Application of extracorporeal membrane oxygenation in the treatment of persistent pulmonary hypertension of the newborn / 中国当代儿科杂志

OBJECTIVES@#To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN).@*METHODS@#A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome.@*RESULTS@#Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment.@*CONCLUSIONS@#ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.

Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide / 中国当代儿科杂志

OBJECTIVES@#To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO).@*METHODS@#A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk.@*RESULTS@#A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2.@*CONCLUSIONS@#Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

Pacientes con corazón univentricular sometidos a cirugía de Glenn / Patients with univentricular heart submitted to Glenn surgery

Resumen Objetivo: Describir las características clínicas, quirúrgicas y posquirúrgicas de pacientes univentriculares sometidos a cirugía de Glenn en un centro de referencia cardiovascular. Método: Estudio descriptivo, retrospectivo, llevado a cabo entre enero de 2012 y diciembre de 2016, en pacientes menores de 18 años que consultaron a una clínica de cuarto nivel, con cardiopatías de fisiología univentricular, definidos por ecocardiografía institucional, presentados en junta médico-quirúrgica, operados o no como primer estadio de paliación y seguidos en el programa de ventrículo único de la institución, posterior a un cateterismo cardiaco para ser presentado en junta médica que definió la realización de cirugía de Glenn. De la historia clínica se recolectaron datos de ecocardiogramas diagnósticos, cateterismos cardiacos, descripciones quirúrgicas y evoluciones. Resultados: Se analizaron 88 pacientes univentriculares, de los cuales el 63% eran hombres y el 36% eran mujeres. La anatomía del ventrículo funcional univentricular derecho estuvo presente en el 38.6% y la morfología funcional izquierda en el 61.4%. Entre las características asociadas con la mortalidad se verificó que el 1.1% tuviera insuficiencia moderada de la válvula atrioventricular y que el 3.4% tuviera insuficiencia grave de la válvula atrioventricular. El 38.6% presentó cifras de presión pulmonar elevadas, medidas por cateterismo cardiaco, y el 46% tenían resistencia vascular pulmonar aumentada. Se usó terapia vasopresora antes de la cirugía de Glenn en nueve pacientes; todos recibieron milrinona. La mortalidad posquirúrgica fue del 18%. Conclusiones: Este estudio evidencia que el diagnóstico y la intervención temprana contribuyen a reducir la morbimortalidad en los pacientes con diagnóstico de corazón univentricular, puesto que sin intervención de segundo estadio de paliación sería mortal para la mayoría de ellos. Así mismo, evidencia la importancia de la implementación de un programa integral para la atención de enfermedades cardiovasculares complejas.

Abstract Objective: To describe the clinical, surgical and post-surgical characteristics of univentricular patients undergoing Glenn’s surgery in a cardiovascular reference center. Method: Descriptive, retrospective study from January 2012 to December 2016, in patients under 18 who consulted a fourth level clinic with cardiopathies of univentricular physiology defined by institutional echocardiography, presented at the surgical medical board, operated or not as the first stage of palliation, followed in the single ventricle program of the institution, later performed a cardiac catheterization to be presented at the medical board that defined the performance of Glenn’s surgery. From the clinical history, data of diagnostic echocardiograms, cardiac catheterizations, surgical descriptions, and evolutions were collected. Results: A total of 88 univentricular patients were analyzed, of which 63% were men and 36% women. The anatomy of the right univentricular functional ventricle was present in 38.6% and 61.4% of left functional morphology. Among the characteristics associated with mortality, it was verified that 1.1% had moderate atrioventricular valve insufficiency and 3.4% had severe atrioventricular valve insufficiency in the patients who participated in the study. 38.6% had pulmonary arterial hypertension detected by cardiac catheterization and 46% had increased pulmonary vascular resistance. The use of vasopressor therapy before Glenn’s surgery was present in 9 patients and of them, the whole had milrinone. The postoperative mortality was 18%. Conclusions: This study shows that diagnosis and early intervention reduce morbidity and mortality in patients with a diagnosis of univentricular heart since without intervention of the second stage of palliation would be fatal for the vast majority of patients. It also demonstrates the importance of a comprehensive program for the care of complex cardiovascular pathologies.

