Progress of genes related to persistent pulmonary hypertension of the newborn / 国际儿科学杂志

Persistent pulmonary hypertension of the newborn(PPHN)is a disease that seriously endangers the life of the newborn caused by one or more factors.The causes mainly include respiratory distress syndrome, meconium aspiration syndrome, infection, congenital diaphragmatic hernia, etc.The pathogenesis of PPHN is still not completely clear, and neurobiochemical, internal environment, genetics and other factors are currently recognized as influencing factors.In recent years, with the rapid development and wide application of genetic testing technology, more and more studies have shown that the occurrence of PPHN may be related to the polymorphism and/or mutation of some genes.This article reviews the research progress of six gene loci that may be related to PPHN in order to provide reference for clinical research.

Role of oral sildenafil in neonates with persistent pulmonary hypertension of newborn

Persistent pulmonary hypertension of newborn is a devastating condition and leads to morbidity and mortality. Even after the increasing use of' NO, ECMO and HFO many patients succumb to death. About 50% of the patients either have rebound hypertension or do not respond to the treatment. Hence the role of phosphodiesterase inhibitors (sildenafil) need to be evaluated. Methods is authors report a retrospective case series of 24 patients with PPHN admitted in NICU and treated with oral sildenafil. Results sildenafil was started on all patients on a mean of 1.46 days and stopped on mean of 3.8 days. Initial fio2 was 100%, which after starting sildenafil decreased gradually to 50% on mean of 10 days. Average length of stay in NICU was 20 days. 17(70.8%) patients survived whereas 7 (29%) expired No improvement in oxygen Index after 48 hours (p<0.05) was the independent predicting risk factor for PPHN related mortality in the expired patients.Conclusion are oral sildenafil can be a used in conjunction with other treatment modalities for PPHN especially in resource limited settings.

Progress of extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn / 中华实用儿科临床杂志

Persistent pulmonary hypertension of the newborn (PPHN) is a serious disease that endangers the life of a newborn.Currently,extracorporeal membrane oxygenation is an important component of life support for PPHN patients who is ineffective of the conventional treatment.In recent years,the domestic related reports have gradually increased.This paper summarizes the related research results at home and abroad in recent years,and expounds its application progress.

Secuestro pulmonar una infrecuente causa de hipertensión pulmonar persistente en el recién nacido reporte de un caso / Pulmonary sequestration an uncommon cause of persistent pulmonary hypertension in the newborn case report

Resumen La hipertensión pulmonar persistente del recién nacido (HPPRN) es una entidad frecuente en las unidades de cuidados intensivos neonatales (UCIN), sin embargo, algunas de sus causas pasan desapercibidas, debido a su baja frecuencia y poca asociación con esta patología. A propósito de un caso en nuestra UCIN, en un neonato a término que presentó HPPRN secundario a una malformación pulmonar, raramente asociada con esta patología en este grupo etareo, ya que se encontró mayor disposición a factores propios del nacimiento, y noxas maternas. El paciente presentó dificultad respiratoria horas después de su nacimiento, con evolución y persistencia de su sintomatología, por lo que se necesitó de diversos medios diagnósticos para establecer su etiología. Es importante destacar que el primer ecocardiograma doppler no mostró ninguna alteración anatómica o funcional, reportado normal; con posterior empeoramiento clínico del neonato, por lo que se ordenó un control ecocardiografico, y se evidenció una presión pulmonar estimada de 71 mmHg; se continuó el estudio etiológico con imágenes complementarias, en esta caso una tomografia de tórax contrastada, y finalmente fue corroborado con un cateterismo cardiaco, lo cual permitió a su vez, manejo terapéutico y corrección de anomalía estructural de vasos pulmonares.

Abstract Persistent pulmonary hypertension of the newborn (PPHN) is a common feature in neonatal intensive care units (NICUs), but some of its causes go unnoticed due to their low frequency and low association with this pathology. A case in our NICU, in a term neonate who presented PPHN secondary to a pulmonary malformation, rarely associated with this pathology in this age group, since it was found more disposition to factors of the birth, and maternal noxas. The patient presented respiratory difficulty hours after birth, with evolution and persistence of their symptoms, which required different diagnostic methods to establish their etiology. It is important to note that the first Doppler echocardiogram did not show any anatomical or functional alterations, which were normal; With subsequent clinical worsening of the neonate, so that an echocardiographic control is ordered, evidencing an estimated pulmonary pressure of 71 mmHg; The etiological study was followed with complementary images, in this case, a contrast-enhanced chest tomography, and finally it was corroborated with cardiac catheterization, allowing, in turn, therapeutic management and correction of structural abnormality of pulmonary vessels.

