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.

[Clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for severe MAS in neonates with meconium-stained amniotic fluid]. / èƒŽç²ªæ±¡æŸ“ç¾Šæ°´æ–°ç”Ÿå„¿å‘ç”Ÿé‡åº¦èƒŽç²ªå¸å ¥ç»¼åˆå¾çš„ä¸´åºŠç‰¹å¾åŠé¢„è­¦å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for the development of severe MAS in neonates with meconium-stained amniotic fluid (MSAF). METHODS: A total of 295 neonates who were hospitalized due to Ⅲ° MSAF from January 2018 to December 2019 were enrolled as subjects. The neonates were classified to a non-MAS group (n=199), a mild/moderate MAS group (n=77), and a severe MAS group (n=19). A retrospective analysis was performed for general clinical data, blood gas parameters, infection indicators, and perinatal clinical data of the mother. The respiratory support regimens after birth were compared among the three groups. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were used to investigate predicting factors for the development of severe MAS in neonates with MSAF. RESULTS: Among the 295 neonates with MSAF, 32.5% (96/295) experienced MAS, among whom 20% (19/96) had severe MAS. Compared with the mild/moderate MAS group and the non-MAS group, the severe MAS group had a significantly lower 5-minute Apgar score (P<0.05) and a significantly higher blood lactate level in the umbilical artery (P<0.05). Compared with the non-MAS group, the severe MAS group had a significantly higher level of interleukin-6 (IL-6) in peripheral blood at 1 hour after birth (P<0.017). In the severe MAS group, 79% (15/19) of the neonates were born inactive, among whom 13 underwent meconium suctioning, and 100% of the neonates started to receive mechanical ventilation within 24 hours. Peripheral blood IL-6 >39.02 pg/mL and white blood cell count (WBC) >30.345×109/L at 1 hour after birth were early predicting indicators for severe MAS in neonates with MSAF (P<0.05). CONCLUSIONS: Meconium suctioning cannot completely prevent the onset of severe MAS in neonates with MSAF. The neonates with severe MAS may develop severe respiratory distress and require mechanical ventilation early after birth. Close monitoring of blood lactate in the umbilical artery and peripheral blood IL-6 and WBC at 1 hour after birth may help with early prediction of the development and severity of MAS.

Surfactant dysfunction disorder masquerading as meconium aspiration syndrome and persistent pulmonary hypertension of the newborn.

About 10% of term neonates present with respiratory distress at birth. The most common aetiologies include transient tachypnoea of the newborn, pneumonia and meconium aspiration syndrome (MAS). Hyaline membrane disease (HMD) in a term infant occurs either as primary HMD, secondary surfactant deficiency or congenital surfactant dysfunction. A detailed history supported with appropriate radiological and laboratory investigations can help a clinician reach a diagnosis. We report a case of surfactant dysfunction disorder which presented as severe MAS and persistent pulmonary hypertension of the newborn. In the infant described, the significant history of a sibling death with severe neonatal respiratory disease led us to think of diffuse developmental lung diseases especially surfactant dysfunction syndromes. Exome sequencing detected a heterozygous missense variation in exon 21 of the ATP binding cassette protein member 3 (ABCA3) gene. Based on the clinical picture supported with the exome sequencing, a diagnosis of surfactant dysfunction disorder (ABCA3 deficiency) was confirmed.

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.

Extra-Corporeal Membrane Oxygenation for Neonatal Respiratory Support.

To review our experience with Extra-Corporeal Membrane Oxygenation (ECMO) for respiratory support in neonates. From 1989 to 2018 2114 patients underwent respiratory ECMO support, with 764 (36%) neonates. Veno-Venous (V-V) cannulation was used in 428 (56%) neonates and Veno-Arterial (V-A) in 336 (44%). Historically V-V ECMO was our preferred modality, but due to lack of suitable cannula in the last 7 years V-A was used in 209/228 (92%) neonates. Mean and inter-quartile range of ECMO duration was 117 hours (inter-quartile range 90 to 164 hours). Overall 724 (95%) neonates survived to ECMO decannulation, with 640 (84%) hospital discharge. Survival varied with underlying diagnosis: meconium aspiration 98% (354/362), persistent pulmonary hypertension 80% (120/151), congenital diaphragmatic hernia 66% (82/124), sepsis 59% (35/59), pneumonia 86% (6/7), other 71% (43/61). Survival was 86% with V-V and 80% with V-A cannulation, better than ELSO Registry with 77% V-V and 63% V-A. Major complications: cerebral infarction/hemorrhage in 4.7% (31.1% survival to discharge), renal replacement therapy in 17.6% (58.1% survival to discharge), new infection in 2.9%, with negative impact on survival (30%). Following a circuit design modification and subsequent reduction in heparin requirement, intracerebral hemorrhage decreased to 9/299 (3.0%) radiologically proven cerebral infarction/hemorrhage. We concluded (1) outcomes from neonatal ECMO in our large case series were excellent, with better survival and lower complication rate than reported in ELSO registry. (2) These results highlight the benefits of ECMO service in high volume units. (3) The similar survival rate seen in neonates with V-A and V-V cannulation differs from the ELSO register; this may reflect the change in cannulation enforced by lack of suitable V-V cannula and all neonates undergoing V-A cannulation.

