Etiology, Diagnosis and Management of Persistent Pulmonary Hypertension of the Newborn in Resource-limited Settings.

Persistent Pulmonary Hypertension of the Newborn (PPHN) is more common in Low and middle income countries (LMICs) due to high incidence of sepsis, perinatal asphyxia and meconium aspiration syndrome. Presence of hypoxic respiratory faillure and greater than 5% difference in preductal and post ductal saturation increases clinical sucipision for PPHN. The availability of Inhaled nitric oxide and extracorporaeal membrane oxygenation is limited but pulmonary vasodilators such as sildenafil are readily available in most LMICs.

Meconium aspiration syndrome: a comprehensive review.

Meconium aspiration syndrome (MAS) is a complex respiratory disease that continues to be associated with significant morbidities and mortality. The pathophysiological mechanisms of MAS include airway obstruction, local and systemic inflammation, surfactant inactivation and persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen and non-invasive respiratory support are the main therapies for many patients. The management of the patients requiring invasive mechanical ventilation could be challenging because of the combination of atelectasis and air trapping. While studies have explored various ventilatory modalities, evidence to date does not clearly support any singular modality as superior. Patient's pathophysiology, symptom severity, and clinician/unit expertise should guide the respiratory management. Early identification and concomitant management of PPHN is critically important as it contributes significantly to mortality and morbidities.

Noninfectious influencers of early-onset sepsis biomarkers.

Diagnostic tests for sepsis aim to either detect the infectious agent (such as microbiological cultures) or detect host markers that commonly change in response to an infection (such as C-reactive protein). The latter category of tests has advantages compared to culture-based methods, including a quick turnaround time and in some cases lower requirements for blood samples. They also provide information on the immune response of the host, a critical determinant of clinical outcome. However, they do not always differentiate nonspecific host inflammation from true infection and can inadvertently lead to antibiotic overuse. Multiple noninfectious conditions unique to neonates in the first days after birth can lead to inflammatory marker profiles that mimic those seen among infected infants. Our goal was to review noninfectious conditions and patient characteristics that alter host inflammatory markers commonly used for the diagnosis of early-onset sepsis. Recognizing these conditions can focus the use of biomarkers on patients most likely to benefit while avoiding scenarios that promote false positives. We highlight approaches that may improve biomarker performance and emphasize the need to use patient outcomes, in addition to conventional diagnostic performance analysis, to establish clinical utility.

Morbidity of conversion from venovenous to venoarterial ECMO in neonates with meconium aspiration or persistent pulmonary hypertension.

BACKGROUND: Outcomes in neonates receiving extracorporeal membrane oxygenation (ECMO) for meconium aspiration syndrome (MAS) and/or persistent pulmonary hypertension (PPHN) are favorable. Infants with preserved perfusion are often offered venovenous (VV) support to spare morbidities of venoarterial (VA) ECMO. Worsening perfusion or circuit complications can prompt conversion from VV-to-VA support. We examined whether outcomes in infants requiring VA ECMO for MAS/PPHN differed if they underwent VA support initially versus converting to VA after a VV trial, and what factors predicted conversion. METHODS: We reviewed the Extracorporeal Life Support Organization registry from 2007 to 2017 for neonates with primary diagnoses of MAS/PPHN. Propensity score analysis matched VA single-runs (controls) 4:1 against VV-to-VA conversions based on age, pre-ECMO pH, and precannulation arrests. Primary outcomes were complications and survival. Data were analyzed using Mann-Whitney U and Fisher's exact testing. Multivariate regression identified independent predictors of conversion for VV patients. RESULTS: 3831 neonates underwent ECMO for MAS/PPHN, including 2129 (55%) initially requiring VA support. Of 1702 patients placed on VV ECMO, 98 (5.8%) required VV-to-VA conversion. Compared with 364 propensity-matched isolated VA controls, conversion runs were longer (190 vs. 127 h, P < 0.001), were associated with more complications, and decreased survival to discharge (70% vs. 83%, P = 0.01). On multivariate regression, conversion was more likely if neonates on VV ECMO did not receive surfactant (OR = 1.7;95%CI = 1.1-2.7;P = 0.03) or required high-frequency ventilation (OR = 1.9;95%CI = 1.2-3.3;P = 0.01) before ECMO. CONCLUSION: Conversion from VV-to-VA ECMO in infants with MAS/PPHN conveys increased morbidity and mortality compared to similar patients placed initially onto VA ECMO. VV patients not receiving surfactant or requiring high-frequency ventilation before cannulation may have increased risk of conversion. While conversions remain rare, decisions to offer VV ECMO for MAS/PPHN must be informed by inferior outcomes observed should conversion be required. LEVEL OF EVIDENCE: Level of evidence 3 Retrospective comparative study.

