Special Issue "Pulmonary Hypertension in Neonates and Infants"

A special issue of Children (ISSN 2227-9067).

Deadline for manuscript submissions: closed (1 July 2020).

Special Issue Editor

Prof. Dr. Satyan Lakshminrusimha
E-Mail Website
Guest Editor
Department of Pediatrics, University of California Davis, UC Davis Children’s Hospital, Sacramento, CA 95817, USA
Interests: oxygenation in lung injury; pulmonary hypertension; diaphragmatic hernia; neonatal resuscitation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pulmonary hypertension (PH), often associated with hypoxemic respiratory failure, is a common condition in both preterm and term neonates. During the postneonatal period, infants with bronchopulmonary dysplasia (BPD) or nutritional deficiencies can also present with PH. There are several controversies pertaining to diagnosis and management of PH in neonates and infants. We invite original research (both clinical and translational) and review articles addressing these controversies. Manuscripts addressing challenges with optimal targets for oxygenation and ventilation in PH and use of inhaled nitric oxide and sildenafil will be considered. We also invite epidemiological studies and interesting case reports followed by a discussion that includes clinical pearls.

Prof. Satyan Lakshminrusimha
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Hypoxemia
  • Pulmonary hypertension
  • Prematurity
  • Respiratory distress
  • Persistent pulmonary hypertension of the newborn (PPHN)
  • Acidosis

Published Papers (7 papers)

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Editorial

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Editorial
Neonatal and Postneonatal Pulmonary Hypertension
Children 2021, 8(2), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/children8020131 - 11 Feb 2021
Cited by 2 | Viewed by 1336
Abstract
During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). [...] Read more.
During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). In infants, PH can present as: (a) primary PH in term neonates (idiopathic), (b) PH secondary to lung disease or hypoplasia in term infants, (c) acute PH in preterm infants with respiratory distress syndrome (RDS), (d) chronic PH with bronchopulmonary dysplasia (BPD) in preterm infants and (e) post-neonatal PH. A hemodynamically significant patent ductus arteriosus (PDA) can exacerbate PH in preterm infants due to increased Qp. Pulmonary vein stenosis (PVS) can complicate BPD with PH. Diagnosis of PH is based on clinical features, echocardiography and, in some intractable cases, cardiac catheterization. Therapy of PH includes oxygen, invasive or non-invasive ventilation, correction of acidosis, surfactant and selective and non-selective pulmonary vasodilators such as inhaled nitric oxide and sildenafil, respectively. Early closure of a hemodynamically significant PDA has the potential to limit pulmonary vascular remodeling associated with BPD and PH. The role of thiamine in pathogenesis of PH is also discussed with the recent increase in thiamine-responsive acute pulmonary hypertension in early infancy. Recognition and prompt therapy of PH can prevent right ventricular dysfunction, uncoupling and failure. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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Research

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Article
Bidirectional Ductal Shunting and Preductal to Postductal Oxygenation Gradient in Persistent Pulmonary Hypertension of the Newborn
Children 2020, 7(9), 137; https://0-doi-org.brum.beds.ac.uk/10.3390/children7090137 - 15 Sep 2020
Cited by 2 | Viewed by 1335
Abstract
Background: The aim was to evaluate the relationship between the direction of the patent ductus arteriosus (PDA) shunt and the pre- and postductal gradient for arterial blood gas (ABG) parameters in a lamb model of meconium aspiration syndrome (MAS) with persistent pulmonary hypertension [...] Read more.
Background: The aim was to evaluate the relationship between the direction of the patent ductus arteriosus (PDA) shunt and the pre- and postductal gradient for arterial blood gas (ABG) parameters in a lamb model of meconium aspiration syndrome (MAS) with persistent pulmonary hypertension of the newborn (PPHN). Methods: PPHN was induced by intermittent umbilical cord occlusion and the aspiration of meconium through the tracheal tube. After delivery, 13 lambs were ventilated and simultaneous 129 pairs of pre- and postductal ABG were drawn (right carotid and umbilical artery, respectively) while recording the PDA and the carotid and pulmonary blood flow. Results: Meconium aspiration resulted in hypoxemia. The bidirectional ductal shunt had a lower postductal partial arterial oxygen tension ([PaO2] with lower PaO2/FiO2 ratio—97 ± 36 vs. 130 ± 65 mmHg) and left pulmonary flow (81 ± 52 vs. 133 ± 82 mL/kg/min). However, 56% of the samples with a bidirectional shunt had a pre- and postductal saturation gradient of < 3%. Conclusions: The presence of a bidirectional ductal shunt is associated with hypoxemia and low pulmonary blood flow. The absence of a pre- and postductal saturation difference is frequently observed with bidirectional right-to-left shunting through the PDA, and does not exclude a diagnosis of PPHN in this model. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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Article
Targeted Therapy for Pulmonary Hypertension in Premature Infants
Children 2020, 7(8), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/children7080097 - 15 Aug 2020
Cited by 3 | Viewed by 1753
Abstract
Pulmonary hypertension (PH) is common in premature infants with bronchopulmonary dysplasia (BPD) and is associated with significant mortality. Despite expert consensus suggesting the use of targeted therapies such as phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids, there is little data on safety and [...] Read more.
Pulmonary hypertension (PH) is common in premature infants with bronchopulmonary dysplasia (BPD) and is associated with significant mortality. Despite expert consensus suggesting the use of targeted therapies such as phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids, there is little data on safety and outcomes in infants with BPD-associated PH (BPD-PH) treated with these medications. We sought to describe the pharmacologic management of BPD-PH and to report outcomes at our institution. Premature infants with BPD-PH born between 2005 and 2016 were included. Follow-up data were obtained through January 2020. A total of 101 patients (61 male, 40 female) were included. Of these, 99 (98.0%) patients were treated with sildenafil, 13 (12.9%) with bosentan, 35 (34.7%) with inhaled iloprost, 12 (11.9%) with intravenous epoprostenol, and nine (8.9%) with subcutaneous treprostinil. A total of 33 (32.7%) patients died during the study period and 10 (9.9%) were secondary to severe to pulmonary hypertension. Of the surviving patients, 57 (83.8%) had follow-up data at a median of 5.1 (range 0.38–12.65) years and 44 (77.2%) were weaned off PH medications at a median 2.0 (range 0–8) years. Mortality for BPD-PH remains high mostly due to co-morbid conditions. However, for those patients that survive to discharge, PH therapies can frequently be discontinued in the first few years of life. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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Review

