Pulmonary Hypertension In Children 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.

Prevalence of pulmonary hypertension in children with obstructive sleep apnea living at high altitude

IntroductionThe prevalence of obstructive sleep apnea (OSA) is 1–4 %. Some reports describe its association with pulmonary hypertension (PH), but its prevalence is unknown. No studies at high altitude have determined the relationship between OSA and PH. The aim of this study was to establish the prevalence of PH in children diagnosed with OSA living in a high-altitude city at 2640 m above sea level. MethodsChildren between 2 and 16 years of age referred to the Sleep Laboratory of the Fundación Neumológica Colombiana in Bogotá with a positive polysomnogram for OSA were included, and a two-dimensional transthoracic echocardiogram (TTE) was performed to evaluate PH. Statistical analysis was performed using median, interquartile range, chi-squared test, and Kruskall-Wallis test. ResultsOf the 55 patients (n: 55), 63.6 % were male, with a median age of 6 years, 14 children (25.5 %) were overweight; 12 children (21.8 %) had mild OSA, 12 (21.8 %) had moderate OSA and 31 (56.4 %) severe OSA. In patients with severe OSA, the minimum saturation during events was 78 % with a desaturation index (DI) of 33.8/hour (p < 0.01). T90 and T85 increased proportionally with OSA severity (p < 0.05). Of the 55 patients with OSA, none had PH according to echocardiography; 4 patients (7.2 %) had pulmonary artery systolic pressure (PASP) at the upper limit of normal (ULN), and it was not related to a higher body mass index (BMI). ConclusionsWe found no association between OSA and PH in children with OSA at high altitude.

Prognostic and diagnostic utility of interleukin-6 in pediatric pulmonary arterial hypertension — a case-control study

Pulmonary arterial hypertension (PAH) in pediatrics is a progressive disease with significant vascular remodeling, right sided heart failure, and death if left untreated. Elevated interleukin-6 (IL-6) level in PAH patients is taken as an independent predictor of adverse outcome including mortality. The aim of this study was to investigate and compare serum levels of IL-6 in children with PAH and healthy matched controls, and correlate between IL-6 and degree of PAH, as well as mortality. IL-6 was measured by ELISA in serum samples in 40 children with PAH (age 1–12 years) and 40 age and sex-matched healthy controls. There was a statistically significant increase in IL-6 level among PAH cases compared with the controls (1.85 ng/L vs 1.30 ng/L, p-value = 0.004). IL-6 at cut off point 1.45 ng/L significantly predict pulmonary hypertension in children (AUC = 0.685, 75% sensitivity, and 65% specificity with p = 0.002). There was no statistically significant association between IL-6 level and degree of PAH (p = 0.218). There was no statistically significant association between IL-6 level and mortality (p = 0.662). Conclusion: IL-6 significantly predict PAH in pediatrics but there is no association between IL-6 level and degree of PAH or mortality. IL-6 may provide a less costly and less invasive method for disease detection.What is Known:• Definitive diagnosis of PAH is made by right heart catheterization, while echocardiography is the gold standard for tracking the course of the disease.What is New:• It was assumed that children with a diagnosis of PAH would have higher serum IL-6 levels than controls. Furthermore, an adverse relationship between the blood IL-6 level and PPAH was predicted.

New aspects in pediatric pulmonary hypertension - Commented 2022ERS/ESC-PH guidelines

Pulmonary hypertension (PH) in childhood differs from that of adulthood particularly in the specific pathophysiology of congenital heart disease-associated pulmonary arterial hypertension, the presence of developmental lung disease, and the frequent association with chromosomal, genetic, and syndromal abnormalities. Treatment of children with PH requires a modified diagnostic algorithm tailored to childhood, as well as pathophysiologically oriented therapeutic strategies. In the current 2022 ERS/ESC-PH guidelines, the specific features of PH in children are highlighted in its own chapter and commented on by the authorship group in this article.

Anesthetic management of children with medically refractory pulmonary hypertension undergoing surgical Potts shunt.