Haematoma complicating subcutaneous fat necrosis of the newborn: a rare complication following therapeutic hypothermia.

A term, large for gestational age male newborn, was admitted to the neonatal intensive care unit with meconium aspiration syndrome and severe hypoxic-ischaemic encephalopathy. The baby was treated with therapeutic hypothermia using a total body cooling blanket. After 48 hours, the baby developed tender, indurated subcutaneous nodules consistent with subcutaneous fat necrosis (SCFN). The lesions started initially over the back but gradually spread to cover both shoulders, upper arms, chest area and both thighs. On day 19 of life, multiple small nodules on the back softened and coalesced to form one sizeable fluctuant swelling over the thoracolumbar area. Over a few hours, the swelling rapidly progressed to a large, tense mass with sloughing of the gangrenous overlying skin. This unusual complication of SCFN required surgical intervention for evacuation and debridement of the haematoma followed by graft repair of the skin defect.

Methemoglobin and the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn.

BACKGROUND: We aimed to investigate whether the change in methemoglobin levels (ΔMHb) predicts oxygenation response to inhaled nitric oxide (iNO) in persistent pulmonary hypertension of the newborn (PPHN) with lung disease, with or without pulmonary hypoplasia. METHODS: In this prospective observational study, infants were categorized based on ΔMHb and oxygenation response (ΔPaO2/FiO2) following iNO: ΔMHb ≤0 or ΔMHb>0, and ΔPaO2/FiO2 < 20 mmHg (Non-responder) or≥20 mmHg (Responder). ΔMHb levels were compared among infants with or without pulmonary hypoplasia. RESULTS: Among infants with pulmonary hypoplasia (n = 28), ΔMHb was not associated with an oxygenation response to iNO or survival without ECMO. Among infants without hypoplasia (n = 29), subjects with ΔMHb>0 following iNO (n = 21) had a greater ΔPaO2/FiO2 (median, 64 mmHg; IQR, 127; p < 0.01) and 100% survival without extracorporeal membrane oxygenation (ECMO) when compared to infants with ΔMHb ≤0 (n = 8; median 10 mmHg; IQR, 33). CONCLUSIONS: PPHN secondary to lung disease without hypoplasia with increased ΔMHb following iNO was associated with better oxygenation response and survival without ECMO compared to subjects without an increase in MHb.

Hypertrophic pyloric stenosis following persistent pulmonary hypertension of the newborn: a case report and literature review.

BACKGROUND: Although persistent pulmonary hypertension of the newborn (PPHN) and infantile hypertrophic pyloric stenosis (HPS) are both well-known diseases that occur in early infancy, PPHN complicated by HPS is rare. As nitric oxide (NO) is an important mediator of biological functions, on both the vascular endothelium and smooth muscle cells, the decreased production of NO might play a role in the pathogenesis of both PPHN and HPS. We present the case of a neonate who developed HPS following PPHN, including a detailed review on research published to date, and we discuss the pathogenesis of PPHN and HPS. CASE PRESENTATION: A female neonate born at 38 weeks of gestation, weighing 3140 g, developed PPHN due to meconium aspiration syndrome. Intensive treatment with high frequency oscillations and inhaled NO were initiated, and sildenafil and bosentan were added. She gradually recovered. At 15 days of age, the patient developed recurrent vomiting after feeding and the diagnosis of HPS was made. Intravenous atropine therapy was started at 20 days of age, but the efficacy was clinically unsatisfactory. The coadministration with transdermal nitroglycerin improved the symptoms, and oral feeding was successfully re-introduced. CONCLUSIONS: Our patient recovered from both PPHN and HPS using NO-related medications. A decrease in NO synthesis is likely to be a common pathway for PPHN and HPS.

Isolated thrombocytopenia in childhood: what if it is not immune thrombocytopenia?