Factores predisponentes para administrar un segundo ciclo de paracetamol o el cierre quirúrgico del ductus arterioso persistente en los recién nacidos pretérmino / Predisposing factors for administering a second paracetamol cycle or surgical closure of the persistent arterial ductus in preterm infants

Contexto: el conducto arterioso es una estructura que forma parte de la circulación fetal normal; en condiciones normales, se cierra espontáneamente en las primeras 24 a 36 horas de vida. En algunas condiciones patológicas, como la prematuridad, sigue siendo permeable. El tratamiento incluye terapia farmacológica y, en casos extremos, asistencia quirúrgica. Propósito: determinar si los factores demográficos, la edad en el momento del diagnóstico, los parámetros antropométricos, las patologías asociadas, la sobrehidratación, la fototerapia, las transfusiones sanguíneas, el uso de drogas inotrópicas y la ventilación mecánica influyen en la respuesta del tratamiento farmacológico con un ciclo de paracetamol en los pacientes con conducto arterioso persistente y en aquellos que requieren un segundo ciclo o el cierre quirúrgico. Sujetos y métodos: Este es un estudio descriptivo, analítico, epidemiológico, transversal, retrospectivo. Muestra: 205 pacientes pretérminos, nacidos en Quito entre noviembre del 2016 y noviembre del 2018 que tuvieron ductus arterioso persistente. Resultados: 103 casos de ducto arterioso persistente con respuesta al tratamiento con un solo ciclo de paracetamol y 102 que no cerraron el ductus; en el momento del diagnóstico la edad fue menor o igual a 72 horas (n = 110; 53,73 %); predominó el sexo masculino (n = 111; 54,14 %), así como la raza mestiza (200; 97.73 %); los diagnósticos al ingreso fueron: riesgo metabólico (n = 147; 71.7 %) y riesgo de sepsis (n = 108; 52.9 %); la edad gestacional promedio fue de 32-37 semanas ; la mayoría de los pacientes presentaron perímetro cefálico, talla y temperatura adecuados; y no requirieron inotrópicos (n = 132; 64,39 %); la mayoría recibió antibióticos (n = 170; 82,71 %); muchos no recibieron alimentación (n = 126; 61,76 %); algunos requirieron Ventilación Mecánica Intermitente (n = 131; 63,7 %). Las patologías asociadas más frecuentes fueron las respiratorias (n = 179; 87.31 %), las metabólicas (n = 160; 78,36 %) y las infecciosas (n = 152; 74,63 %); en cuanto a los hallazgos ecocardiográficos, se encontró un tamaño del ductus mayor a 1,4mm/kg (n = 110; 53,62 %), un patrón de flujo en cierre (n = 99; 48,55 %), sin inversión de flujo (n = 157; 76,81 %), una fracción de acortamiento mayor o igual a 35 % (n = 162; 78.99 %), sin dilatación de las cavidades izquierdas (n = 184; 89,86 %); los cofactores asociados fueron: fototerapia (n = 113; 55,07 %), transfusión sanguínea (n = 83; 40,58 %), uso de furosemida (n = 58; 28,26 %) y sobrehidratación (n = 55; 26,81 %). Conclusiones: las variables asociadas a una no respuesta a un solo ciclo de paracetamol fueron la edad en el momento del diagnóstico, mayor a 72 horas; la temperatura al nacer menor a 36,5° C; las transfusiones, el uso de furosemida y la sobrehidratación.

