre

Background: Persistent pulmonary hypertension in newborns (PPHN) remains a significant cause of perinatal morbidity and mortality. Early recognition of factors that increase the risk of PPHN is of great importance in either to prevent or to treat PPHN optimally. Aim was to study the neonatal predisposing factors, profile and outcome of PPHN.Methods: This retrospective study was conducted in level III neonatal care unit, a rural referral centre of North Karnataka, India from January 2018 to April 2020.Results: During the study period a total of 50 infants with PPHN were identified with the incidence of 5.43/1000 live births. Mean gestation age (±SD) was 38.28±2.49 weeks and mean birth weight (±SD) was 2624±512 gm. The most noted risk factors were meconium aspiration syndrome (42%), birth asphyxia (16%), RDS (10%), positive pressure ventilation at birth (52%) and male gender (62%). Out of 50 infants with PPHN, high mortality was seen in low birth weight babies (66.6%). Use of sildenafil showed increased mortality (56.2%) whereas use of surfactant scored better with decreased mortality of 42.8%.Conclusions: Major risk factors for PPHN are MAS, birth asphyxia, RDS and low birth weight. Poor prognosis is seen in male gender, prematurity and CDH with increased risk of mortality. The use of systemic pulmonary vasodilators can be considered with caution and use of surfactant has a role in management of PPHN.

Pentraxin 3 – possible uses in neonatology and paediatrics

Pentraxin 3 (PTX3) is a multifunctional acute phase protein belonging to the family of long pentraxins, which is synthesised in numerous cells of the body under the influence of proinflammatory factors and locally at the site of inflammation. Under physiological conditions, PTX3 is stored in neutrophil granules, where there is a constant pool of glycoproteins. Increased pentraxin 3 levels in blood serum are observed as early as 1 hour after a damaging stimulus. Elevation of PTX3 serum levels can be used to diagnose fertility disorders in women as well as in pregnancy pathology, women at risk of pre-eclampsia, gestational diabetes, premature rupture of membrane and preterm delivery. The biological function of PTX3 is not fully understood, especially in the population of newborns and children. So far, no reference values for PTX3 levels in newborns and children have been developed. This protein can be used as a marker of pulmonary hypertension in newborns as well as to assess the degree of respiratory failure in premature infants. In older children, it is useful in the assessment of the severity of meningococcal disease and sepsis as well as in the treatment of childhood asthma. There are studies available in which blood levels of PTX3 significantly correlate with the severity of kidney damage in Henoch–Schönlein macular degeneration in children, and the evaluation of this protein in urine is used to detect renal parenchymal destruction after pyelonephritis.

PROBLEMS AND MANAGEMENT RESERVES OF NEWBORNS WITH PULMONARY HYPERTENSION

Pulmonary hypertension (PH) is a syndrome connected with significant morbidity and mortality of patients. The lack of sufficient randomized and controlled studies in children, especially infants, makes PH management challenging, as most therapeutic strategies are based on extrapolation from adult studies and the expert consensus. The most common causes of PH in newborns are maladaptation of postnatal circulation, the presence of pulmonary vascular malformations or intrauterine growth retardation, and in premature infants they are underdevelopment and immaturity of pulmonary vessels, severe bronchopulmonary dysplasia. Pulmonary hypertension in newborns is promoted by chronic maternal diseases, using certain medications, pathology of pregnancy and childbirth, the presence of congenital heart defects with enrichment of the small circulation and lungs, accompanied by abnormal vascular structure and developmental disorders. There is a universal diagnostic algorithm of PH in pediatric practice which includes echocardiography, ECG, radiography, and for moderate and severe cases - genetic and serological laboratory tests, magnetic resonance imaging of the heart and lungs, as well as cardiac catheterization with a vasoreactivity test.Treatment of PH in newborns involves a multidisciplinary approach, ranging from a lung protection strategy in preterm infants to the use of vasodilation therapy. The main problems in the management of newborns with PH are the lack of standardization of echocardiographic parameters for newborns, the lack of a single decision on timing and the need for PH screening in the population of premature infants, lack of controlled studies and development of a single therapeutic strategy for premature infants and patients of gestational age; and the lack of clear criteria for inclusion in the National Register of PH patients.

Diazoksit Tedavisine Bağlı Nadir Bir Yan Etki: Pulmoner Hipertansiyon

We present a newborn diagnosed with Beckwith-Wiedemann syndrome and hypoglycemia, and developed pulmonary hypertension due to initiated diazoxide treatment because of these indications. Beckwith-Wiedemann syndrome was considered due to abdominal wall defect, macrosomia, macroglossia and hypoglycemia in a 34 week newborn with respiratory distress, hypoglycemia and syndromic appearance. Blood glucose level was measured as 1 mg/dL. Oral feeding, glucose infusion, prednisolone and then diazoxide treatment were started. At the first admission transthoracic echocardiographic examination, ventricular and atrial septal defects were detected. Control echocardiography performed under diazoxide treatment, showed development of enlarged right heart chambers, severe tricuspid regurgitation, and pulmonary hypertension. The development of pulmonary hypertension was thought to be related to diazoxide treatment. Diazoxide was discontinued after the patient became normoglycemic during follow--up period. Subsequently performed echocardiography revealed that the systolic pulmonary artery pressure regressed to 20 mmHg, and cardiac chambers returned to their physiologic balance. The patient without any problem during monitorization was discharged with the recommendation to attend further controls visits. In this case report, it was aimed to be reminded that pulmonary hypertension can develop due to diazoxide treatment, and it can regress with discontinuation of diazoxide. Besides, transthoracic ECHO should be performed to check for the development of pulmonary hypertension in newborns treated with diazoxide.