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.

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.

Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord.

OBJECTIVE: To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. STUDY DESIGN: We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. RESULTS: Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. CONCLUSIONS: Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.

[Respiratory disorders in preterm and term neonates: an update on diagnostics and therapy]. / Respiratorische Erkrankungen bei Früh- und Neugeborenen - Aktuelle Diagnostik und Therapie.

Respiratory disorders remain a major problem in postnatal adaptation. In term neonates, an increased incidence of the risk for transient tachypnoea of the neonate has been observed during the past decade, most likely secondary to an increased usage of primary Caesarean section. The disorder is mainly caused by a delayed resorption of foetal lung fluid. Further disorders in term neonates include meconium aspiration syndrome and congenital diaphragmatic hernia leading to impaired gas exchange and pulmonary hypertension. In preterm neonates, respiratory distress syndrome is the main disorder leading to severe acute and long-term impaired gas exchange. Prenatal administration of glucocorticoids and postnatal surfactant therapy remains an established principle in perinatal care for very preterm neonates. The most relevant long-term sequelae, bronchopulmonary dysplasia, is currently being observed in about 15% of preterms with less than 32 weeks of gestation and is associated with severe pulmonary and extrapulmonary consequences. Due to the overall improvement in perinatal care, respiratory disorders still remain a major problem in pulmonary adaptation. However, mortality secondary to neonatal lung failure has been decreased substantially by the improvements in the whole field of perinatal medicine.

Congenital lobar emphysema: is surgery routinely necessary?

Congenital lobar emphysema (CLE) is a rare congenital abnormality characterised by overinflation of a pulmonary lobe. Its aetiology is unknown. The management of CLE has traditionally been surgical. A newborn boy with a birthweight of 2.5 kg was delivered at full-term by caesarian section due to food delivery. There was no marked respiratory distress at birth, and little meconium stained liquor was seen on the skin. The initial diagnosis was meconium aspiration syndrome. After computed tomography of the thorax, CLE was diagnosed. The patient was observed throughout for a week and the CT of the thorax was repeated, which revealed that the emphysema had resolved. The nonoperative approach should be considered in asymptomatic patients with CLE.

[Congenital bronchobiliary fistula: a case report]. / Fistule bronchobiliaire congénitale : à propos d'une observation.

Congenital bronchobiliary fistulas (CBBF) are rare developmental anomalies. We report a case of a 6-day-old newborn who presented with respiratory distress and bilioptysis, originally involving a meconium aspiration syndrome. The diagnosis was confirmed by bronchoscopy. Surgery was performed at the age of 26 days and the newborn died the following day. Operative opacification showed communication between the carina and the biliary system. We review the clinical characteristics of CBBF and the value of early diagnosis and surgical treatment to prevent pulmonary complications due to bile salts.

Albumin lavage does not improve the outcome of meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome is still a serious condition with high mortality and morbidity. No specific treatment is yet available, although surfactant is known to reduce the need for extracorporeal membrane oxygenation and surfactant lavage has shown promising results in animal studies. Our group has previously shown reduced oxygenation index in an experimental model of meconium aspiration syndrome in newborn pigs when mixing albumin with meconium before endotracheal instillation. Lung compliance increased when albumin was instilled after meconium as a rescue. The aim of this study was to combine the effect of albumin and lavage. METHODS: Sixteen newborn pigs (six in the meconium-albumin group, six in the meconium group, and four control animals) were anesthetized and tracheotomized. Meconium 4 mL/kg was instilled endotracheally. After five minutes, albumin 15 mL/kg was instilled in the meconium-albumin group followed by endotracheal suctioning. The observation time was six hours. Respiratory and hemodynamic parameters were measured. The terminal complement complex and proinflammatory cytokines were analyzed in plasma. RESULTS: Oxygenation index, ventilatory index, and the terminal complement complex (sC5b-9) increased significantly in both groups, but significantly more in the meconium-albumin group. Compliance decreased, but significantly more in the meconium-albumin group. The terminal sC5b-9 complex increased in both groups, but significantly more in the meconium-albumin group. Tumor necrosis factor-alpha, interleukin (IL)- 1beta, and IL-6 increased significantly in both groups. CONCLUSION: Albumin-lavage did not improve the outcome of experimental meconium aspiration syndrome.