INTRODUCTION: Childhood immune thrombocytopenia (ITP) remains a diagnosis of exclusion when isolated thrombocytopenia is not part of another disease process. In practice, the diagnosis of ITP can only be confirmed when thrombocytopenia resolves or is excluded after the recognition of a primary cause. METHODS: The records of 87 consecutive children with isolated thrombocytopenia seen over a nine-year period in a private paediatric haematology practice were reviewed retrospectively. Children in whom a primary cause was eventually found were the subjects of a further descriptive study. RESULTS: 9 (10%) children with isolated thrombocytopenia were not diagnosed with ITP because a primary disease was found. Of these nine cases, four had thrombocytopenia recognised during the neonatal period, consisting of perinatal cytomegalovirus infection (n = 2), meconium aspiration pneumonia (n = 1) and transient abnormal myelopoiesis associated with Down syndrome (n = 1). The remaining five children were each found to have familial thrombocytopenia, portal hypertension, cutaneous mastocytosis, May-Hegglin anomaly and systemic lupus erythematosus. Two of them had a history of failure of response to corticosteroid therapy. CONCLUSION: Secondary thrombocytopenia is not uncommon in a tertiary paediatric specialty practice with adequate evaluation. Thrombocytopenia occurring during the newborn period and failure of steroid therapy are predictive of secondary cases.

To study prevalence of persistent pulmonary hypertension in newborn with meconium aspiration syndrome in western Rajasthan, India: a prospective observational study.

AIM: To study the prevalence of persistent pulmonary hypertension (PPHN) in newborn with meconium aspiration syndrome (MAS) in western Rajasthan, India. MATERIAL AND METHODS: Hundred full-term newborns who had features of MAS at birth were included in this survey and were evaluated for PPHN using laboratory investigations, including pulse oximetry, ABG, chest X-ray, ECG and 2D color echocardiography. RESULTS: Nineteen neonates showed PPHN, of them 16 had a shunt reversal at PFO level and the rest at PDA level. Most of these newborns were delivered by emergency cesarean section and were unplanned. A majority of neonates of PPHN (84.21%) were diagnosed within 48 h of life and 73.69% had Downey's score more than 6. Neonates of PPHN had mean PH 7.21 ± 0.07, mean PCO2 53.73 ± 6.8, mean PaO2 61.10 ± 10.61 and mean PaO2/FiO2 144.03 ± 46.31. CONCLUSIONS: PPHN is a genuine problem in MAS-born neonates and is commonly seen in neonates born by unplanned and unmonitored delivery, and the prevalence of PPHN can be reduced by providing good antenatal care, regular follow up of high-risk pregnancy. 2D echocardiography is an important point of care in the diagnosis of PPHN in nursery and should be promoted in nurseries of developing countries as being engaged in developed countries for more reliable treatment.

Síndrome da aspiração meconial: identificando situações de risco obstétricos e neonatais / Síndrome de aspiración de meconio: identificando situaciones de riesgo obstétrico y neonatal / Meconium aspiration syndrome: identifying obstetric and neonatal risk situations

Objective: To identify situations of obstetric and neonatal risk that favored meconium aspiration syndrome as well as complications in clinical evolution presented by these neonates. Method: It is a quantitative, retrospective study and documentary analysis, conducted from January 2009 to December2010. Data from 40 medical records were recorded in a database and analyzed using descriptive statistical analysis software. Results: 67.5 % of mothers had fewer than six prenatal consultations and 42.5% had complications during pregnancy. Cesarean section predominated with 75%, indicated by fetal distress. There were 90% of neonates had an average gestational age of 37 weeks or more, 82.5 % had an Apgar score below 7, requiring resuscitation at birth and ventilatory support. Conclusion: Proper monitoring of pregnant women through out pregnancy cycle and in labor as well as the need to care for neonates in the delivery room can reduce the incidence of the syndrome.

Objetivo: Identificar as situações de risco obstétricas e neonatais que favorecem a síndrome da aspiração meconial, bem como as complicações na evolução clínica apresentadas por esses neonatos. Método: Estudo quantitativo, retrospectivo e de análise documental, realizado entre janeiro de 2009 a dezembro de 2010. Os dados dos 40 prontuários consultados foram registrados em banco de dados e analisados por meio de software para análise estatística descritiva. Resultados: Quanto às genitoras, 67,5% tiveram menos que seis consultas de pré-natal e 42,5% intercorrências na gestação. Predominou o parto cesáreo em 75%, indicados por sofrimento fetal. Dos neonatos, 90% apresentaram idade gestacional de 37 semanas ou mais; 82,5% tiveram Apgar abaixo de 7, necessitando de reanimação ao nascer e suporte ventilatório. Conclusão: O acompanhamento adequado da gestante em todo ciclo grávido e no trabalho de parto, bem como o atendimento preciso do neonato na sala de parto podem reduzir a incidência da síndrome.