Application of noninvasive high frequency oscillatory ventilation in neonates with meconium aspiration syn-drome with pulmonary hypertension after extubation / 实用医学杂志

Objective To investigate the clinical value of nasal noninvasive high frequency oscillatory ven-tilation(NHFOV)as a respiratory support after exbutation by comparing it with nasal continuous positive airway pressure(NCPAP)in neonates with meconium aspiration syndrome(MAS)and persistent pulmonary hypertension (PPHN).Methods Infants of MAS with PPHN after exbutation from intensive care unit were randomly divided in-to NHFOV and NCPAP groups. The value of blood oxygen Pressure(PaO2),carbon dioxide partial pressure(Pa-CO2)and PaO2/FiO2at 1 h,12 h,24 h after exbutation were monitored.Results The NHFOV group showed low-er PaCO2than the NCPAP group at 1 h,12 h and 24 h after noninvasive respiratory support[1 h:(41.1 ± 7.2)vs. (45.4 ± 6.7),P=0.000;12 h:(38.9 ± 3.1)vs.(44.6 ± 5.2),P=0.000;24 h:(35.1 ± 8.2)vs.(43.2 ± 7.1),P=0.000].There were no statistically significant difference of both PaO2and PaO2/FiO2at 1 h,12 h,24 h between the two groups(P>0.05).11.43% infants were failed to be extubated in NHFOV group,but 35.29% in NCPAP group, and there was significant difference between the two groups(P=0.021). Conclusion Compared with NCPAP, NHFOV can better reduce carbon dioxide retention in the sequential therapy for neonates after extubation,and it can also decrease the rate of extubation failure.

Comparison between Patients with Persistent Pulmonary Hypertension of Neonates Concomitant with Parenchymal Lung Disease and Idiopathic Persistent Pulmonary Hypertension of Neonates

PURPOSE: We aimed to compare the clinical characteristics between neonates with persistent pulmonary hypertension of neonates (PPHN) with parenchymal lung disease (PLD) and those with idiopathic PPHN. METHODS: We reviewed the medical records of 67 neonates with gestational ages not lesser than 34⁺⁰ weeks who were born at Inje University Sanggye Paik Hospital between June 1, 2005 and December 31, 2016. We excluded 10 neonates who presented with congenital anomalies (n=3), dextrocardia (n=1), triple X syndrome (n=1), death before treatment (n=1), neonatal asphyxia (n=2), and congenital diaphragmatic hernia (n=2). Neonates were categorized into 2 groups—PPHN with PLD (PLD group, those diagnosed with PLD such as respiratory distress syndrome or meconium aspiration syndrome, n=36) and idiopathic PPHN (idiopathic group, n=21). We compared the clinical characteristics, treatment, and laboratory findings between the groups. RESULTS: The PLD group neonates showed a greater requirement for positive pressure ventilation in the delivery room, higher frequency of meconium staining of amniotic fluid, and greater need for surfactant application than those belonging to the idiopathic group. In contrast, epinephrine use was more common in the idiopathic PPHN group than in the PLD group. The 1-minute Apgar score and pH observed on initial capillary blood gas analysis were lower in the PLD than in the idiopathic group. Severity scores were higher in the idiopathic than in the PLD group 4–7 days after birth. CONCLUSION: In our study, an overall simplified severity score in the first week after birth was higher in the idiopathic than in the PLD group. These results were particularly statistically significant over postnatal days 4–7.

Serum Enzymes in Predicting the Severity of Meconium Aspiration Syndrome in Newborn / 대한주산의학회잡지