Context: The ductus arteriosus is part of the normal fetal circulation, that normally closes spontaneously in the first 24 to 36 hours of life. In some pathological conditions, such as prematurity, it continues to be permeable. Treatment includes pharmacological therapy and in extreme cases surgical assistance. Purpose: To determine if demographic factors, age of diagnosis, anthropometric parameters, associated pathologies, overhydration, phototherapy, blood transfusions, use of inotropic drugs, mechanical ventilation influence the response of pharmacological treatment with a paracetamol cycle in patients with persistent ductus arteriosus and those that require a second cycle or surgical closure. Subjects and methods: This is a descriptive, analytical, epidemiological, cross-sectional, retrospective study. Sample: 205 preterm patients born from November 2016 to November 2018 in Quito with persistent ductus arteriosus. Results: 103 patients responded to treatment with a single cycle of paracetamol and 102 did not, age at diagnosis less than or equal to 72 hours (n = 110, 53.73%), male sex (n = 111 54.14%), mestizo (200, 97.73%), diagnosis at admission: metabolic risk (n = 147, 71.7%), risk of sepsis (n = 108, 52.9%), gestational age 32-37 SG (n = 85, 41.67%), the majority of the patients presented adequate head circunference, height and temperature, did not require inotropics (n = 132, 64.39), used antibiotics (n = 170, 82.71%), did not receive food (n = 126, 61.76%), required Intermittent Mandatory Ventilation(n = 131, 63.7%), among the associated pathologies the most frequent were: respiratory (n = 179, 87.31%), metabolic (n = 160, 78.36%), infectious (n = 152, 74.63%), echocardiographic findings: ductus size greater than 1.4mm / kg (n = 110, 53.62%), flow pattern at closure ( n = 99; 48.55%), without flow reversal (n = 157; 76.81%), shortening fraction greater than or equal to 35% ( n = 162; 78.99%), without dilatation of left cavities (n = 184; 89.86%), associated cofactors: phototherapy (n = 113, 55.07%), blood transfusion (n = 83, 40.58%), use of furosemide (n = 58, 28.26%) and overhydration ( n = 55, 26.81%) Conclusions: The variables associated with non-response to a single cycle of paracetamol were age at diagnosis greater than 72 hours, temperature at birth less than 36.5 ° C, transfusions, use of furosemide and overhydration.

Inhaled Iloprost as a First-Line Therapy for Persistent Pulmonary Hypertension of the Newborn

PURPOSE: Persistent pulmonary hypertension of the newborn (PPHN) is a potentially fatal disease. Inhaled iloprost, a stable analogue of prostacyclin, has recently been used as a therapeutic option. However, there are no clinical guidelines on the use of iloprost, specifically for neonates. This study aimed to suggest the use of inhaled iloprost as a rescue therapy for PPHN based on our experience.METHODS: The efficacy and adverse events of inhaled iloprost were evaluated prospectively in nine full-term neonates with PPHN. We monitored the following parameters: fraction of inspired oxygen (FiO₂), respiratory severity score (RSS), heart rate, and mean blood pressure.RESULTS: The inhalation dose was 1 to 2 µg/kg initially, and 4 to 8 inhalations per day were applied over 2 to 8 days, except in the case of one neonate who died 2 days after birth. Echocardiographic findings, changes in FiO₂, and RSS improved within the next 7 days in eight of the nine patients. Severe side effects on heart rate and blood pressure were not observed.CONCLUSION: Our experience suggests that inhaled iloprost can be used as a first-line treatment in newborn infants with PPHN when inhaled nitric oxide is not available. To the best of our knowledge, this report is the first prospective case series on the use of inhaled iloprost in PPHN.

Role of calcium-sensing receptor in neonatal mice with persistent pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of calcium-sensing receptor (CaSR) agonists and antagonists on the expression of CaSR in neonatal mice with persistent pulmonary hypertension (PPHN), and to clarify the role of CaSR in neonatal mice with PPHN.</p><p><b>METHODS</b>Forty-nine neonatal mice were randomly divided into four groups: control (n=10), hypoxia (PPHN; n=11), agonist (n=13), and antagonist (n=15). The mice in the PPHN, agonist, and antagonist groups were exposed to an oxygen concentration of 12%, and those in the control group were exposed to the air. The mice in the agonist and antagonist groups were intraperitoneally injected with gadolinium chloride (16 mg/kg) and NPS2390 (1 mg/kg) respectively once daily. Those in the PPHN and the control groups were given normal saline daily. All the mice were treated for 14 consecutive days. Hematoxylin and eosin staining and immunohistochemistry were used to observe the changes in pulmonary vessels. Laser confocal microscopy was used to observe the site of CaSR expression and measure its content in lung tissues. qRT-PCR and Western blot were used to measure the mRNA and protein expression of CaSR in lung tissues.</p><p><b>RESULTS</b>Compared with the control group, the PPHN group had significant increases in the pulmonary small artery wall thickness and the ratio of right to left ventricular wall thickness (P<0.05), which suggested that the model was successfully prepared. Compared with the control group, the PPHN group had a significant increase in the mRNA and protein expression of CaSR (P<0.05), and the agonist group had a significantly greater increase (P<0.05); the antagonist group had a significant reduction in the mRNA and protein expression of CaSR (P<0.05).</p><p><b>CONCLUSIONS</b>CaSR may play an important role in the development of PPHN induced by hypoxia in neonatal mice.</p>