Serum cytokine and chemokine profiles in neonates with meconium aspiration syndrome.

OBJECTIVES: Various inflammatory cytokines and chemokines are thought to be associated with the pathophysiology of meconium aspiration syndrome. To clarify any such association, we compared various serum cytokine and chemokine profiles in patients with and without meconium aspiration syndrome. PATIENTS AND METHODS: Using a highly sensitive fluorescence microsphere method, 17 types of cytokines and chemokines in sera were measured in 11 neonatal patients with meconium aspiration syndrome, 16 neonatal patients without meconium aspiration syndrome, and 9 healthy children. RESULTS: The concentrations of 8 types of proinflammatory cytokines and chemokines were significantly higher in the meconium aspiration syndrome group than in healthy controls: interleukin-1beta, interleukin-6, interleukin-8, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-gamma, macrophage inflammatory protein-1beta, and tumor necrosis factor-alpha. Six types of proinflammatory cytokines and chemokines were significantly higher in the meconium aspiration syndrome group than in the nonmeconium aspiration syndrome group: interleukin-6, interleukin-8, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha. Serum concentrations of interleukin-10 (anti-inflammatory cytokine) in the meconium aspiration syndrome group were higher than those in both the nonmeconium aspiration syndrome group and healthy children group (P = .007 and 0.001, respectively). CONCLUSIONS: Most types of proinflammatory cytokines and chemokines in sera of neonates with meconium aspiration syndrome were higher than those without meconium aspiration syndrome, giving support to the suggestion that elevated levels are associated with the pathogenesis of meconium aspiration syndrome.

Morphological changes in the lungs of meconium-stained piglets.

Meconium staining of the skin is a common event associated with fetal hypoxia, stillbirths, weak-born piglets, and neonatal mortality. Aspiration of meconium leads to meconium aspiration syndrome (MAS). This study was undertaken to assess the relationship between the degree of meconium staining of the skin at birth, meconium aspiration, and pulmonary changes in porcine neonates. A total of 353 farrowing sows and 3,693 born piglets were monitored during parturition and for 15 days after delivery. Umbilical cords were classified as normal or ruptured. Meconium staining in the skin was graded as nonstained, mildly, moderately, and severely stained. Mortality from birth to 15 days of age was 8.4%. The lungs from 60 meconium-stained piglets and 60 lungs from nonstained piglets were collected and microscopically examined for meconium aspiration and inflammation. Rupture of the umbilical cord was significantly higher (P < 0.01) in meconium-stained piglets. Microscopically, 32% and 40% of the lungs had evidence of meconium for the stained and nonstained groups, respectively. The microscopic grade of meconium aspiration and inflammatory cells was not different between nonstained and meconium-stained piglets. Aspiration of meconium induced a granulomatous response in the lungs. It was concluded that the grade of meconium staining is a good indicator of fetal hypoxia, but not a good predictor for meconium aspiration and MAS in piglets.

Diagnosis and management of clostridium perfringens sepsis and uterine gas gangrene.

The progression of Clostridium perfringens endomyometritis to gas gangrene is a rare, but greatly feared complication in the obstetrical patient. While endometritis following cesarean delivery is a common complication, recognition of C. perfringens as the pathogen as well as its progression to gas formation in the myometrium is essential to the survival of the patient. We present a patient that we recently cared for, and review the bacteriology, clinical diagnosis, and management.

Local interstitial emphysema caused by meconium aspiration: report of one case.

A neonate of meconium aspiration syndrome presented with respiratory distress and bilateral pneumothorax. The image studies, including chest X-ray, chest computed tomography and operation finding all showed cystic changes in the right lung. Therefore congenital cystic lesions of lung was the first impression. However, the pathologic report disclosed meconium aspiration with interstitial emphysema.

Advances in management of meconium aspiration syndrome.

