Persistent Pulmonary Hypertension Of Newborn Research Articles

Neurodevelopmental outcome in children between one and five years after persistent pulmonary hypertension of term and near-term newborns.

Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1-2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented. The main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN. All of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents. Fifty-five children (81% of answers) with a median age of 36 months (11-68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age. This study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

Clinical phenotype of pulmonary vascular disease requiring treatment in extremely preterm infants

BackgroundPulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment.MethodsThis study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups.ResultsAmong the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment.ConclusionsThis study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants.

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.

Milrinone in persistent pulmonary hypertension of newborn: a scoping review.

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

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.

Challenges in clinical identification of right ventricular dysfunction in preterm infants with persistent pulmonary hypertension of the newborn

BackgroundRight ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. MethodsForty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as “low” or “normal” using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. ResultsMean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41±7 vs. 47±9 mmHg, p = 0.02) and higher shock index (4.02±0.80 vs. 3.44±0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32–0.77). ConclusionsThe non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants.

Comparison of treprostinil and oral sildenafil for the treatment of persistent pulmonary hypertension of the newborn: a retrospective cohort study.

This study aims to evaluate the effectiveness of treprostinil and oral sildenafil in managing persistent pulmonary hypertension of newborns (PPHN). We conducted a retrospective cohort study of 42 neonates with PPHN treated with continuous intravenous treprostinil or oral sildenafil from January 2020 to October 2022 in China. Outcomes assessed included echocardiographic pulmonary artery systolic pressure (PASP), shunt direction, and arterial blood gas measures. Treprostinil lowered PASP and improved oxygenation significantly better than sildenafil on days 1, 2, and 3 of treatment (P < 0.05). Treprostinil also corrected shunt direction faster than sildenafil (P < 0.05). The duration of mechanical ventilation, length of NICU stay, and overall hospital stay did not significantly differ between the two groups (P > 0.05). Treprostinil effectively lowers pulmonary artery pressure and improves oxygenation in neonates with PPHN, without being associated with severe complications. It may serve as a beneficial adjunct therapy for neonates with PPHN.

Characteristics of Newborn with Persistent Pulmonary Hypertension (PPHN) Admitted In Neonatal Intensive Care Unit in a Tertiary Care Hospital

Objectives: To find the frequency, aetiologies, treatment options and outcomes in neonates with persistent pulmonary hypertension of the new-born and to identify risk factors associated with severe pulmonary hypertension. Study Design: Prospective longitudinal study. Place and Duration of Study: Neonatal Intensive Care Unit, Fatima Memorial Hospital, Lahore Pakistan, from Apr to Oct2020. Methodology: All neonates admitted to the Neonatal Unit with signs and symptoms suggestive of PPHN and confirmed on echocardiography were included in the study. Multiple maternal and neonatal risk factors leading to PPHN were identified. Results: A total of 70 neonates with persistent pulmonary hypertension were identified. The all-cause mortality rate was 18.6% (13 of 70). Pneumonia was the primary cause of pulmonary hypertension (64.3%). Pneumonia was the primary cause of pulmonary hypertension (64.3%). Out of 72, 46(65.7%) were male and 24(34.3%) were female. The mean gestational age was 35.38±3.39 weeks. On binary logistic regression analysis, severe pulmonary hypertension showed a significant association with maternal septic risk factors (OR 0.26, p=0.03, emergency section (OR 3.69, p=0.05). Conclusions: The persistent pulmonary hypertension of newborns in the current study was higher than in Western countries. Pneumonia and sepsis are the primary aetiologies of developing PPHN. Maternal septic risk factors and emergency section are associated with an increased risk of severe pulmonary hypertension.

Novel scoring tool of hypoxemic respiratory failure and pulmonary hypertension for defining severity of persistent pulmonary hypertension of newborn

ObjectiveTo obtain preliminary validity data for a hypoxemic respiratory failure/pulmonary hypertension (HRF/PH) score for classifying persistent pulmonary hypertension of the newborn (PPHN).Study designRetrospective chart review of 100 consecutive neonates admitted to a Children’s hospital from 2016–2021 with PPHN, gestational age ≥34 weeks, and echocardiograms in the first week. We assessed the correlation between HRF/PH score and short-term outcomes using linear and logistic regressions.ResultsHRF/PH scores ranged 2–12 (mean 8.5), and were classified mild (0–5), moderate (6–10), and severe (11–15), with 6%, 77% and 17% infants in respective categories. HRF/PH score category correlated with invasive ventilation, nitric oxide, high frequency ventilation, vasoactive infusions, extracorporeal life support and death. HRF/PH score category did not correlate with duration of support or length of stay.ConclusionThe HRF/PH score offers a promising representation of disease severity for PPHN. The tool requires further validation in prospective studies and evaluation for long-term outcomes.