Lung Ultrasonography for the Diagnosis of Respiratory Distress Syndrome in Late Preterm Infants: Changing Incidence – A Single Center Experience

PURPOSE: Ultrasonography is non-ionizing, easy to operate, and performed at bedside in neonatal intensive care unit (NICU). We investigated the incidence of respiratory distress syndrome (RDS) with or without using lung ultrasound (LUS) in late preterm infants with postnatal respiratory difficulties. METHODS: We retrospectively reviewed medical records of 494 late preterm infants born at 34–36 weeks' gestation at Keimyung University Dongsan Medical Center. Fifty infants with postnatal respiratory difficulties were admitted to the NICU between May 2015 to October 2015 (period I), and forty-one were between November 2015 to February 2016 (period II). The diagnosis of RDS was based on chest radiography in period I. LUS was additionally performed at bedside in period II. All infants with RDS were received exogenous surfactant therapy. RESULTS: The overall incidence of RDS with surfactant replacement therapy was decreased in period II period II (9.4%, 20/212) compared to period I (14.5%, 41/282) (P=0.088). In terms of infants with postnatal respiratory difficulties, the incidence of RDS in period II (48.8%, 20/41) was significantly lower than that in period I (82.0%, 41/50) (P=0.001). There are no difference in the rate of reintubation, repeated doses of surfactant, oxygen demand at 48 hours after birth, air leak syndrome, pulmonary hemorrhage, persistent pulmonary hypertension of newborn, and mortality (P> 0.05). CONCLUSION: We could decrease the incidence of RDS with surfactant replacement therapy by using LUS in late preterm infants with postnatal respiratory difficulties. Further prospective studies are needed to apply LUS clinically to diagnose RDS.

Tracheal Bronchus with Persistent Pulmonary Hypertension of the Newborn: A Case Report

Tracheal bronchus is an uncommon anomaly in which an ectopic bronchus originates directly from the supracarinal trachea. It is usually an asymptomatic anatomical variant incidentally found on computed tomography or bronchoscopy. However, it can present with symptoms, such as chronic cough, wheezing, atelectasis, and recurrent pneumonia. We report a case of tracheal bronchus diagnosed in the neonatal period, in which the term baby presented with respiratory distress and persistent pulmonary hypertension of the newborn after birth, but no other congenital anomaly was found on further evaluation.

A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is an autosomal dominant, fatal developmental disorder of the lungs, with a mortality rate of about 100%. ACD/MPV is caused by mutations in FOXF1. Herein, we describe a newborn boy with ACD/MPV carrying a novel pathogenic variant of FOXF1. The patient developed respiratory distress and severe pulmonary hypertension on the first day of life. Despite aggressive cardiorespiratory management, including veno-venous extracorporeal membrane oxygenation, his condition deteriorated rapidly, and he died within the first month of his life. Lung histology showed the characteristic features of ACD/MPV at autopsy. Sequence analysis of FOXF1 from genomic DNA obtained from autopsied lung tissue revealed that the patient was heterozygous for a novel missense variant (c.305T>C; p.Leu102Pro). Further analysis of both parents confirmed the de novo occurrence of the variant. To the best of our knowledge, this is the first report of genetically confirmed ACD/MPV in Korea.