Objetivo: Identificar las situaciones de riesgo obstétrico y neonatal que favoreció el síndrome de aspiración de meconio y complicaciones en la evolución clínica que presentan estos neonatos. Método: Estudio cuantitativo, retrospectivo y de análisis documental, realizado a partir de enero 2009 a diciembre2010. Los datos de 40 historias clínicas se registraron en una base de datos y se analizaron con el software de análisis estadístico descriptivo. Resultados: En cuanto a las madres, el 67,5 % tenían menos de seis consultas prenatales y un 42,5 % de complicaciones durante el embarazo. Cesárea predominó en el 75%, indicado por sufrimiento fetal. De los recién nacidos, el 90% tenían una media de edad gestacional de 37 semanas o más, el 82,5% tenía una puntuación de Apgar por debajo de 7, necesitando reanimación al nacery el apoyo ventilatorio. Conclusión: El control adecuado de la mujer embarazada durante el ciclo de embarazo y en el parto, así como la necesidad de cuidar a los recién nacidos en la sala de parto puede reducir la incidencia del síndrome.

Tracheal suctioning improves gas exchange but not hemodynamics in asphyxiated lambs with meconium aspiration.

BACKGROUND: Current neonatal resuscitation guidelines recommend tracheal suctioning of nonvigorous neonates born through meconium-stained amniotic fluid. METHODS: We evaluated the effect of tracheal suctioning at birth in 29 lambs with asphyxia induced by cord occlusion and meconium aspiration during gasping. RESULTS: Tracheal suctioning at birth (n = 15) decreased amount of meconium in distal airways (53 ± 29 particles/mm(2) lung area) compared to no suction (499 ± 109 particles/mm(2); n = 14; P < 0.001). Three lambs in the suction group had cardiac arrest during suctioning, requiring chest compressions and epinephrine. Onset of ventilation was delayed in the suction group (146 ± 11 vs. 47 ± 3 s in no-suction group; P = 0.005). There was no difference in pulmonary blood flow, carotid blood flow, and pulmonary or systemic blood pressure between the two groups. Left atrial pressure was significantly higher in the suction group. Tracheal suctioning resulted in higher Pao2/FiO2 levels (122 ± 21 vs. 78 ± 10 mm Hg) and ventilator efficiency index (0.3 ± 0.05 vs.0.16 ± 0.03). Two lambs in the no-suction group required inhaled nitric oxide. Lung 3-nitrotyrosine levels were higher in the suction group (0.65 ± 0.03 ng/µg protein) compared with the no-suction group (0.47 ± 0.06). CONCLUSION: Tracheal suctioning improves oxygenation and ventilation. Suctioning does not improve pulmonary/systemic hemodynamics or oxidative stress in an ovine model of acute meconium aspiration with asphyxia.

Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome.

BACKGROUND: It is suggested that there may be expanded use of surfactant replacement for the neonatal diseases such as meconium aspiration syndrome (MAS), pneumonia and possibly bronchopulmonary dysplasia (BPD). OBJECTIVE: To evaluate the characteristics and short-term outcome of the neonates given exogenous surfactant because of the diseases other than respiratory disease syndrome (RDS). METHODS: This retrospective study included 35 neonates admitted to the neonatal intensive care unit from January 2012 to December 2012 for an expanded use of surfactant. Data related to gestational age, birth weight, gender and perinatal risk factors were obtained from the patients' records. The short-term prognosis was also noted. RESULTS: The diagnosis was sepsis in 16 patients, eight MAS, seven transient tachypnea of the newborns (TTN) and four BPD. Mean gestational age was 35.6 ± 4.5 weeks and mean birth weight was 2661 ± 981 g. Of overall cases, 65% were boys and 35% girls. The mortality rate was 17%. Of six fatal cases, three was with BPD, two with sepsis and one with MAS. CONCLUSION: We think that surfactant replacement may be life saver in the neonatal diseases other than RDS such as BPD, MAS and sepsis by rapidly improving oxygenation. Further investigation is necessary to validate the significance of expanded use of surfactant.

Changes in mean arterial blood pressure during sildenafil use in neonates with meconium aspiration syndrome or sepsis.

