Persistent Pulmonary Hypertension Of Neonate Research Articles

Comparison of Milrinone with Sildenafil for the Treatment of Persistent Pulmonary Hypertension of the Newborn

Objective: To compare milrinone with sildenafil for the treatment of persistent pulmonary hypertension of the newborn. Methodology: A single blinded randomized control trial was conducted in Department of Pediatrics, Aziz Fatima Hospital Faisalabad from October 2022 to September 2023. 160 infants of persistent pulmonary hypertension were included through non probablity consecutive sampling. Group 1 infants (n = 80) received a loading dose of milrinone intravenously administered over a 60-minute period at a dose of 50 µg/kg. Group 2 infants (n = 80) received sildenafil (2mg per kg per dose three times a day). The medication was continued until extubation. The primary outcome variables were the mortality and duration of hospital stay. Results: Ninety two(57.5%) of the one hubdred & sixty newborns in total were male. 111(69.4%) of the total, were full-term babies. In 114(71.2%) infants, the mode of delivery was C-section. Mortality was observed in 7 (8.8%) patients in milrinone group and 17 (21.2%) patients in sildenafil group with p-value = 0.027. Duration of hospital stay was less in milrinone group as compared to sildenafil group (14.22±3.75 days vs 17.72±5.7 days) with p-value = 0.0001. Conclusion: Milrinone has been proven to be a promising therapeutic choice for persistent pulmonary hypertension in neonates, and it is effective in doing so in low resource settings.

Quality Improvement in the Management of Neonatal Persistent Pulmonary Hypertension of the Newborn (PPHN) that Reduced the Need for ECMO

Quality Improvement in the Management of Neonatal Persistent Pulmonary Hypertension of the Newborn (PPHN) that Reduced the Need for ECMO

Use of sildenafil for the treatment of neonatal persistent pulmonary hypertension

Introduction: Persistent pulmonary hypertension of the newborn is a neonatal respiratory and vascular pathology with a high mortality rate. Furthermore, its prevalence is 1 to 2 per 1000 live births, accounting for 8%-10% of neonatal deaths. The therapeutic approach involves supporting pulmonary recruitment and pharmacological vasodilation, most notably sildenafil. Methodology: The study is a narrative review of the literature that was carried out from the PUBMED database using the keywords “Persistent Pulmonary Hypertension of the Newborn” and “Sildenafil”, with the time filter in the last 30 years (1994- 2023). Discussion: Physiologically, during fetal life, the lungs remain filled with fluids, but immediately after birth, pulmonary vascular resistance decreases drastically, allowing alveolar oxygen tension and ventilation to be possible. However, in the pathogenesis of neonatal persistent pulmonary hypertension, there is an increase in pulmonary vascular resistance and remodeling of the vascular structure after birth, which potentiate this exaggerated vasoconstriction. Therefore, the standard exam for investigating the pathology is echocardiography. Sildenafil is a drug used to treat neonatal persistent pulmonary hypertension, as it enhances better blood flow and better delivery of oxygen to tissues, through its physiopharmacology aimed at vasodilation secondary to inhibition of phosphodiesterase-5. Conclusion: Neonatal persistent pulmonary hypertension is still one of the main neonatal pathologies with high morbidity and mortality in the neonatal population, due to the complexity of presentations and the variation in therapeutic responses to pharmacotherapy.

A Brazilian Neonatal Unit's Experience with Functional Echocardiography and Diagnostic Findings in Congenital Heart Disease