Pulmonary hypertension in children is associated with high rates of adverse events under anesthesia. In children who have failed medical therapy, a posttricuspid shunt such as a Potts shunt can offload the right ventricle and possibly delay or replace the need for lung transplantation. Intraoperative management of this procedure, during which an anastomosis between the pulmonary artery and the descending aorta is created, is complex and requires a deep understanding of the pathophysiology of acute and chronic right ventricular failure. This retrospective case review describes the intraoperative management of children undergoing surgical creation of a Potts shunt at a single center. A retrospective case review of all patients under the age of 18 who underwent Potts shunt between April 2013 and June 2022. Medical records were examined, and clinical data of demographics, intraoperative vital signs, anesthetic management, and postoperative outcomes were extracted. Twenty-nine children with medically refractory pulmonary hypertension underwent surgical Potts shunts with a median age of 12 years (range 4 months to 17.4 years). Nineteen Potts shunts (65%) were placed via thoracotomy and 10 (35%) were placed via median sternotomy with use of cardiopulmonary bypass. Ketamine was the most frequently utilized induction agent (17 out of 29, 59%), and the majority of patients were initiated on vasopressin prior to intubation (20 out of 29, 69%). Additional inotropic support with epinephrine (45%), milrinone (28%), norepinephrine (17%), and dobutamine (14%) was used prior to shunt placement. Following opening of the Potts shunt, hemodynamic support was continued with vasopressin (66%), epinephrine (62%), milrinone (59%), dobutamine (14%), and norepinephrine (10%). Major intraoperative complications included severe hypoxemia (21 out of 29, 72%) and hypotension requiring boluses of epinephrine (10 out of 29, 34.5%) but no patient suffered intraoperative cardiac arrest. There were four in-hospital mortalities. A Potts shunt offers another palliative option for children with medically refractory pulmonary hypertension. General anesthesia in these children carries high risk for pulmonary hypertensive crises. Anesthesiologists must understand underlying physiological mechanisms responsble for acute hemodynaic decompensation during acute pulmonary hypertneisve crises. Severe physiological perturbations imposed by thoracic surgery and use of cardiopulmonay bypass can be mitigated by aggresive heodynamic support of ventricle function and maintainence of systemic vascular resistance. Early use of vasopressin, before or immidiately after anesthesia induction, in combination with other inotropes is a useful agent during the perioperative care of thes. Early use of vasopressin during anesthesia induction, and aggressive inotropic support of right ventricular function can help mitigate effects of induction and intubation, single-lung ventilation, and cardiopulmonary bypass. Our single center expereince shows that the Potts shunt surgery, despite high short-term mortaility, may offer another option for palliation in children with medically refractory pulmonary hypertension.

Dual-energy computed tomography to detect early pulmonary vascular changes in children with sickle cell disease: a pilot study.

Pulmonary hypertension (PH) is a rare but fatal complication of sickle cell disease (SCD) that is possibly reversible if treated early. Dual-energy computed tomography (DECT) is a valuable tool for diagnosing PH. We attempted to determine if DECT can detect early signs of PH in children with SCD. This prospective observational pilot study was conducted at the Geneva University Hospitals and was approved by the local human ethics committee (CCER 2019-01975). A written informed consent was obtained from the patients and/or their legal guardian. Eight children (consisting of five girls and three boys) with homozygous SCD were included in the study. They underwent full cardiological workup using transthoracic echocardiography (TTE) and cardiopulmonary exercise test (CPET), as well as DECT. The median age of the children was 11 years old (range 8-12). All patients exhibited a normal biventricular systo-diastolic function using the TTE. The median tricuspid regurgitant jet velocity value was 2.24 m/s (range 1.96-2.98). Four children were found to have signs of vasculopathy detected on DECT. Of them, two had abnormal screening test results. They both had an increased VE/VCO2 slope during CPET and an increased TVR of >2.5 m/s on TTE. DECT is capable of identifying early signs of pulmonary vascular disease in children with SCD. Further studies are needed to understand the correlation between DECT abnormalities and hemodynamic pulmonary circulation better.

Impact of Asthma Phenotypes on Myocardial Performance and Pulmonary Hypertension in Children and Adolescents With Moderate to Severe Persistent Asthma.