Meconium Aspiration Syndrome (MAS) is a leading cause of respiratory distress in the newborn. Antenatal diagnosis of meconium stained amniotic fluid and fetal distress is important to reduce morbidity and mortality in the neonates. Amnioinfusion of saline and tracheal suctioning of meconium are preventive interventions. Babies with MAS who continue to have respiratory distress need to be put on conventional ventilators. Increasing hypoxia, hypercarbia and barotrauma warrants changing to high frequency oscillatory ventilation. Pulmonary hypertension is an important complication which should be promptly recognized. Nitric oxide therapy used with high frequency ventilation has improved the outcome of babies with severe MAS and pulmonary hypertension. Some of these babies who continue to worsen clinically need to be put on ECMO circuit. Surfactant infusion in babies with MAS has been shown to improve gas exchange, resolve pulmonary hypertension and decrease oxygenation index. Total and partial liquid ventilation with perflurocarbon improves oxygenation, increases lung expansion and increases pulmonary blood flow in model studies of animals with MAS. Surfactant infusion and liquid ventilation are newer promising modes of therapeutic interventions in babies with severe MAS.

[Two cases of newborns with persistent pulmonary hypertension syndrome -- difficulties in diagnosis and treatment]. / Sindrom na persistirashta pulmonalna khipertenziia pri novorodeni--trudnosti v diagnostikata i lechenieto s primer na dva sluchaia.

The persistent pulmonary hypertension syndrome is a heavy and very often a lethal complication in the neonatal period. It is more common in full-term infants with perinatal asphyxia, meconium aspiration or inborn infection. We discuss two clinical cases of newborns, delivered by Caesarian section in the 38th week of gestation without history of prenatal asphyxia or inborn infection. The main clinical symptom was a progressive lung failure that finally lead to mechanical ventilation. Both infants had clinical symptoms of pulmonary hypertension and intracranial hemorrhages (proved by ultrasound). During autopsy, bilateral pneumonia and intracranial hemorrhages were found in both infants and in one of them meconium aspiration and suprarenal gland hemorrhages were proven. In conclusion we may say that the diagnosis of persistent pulmonary hypertension is often very difficult and the conventional methods of mechanical ventilation and medicament treatment cannot always prevent the infant's lethal outcome.

Amnioinfusión transcervical en trabajo de parto con meconio espeso

El objetivo de este estudio es evaluar el efecto de la amnioinfusión salina transcervical sobre el resultado perinatal en pacientes con trabajo de parto complicado con meconio. Estudio prospectivo con control histórico, realizado en el Hospital Ramón González Valencia, en 115 pacientes en trabajo de parto con meconio espeso, de las cuales 55 fueron sometidas a amnioinfusión. El volumen de solución salina oscila entre 500 y 800 cc. En el grupo de amnioinfusión hubo disminución en la frecuencia de puntajes bajos de Apgar (<7), reducción en el hallazgo de meconio debajo de cuerdas vocales (12.7 por ciento vs. 50.9 por ciento) y en la necesidad de ventilación mecánica positiva (1.9 por ciento vs. 33.3 por ciento). Concluímos que la amnioinfusión transcervical mejora el resultado perinatal reduciendo la incidencia de síndrome de Broncoaspiración de meconio, disminuye el síndrome de dificultad respiratoria neonatal, presencia de meconio bajo cuerdas vocales y necesidad de ventilación mecánica

Líquido meconial y sindrome de aspiración meconial. Letalidad, mortalidad y factores asociados / Meconium aspiration syndrome. Letality, mortality and their associated factors

De los 3,872 nacimientos atendidos en el HNCH durante el año 1990, 470 (12.1 por ciento) presentaron líquido amniótico meconial, fueron estudiados retrospectivamente 456 neonatos, de los cuales 39 (8.5 por ciento) desarrollaron el Sindrome de Aspiración Meconial (SAM), asociándose a su presencia los siguientes factores de riesgo: líquido meconial espeso, cesárea, apgar bajo, taquicardia fetal, distocia de cordón, parto disfuncional y toxemia, sirviendo su presentación como señal de alerta para el médico tratante. La aspiración traqueal se realizó con mayor frecuencia en neonatos deprimidos y con probable lesión pulmonar por asfixia lo que explicaría la mayor frecuencia de SAM asociada con este procedimiento. La letalidad por Sam fue de 10.2 por ciento, con un riesgo de morir 15.3 veces mayor que los neonatos sin SAM. Lo que demuestra que el SAMaún sigue siendo una patología frecuente asociado a una alta morbimortalidad, siendo importante para su prevención la detección temprana de factores perinatales y una atención perinatal combinada.