Introduction: The diagnosis of congenital heart diseases is a challenge for pediatricians due to the diversity of clinical presentations and symptoms, just like several other diseases prevalent in the neonatal period. Often the diagnosis is established during the gestation period, sometimes the hypothesis is formulated by neonatal screening. However, several cases will require clinical suspicion from the pediatrician. Given the possibility of this diagnosis, the evaluation of the infant cardiologist is essential. Unfortunately, this professional is not always readily available. In the intensive care units, health professionals use heart rate, blood pressure, capillary refill, urinary output and acid-base balance for hemodynamic analysis. These data are significant, but nonspecific. Thus, functional echocardiography can improve hemodynamic evaluation with positive impact on diagnosis. Our objective was to conduct a retrospective analysis of hospitalizations in a Brazilian neonatal unit, with the goal of identifying the diagnoses of congenital heart diseases made by a researcher using functional echocardiography, from July 2015 to September 2017, having as inclusion criteria; clinical manifestations of distress or respiratory failure, characterized by tachypnea, signs of dyspnea, need for oxygen therapy or ventilatory support and/or hemodynamic instability, characterized by tachycardia, cyanosis, cold extremities, prolonged capillary filling time, fine pulses and/or hypotension, low urinary output. Results: During the 26 months of the study, 362 neonates were hospitalized. Of these, 223 were included in the research for presenting cardiorespiratory manifestations. We observed three cases of obstructive shock related to cardiac tamponade, 18 cases of congenital heart disease, five cases of hypertrophic myocardiopathy, seven cases of myocardial dysfunction not related to structural heart disease, 46 cases of neonatal persistent pulmonary hypertension and 27 cases of patent ductus arteriosus (six with hemodynamics repercussion). Conclusions: The results showed functional and/or anatomical changes in 105 patients analyzed (46.7%), identified a diversity of structural cardiopathies, improved hemodynamic evaluation with impact on the therapeutic approach. While using functional echocardiography in neonates, clinicians should be aware that undiagnosed critical congenital heart defects can present during this period. They should acknowledge the limitations of skills, and it should not be used as a screening tool for diagnosing or excluding congenital heart defects. A patient with a suspected critical congenital heart defect should be quickly referred to a pediatric cardiologist, even if this implies out-of-hospital patient’s transportation. We assume that the systematic implementation of this technology by the medical team can improve diagnostic accuracy, which can positively impact the therapy used. Keywords: Critical care, neonatology, ultrasonography, echocardiography, point-of-care systems, cardiac tamponade, hypertension pulmonary, heart defectal congenits.

Can Functional Echocardiography be Useful in the Diagnosis of Congenital Heart Disease? Review of Two Cases of Transposition of Great Arteries

Introduction: Congenital heart diseases represent the most frequent form of malformation and can be diagnosed by fetal echocardiography, neonatal screening or clinical signs. Whenever this is suspected, a pediatric cardiologist should be contacted, and comprehensive echocardiography performed. But the availability of a specialist for immediate implementation is not the reality of many services. As functional echocardiography is often carried out in neonatal units because of its utility in several clinical situations, we consider its usefulness in diagnosing congenital heart diseases. Case reports: we report two cases of transposition of the great arteries diagnosed by functional echocardiography. Case 1 was a premature neonate transferred to the neonatal unit with a suspected diagnosis of respiratory distress syndrome and sepsis without improvement with initial treatment. Functional echocardiography on admission allowed the diagnosis of transposition of the great arteries. Case 2 was a full-term neonate with early cyanosis, with functional echocardiography suggesting transposition of the great arteries and the images used for discussion with a specialist from a reference center, speeding up the transfer. Discussion: early recognition of critical heart disease is essential to improve prognosis. Diagnosis of these diseases can be performed by fetal echocardiography, neonatal screening and clinical signs. When congenital heart structural defect is likely, pediatric cardiologist should be consulted and comprehensive echocardiography promptly performed. Functional echocardiography has been performed in neonatal units with the aim of analyzing the patent ductus arteriosus and ventricular function, diagnosing cardiac tamponade and neonatal persistent pulmonary hypertension. As not all services have a pediatric cardiologist readily available, we considered whether functional echocardiography could help in the diagnostic conclusion through systematic analysis of cardiac images. Conclusion: we reinforce that comprehensive echocardiography performed by a specialist is the first option or performed as soon as possible when congenital heart disease is the main hypothesis.

Pilot Study Investigating Brain Natriuretic Peptide, Troponin, Galectin-3, and miRNA-126a-5p as Biomarkers of Persistent Pulmonary Hypertension in Neonates with Hypoxic-Ischemic Injury Receiving Therapeutic Hypothermia.