Asthma is characterized by chronic inflammation and remodeling of pulmonary vessels and airway wall resulting in pulmonary hypertension (PH). Increased afterload on right ventricle (RV) myocardium leads to RV diastolic dysfunction (RVDD). Echocardiography is an excellent tool to detect these changes early. Using echocardiography, we assessed the impact of clinical asthma phenotypes on myocardial performance and PH in children with asthma. Sixty children with moderate or severe persistent asthma and 60 age and gender-matched healthy controls were enrolled. As per clinical phenotypes, children with asthma were classified into early wheezers (n = 30) and late wheezers (n = 30). Pulmonary function tests (PFT) and echocardiography, both conventional and pulse wave (PW), were performed. Children with asthma had significant RVDD and higher incidence (33%) of PH. Myocardial performance index (MPI) was poor in asthmatics, 0.41 (0.04) compared to controls, 0.38 (0.03). Measures for PH such as tricuspid regurgitation (TR) gradient, TR velocity, and pulmonary artery pressure (PAP) were significantly higher in cases. Among clinical asthma phenotypes, there was no difference in left ventricular ejection fraction (LVEF) between early 64.3% (4.6) and late wheezers 65.6% (4.4). MPI was better in late wheezers at 0.41 (0.05) than in early wheezers at 0.40 (0.03). TR gradient, TR velocity, and PAP were significantly higher in early wheezers. The odds ratio for the development of PH was 0.74 (CI 0.25 - 2.17), and for the development of RVDD was 3.2 (CI 0.77 - 13.8), both in favor of early wheezers. Children with asthma, particularly early-onset wheezers are at increased risk of developing PH and RVDD. We suggest annual screening by conventional echocardiography and pulse wave Doppler imaging for early diagnosis and timely initiation of management.

Clinical and Paraclinical Findings of Primary Pulmonary Hypertension in Children

Background: Given the significant morbidity and mortality of juvenile pulmonary arterial hypertension (PAH), understanding the clinical and paraclinical findings of this condition can aid in the early diagnosis and identification of helpful factors in its treatment. Objectives: This study aimed to evaluate the clinical and paraclinical findings of idiopathic pulmonary arterial hypertension (iPAH) in children. Methods: This cross-sectional study was carried out on 20 children with iPAH who were assessed in terms of pulmonary hypertension or hospitalized at the cardiac ward of Imam Reza hospital, Mashhad, Iran, during January 2018 to October 2001. The clinical data, chest X-ray (CXR), electrocardiographic, echocardiographic, cardiac catheterization findings, and mortality results were extracted from the medical records and recorded in a researcher-made questionnaire. Results: The current study’s findings revealed a higher prevalence of iPAH in females (70%) than men, as well as in term neonates compared to preterm newborns. The most common clinical findings were active dyspnea, heart murmur, and cyanosis. Prominent pulmonary conus, right atrial enlargement (RAE), and right ventricular hypertrophy (RVH) were the most common CXR findings. The right axis deviation, RVH, and RAE were the most common abnormal findings of electrocardiography, respectively. Based on echocardiographic findings, dilated right atrium and dilated right ventricle were reported in all subjects. The mean of tricuspid regurgitation pressure gradient (TRPG) and peak systolic pressure gradient (PSPG) were 76.33 ± 22.8 and 44.2 ± 13.18 mmHg, respectively. The mean ratios of systolic pulmonary artery pressure (PAP), diastolic PAP, and mean pulmonary artery pressure (mPAP) to aortic systolic pressure were estimated at 0.92, 0.78, and 0.88, respectively. The results confirmed a significant relationship between mPAP and consanguinity (P = 0.03). In addition, the findings demonstrated a correlation between echocardiographic findings (i.e., TRPG and PSPG) and systolic PAP, diastolic PAP, and mPAP (P &lt; 0.05). In total, 56.3% of the patients expired, most of whom (37.5%) were the younger children. Conclusions: The findings suggest that IPAH should be considered as a possible diagnosis in various clinical manifestations, including respiratory distress, hepatomegaly, ascites and even neurological symptoms. Since there are no specific symptoms, therefore a set of history, physical examination, laboratory findings, and clinical suspicion should be taken into consideration.

Severity of preterm birth and the risk of pulmonary hypertension in childhood: A population-based cohort study in Sweden.