PURPOSE: Meconium aspiration syndrome (MAS), often progresses to respiratory failure and its' serious complication, persistent pulmonary hypertension of the newborn (PPHN) is a major cause of neonatal mortality. Early recognition of infants at the risk for respiratory failure in MAS patients is necessary for treatment. So we aimed to identify serum enzymes such as lactate dehydrogenase (LDH), aspartate transaminase (AST), and alanine transaminase (ALT) as serum biologic marker for early detection of respiratory failure in MAS patients. METHODS: Infants admitted within 24 hours after birth to Neonatal Intensive Care Unit of Dongguk University Ilsan Hospital and diagnosed with MAS from August 2005 to March 2014 were analyzed retrospectively. Serum enzymes were measured on admission. RESULTS: Of the total 60 patients diagnosed with MAS, 28 were in the positive pressure ventilation (PPV) group and 32 were in the non-PPV group. Six patients progressed to PPHN. Only serum LDH was significantly higher in the PPV group than the non-PPV group (median 1,123 vs. 831, P =0.01). Using the ROC curves, the cut-off value of 964 U/L for LDH offered the best predictive value for PPV requirement (sensitivity 61% and specificity 81%). Serum LDH was significantly higher in MAS with PPHN group than MAS without PPHN group (median 1,791 vs. 904, P =0.013). But serum AST, ALT were not predicting factor for the requirement of respiratory support and development of PPHN among MAS patients. CONCLUSION: LDH might be a good predicting factor for the requirement of respiratory support and development of PPHN among MAS patients.

Risk Factors of Persistent Pulmonary Hypertension of the Newborn in Neonates with Respiratory Diseases / 대한주산의학회잡지

PURPOSE: This study aimed to identify the risk factors of persistent pulmonary hypertension of the newborn (PPHN) in neonates with respiratory diseases. METHODS: We retrospectively analyzed 58 term newborn infants with respiratory diseases who were admitted to the neonatal intensive care unit of the Seoul Eulji Hospital between January 2008 and July 2014 and required airway intubation and mechanical ventilation within 24 hours of admission. The infants were divided into a PPHN group and a non-PPHN group. Their clinical characteristics; diagnoses at admission; initial blood test results; and changes in vital signs, blood gas analysis results, and ventilator parameters that occurred within 48 hours of admission were investigated. RESULTS: There were 16 infants in the PPHN group and 42 infants in the non-PPHN group. The incidence of secondary PPHN was 27.6%. The incidence of PPHN was significantly higher in infants with respiratory distress syndrome (RDS) associated with extrapulmonary air leakage and meconium aspiration syndrome (MAS) with secondary RDS as the cause. Respiratory rate over 80 breaths/min (P=0.032, OR 11.3, 95%, CI 1.23-103.57) and FiO2 over 0.8 (P=0.013, OR 16.8, 95% CI 1.82-154.68), when measured 6 hours after admission, were found to be statistically significant risk factors. CONCLUSION: The results suggest that there is an increased risk of PPHN during treatment of respiratory diseases when aggravation of tachypnea and increase in ventilator parameters are observed after 6 hours of admission.

Comorbid Risk Factors of Persistent Pulmonary Hypertension of the Newborn in Infants with Meconium Aspiration Syndrome

PURPOSE: Persistent pulmonary hypertension (PPHN) is considered an important prognostic factor in meconium aspiration syndrome (MAS). The aim of this study was to determine the comorbid risk factors for PPHN in infants with MAS. METHODS: We retrospectively analyzed 60 infants diagnosed with MAS and admitted to the neonatal intensive care unit of the Sanggye Paik Hospital from January 2007 to April 2013. There were 28 infants (47%) with PPHN and 32 infants (53%) without PPHN. Clinical characteristics, laboratory findings within 24 hours after birth, and initial capillary blood gas analysis results were compared between infants with and without PPHN. RESULTS: Incidence of PPHN was associated with the severity of MAS (P<0.001). The PPHN group had a greater incidence of hypotension and hypoxic-ischemic encephalopathy within 24 hours of birth compared to the non-PPHN group. The PPHN group also had a lower initial pH. However, there was no significant difference for laboratory findings within 24 hours of birth and initial capillary blood gas analysis. In the multivariate analysis, hypotension within 24 hours of birth (P=0.046, odds ratio 11.494, 95% confidence interval 1.048-125.00) was found to be a significant comorbid factor for PPHN in infants with MAS. CONCLUSION: Infants with MAS who develop hypotension within 24 hours of birth should be closely monitored for development of PPHN.

Persistent Pulmonary Hypertension of the Newborn in a Preterm Infant Exposed to Methotrexate During the Early Gestational Period / 대한주산의학회잡지

Methotrexate (MTX) is used in the reproductive aged females for the management of medical conditions such as ectopic pregnancy, autoimmune diseases and malignancies. Because of its antimetabolite effect, exposure to MTX during the fetal period can cause multiple anomalies. The most common anomalies related to intrauterine MTX exposure include growth retardation, craniofacial dysmorphism, central nervous system anomalies, cardiac anomalies and skeletal defects. We report a premature baby boy born after 27(+5) weeks of gestation who presented intrauterine growth restriction, single umbilical artery, small chest and anomalies of rib and thoracic vertebra. His mother had received 50 mg of MTX for the treatment of misdiagnosed ectopic pregnancy at 5th week of gestation. During the hospitalization, he was ventilator dependent and pulmonary hypertension persisted despite medical treatment including nitric oxide and sildenafil. Open lung biopsy revealed nonspecific findings suggestive of lung hypoplasia. He died at 141 days after birth due to respiratory failure.