The objective was to evaluate the utility of brain natriuretic peptide (BNP), troponin, galectin-3 (Gal-3), and microRNA (miRNA)-126a-5p as screening biomarkers for persistent pulmonary hypertension of the newborn (PPHN) by comparing expression in serum of infants with hypoxic-ischemic injury that develop PPHN to those that do not. This was a prospective, observational pilot study including neonates with hypoxic-ischemic injury undergoing therapeutic hypothermia (TH) at two regional perinatal medical centers. PPHN in this population was diagnosed clinically and confirmed by echocardiogram. Serial measurements of biomarkers were performed from 6 to 96 hours post-TH initiation in 40 patients. Of 40 infants in the study, 10 (25%) developed PPHN and 30 (75%) did not. Baseline demographics and hemodynamics were similar between the groups. Patients with PPHN had a significantly higher need for vasopressors compared with patients without PPHN (70 vs. 27%, p = 0.007). Mean serum BNP and troponin levels were significantly higher in the PPHN group peaking at 12 to 24 hours and decreasing following PPHN treatment initiation. miRNA-126a-5p expression was increased in patients with PPHN compared with patients without, with statistical significance detected at 12 hours (p = 0.005) and 96 hours (p = 0.01). Mean circulating Gal-3 levels were not statistically different between the two groups; however, Gal-3 was elevated in all patients with hypoxic-ischemic injury on TH compared with healthy infants from prior studies. BNP and troponin are readily available, low-cost biomarkers that showed significant serial elevations in the PPHN group of the study and, thus, may have value in screening for PPHN in the setting of hypoxic-ischemic encephalopathy (HIE). Gal-3 was elevated in all patients with HIE and may be a useful biomarker of hypoxic injury in infants being evaluated for TH. Elevations in miRNA-126a-5p were not consistently seen in this study. Larger studies are required to establish an association between PPHN and these biomarkers in patients with and without HIE. · Serum biomarkers of persistent pulmonary hypertension of the newborn. · Serum biomarkers of hypoxic-ischemic injury.

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<0.01). For the diagnosis of PPHT, UC NT-proBNP cut-off value was >2760.5 pg/ml, sensitivity was 90.7%, and specificity was 96.6% (p<0.01). For NT-proBNP at 72 hours, the cut-off value was >1414 pg/ml, sensitivity was 95.9%, and specificity was 91.2% (p<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. 

Clinical Effect of Sildenafil Combined with Alveolar Surfactant in the Treatment of Neonatal Persistent Pulmonary Hypertension

Clinical Effect of Sildenafil Combined with Alveolar Surfactant in the Treatment of Neonatal Persistent Pulmonary Hypertension

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.
 Objectives: To estimate incidence, risk factors; and outcome within limited resources – conventional ventilation, sildenafil, dobutamine and milrinone therapy.
 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.
 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.
 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.

Sildenafil for pulmonary hypertension in neonates: An updated systematic review and meta-analysis.

To provide an updated review and meta-analysis on the efficacy and safety of sildenafil for treating persistent pulmonary hypertension in neonates (PPHN). PubMed/Medline, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science were searched from the inception of publication to January 2021. The principal outcomes include oxygenation parameters, hemodynamic metrics and echocardiographic measurements, as well as adverse outcomes. A total of eight studies were included with 216 term and premature neonates with PPHN. Compelling evidence showed the use of sildenafil could improve the prognosis of PPHN neonates, compared with baseline or placebo in neonates with PPHN, and a time-dependent pattern of the improvements can be observed. After 24 h of treatment, the Oxygenation index suggested a steady decrease (SD: -1.80, 95% confidence interval [CI]: -2.92, -0.67) and sildenafil exerted peak effects after 72 h of treatment (SD: -4.02, 95% CI: -5.45, -2.59). No clinically significant side effects were identified. Egger's test and funnel plots of the major outcomes were performed, and the publication bias was not significant. Improvements were shown in oxygenation index, pulmonary arterial pressure, and adverse outcomes after using sildenafil for PPHN in neonates. However, future research with robust longitudinal or randomized controlled design is still needed.