Preterm birth (<37 completed gestational weeks) has been linked to pulmonary hypertension (PH), but the relationship to severity of preterm birth has not been studied. We investigated associations between extremely (<28 weeks), very (28-31 weeks), moderately (32-36 weeks) preterm birth, early-term birth (37-38 weeks) and later PH. Additionally, we explored associations between birthweight for gestational age and PH. This registry-based cohort study followed 3.1 million individuals born in Sweden (1987-2016) from 1 up to a maximum of 30 years of age. The outcome was diagnosis or death from PH in national health registers. Adjusted hazard ratios (HR) were estimated using Cox regression analysis. Unadjusted and confounder-adjusted incidence rate differences were also calculated. Of 3,142,812 individuals, there were 543 cases of PH (1.2 per 100,000 person-years), 153 of which in individuals without malformations. Compared with individuals born at 39 weeks, adjusted HRs with 95% confidence interval (CI) for PH for extremely, moderately, and very preterm birth were 68.78 (95% CI 49.49, 95.57), 13.86 (95% CI 9.27, 20.72) and 3.42 (95% CI 2.46, 4.74), respectively, and for early-term birth 1.74 (1.31, 2.32). HRs were higher in subjects without malformations. There were 90 additional cases of PH per 100,000 person-years in the extremely preterm group (50 after excluding malformations). Very small for gestational age (below 2 SD from estimated birthweight for gestational age and sex) was also associated with increased risk of PH (adjusted HR 2.02, 95% CI 1.14, 3.57). We found an inverse association between gestational age and later PH, but the incidence and absolute risks are low. The severity of preterm birth adds clinically relevant information to the assessment of cardiovascular risks in childhood.

Application of lung ultrasound in monitoring bronchopulmonary dysplasia and pulmonary arterial pressure in preterm infants.

The aim of this study was to evaluate the application value of lung ultrasound in monitoring bronchopulmonary dysplasia (BPD) and pulmonary artery pressure in premature infants. A total of 98 preterm infants diagnosed with BPD in the Fourth Hospital in Shijiazhuang were recruited, and their disease severity was classified as mild (n=32), moderate (n=33), or severe BPD (n=33) based on gestational age and oxygen concentration. Lung ultrasonography of the children was performed. The correlation between lung ventilation scores and disease severity was statistically analyzed, and the discrete optimization results were documented. The pulmonary hypertension indexes of the three groups of children were compared. Aberrant alterations of the pleural line were observed in all included children, and the B-line rose as the disease progressed. The duration of invasive ventilation, medication, and hospital stay increased with disease exacerbation (p<0.05). The three groups significantly differed in terms of ultrasound pulmonary ventilation scores and clinical severity (p<0.05). Only mild BDP was identified by lung ultrasound on the first day of birth (T1), and severe BDP was detectable during the first and second week (T2-T3) as well as the third and fourth week (T4-T5). Severe BPD was associated with significantly higher levels of pulmonary hypertension indices vs. mild and moderate BPD (p<0.05). Pulmonary ultrasonography demonstrates great potential to predict pulmonary hypertension in children and assesses the disease severity. Pulmonary ultrasound allows for dynamical real-time observation of the pulmonary lesions in children with pulmonary hypertension, thereby revealing the severity of pulmonary hypertension in premature children.

An electrocardiographic score to predict pulmonary hypertension in children with atrial septal defect

BackgroundIn limited resource settings, identification of factors that predict the occurrence of pulmonary hypertension(PH) in children with atrial septal defect(ASD) is important to decide which patients should be prioritized for defect closure to prevent complication. Echocardiography and cardiac catheterization are not widely available in such settings. No scoring system has been proposed to predict PH among children with ASD. We aimed to develop a PH prediction score using electrocardiography parameters for children with ASD in Indonesia.MethodsA cross-sectional study reviewing medical record including ECG record was conducted among all children with newly diagnosed isolated ASD admitted to Dr Sardjito Hospital in Yogyakarta, Indonesia during 2016–2018. Diagnosis of ASD and PH was confirmed through echocardiography and/or cardiac catheterization. Spiegelhalter Knill-Jones approach was used to develop PH prediction score. Accuracy of prediction score was performed using a receiver operating characteristic (ROC) curve.ResultsOf 144 children, 50(34.7%) had PH. Predictors of pulmonary hypertension were QRS axis ≥120°, P wave ≥ 3 mm at lead II, R without S at V1, Q wave at V1, right bundle branch block (RBBB), R wave at V1, V2 or aVR > normal limit and S wave at V6 or lead I > normal limit. ROC curve from prediction scores yielded an area under the curve (AUC) 0.908(95% CI 0.85–0.96). Using the cut-off value 3.5, this PH prediction score had sensitivity of 76%(61.8–86.9), specificity 96.8%(91.0-99.3), positive predictive value 92.7%(80.5–97.5), negative predictive value 88.4%(82.2–92.6), and positive likelihood ratio 23.8(7.7–73.3).ConclusionsA presence of PH in children with ASD can be predicted by the simple electrocardiographic score including QRS axis ≥120°, P wave ≥3 mm at lead II, R without S at V1, Q wave at V1, RBBB, R wave at V1, V2 or aVR > normal limit and S wave at V6 or lead I > normal limit. A total score ≥ 3.5 shows a moderate sensitivity and high specificity to predict PH among children with ASD.