The aim of this study was to evaluate changes in mean blood pressure (MBP) in late preterm and term newborns with meconium aspiration syndrome (MAS) or sepsis who, in addition to inhaled nitric oxide (iNO), received enteral sildenafil for treatment of persistent pulmonary hypertension of the newborn. Data on sildenafil dosing, MBP, and vasopressor/inotrope use were collected for 72 hours after initiation of sildenafil. Groups were compared between "low dose" (<3 mg·kg·d) versus "high dose" (≥ 3 mg·kg·d) and "early" (<7 postnatal days) versus "late" (≥ 7 postnatal days) administration of sildenafil. Seventeen patients were identified. Ten and 7 patients received "low-dose" and "high-dose" sildenafil, respectively, and 8 and 9 patients were started on sildenafil "early" and "late," respectively. At the doses used, sildenafil treatment of infants with MAS and sepsis was not associated with changes in MBP. In addition, vasopressor/inotropic support was weaned in all groups. During the first 72 hours of enteral sildenafil administration in neonates with pulmonary hypertension of the newborn secondary to MAS or sepsis, no significant decrease in MBP or increase in vasopressor/inotrope requirement occurred.

Realidad de la circulación de membrana extracorpórea neonatal en Colombia: descripción de los primeros casos / Current state of neonatal extracorporeal membrane oxygenation in Colombia: description of the first cases

La oxigenación de membrana extracorpórea se considera una terapia de rescate y soporte vital compleja, con beneficios en enfermedades cardiorrespiratorias durante el periodo neonatal, que cumple con las características de ser reversible en recién nacidos mayores de 34 semanas. El criterio de selección de los pacientes y el momento oportuno en que se indica son críticos para el resultado final, si bien las nuevas alternativas de manejo en falla respiratoria hipoxémica en recién nacidos a término y casi a término han generado una disminución de su uso, excepto en la hernia diafragmática, que continúa siendo una enfermedad compleja donde podría tener alguna aplicabilidad. Si bien nuestra experiencia está iniciándose, el entrenamiento constante hará de la oxigenación de membrana extracorpórea una opción para pacientes complejos en quienes la terapia máxima fracasa. Se hace un informe de los primeros casos neonatales por falla respiratoria hipoxémica manejados en la Fundación Cardiovascular de Colombia.

Extracorporeal membrane oxygenation is considered a rescue therapy and complex vital support with benefits in cardiorespiratory diseases during neonatal period that fulfil the characteristics of being reversible in neonates older than 34 weeks. The criteria for patient selection and its prompt use are critical for the final result. Even though new alternatives for management of hypoxemic respiratory failure in full term and almost full term neonates have decreased its use, congenital diaphragmatic hernia continues being a complex disease where it can have some applicability. Even though our experience is beginning, constant training will make of extracorporeal membrane oxygenation an option for complex patients in whom maximum therapy fails. This is a report of the first neonatal cases of hypoxemic respiratory failure managed at Fundación Cardiovascular de Colombia.

Update on PPHN: mechanisms and treatment.

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of failed circulatory adaptation at birth, seen in about 2/1000 live born infants. While it is mostly seen in term and near-term infants, it can be recognized in some premature infants with respiratory distress or bronchopulmonary dysplasia. Most commonly, PPHN is secondary to delayed or impaired relaxation of the pulmonary vasculature associated with diverse neonatal pulmonary pathologies, such as meconium aspiration syndrome, congenital diaphragmatic hernia, and respiratory distress syndrome. Gentle ventilation strategies, lung recruitment, inhaled nitric oxide, and surfactant therapy have improved outcome and reduced the need for extracorporeal membrane oxygenation (ECMO) in PPHN. Newer modalities of treatment discussed in this article include systemic and inhaled vasodilators like sildenafil, prostaglandin E1, prostacyclin, and endothelin antagonists. With prompt recognition/treatment and early referral to ECMO centers, the mortality rate for PPHN has significantly decreased. However, the risk of potential neurodevelopmental impairment warrants close follow-up after discharge for infants with PPHN.

Survival of newborn infants with severe respiratory failure before and after establishing an extracorporeal membrane oxygenation program.