Oral Sildenafil in Persistent Pulmonary Hypertension of the Newborn

PURPOSE: To evaluate the effect of oral sildenafil therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN) METHODS: We conducted a retrospective review of 32 neonates > or =35 weeks' gestation and fraction of inspired oxygen (FiO2) 1.0 with PPHN. The first dose (0.5 mg/kg) of oral sildenafil was started and 1 mg/kg was given every 6 hour thereafter. Mean airway pressure (MAP), FiO2, oxygenation index (OI), mean arterial blood pressure (MBP) were documented before and 6, 12, 24, and 48 hours after sildenafil. For adverse effects, gastrointestinal symptoms, brain ultrasound, funduscopy and auditory brainstem response results were evaluated. RESULTS: The underlying diseases of PPHN (n=32) were meconium aspiration syndrome (n=9), respiratory distress syndrome (n=8), pneumonia (n=3), and idiopathic (n=12). Thirty-one neonates survived; 3 neonates were transferred for inhaled nitric oxide (iNO) and all of them survived. In 28 infants, FiO2 and OI improved significantly by 6 hours and MAP improved significantly by 48 hours after initiation of sildenafil. There were no clinically significant adverse effects of sildenafil. CONCLUSION: Sildenafil may be an effective and safe agent for near-term and term neonates with PPHN, providing significant improvement in oxygenation, and thus may be especially useful in the treatment of PPHN in hospitals without iNO.

The Therapeutic Effect of Inhaled Iloprost in Newborn Infants with Severe Persistent Pulmonary Hypertension Refractory to Inhaled Nitric Oxide / 대한주산의학회잡지

Inhaled iloprost, a stable carbacyline derivative of prostacyclin, has been used recently for the treatment of adults with pulmonary hypertension but only few reports are available about its use in neonatal critical care. We report therapeutic trial of inhaled iloprost in newborn infants with persistent pulmonary hypertension of the newborn (PPHN) who did not respond to inhaled nitric oxide (iNO). Inhaled iloprost (Ventavis(R), Bayer Shering Pharma, Germany) was effective in neonates with severe PPHN who showed inadequate response to iNO. We suggest that inhaled iloprost could be considered as an additional therapeutic option in PPHN refractory to iNO.

Effect of conventional ventilation and inhaled nitric oxide In Infants with persistent pulmonary hypertension of the newborn / 中国小儿急救医学

Objective To evaluate the effects of inhaled nitric oxide (iNO) therapy combined with conventional ventilation in the infants with persistent pulmonary hypertension of the newborn (PPHN).Methods NO inspiration was added for 22 infants with PPI-IN ventilated with FiO2≥0. 9,PIP≥30 cm H2O,PEEP≥3 cm H2O,RR≥50 bpm for 4～6 hours,with SpO2 still < 90% and PaO2 <55 mm Hg. The iNO concentration started at (10～20)×10-6 for 20 infants,and (20～40)×10-6 for 2 infants. The iNO would be stopped when the concentration reached 40×10 -6 without any sign of improvement. The SpO2 ,blood gas analyses,blood pressure, heart rate and NO: concentration were moraitored during therapy and the resulting data compared to readings before administration of int. Results Clinical situation were significantly improved in 20 (91%) of the infants with SpO2 gradually going up after 10 minutes of int. Before iNO,mean Fit2 was 0. 9±0. 1 ,SpO2 was(76. 3±13.3)% ,and Pat2 was (46. 4±10. 1 ) man Hg. From 1 to 6 hours after iNO,SpO2 increased to(95. 1±3.8)% ,Pat2 increased to(92. 8±24.7) mm Hg,FiO2 decreased to 0.6 s0. 1.The differences were significant (P < 0. 01 ). Eighteen of 22 (82%) infants surviving. Conclusion iNO is effective in alleviating PPHN in infants. There are no remarkable side effects. It is more beneficial to start the iNO concentration at (10～20)×10-6 while some infants may need NO concentration at up to (20～40)×10-6.