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus / Ibuprofen, indometacina e fechamento do canal arterial

The ductus arteriosus connects the pulmonary artery with the aorta and allows right ventricular blood to bypass the unexpanded lungs. In mature infants, the ductus arteriosus closes after birth. Patent ductus arteriosus occurs in 70% of preterm infants with a birth weight < 1,000 grams. Failure of the ductus arteriosus to close has been associated with intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. The drugs used to treat the patent ductus arteriosus are ibuprofen and indomethacin which are potent non-selective inhibitors of cyclo-oxygenase (COX) and therefore inhibit prostaglandin E2 synthesis. Prostaglandin E2 relaxes smooth muscle and tends to inhibit the closure of the patent ductus arteriosus. Intravenous ibuprofen and indomethacin inhibit prostaglandin E2 synthesis and thereby close the patent ductus arteriosus with similar efficacy. Indomethacin reduces the blood flow velocity in kidneys, intestine and brain. Ibuprofen has less effect on blood flow velocity in these organs. There is a significant increase in serum creatinine after indomethacin administration but not after ibuprofen and infants treated with ibuprofen have higher creatinine clearance. Oliguria (urine output < 1 ml/kg/h) occurs more frequently with indomethacin than with ibuprofen. Indomethacin requires furosemide for urine output more often than ibuprofen. Ibuprofen reduces the risk of necrotizing enterocolitis and transient renal insufficiency and it is the drug of choice for closing the patent ductus arteriosus. Ibuprofen and indomethacin may be administered orally. In conclusion, intravenous ibuprofen and indomethacin close the patent ductus arteriosus at the same rate, but indomethacin is more toxic than ibuprofen.

O canal arterial conecta a artéria pulmonar com a aorta e permite que o sangue oriundo do ventrículo direito evite passar pelos pulmões fetais não expandidos. Em recém-nascidos maduros, o canal arterial se fecha após o nascimento. A persistência do canal arterial ocorre em 70% dos recém-nascidos prematuros com peso de nascimento < 1.000 gramas. O não fechamento do canal arterial associa-se a hemorragia intraventricular, enterocolite necrosante, displasia bronco-pulmonar, leucomalacia periventricular, insuficiência renal e hipertensão pulmonar persistente. Os medicamentos utilizados para tratar a persistência do canal arterial são o ibuprofeno e a indometacina. Ambos são potentes inibidores não seletivos da ciclo-oxigenase e inibem a síntese de prostaglandina E2. Esta relaxa a musculature vascular lisa e tende a inibir o fechamento do canal arterial. O ibuprofeno e a indometacina inibem a síntese de prostaglandina E2 e favorecem o fechamento do canal arterial. A indometacina reduz a velocidade do fluxo sanguíneo renal, intestinal e cerebral. O Ibuprofeno tem efeito menor sobre a velocidade do fluxo de sangue nesses órgãos. Há um aumento significativo da creatinina sérica após a administração de indometacina, mas não após o ibuprofeno; por isso, recém-nascidos tratados com ibuprofeno têm maior depuração da creatinina. A oligúria ocorre mais frequentemente com a indometacina vs. ibuprofeno. A indometacina requer furosemida para a produção de urina mais frequentemente do que o ibuprofeno. O ibuprofeno reduz o risco de enterocolite necrotizante e de insuficiência renal transitória e é a droga de escolha para o fechamento do canal arterial patente. O ibuprofeno e a indometacina podem ser ministrados por via oral. Em conclusão, o ibuprofeno e a indometacina fecham o canal arterial patente com a mesma velocidade, mas a indometacina é mais tóxica.

Clinicopathological analysis of pulmonary vascular disease in 38 neonates died of respiratory failure / 南方医科大学学报

We reviewed the data of 38 neonates who died of respiratory failure. Paraffin sections of the autopsy lung samples were examined with HE staining or immunolabeling for CD34, CD68 and CK to observe the development of the pulmonary vessels and detect potential pulmonary vascular diseases (PVDs). Five cases were identified to have PVDs, including pulmonary hypertensive vascular remodeling in 3 cases and alveolar capillary dysplasia in 2 cases. The result indicated that PVD was one of the important reasons for respiratory failure in these neonates.