Persistent pulmonary hypertension in neonates with perinatal asphyxia and therapeutic hypothermia: a frequent and perilous combination

Therapeutic hypothermia in neonates with perinatal asphyxia may increase the risk of PPHN. This potentially affects outcome. Objectives (1) To investigate whether neonates with perinatal asphyxia and therapeutic hypothermia more often developed PPHN compared to a control group with perinatal asphyxia not treated with hypothermia; (2) To identify risk factors for severe PPHN during hypothermia and evaluate short-term outcome. Methods This single-center retrospective cohort study included (near-)term neonates with perinatal asphyxia admitted between 2004 and 2016. Neonates with perinatal asphyxia and hypothermia were compared to a historical control group without hypothermia. Primary outcome was PPHN, defined as severe hypoxemia requiring mechanical ventilation and inhaled nitric oxide, confirmed by echocardiography. Short-term adverse outcome was defined as mortality within one month and/or severe brain injury on MRI. Results Incidence of PPHN was 23% (26/114) in the hypothermia group and 11% (8/70) in controls. In multivariate analysis, PPHN was 2.5 times more common among neonates with hypothermia. Neonates developing PPHN during hypothermia often had higher fraction of inspired oxygen at baseline. PPHN was not associated with a higher risk of severe brain injury. However, early mortality was higher and three infants died due to severe refractory PPHN during hypothermia. Conclusions In this study PPHN occurred more often since the introduction of therapeutic hypothermia. This was usually reversible and did not lead to overall increased adverse outcome. However, in individual cases with PPHN deterioration occurred rapidly. In such cases the benefits of hypothermia should be weighed against the risk of a complicated, fatal course.

Repurposing of the PDE5 Inhibitor Sildenafil for the Treatment of Persistent Pulmonary Hypertension in Neonates.

Nitric oxide (NO), an important endogenous signaling molecule released from vascular endothelial cells and nerves, activates the enzyme soluble guanylate cyclase to catalyze the production of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate. cGMP, in turn, activates protein kinase G to phosphorylate a range of effector proteins in smooth muscle cells that reduce intracellular Ca2+ levels to inhibit both contractility and proliferation. The enzyme phosphodiesterase type 5 (PDE5) curtails the actions of cGMP by hydrolyzing it into inactive 5'-GMP. Small molecule PDE5 inhibitors (PDE5is), such as sildenafil, prolong the availability of cGMP and therefore, enhance NO-mediated signaling. PDE5is are the first-line treatment for erectile dysfunction but are also now approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Persistent pulmonary hypertension in neonates (PPHN) is currently treated with inhaled NO, but this is an expensive option and around 1/3 of newborns are unresponsive, resulting in the need for alternative approaches. Here the development, chemistry and pharmacology of PDE5is, the use of sildenafil for erectile dysfunction and PAH, are summarized and then current evidence for the utility of further repurposing of sildenafil, as a treatment for PPHN, is critically reviewed.

Comparison of the effects of bosentan and sildenafil in the treatment of persistent pulmonary arterial hypertension in infants