Neonatal respiratory distress: recent progress in understanding pathogenesis and treatment outcomes / 소아과

Transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), and persistent pulmonary hypertension (PPHN) are the three most common disorders that cause respiratory distress after birth. An understanding of the pathophysiology of these disorders and the development of effective therapeutic strategies is required to control these conditions. Here, we review recent papers on the pathogenesis and treatment of neonatal respiratory disease.

Two Cases of Neonatal Persistent Pulmonary Hypertension Treated by Veno-venous Extracorporeal Membrane Oxygenation (V-V ECMO)

Persistent pulmonary hypertension in newborns (PPHN) is a disorder of the vascular transition from fetal to neonatal circulation. It results in cyanosis due to right-to-left shunting of the blood through the ductus arteriosus and/or foramen ovale manifesting as hypoxemic respiratory failure. We managed two cases of PPHN after meconium aspiration with high frequency oscillating ventilators and inhaled nitric oxide. They did not respond to conventional management. Veno-venous extracorporeal membrane oxygenation (ECMO) was provided, and ECMO weaning was possible resulting survivals in two cases. We report two PPHN cases, which were treated successfully with veno-venous ECMO for the first time in Korea.

eNOS Gene Polymorphisms in Perinatal Hypoxic-Ischemic Encephalopathy

BACKGROUND: In perinatal hypoxic-ischemic encephalopathy (HIE), cerebral blood flow is impaired and the activity of nitric oxide systhase (NOS) is markedly increased. For the association with the development of a stroke, the endothelial NOS (eNOS) polymorphisms are well-known. METHODS: Three clinically relevant polymorphisms of the eNOS gene were determined in 37 term/near-term infants with perinatal HIE (HIE group) and 54 normal term newborn infants without any perinatal problems (control group) using a polymerase chain reaction with or without restriction fragment enzyme digestion. The differences in the genotype, allele, and haplotype frequencies were evaluated between the groups. RESULTS: The analysis of the allele frequencies showed that the G allele of Glu298Asp was more frequent in the HIE group than in the controls. The comparisons between the controls and each subgroups with complications that occurred with HIE showed that the TC genotype and C allele of T(-786)C were more common in patients with persistent pulmonary hypertension of the newborn (PPHN) than in the controls. The frequency of the A b T haplotype was lower in the HIE patients than in the controls. CONCLUSIONS: The G allele of Glu298Asp was associated with perinatal HIE, while the TC genotype and C allele of T(-786)C were associated with PPHN.

Clinical characteristics of severe meconium aspiration syndrome / 소아과

PURPOSE: This study aims to describe the clinical characteristics of severe meconium aspiration syndrome (MAS) which required mechanical ventilation over 48 h and to delineate the progress of respiratory failure and radiographic findings in severe MAS. METHODS: Twelve infants admitted to the Neonatal Intensive Care Unit (NICU) of the Seoul National University Bundang Hospital diagnosed with severe MAS from January 2004 to July 2007 were analyzed retrospectively. RESULTS: The presence of persistent pulmonary hypertension of the newborn (PPHN) is the only independently significant risk factor for a longer hospital stay and longer duration of mechanical ventilation. Surfactant replacement therapy (SRT) was not randomized but only performed in infants with radiographic findings for respiratory distress syndrome (RDS). In the presence of radiographic findings for RDS, the duration of high-frequency oscillatory ventilation was significantly longer. PPHN developed in 8 infants (75%). The PPHN group had a significantly longer duration of mechanical ventilation. All infants who received SRT showed radiographic improvement within 12 h, but there was no significant change in the severity score during the same period. Infants without the PPHN complications showed significant decrease in the severity score within 12 h after SRT, whereas infants with PPHN complications did not. CONCLUSION: The clinical course of severe MAS differed significantly depending on the development of PPHN. SRT conferred radiographic improvement in infants who showed radiographic findings for RDS, but did not influence the clinical course of MAS significantly.