The Association between Admission Hypothermia and Neonatal Outcomes in Very Low Birth Weight Infants

PURPOSE: We aimed to evaluate the effect of admission hypothermia on neonatal outcomes in very low birth weight infants (VLBWIs). METHODS: Medical records of 153 preterm infants, with birth weights <1,500 g and gestational ages <32 weeks, were retrospectively reviewed. The clinical characteristics and neonatal outcomes in infants who experienced moderate hypothermia during the first hour of life (Group I) were compared to those in infants with mild hypothermia or normothermia (Group II). RESULTS: Fifty of 153 infants experienced moderate hypothermia after birth. Group I had lower birth weight than Group II (867.8±304.4 g vs. 1,140.3±247.5 g, P<0.001), and were younger than Group II (27.6±2.6 weeks vs. 29.1±1.9 weeks, P<0.001). Adjusted proportion of moderate to severe bronchopulmonary dysplasia (BPD) and persistent pulmonary hypertension of newborn (PPHN) were higher in Group I than in Group II (56% vs. 21.8%, P=0.005), (9.1% vs. 1.5%, P=0.019). Multiple logistic regression analysis that did not control for PPHN (model II) showed that gestational age (Odds ratio [OR] 0.93, P=0.001), moderate hypothermia (OR 4.07, P=0.013), and surgical patent ductus arteriosus (OR 4.96, P=0.023) were associated with moderate to severe BPD. Association of moderate hypothermia with moderate to severe BPD was invalid when further multiple logistic regression analysis adjusting for PPHN (model I), which had a strong association with moderate to severe BPD (OR=15.46, P=0.039), was performed. CONCLUSION: Moderate hypothermia after birth in VLBWIs was associated with PPHN and moderate to severe BPD. The association between moderate hypothermia and moderate to severe BPD might be mediated by PPHN.

Ruptured Tricuspid Valve Papillary Muscle in a Neonate with Intractable Persistent Fetal Circulation

Unguarded tricuspid regurgitation (TR) due to a flail tricuspid leaflet is a rare condition of newborn cyanosis. A high perinatal mortality has been associated with this fatal condition. But, there are feasible surgical repairs to improve survival. We report the case of a male full-term neonate with intractable hypoxia. He had profound tricuspid insufficiency and leaflet prolapse caused by a ruptured papillary muscle supporting the anterior leaflet of the tricuspid valve. He presented with severe cyanosis and respiratory distress immediately after birth. Despite medical management, the pulmonary vascular resistance was not decreased and a low cardiac output persisted. Initial stabilization was accomplished with nitric oxide and extracorporeal membrane oxygenation. The tricuspid valve repair surgery was successfully performed subsequently. TR resulting from papillary muscle rupture is a potentially lethal condition. Timely diagnosis and proper surgical treatment can be lifesaving.

Research advances in persistent pulmonary hypertension of the newborn secondary to congenital diaphragmatic hernia / 中国当代儿科杂志

Persistent pulmonary hypertension of the newborn (PPHN) secondary to congenital diaphragmatic hernia (CDH) is one of the main reasons for high mortality of the newborn and a factor that leads to respiratory and circulatory failure in newborns with CDH. PPHN secondary to CDH is severe and difficult to treat, with poor prognosis. Therefore, prenatal intervention aims for preventing the pathological process of CDH, especially the etiological treatment for impeding the development of PPHN, has become a research focus. Given unknown causes and poor outcomes of PPHN, this article summarizes the research advances in pathogenesis and treatment of PPHN secondary to CDH based on related studies so as to provide a reference for relevant studies and clinical treatment.

Clinical Indications for Inhaled Nitric Oxide Therapy in Neonates

Nitric oxide (NO) is a colorless, odorless gas that acts as a potent pulmonary vasodilator. When administered via inhalation, NO rapidly diffuses across the alveolarcapillary membrane and binds to hemoglobin, and thus has little effect on the systemic circulation. NO was approved by the United States Food and Drug Administration (US FDA) for the treatment of hypoxic respiratory failure associated with pulmonary hypertension in 1999. Neonatal hypoxic respiratory failure may be caused by persistent pulmonary hypertension of the newborn and other diseases such as meconium aspiration syndrome, sepsis, birth asphyxia, and respiratory distress syndrome that contribute to pulmonary arterial hypertension. Inhaled NO is the only approved treatment in term and late preterm (>34 weeks) neonates with hypoxic respiratory failure associated with pulmonary hypertension, and it reduces the need for extracorporeal membrane oxygenation. The present article will review the clinical indications for US FDA-approved inhaled NO therapy according to evidence-based clinical studies.