Background: Persistent pulmonary hypertension (PPHN) is a life-threatening condition in neonates. In developing countries, mortality is estimated to be around 10%–20% due to lack of access to the main drug, inhaled nitric oxide. Bosentan as an endothelin type A and B receptor antagonist and sildenafil as a phosphodiesterase inhibitor type 5 are effective in reducing pulmonary vascular resistance and pulmonary artery pressure (PAP). Materials and Methods: A double-blind clinical trial was conducted at the intensive care unit of Akbarabadi Hospital Tehran between October 2017 and September 2019. The efficacy, safety, and possible side effects of bosentan and sildenafil were evaluated in neonates suffering from PPHN. Echocardiographic findings, duration of oxygen dependency, invasive ventilation support requirement, duration of medication, short-term outcomes including blood pressure, white blood cell, and hemoglobin counts were compared between the two groups. Results: Bosentan is as effective as sildenafil in reducing PAP and improving cardiac output. The duration of treatment with bosentan was significantly shorter than that of sildenafil (P = 0.002). The time of oxygen demand was similar between both the groups, ranging from 15 to 17 days (P = 0.198). The need for invasive ventilation support was similar in both the groups (P = 0.989). Although PAP and the severity of tricuspid valve insufficiency were higher before treatment, the third echocardiographic findings such as pulmonic insufficiency (P = 0.194), tricuspid regurgitation (P = 0.368), and ejection fraction (P = 0.160) were similar in bosentan and sildenafil groups. The need for supportive inotropic drugs was similar in both the groups. There was no statistically significant difference in the mean of blood pressure, white blood cell, and hemoglobin counts between the two groups.Conclusion: Bosentan is effective in the treatment of PPHN in neonates and reduces it over a shorter period of time. It is more efficient in reducing PAP and decreases the severity of tricuspid valve insufficiency in a shorter time compared to sildenafil.

Phenotype characterisation of TBX4 mutation and deletion carriers with neonatal and paediatric pulmonary hypertension

Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated with TBX4 variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carrying TBX4 rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entire TBX4 locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4 mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

Time to peak velocity in the main pulmonary artery as a marker of persistent pulmonary hypertension in neonates.

To assess right ventricular systolic time intervals, specifically, time to peak velocity (TPV) in the pulmonary artery as a marker of persistent pulmonary hypertension of the newborn (PPHTN). This was a retrospective case-control study of 30 infants with pulmonary hypertension requiring intensive care management. Cardiac ultrasounds were re-analysed, comparing TPV measurements to a group of 31 controls who had cardiac ultrasounds performed for incidental murmurs with structurally normal hearts. Time to peak velocity was significantly shorter in the PPHTN group compared to controls, 47 vs. 95ms, respectively. This was statistically significant with a P-value of <0.001. Time to peak velocity in the pulmonary artery is a useful marker of PPHTN in the first week of life. This measurement is especially useful if neither tricuspid regurgitation or a patent ductus are present for interrogation on ultrasound.

Inhaled Nitric Oxide in Treatment of Persistent Pulmonary Hypertension of Neonate: An Insight into Biochemical Pathways

Inhaled Nitric Oxide in Treatment of Persistent Pulmonary Hypertension of Neonate: An Insight into Biochemical Pathways

Analysis of the risk factors of persistent pulmonary hypertension in neonates

Objective To investigate the high risk factors of persistent pulmonary hypertension (PPHN) in preterm and full-term neonates. Methods Fifty-six newborns with PPHN were divided into preterm neonates group and the full-term neonates group according to their gestational ages.The relationship between PPHN and high risk factors such as the primary diseases, mother′s complications during pregnancy, and the prognosis were analyzed retrospectively in each group.A retrospective review of lung samples of 3 neonates who died of respiratory failure were carried out. Results Thirty-one (55.36%) out of 56 neonates with PPHN including 27 preterm and 29 full-term newborns had parenchyma diseases.The first and the second primary diseases were meconium aspiration syndrome (MAS, 9/29 cases, 31.03%) and congenital heart diseases (8/29 cases, 27.59%) in the full-term group, and respiratory distress syndrome (RDS, 16/27 cases, 59.26%) and infection (8/27 cases, 29.63%) in preterm group, respectively.There were 15 cases (55.56%) whose mothers had complications during pregnancy among the 27 preterm neonates, and 8 cases (27.59%) among the 29 full-term neonates.The morbidity of mothers′ complications during pregnancy in preterm neonates was higher than that in full-term neonates (χ2=4.519, P=0.034). The mortality rate was 33.33% (9/27 cases) in the preterm neonates group while 27.59% (8/29 cases) in the full-term neonates group.There was no significant difference in mortality rate between each group (χ2=0.218, P=0.640). The primary diseases were RDS (9/9 cases, 100%) and MAS (4/8 cases, 50%) in preterm and full-term neonates who died of PPHN, respectively.One case of pulmonary hypertensive vascular remodeling, 1 case of alveolar capillary dysplasia (ACD) and 1 case of interstitial pneumonia were found in 3 lung samples of neonates died of PPHN. Conclusions The ratio of preterm increased in neonates with PPHN.RDS and infection were the first two primary diseases in preterm neonates with PPHN.MAS was the first primary disease in full-term neonates with PPHN.Primary pulmonary hypertension should be considered for neonates with severe PPHN. Key words: Persistent pulmonary hypertension; Infant, newborn; Risk factor; Primary persistent pulmonary hypertension