0797 Correlation between Obstructive Sleep Apnea and Echocardiography Parameters in Infants and Preschool Children with Down Syndrome

Abstract Introduction Down syndrome (DS) is one of the most common genetic disorders caused by the Trisomy of chromosome 21. Children with DS secondary to the unique airway anatomy and hypotonia, are at risk for obstructive sleep apnea (OSA). Untreated OSA in children can lead to serious complications because of chronic hypoxia leading to Pulmonary hypertension (PHTN) and Cor pulmonale. An overnight polysomnogram (PSG), the gold standard for diagnosing OSA in children, should be performed within 4 years per American Academy of Pediatrics recommendations. However, OSA in DS has been observed at a much younger age. Methods In this single-center retrospective study, data was collected by reviewing the medical records and PSG REDCap database from 2019-2021. Patients with ICD code 10 diagnosis of DS between 0 to 4 years of age who underwent PSG and echocardiography were included. Our primary aim was to assess the severity of OSA in preschool children and describe echocardiogram parameters in DS patients with OSA. We hypothesized that there will be differences in polysomnogram parameters of DS children with and without PHTN. Results 61 patients met the criteria for the study with the mean age being 11.3 months. 3 patients (5.4%) did not have OSA (apnea hypopnea index (AHI)&amp;lt; 1/hr), 11 patients (19.6%) had mild OSA (AHI 1-4.9/hr), 12 patients (21.4%) had moderate OSA (AHI 5-10/hr), 30 patients had severe OSA (AHI &amp;gt;10/hr). Five patients with missing AHI values were excluded for subsequent analyses. Echocardiogram parameters were compared using the described AHI cut offs to define severity of OSA. OSA was observed to be significantly higher in the group with elevated RV systolic pressure. Conclusion Although our study did not find any difference in PSG findings in young children with DS with and without PHTN, obstructive apnea index was significantly elevated in young children with elevated RV systolic pressure. OSA is a significant contributor to the development of PHTN in children with DS. Children with DS are at higher risk for PHTN due to their unique pulmonary vasculature. As PHTN is a significant comorbidity of DS, it is important to perform PSGs early during childhood to detect and treat OSA. Support (if any)

The importance of echocardiography in the instrumental diagnosis of pulmonary hypertension in children with bronchopulmonary dysplasia

Early detection of such a formidable complication of bronchopulmonary dysplasia (BPD) as pulmonary hypertension (PH) is an urgent problem in pediatrics. Echocardiography is currently recognized as the most accessible and non-invasive method for determining pressure in the pulmonary artery. Disorders of alveogenesis and angiogenesis of the vessels of the small circulatory circle in premature infants forming BPD require careful echocardiographic control with using additional analysis of changes in the systolic eccentricity index (EI) as a reliable marker of PH in BPD infants. To increase the information content, it is also necessary to expand the use of EchoCG data in combination with analysis of the blood content of B type natriuretic peptide or the N-terminal pro-B-type natriuretic peptide.

Muscle strength is reduced in children with pulmonary arterial hypertension.

Muscle strength is decreased in adults with pulmonary arterial hypertension (PAH). We aim to investigate muscle strength in children with PAH in relation to a cohort of healthy children, and investigate correlations with disease severity markers. This prospective study included children with PAH aged 4-18 years, who visited the Dutch National Referral Center for Pulmonary Hypertension in Childhood between October 2015 and March 2016. Muscle strength was assessed using handgrip strength and maximum voluntary isometric contractility (MVIC) of four peripheral muscles. Dynamic muscle function was evaluated with the Bruininks-Oseretsky test of motor proficiency (BOT-2). These measurements were compared with those in two cohorts of healthy children and correlated with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP), and time since diagnosis. Eighteen children with PAH aged 14.0 [interquartile range: 9.9-16.0] years showed reduced muscle strength. Handgrip strength z-score -2.4 ± 1.2, p < 0.001, total MVIC z-score -2.9 ± 1.2, p < 0.001, and BOT-2 z-score -1.0 ± 0.9, p < 0.001. 6MWD (67 ± 11% predicted) correlated with most muscle measurements (r = 0.49-0.71, p = 0.001). Dynamic muscle function (BOT-2) differed between WHO-FC, whereas handgrip strength and MVIC did not. NT-proBNP and time since diagnosis did not show significant correlations with muscle strength measurements. Muscle strength was significantly reduced in children with PAH and correlated with 6MWD, but not with disease severity markers WHO-FC and NT-pro-BNP. The nature of this reduced muscle strength is yet unclear, but its occurrence in children with seemingly mild or well-controlled PAH supports the concept of PAH being a systemic syndrome involving peripheral skeletal muscles.