Clinical Application of Inhaled Nitric Oxide Therapy in Persistent Pulmonary Hypertension of the Newborn

Inhaled nitric oxide (iNO) is recognized as a potent and selective pulmonary vasodilator that does not decrease systemic vascular tone. The therapeutic application of iNO in human was first described in 1991. Subsequent reports showed that iNO therapy was effective to improve oxygenation in infants with persistent pulmonary hypertension of the newborn (PPHN). Owing to its selective pulmonary vasodilator effects, iNO therapy is an important treatment for term newborns with hypoxemic respiratory failure due to PPHN. The Food and Drug Administration of the United States of America first approved iNO in 1999 for use as a medical gas to treat hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in term and late preterm neonates. Thereafter, iNO therapy is clinically applied to treat PPHN in term and late preterm neonates without consensus. In this review, we focused on the clinical practice of iNO therapy in PPHN. Based on published studies, we discuss iNO initiation and withdrawal methods, respiratory support devices that complement iNO therapy, and the patient and gas monitoring during iNO therapy.

Prognosis and Side Effects of Inhaled Nitric Oxide Treatment in Persistent Pulmonary Hypertension of the Newborn

Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator agent that improves arterial oxygenation and subsequent clinical outcomes for newborn infants with persistent pulmonary hypertension of the newborn (PPHN). Along with beneficial pharmacological properties, iNO also shows toxicological effects. Although the side effects of iNO have not been fully understood, these need to be thoroughly considered and monitored for the safe and effective clinical use of iNO. This article presents a review of the side effects of iNO and short-term and long-term clinical prognosis in newborn infants > or =34 weeks' gestation with PPHN.

Foramen oval permeable / Patent foramen ovale

La frecuencia del foramen oval permeable es del 25% en la población general. En 40% de los eventos cerebrales isquémicos no hay una causa demostrable, pero en este grupo de pacientes el 46% tienen foramen oval permeable demostrable; una vez que este es capaz de permitir un cortocircuito de derecha a izquierda, existe la posibilidad del paso de un trombo que cause un evento isquémico vascular cerebral. Caso clínico: Paciente de 24 años que sufrió dos episodios de ataque isquémico transitorio sin causa determinada, dentro de los estudios de imágenes se le realizó eco-cardiograma y se encontró presencia de foramen oval permeable. Una vez que se diagnosticó la presencia del foramen oval sin otra causa que explicara el evento isquémico transitorio y además por tener cortocircuito espontáneo, se decidió el cierre percutáneo. Conclusión: en este caso se decidió por el procedimiento quirúrgico y se tomó el tamaño del foramen, los ataques isquémicos reincidentes y la edad de la paciente. Los resultados en un periodo de 2 años han sido totalmente satisfactorios...(AU)

Changes in plasma levels of atrial natriuretic peptide, endothelin-1 and von Willebrand factor among newborns with persistent pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the changes in plasma levels of atrial natriuretic peptide (ANP), endothelin-1 (ET-1) and von Willebrand factor (vWF), and their significance among newborns with persistent pulmonary hypertension (PPH).</p><p><b>METHODS</b>Sixty-six newborns with PPH (case group) (mild: 26 cases; moderate: 21 cases; severe: 19 cases), as well as 40 newborns without PPH (control group) who were hospitalized in the same period, were enrolled. The control group underwent echocardiography on admission. The case group underwent echocardiography before treatment (with refractory hypoxemia) and after 7 days of treatment for measurement of pulmonary artery systolic pressure (PASP). Meanwhile, plasma levels of ANP, ET-1 and vWF were measured using ELISA.</p><p><b>RESULTS</b>Before treatment, the case group had significantly higher plasma levels of ANP, ET-1 and vWF than the control group (P<0.05), and these indices increased as PASP rose. After 7 days of treatment, the children with mild or moderate PPH showed normal PASP, and their plasma levels of ANP, ET-1 and vWF were not significantly different from those of control group. The children with severe PPH had significant decreases in all indices, but they were significantly higher than those of the control group. Plasma levels of ANP, ET-1 and vWF were significantly positively correlated with PASP before and after treatment (P<0.01).</p><p><b>CONCLUSIONS</b>Changes in plasma levels of ANP, ET-1 and vWF can reflect PASP in newborns with PPH during treatment. Dynamic monitoring of these indices can help to judge the severity of PPH and guide treatment.</p>