Pathophysiology of Persistent Pulmonary Hypertension of the Newborn / 소아과

Persistent pulmonary hypertension of the newborn(PPHN) is a disorder characterized by persistence of the pattern of fetal circulation after birth due to a sustained elevation of pulmonary vascular resistance. The two primary events in the pathophysiology of neonatal pulmonary hypertension are hypoxic pulmonary vasoconstriction(HPV) and hypoxic pulmonary vascular remodeling(HPR). Chronic hypoxemia may cause increased muscularity of the pulmonary arteries and extension of the muscularity to more distal arteries. The mechanisms underlying neonatal hypoxic pulmonary vascular remodeling are complex and multifactorial, requiring the involvement of endothelial, vascular smooth muscle, and adventitial cells. Endothelin-1(ET-1) has strong vasoactive properties, and acts via two different receptors, ETA and ETB. In pulmonary artery, ETA receptors mediate vasoconstriction and are found on vascular smooth muscle cells, while ETB receptors that are mostly located on endothelial cells mediate vasodilation by NO and prostacyclin release. eNOS derived NO is an important mediator of pulmonary vascular response to chronic hypoxia. Atrial natriuretic peptides(ANP) plays an important role in the regulation of pulmonary arterial pressure. Vascular endothelial growth factor (VEGF) release is increased in hypoxic pulmonary arterial smooth muscle cells, and hence may be involved in hypoxic pulmonary artery remodeling and edema. Retinol is essential for fetal lung morphogenesis and subsequent normal neonatal lung growth and maturation. ATP-sensitive potassium channels may be involved in the later stage of hypoxia. Activation of these channels may counteract the vasoconstrictive effect of hypoxia.

Factors Affecting the Response to Inhaled Nitric Oxide Therapy in Persistent Pulmonary Hypertension of the Newborn Infants

Persistent pulmonary hypertension of the newborn infant (PPHN), is a clinical syndrome characterized by elevated pulmonary vascular resistance, resulting from reactive vasoconstriction or structural remodeling of the pulmonary vasculature. Although inhaled nitric oxide (iNO) has emerged as a novel selective treatment of PPHN, responses to iNO are variable according to the etiologies or the clinical situation. A retrospective chart review of 51 newborn infants with PPHN and treated with iNO, was undertaken to evaluate the factors affecting response to iNO. Response to iNO was defined as a reduction in the oxygenation index (OI) of more than 20%, or disappearance of the difference in oxygen saturation between preductal and postductal circulation after iNO therapy. The patients were divided into two groups; the responder group and the non- responder group. Respiratory distress syndrome (RDS) was more commonly associated with PPHN in the responder group than in the non-responder group (p < 0.05), while there were many more patients with congenital diaphragmatic hernia (CDH) in the non-responder group than in the responder group (p < 0.05). Infants with meconium aspiration syndrome (MAS) were similar in both of the two groups. Initial OI, initial mean airway pressure (MAP), and initial and peak NO concentration were significantly lower in the responder group compared to the non-responder group (p < 0.05). Rapid response (response to iNO within the first hour) was shown in 74% of the responder group and 33% of the nonresponder group (p < 0.05). There was no significant differences in the initial chest radiographic findings, such as normal, focal or bilateral diffuse infiltration, with the exception of CDH, between each group. Lower initial OI, lower initial MAP and significant response within the first hour were shown to be favourable factors in response to iNO therapy. Patients with RDS associated with PPHN responded much better to iNO than those with other diseases.

Comparison of Treatment Outcomes in Persistent Pulmonary Hypertension of the Newborn

PURPOSE: To compare the efficacy of conventional strategy versus high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for the treatment of full term neonates with persistent pulmonary hypertension (PPHN). METHODS: Full term infants admitted with diagnosis of PPHN to neonatal intensive care units of Asan Medical Center from a period of 1994 to 2001 were included. The major exclusion criteria included congenital anomalies and pulmonary hypoplasia caused by various etiologies. Demographic, therapeutic responses and outcomes were compared between two study phases depending upon treatment modalities used: phase 1 (January 1994-July 1997) using conventional strategy and phase II (July 1997-December 2001) using either conventional strategy or/with iNO or HFOV with iNO. RESULTS: A total of 16 patients and 32 patients were enrolled in phase I and phase II studies, respectively. The primary diagnosis for PPHN included idiopathic (n=12), hyaline membrane disease (n=16), meconium aspiration syndrome (n=11), and sepsis (n=10). Statistically significant improvements were noted in survival, oxygenation index and alveolar- arterial oxygen tension difference during phase II than phase I study period. 75% of those infants treated with iNO showed good responses. Improvements in duration of ventilator use, oxygen supplementation, hospitalization were noted during phase II study period, however, not statistically significant compared to phase I study period. The impairments in neurodevelopmental outcomes were noted in 1 and 2 patients during phase I and phase II study periods, respectively. CONCLUSION: We conclude that HFOV and iNO are more efficacious and safe rescue mode of treatment than conventional strategy for full term infants with PPHN.