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10-40% w/w) and partially pre-gelatinized starch (PPGS; 2-10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.

Can Maternal Exercise Prevent High-Altitude Pulmonary Hypertension in Children?

Leslie, Eric, Ann L. Gibson, Laura V. Gonzalez Bosc, Christine Mermier, Sean M. Wilson, and Michael R. Deyhle. Review: can maternal exercise prevent high-altitude pulmonary hypertension in children? High Alt Med Biol. 24:1-6, 2023.-Chronic high-altitude exposure reduces oxygen delivery to the fetus during pregnancy and causes pathologic pulmonary artery remodeling, This increases the risk of high-altitude pulmonary hypertension (PH), which is a particularly fatal disease that is difficult to treat. Therefore, finding ways to prevent high-altitude PH, including during the neonatal period, is preferable. Cardiorespiratory exercise can improve functional capacity and quality of life in patients with high-altitude PH. However, similar to other treatments and surgical procedures, the benefits are not enough to cure the disease after a diagnosis. Cardiorespiratory exercise by mothers during pregnancy (i.e., maternal exercise) has not been previously evaluated to prevent the development of high-altitude PH in children born and living at high altitude. This focused review describes the pathophysiology of high-altitude PH and the potential benefit of maternal exercise for preventing the disease caused by high-altitude pregnancies.

Sleep disordered breathing and its relation to stroke and pulmonary hypertension in children with sickle cell disease: a single-center cross-sectional study

Sleep disordered breathing (SDB) is a common underdiagnosed sequela of sickle cell disease (SCD) that has been linked to the frequency of vaso-occlusive crises. To determine the frequency of SDB in children with SCD and its association to SCD-related complications, thirty children and adolescents with SCD at their steady state underwent clinical, laboratory, and radiological assessment using transcranial duplex (TCD) and echo assessment of tricuspid regurge velocity (TRV). All participants had an overnight polysomnography after completing the modified STOP-Bang questionnaire. The mean age of the studied cohort was 10.2 years, with male: female ratio 1.7:1. Six children (20%) had high-risk for obstructive sleep apnea (OSA), while nine (30%) were at intermediate risk. Sleep apnea defined as apnea (AHI) > 1 event/hour was found among 18/30 (60%) subjects (14 males and 4 females). Children with AHI > 5 (moderate to severe OSA) had significantly higher TRV (p = 0.007) and left MCA flow velocity (p = 0.049) when compared to those with AHI < 5. Children with AHI > 5 were at higher risk of OSA according to the modified STOP-Bang questionnaire (p = 0.02). AHI positively correlated with TRV (r = 0.53, p = 0.003), right MCA flow velocity (r = 0.45, p = 0.013), and left MCA flow velocity (r = 0.55, p = 0.002), and negatively correlated to BMI-SDS (r = − 0.48, p = 0.008). The high frequency of OSA in the studied cohort with SCD and its association with increasing risk of PH and TCD changes highlights the importance of early detection and management of OSA in children with SCD.