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.

Non cardiac central cyanosis in the newborn: A case report of persistent pulmonary hypertension of newborn (PPHN) and review of literature

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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.

Risk Factors of Neonatal Acute Respiratory Distress Syndrome Based on the Montreux Definition in Neonates with Sepsis: A Retrospective Case-Control Study.

The aim of the study is to analyze the risk factors for neonatal acute respiratory distress syndrome (NARDS) development based on the Montreux definition among near- and full-term neonates with sepsis and received meropenem. This was a single-center, case-control, retrospective trial from January 2019 to June 2020. Newborns of gestational ages (GAs) ≥35 weeks, diagnosed with sepsis and received meropenem were included. Patients who developed NARDS subsequently were defined as the study group (NARDS group), while the others without NARDS were enrolled in the control group (non-NARDS group). Out of 213 eligible neonates, NARDS occurred in 52 (24.4%) cases. In univariate analysis, infants with NARDS had a lower GA and birth weight, but a higher rate of premature birth (p <0.05). The median onset times of sepsis were earlier among neonates with NARDS compared with those without NARDS (1 [1,1] vs. 6 [1,15] days, p <0.001). Neonates with NARDS were more likely to suffer from early-onset sepsis (EOS), persistent pulmonary hypertension of newborns, pulmonary hemorrhage, septic shock, and patent ductus arteriosus (p <0.05). During labor, women whose neonates experienced NARDS were more likely to have a cesarean delivery (67.3 vs. 46.6%, p = 0.009) and likely to receive at least one dose of corticosteroids (21.2 vs. 5.0%, p = 0.001). In multivariable analyses, factors remaining independently associated with NARDS were premature birth, cesarean delivery, EOS, and septic shock. Compared with conventional inflammatory markers for NARDS, procalcitonin (PCT) was correlated with septic neonates who developed NARDS (p = 0.012) but had a low diagnostic value (area under the curve [AUC] = 0.609). C-reactive protein, white blood cells, and PLT did not correlate with morbidity of NARDS (AUC <0.05 and p >0.05). Premature birth, cesarean delivery, EOS, and septic shock were independently associated with NARDS among near- and full-term septic neonates. PCT showed limited predictive value for NARDS. · NARDS is serious and sepsis is proved as a cause for it.. · But rare study suggests the risk factors of NARDS based on the Montreux definition.. · This study may first found the independent risk factors associated with NARDS in septic neonates..

Management of Pulmonary Hypertension in Preterm Infants—A Review

Persistent pulmonary hypertension of newborn is being increasingly diagnosed in extremely premature infants, especially if associated with preterm prelabour rupture of membranes and lung hypoplasia. Late-onset pulmonary hypertension (PH) associated with bronchopulmonary dysplasia is because of pulmonary vascular remodeling and altered vasoreactivity. PH in both these settings is associated with around 20% increase in higher mortality and morbidity. The steps in the management of early-onset PH in these neonates, like in term infants, are supportive measures, oxygenation, lung recruitment, and ventilation. In extremely preterm infants, PH occurs because of the paucity of the pulmonary vascular bed and may not respond well to pulmonary vasodilators, such as iNO and sildenafil. Magnesium sulfate can be effective in reducing the pulmonary pressure, especially in resource-limited settings. Milrinone is considered in neonates with PH and poor cardiac function. In preterm infants with PH secondary to bronchopulmonary dysplasia, the emphasis is on oxygen therapy, nutrition, and correction of comorbidities along with some role of vasodilators.

N-TERMINAL PROHORMONE OF BRAIN NATRIURETIC PEPTIDE IN THE DIAGNOSIS AND MANAGEMENT OF PERSISTENT PULMONARY HYPERTENSION IN NEWBORNS