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Review
Thiamine-Responsive Acute Pulmonary Hypertension of Early Infancy (TRAPHEI)—A Case Series and Clinical Review
Children 2020, 7(11), 199; https://0-doi-org.brum.beds.ac.uk/10.3390/children7110199 - 28 Oct 2020
Cited by 4 | Viewed by 1618
Abstract
Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of high pulmonary vascular resistance (PVR) commonly seen all over the world in the immediate newborn period. Several case reports from India have recently described severe pulmonary hypertension among infants in the postneonatal [...] Read more.
Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of high pulmonary vascular resistance (PVR) commonly seen all over the world in the immediate newborn period. Several case reports from India have recently described severe pulmonary hypertension among infants in the postneonatal period. These cases typically present with respiratory distress in 1–6-month-old infants, breastfed by mothers on a polished rice-based diet. Predisposing factors include respiratory tract infection such as acute laryngotracheobronchitis with change in voice, leading to pulmonary hypertension, right atrial and ventricular dilation, pulmonary edema and hepatomegaly. Mortality is high without specific therapy. Respiratory support, pulmonary vasodilator therapy, inotropes, diuretics and thiamine infusion have improved the outcome of these infants. This review outlines four typical patients with thiamine-responsive acute pulmonary hypertension of early infancy (TRAPHEI) due to thiamine deficiency and discusses pathophysiology, clinical features, diagnostic criteria and therapeutic options. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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Review
How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?
Children 2020, 7(10), 180; https://0-doi-org.brum.beds.ac.uk/10.3390/children7100180 - 13 Oct 2020
Cited by 4 | Viewed by 1560
Abstract
Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO2) in the alveolus (PAO2) and pulmonary artery (PaO2) are the main factors that influence hypoxic [...] Read more.
Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO2) in the alveolus (PAO2) and pulmonary artery (PaO2) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and a target range of 91–95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial PaO2, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO2, and SpO2 in the management of PPHN. Translational and clinical studies suggest maintaining a PaO2 of 50–80 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO2 or PO2. Also, most critically ill patients have umbilical arterial catheters and postductal PaO2 may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 target ranges for the management of PPHN and compare outcomes. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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Review
Pulmonary Hypertension with Prolonged Patency of the Ductus Arteriosus in Preterm Infants
Children 2020, 7(9), 139; https://0-doi-org.brum.beds.ac.uk/10.3390/children7090139 - 16 Sep 2020
Cited by 5 | Viewed by 1086
Abstract
There continues to be a reluctance to close the patent ductus arteriosus (PDA) in premature infants. The debate on whether the short-term outcomes translate to a difference in long-term benefits remains. This article intends to review the pulmonary vasculature changes that can occur [...] Read more.
There continues to be a reluctance to close the patent ductus arteriosus (PDA) in premature infants. The debate on whether the short-term outcomes translate to a difference in long-term benefits remains. This article intends to review the pulmonary vasculature changes that can occur with a chronic hemodynamically significant PDA in a preterm infant. It also explains the rationale and decision-making involved in a diagnostic cardiac catheterization and transcatheter PDA closure in these preterm infants. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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Review
Signaling Pathways Involved in the Development of Bronchopulmonary Dysplasia and Pulmonary Hypertension
Children 2020, 7(8), 100; https://0-doi-org.brum.beds.ac.uk/10.3390/children7080100 - 18 Aug 2020
Cited by 5 | Viewed by 1669
Abstract
The alveolar and vascular developmental arrest in the premature infants poses a major problem in the management of these infants. Although, with the current management, the survival rate has improved in these infants, but bronchopulmonary dysplasia (BPD) is a serious complication associated with [...] Read more.
The alveolar and vascular developmental arrest in the premature infants poses a major problem in the management of these infants. Although, with the current management, the survival rate has improved in these infants, but bronchopulmonary dysplasia (BPD) is a serious complication associated with a high mortality rate. During the neonatal developmental period, these infants are vulnerable to stress. Hypoxia, hyperoxia, and ventilation injury lead to oxidative and inflammatory stress, which induce further damage in the lung alveoli and vasculature. Development of pulmonary hypertension (PH) in infants with BPD worsens the prognosis. Despite considerable progress in the management of premature infants, therapy to prevent BPD is not yet available. Animal experiments have shown deregulation of multiple signaling factors such as transforming growth factorβ (TGFβ), connective tissue growth factor (CTGF), fibroblast growth factor 10 (FGF10), vascular endothelial growth factor (VEGF), caveolin-1, wingless & Int-1 (WNT)/β-catenin, and elastin in the pathogenesis of BPD. This article reviews the signaling pathways entailed in the pathogenesis of BPD associated with PH and the possible management. Full article
(This article belongs to the Special Issue Pulmonary Hypertension in Neonates and Infants)
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