Increased Plasma Caspase-3 in Children with Down Syndrome is Associated with an Increasing Risk of Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is the one of the comorbidities in children with Down syndrome. The pathogenesis of this pulmonary hypertension remains to be investigated, although endothelial dysfunction and apoptotic activity are among the proposed mechanisms. Caspase-3, a key regulator of apoptosis and appears to be an attractive predictor of pulmonary hypertension in children with Down syndrome. Subjects and Method: A cross-sectional observational clinical study was performed in Dr. Moewardi General Hospital in Surakarta-Indonesia between January and March 2021 involving clinically diagnosed children with Down syndrome. Sampling method was using a consecutive sampling. The independent variable was plasma caspase-3 level and the dependent variable were the presence of pulmonary hypertension and congenital heart defects (CHD). Clinical data documentation, blood collection and echocardiography were performed on enrollment day. We first determined the plasma level of caspase-3 in 36 children with Down syndrome with CHD (n=18) and without CHD (n=18) and further determined the risk of having pulmonary hypertension using the plasma caspase-3 level. We also determined the biomarker performance of caspase-3 using a receiver-operating characteristic (ROC) analysis. Results: Children with Down syndrome with PH had a higher plasma caspase-3 compared to those without PH ( p&lt; 0.001). In those with both CHD and PH, the plasma caspase-3 level was also high although not statistically significant ( p =0.145). The highest plasma caspase-3 level was observed in subjects with PH without CHD ( p &lt;0.01). Relative risk and ROC analysis demonstrated that increased plasma caspase-3 level increased the risk to have PH 5 times (RR=5.00, 95% CI 1.74 –14.34; p &lt;0.001) and predicted the incidence of PH in children with Down syndrome (AUC 0.88, CI 0.76 – 0.99). Conclusion: An elevation in plasma caspase-3 level of Down syndrome children is associated with the increasing risk of having PH regardless the presence of CHD. Journal of Maternal and Child Health (2023), 08(01): 23-32 https://doi.org/10.26911/thejmch.2023.08.01.03

Predictors of pulmonary hypertension among children with atrial septal defects (ASD)

ABSTRACT Introduction: Atrial septal defect (ASD) is a common congenital heart disease in children that uncommonly presents with pulmonary hypertension. Much is not known about the exact predictor of PAH in children with ASD. Objectives: This study aimed to determine the predictors of pulmonary hypertension in children with ASD. Patients and Methods: This was a descriptive analysis of children with ASD carried out in three different institutions over a five-year period. Data entry and analysis were done using IBM Statistical Package for Social Sciences (SPSS) statistical software, version 25. Results: The majority of the participants, 52.2%, had pulmonary hypertension and 62.5% of them occurred as mild pulmonary hypertension. There was a very weak positive correlation between pulmonary hypertension and the size of atrial septal defect, increases in size of atrial septal defect correlate with increases in pulmonary hypertension and this was found not to be statistically significant (n = 67, r = 0.193, p = 0.118). There was a positive correlation between the size of atrial septal defect and the age of participants in months, increases in age correlate with increases in size of atrial septal defect and this was found to be statistically significant (n = 67, r = 0.357, p = 0.003).The highest proportion of respondents who had pulmonary hypertension, 64.7%, was seen among children less than 1 year old while the least proportion, 27.3%, was within 1–5 years, and the difference in proportions was found to be statistically significant (χ2 = 8.187, p = 0.017). Conclusion: Pulmonary hypertension in children with ASD occur usually in the mild form. Age is the only strong predictor of PAH in children with isolated ASD.

Tricuspid regurgitation pressure gradient to diagnose pulmonary hypertension: a diagnostic accuracy study

Background Pulmonary hypertension carries significant morbidity and mortality in children. Early diagnosis and management may improve outcomes in children with pulmonary hypertension. Heart catheterization, a gold standard for diagnosing pulmonary hypertension, is an invasive procedure and not widely available. Echocardiography can be used as an alternative diagnostic tool for pulmonary hypertension.&#x0D; Objective To determine the diagnostic value of tricuspid regurgitation pressure gradient on echocardiography compared to heart catheterization to diagnose pulmonary hypertension in children.&#x0D; Methods This diagnostic test study was done with medical record data of children with acyanotic congenital heart disease who underwent cardiac catheterization and echocardiography procedures from January 2018 to December 2020 at Dr. Sardjito Hospital, Yogyakarta, Indonesia.&#x0D; Data were analyzed to obtain sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios.&#x0D; Results A total of 98 children with acyanotic congenital heart disease were included. The sensitivity and specificity of the tricuspid regurgitation pressure gradient to determine pulmonary artery pressure compared to heart catheterization were 64.4% and 54.5%, respectively. The positive likelihood ratio was 1.42. The pre-test and post-test probability of this study were 88.7% and 91.7%, respectively.&#x0D; Conclusion Tricuspid regurgitation pressure gradient measured using echocardiography has poor sensitivity and specificity to diagnose pulmonary hypertension.