BACKGROUND: Severe hypoxic respiratory failure is a leading cause of neonatal mortality in Chile. Extracorporeal membrane oxygenation improves survival in neonates with hypoxic respiratory failure. OBJECTIVE: To determine the impact of the establishment of a Neonatal Extracorporeal Membrane Oxygenation Program on the outcome of newborns with severe hypoxic respiratory failure in a developing country. DESIGN/PATIENTS: Data of newborns (birthweight > 2,000 g and gestational age ≥ 35 wk) with hypoxic respiratory failure and oxygenation index greater than 25 were compared before and after extracorporeal membrane oxygenation was available. Extracorporeal membrane oxygenation was initiated in infants with refractory hypoxic respiratory failure who failed to respond to inhaled nitric oxide/high-frequency oscillatory ventilation. MAIN RESULTS: Data from 259 infants were analyzed; 100 born in the pre-extracorporeal membrane oxygenation period and 159 born after the extracorporeal membrane oxygenation program was established. Patients were similar in terms of risk factors for death for both periods except for a higher oxygenation index and a greater proportion of outborn infants during the extracorporeal membrane oxygenation period. Survival significantly increased from 72% before extracorporeal membrane oxygenation to 89% during the extracorporeal membrane oxygenation period (p < 0.01). During the extracorporeal membrane oxygenation period, 98 of 159 patients (62%) with hypoxic respiratory failure were rescued using inhaled nitric oxide/high-frequency oscillatory ventilation, whereas 61 (38%) did not improve; 52 of these 61 neonates were placed on extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation survival rate to discharge was 85%. After adjusting for potential confounders, the severity of the pretreatment oxygenation index, a late arrival to the referral center, the presence of a pneumothorax, and the diagnosis of a diaphragmatic hernia were significantly associated with the need for extracorporeal membrane oxygenation or death. CONCLUSIONS: The establishment of an extracorporeal membrane oxygenation program was associated with a significant increase in the survival of newborns more than or equal to 35 weeks old with severe hypoxic respiratory failure.

Septic neonate rescued by polymyxin B hemoperfusion.

Sepsis caused by group B streptococcus has been well controlled with aminobenzylpenicillin, but the incidence of Escherichia coli sepsis has increased in proportion. E. coli is a Gram-negative bacillus associated with poor prognosis due to the release of endotoxins. Conventional treatment with antibiotics alone may not be sufficient because the inflammatory response exacerbates the unstable hemodynamic status. Polymyxin B hemoperfusion has been established as a treatment option for septic shock in adults. Polymyxin B hemoperfusion adsorbs endotoxins and cannabinoids such as anandamide and 2-arachidonoylglycerol. Reported herein is a case of severe septic shock induced by E. coli. The concomitant use of polymyxin B hemoperfusion rapidly reduced the requirement for catecholamines and the patient was discharged without short-term neurological or respiratory sequelae. It is suggested that polymyxin B hemoperfusion might be an innovative therapy for severe sepsis, and could improve outcome.

Meconium aspiration delays normal decline of pulmonary vascular resistance shortly after birth through lung parenchymal injury.

BACKGROUND: Persistent pulmonary hypertension of the newborn is often associated with meconium aspiration syndrome (MAS) or perinatal asphyxia. OBJECTIVE: To determine the effect of meconium or asphyxia on pulmonary arterial pressure and circulating levels of vasoactive substances, we conducted a prospective study of 54 term infants, including infants with meconium-stained amniotic fluid with normal (MSAF) or abnormal (MAS) chest X-ray findings, infants with perinatal asphyxia, and controls. The purpose of this study was to determine the group most likely to have elevated pulmonary arterial pressure and a disturbed balance between vasoactive substances. METHODS: To estimate the pulmonary arterial pressure by echocardiography, we used the ratio of the right to left systolic ventricular pressure (RVP/LVP ratio). We measured the plasma concentrations of endothelin-1 (ET-1), cyclic guanosine monophosphate (cGMP) as an indicator of nitric oxide (NO) production, and 6-keto-prostaglandin F(1)α (6-keto-PGF(1)α) for the estimation of prostacyclin concentration. We also measured KL-6 as a marker of lung injury. RESULTS: The RVP/LVP ratio was significantly higher in the MAS group than the other groups on day 0. Although ET-1 and 6-keto-PGF(1)α levels were comparable among all groups, the cGMP level on days 3-5 and the KL-6 level throughout the first postnatal week were significantly higher in the MAS group. CONCLUSIONS: It is possible that meconium aspiration delays normal decline of pulmonary vascular resistance shortly after birth through lung parenchymal injury. The subsequent increase of cGMP in MAS may be an adaptive response to prevent further elevation of pulmonary arterial pressure by inducing NO.