EDN1 Gene Variant is Associated with Neonatal Persistent Pulmonary Hypertension.

Recent studies have suggested associations between certain genetic variants and susceptibility to persistent pulmonary hypertension of the newborn (PPHN). The aim of the study was to evaluate the association of EDN1, NOS3, ACE and VEGFA genes with PPHN. Neonates with respiratory distress were enrolled in the study, whose gestational age ≥34 weeks, age ≤3 days. They were divided into PPHN and non-PPHN group. The EDN1, NOS3, ACE and VEGFA genes were detected by next-generation sequencing, and the results were validated by Sanger sequencing. Serum endothelin-1 (ET-1) levels were quantified by ELISA. A total of 112 neonates were enrolled (n = 55 in PPHN group; n = 57 in non-PPHN group). There is a significantly difference in the genotype distribution of EDN1 rs2070699 between the PPHN and non-PPHN group (P = 0). A higher frequency of the rs2070699 T allele was observed in the PPHN group (54.5% vs 27.2%; OR = 3.89; 95%CI 1.96–7.72). The rs2070699 T allele was associated with higher ET-1 levels (3.333 ± 2.517 pg/mL vs 1.223 ± 0.856 pg/mL; P = 0.002) and a longer ventilation period (5.8 ± 2.6 days vs 3.6 ± 3.3 days; P = 0). The results suggest there is an association between EDN1 and PPHN. The presence of the rs2070699 T allele increased the risk of PPHN in neonates with respiratory distress.

Outcome of oral sildenafil in neonatal persistent pulmonary hypertension of non-cardiac causes.

Despite recent treatment modalities, mortality from persistent pulmonary hypertension (PPHN) remains significant. In instances where infants do not respond to inhaled nitric oxide (iNO), oral sildenafil could hold promise as a selective pulmonary vasodilator. Further studies are still needed to explore its efficacy and safety in newborns with PPHN. To validate the efficacy of oral sildenafil on oxygenation and its short-term safety in newborns with persistent pulmonary hypertension. A total of 27 newborns ≥36 weeks gestational age were admitted to NICU with oxygenation index (OI) ≥15 and confirmed diagnosis of PPHN with echocardiography. Oral sildenafil given at a dose of 1-2 mg/kg every 6 hours. We monitored improvement in oxygenation, safety and short-term outcomes. Among 27 newborns, oral sildenafil was efficacious in 21 patients (78%) with reduction of OI from 34.9 ± 9.6 to 13 ± 3.2 (p < 0.001), increase of PaO2 from 42.4 ± 13.5 to 78 ± 11.5 mmHg (<0.001), and reduction of FiO2 from 1.0 ± 0 to 0.3 ± 0.06 (<0.001). OI decreased by 6.3 % from baseline after the first dose of sildenafil and continued to decrease with subsequent doses. In 6 patients (22%) sildenafil did not work; 5/6 patients (18%) transferred to another tertiary NICU and one patient (4%) died of sepsis. None of the patients had significant systemic hypotension. Oral sildenafil is a promising pulmonary vasodilator in patients with PPHN, particularly in medical facilities with no available iNO and ECMO. It is well tolerated with no significant short term complications.

Does SSRI Use During Pregnancy Increase the Risk for PPHN

Neonatal persistent pulmonary hypertension (PPHN) presents as critical hypoxemia during the first few days of life and is associated with significant