Objective: This study aimed to investigate the levels and utility of amino/N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in the diagnosis of neonatal persistent pulmonary hypertension (PPHT). Materials and Methods: Infants born at ≥34 weeks of gestation were included in this retrospective cross-sectional study. In total, 33 newborns diagnosed with PPHT were included in the patient group and 50 healthy newborns were included in the control group. Patient and control groups were compared in terms of plasma NT-proBNP levels measured in the umbilical cord (UC) and at 72 hours of life. Results: The NT-proBNP levels in UC and at 72 hours were significantly higher in neonates with PPHT compared to controls (p&lt;0.01). For the diagnosis of PPHT, UC NT-proBNP cut-off value was &gt;2760.5 pg/ml, sensitivity was 90.7%, and specificity was 96.6% (p&lt;0.01). For NT-proBNP at 72 hours, the cut-off value was &gt;1414 pg/ml, sensitivity was 95.9%, and specificity was 91.2% (p&lt;0.01). The mean UC NT-proBNP levels were 1094.7±603 pg/ml and mean NT-proBNP levels at 72 hours were 875.7±423 pg/ml in the control group. Conclusion: NT-proBNP levels are high during the initial days of life. They are useful in the diagnosis and follow-up of PPHT in newborns with hypoxemic respiratory failure and high fraction of inspired oxygen (FiO2) requirement, especially in cases where transthoracic echocardiography (TTE) cannot be performed.&nbsp;

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.

Title: Clinical Profile of Persistent Pulmonary Hypertension in Neonates with Role of Sildenafil in its Outcome: Rural India NICU Experience

Background: Persistent pulmonary hypertension of newborn (PPHN) result from failure of normal fall in pulmonary vascular resistance at or shortly after birth. It is associated with high mortality and morbidity.&#x0D; Objectives: To estimate incidence, risk factors; and outcome within limited resources – conventional ventilation, sildenafil, dobutamine and milrinone therapy.&#x0D; Methods: This prospective study was carried out on cases of PPHN admitted between March 2017 to August 2018. PPHN was suspected clinically, and then confirmed by echocardiography.&#x0D; Results: Out of 2811 inborn live births 12 (0.43%) developed PPHN. Out of total 942 NICU admissions, PPHN was diagnosed in 40(4.2%). 32 (80%) were full term, 6 (15%) were late preterm and 2(5%) were post term neonates. 25(62.5%) were male. Major etiological factors were asphyxia 19(47.5%), EOS (early onset sepsis) 18(45%) and MAS (meconium aspiration syndrome) 12(30%). 20(50%) responded to oral sildenafil and dobutamine therapy, 6 more responded with addition of milrinone. The overall survival rate was 26(65%) and poor outcome in 14 (35%) in our study. Median duration of respiratory support was 1.5(1 – 6) days in those with poor outcome and 6(4 – 7) in those survived. Duration of hospital stay was 1.5(1 – 6) days in poor outcome and 17(13 – 22) in those survived.&#x0D; Conclusions: Asphyxia, EOS and MAS are common causes of PPHN. Severity of respiratory distress on admission is correlated with mortality rather than etiological factors. Conventional ventilation, dobutamine, sildenafil and milrinone therapy are mainstay of treatment of PPHN cases in resource limited settings, and helps to reduce mortality to some extent.

Effectiveness of oral sildenafil for neonates with persistent pulmonary hypertension of newborn (PPHN): a prospective study in a tertiary care hospital

Introduction The prevalence of persistent pulmonary hypertension of newborn (PPHN) has been estimated 1.9/1000 live births. Although the efficacy of inhaled nitric oxide and extracorporeal membrane oxygenation in PPHN is well established but it is difficult to administer and monitor in resource limited countries. Owing to this, other treatment options need to be evaluated. Method This is a prospective observational study conducted in the Pediatric Cardiology Department, NICVD, Karachi, from February 2020 to October 2020 after the approval from the Institutional Ethical Review Committee. All the neonates referred to our Unit were screened by echocardiography (echo) and those who fulfilled the inclusion criteria were included. Echo were done before starting sildenafil and after 72 h to assess the pressure gradient across tricuspid valve and right to left or bidirectional shunt across patent ductus arteriosus , patent foramen ovale , or both. Sildenafil was started with a dose of 1 mg/kg/dose thrice a day and increased to 2 mg/kg/dose after 48 h if partial pressure of oxygen (PO 1 ] did not increase. In neonates who did not respond to increased dose of Sildenafil were added on oral Bosentan 1 mg/kg/dose twice a day. Results Total 82 newborns were enrolled. Fifty-two patients improved after 48 h so were continued on same treatment. Sildenafil dose was increased in 30 (37.9%) patients whose PO2 did not increase to at least 10% from baseline after 48 h of starting treatment. Three patients expired within 48–72 h. Out of 27 remaining patients, only four responded whereas 23 patients did not show any improvement. In these patients, Bosentan was supplemented along with sildenafil. Conclusion The results of our study show effectiveness of oral Sildenafil in treating PPHN. The overall improvement observed in the patients was overwhelming. Combination of Sildenafil with Bosentan is beneficial in patients who did not respond on Sildenafil alone.