Óxido nítrico inalatório no tratamento da hipertensão pulmonar persistente do recém-nascido / Inhaled nitric oxide to treat persistent pulmonary hypertension of the newborn

Objetivos: conhecer as indicações do uso de NOi, dose média utilizada e resposta ao tratamento em recém-nascidos internados em Unidade de Terapia Intensiva Neonatal. Métodos: foram analisados 62 prontuários e considerados dois grupos de recém-nascidos (RN) de acordo com o desfecho para sobrevida (n=39) ou óbito (n=23). Testes t-Student e binomial, p<0,05. Resultados: do total, 47 eram masculinos, 18 nasceram de parto normal e 44 de cesariana. Os RNs que sobreviveram tinham maior idade gestacional clínica e mais peso ao nascimento (p<0,05). Cardiopatia congênita, hipoplasia pulmonar, sepse e síndrome da membrana hialina (SMH) foram mais frequentes nos RNs que evoluíram para óbito, enquanto que a síndrome de aspiração de mecônio (SAM)estava mais presente nos RNs que sobreviveram (p<0,05). Não houve diferença significativa quanto a: asfixia perinatal, hérnia diafragmática, hipertensão pulmonar persistente neonatal (HPPN) e taquipneia transitória do recém-nascido (p>0,05). A dose inicial de NOi e a duração do tratamento foram maiores nos RNs que sobreviveram (p<0,05). A idade de início do tratamento, a dose máxima de NOi e o tempo de ventilação mecânica não apresentaram diferenças entre os grupos (p>0,05). O índice de oxigenação foi significativamente mais alto nos óbitos (p<0,05). Não foram observados efeitos colaterais. Conclusões: a terapia com NOi foi indicada principalmente na asfixia perinatal, SAM, SMH e sepse. As doses de NOi entre 15 e 30 ppm mostraram-se seguras e a diminuiçãodo índice de oxigenação sugere resposta positiva ao tratamento.

Objectives: To know the inhaled nitric oxide (iNO) use indications, the average used dose, and the reaction to treatment in newborns hospitalized at the Neonatal Intensive Care Unit. Methods: 62 medical records were analyzed and two newborn groups were considered according to the survival (n=39) or death (n=23) outcome. t-Student and binomial tests, p<0.05. Results: From the total, 47 subjects were male, 18 were born from natural childbirth, and 44 from cesarean section. The newborns that survived had a higher clinical gestational age and more weight at birth (p>0.05). Congenital heart defect, pulmonary hipoplasia, sepsis, and hyaline membrane syndrome (HMS) were more frequent in newborns that evolved to death, while the meconium aspiration syndrome (MAS) was more present in the ones that survived (p<0.05). There was no significant difference concerning: perinatal asphyxia, diaphragmatichernia, neonatal persistent pulmonary hypertension (NPPH), and newborn transient taquipneia (p>0.05). The iNO initial dose and treatment time were superior in newborns that survived (p<0.05). Age in the beginning of the treatment, maximum doses of iNO, and time of mechanical ventilation did not present significant differences between the groups (p>0.05).The oxygenation index was significantly higher in the deceased ones (p<0.05). No adverse effects were seen. Conclusions: Therapy with iNO was mainly indicated for perinatal asphyxia, MAS, HMS, and sepsis. iNO doses between 15 and 30 ppm proved to be safe, and the decrease of the oxygenation index suggests a positive reaction to the treatment.