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Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound has received increasing attention from neonatal physicians. Nevertheless, clear reference standards and guideline limits are needed for accurate application of this diagnostic modality. This document aims to summarize expert opinions and to provide precise guidance to help facilitate the use of the lung ultrasound in the diagnosis of neonatal lung diseases.

Severe bronchopulmonary dysplasia (BPD) is common disease, especially for the tiniest infants with gestational age

Aspiration of meconium produces a syndrome characterized by hypoxia, hypercapnia, and acidosis. Perinatal hypoxia, acute airway obstruction, pulmonary inflammation, pulmonary vasoconstriction, pulmonary hypertension, and surfactant inactivation all play a role in the pathogenesis of meconium aspiration syndrome (MAS). Most aspiration of meconium probably occurs before birth. Following aspiration, meconium can migrate to the peripheral airway, leading to airway obstruction and subsequent lung inflammation and pulmonary hypertension. The presence of meconium in the endotracheal aspirate automatically establishes the diagnosis of meconium aspiration. MAS can be diagnosed in any infant born with meconium staining of amniotic fluid who develops respiratory distress at or shortly after birth and has positive radiographic findings. Prevention of intrauterine hypoxia, early cleaning (suctioning) of the airway, and prevention and treatment of pulmonary hypertension are essential in the management of MAS. Recent studies suggest that avoidance of postterm delivery may reduce the risk of intrauterine hypoxia and the incidence of MAS. Routine intrapartum naso- and oropharyngeal suction does not appear to affect the incidence and outcome of MAS. Endotracheal suction now is reserved only for infants who are depressed or have respiratory distress at birth. Mortality of MAS has improved; the causes of death are related primarily to hypoxic respiratory failure associated with irreversible pulmonary hypertension. Morbidity is affected mostly by perinatal hypoxia.

1. There was no clear correlation between the tracheal aspirate cytokines and the elevation of pulmonary arterial pressure in newborn piglets with MAS. The use of dexamethasone significantly suppressed tracheal aspirate cytokines but did not significantly alter pulmonary arterial pressure. Dexamethasone significantly increased the cardiac stroke volume and blood pressure. 2. Early dexamethasone therapy (< 12 hrs) for one week in infants with MAS significantly improved pulmonary ventilation and facilitated weaning from mechanical ventilation. 3. The mechanisms for the improvement in cardiopulmonary status following early dexamethasone therapy in MAS remain unclear. An overall improvement in cardiac hemodynamics, along with a significant decrease in lung inflammation may be responsible for the improvement.

BACKGROUND: Early postnatal use of dexamethasone in infants with respiratory distress syndrome (RDS) has been shown effectively to improve pulmonary status and to allow early weaning off mechanical ventilation. However, the mechanisms to explain the beneficial effects of dexamethasone in ventilatory dependent preterm infants remain unclear. METHODS: A double blind, placebo controlled study was performed to determine the change in pulmonary ventilation of premature infants with RDS as a result of dexamethasone treatment, and to evaluate the effect of dexamethasone on the levels of surfactant-associated proteins A (SP-A) and D (SP-D) in the tracheal fluid from 34 premature infants with RDS and 29 control subjects. RESULTS: Dexamethasone treatment decreased fractional inspired oxygen concentration (FIO2), arterial carbon dioxide tension (PCO2), mean airway pressure (MAP), and facilitated successful weaning from mechanical ventilation. SP-A concentrations in the tracheal aspirates were increased at days 7 and 14, and SP-D concentrations were increased during the period from days 3 to 14 in the dexamethasone treated group compared with the control group. However, albumin levels in the tracheal aspirate samples were decreased after dexamethasone treatment over the period from days 3 to 14. There was an inverse correlation between PCO2 values and SP-A concentrations. CONCLUSIONS: These results suggest that early use of dexamethasone can improve pulmonary status and also increase SP-A and SP-D levels in the tracheal fluid in premature infants with RDS.

Maturational changes in theophylline disposition were evaluated in 52 infants (gestational age, 24 to 40 weeks; postnatal age, 2 to 69 weeks) receiving maintenance theophylline therapy. Theophylline and metabolites were measured in serum and urine at steady state, and the influence of clinical parameters on the maturational changes was analyzed by multiple stepwise linear regression. Theophylline clearance and urine metabolite pattern reached adult values at 55 weeks' postconceptional age. Serum caffeine concentrations greater than 1 microgram/ml occurred in infants up to 50 weeks' postconceptional age. Disappearance of serum caffeine concentrations and maturation of theophylline clearance were primarily related (p < 0.001) to development of the demethylation pathway to 3-methylxanthine. Postconceptional age was the major factor (p < 0.001) explaining the interpatient variability in theophylline clearance (r2 = 0.57), serum caffeine to theophylline ratio (r2 = 0.46), and urinary excretion of theophylline (r2 = 0.51), caffeine (r2 = 0.49), 1,3-methyluric acid (r2 = 0.32), 1-methyluric acid (r2 = 0.53), and 3-methylxanthine (r2 = 0.58). Our findings indicate that postconceptional age rather than postnatal age should be used as a maturational marker during theophylline therapy in infancy.

Acute respiratory failure caused by different origins continues to be the major etiology of morbidity and mortality in critical neonates. There has been much advancement in neonatal respiratory care, but a few neonates with severe respiratory failure continue to be candidates for extracorporeal membrane oxygenation or survive with chronic lung diseases (CLD). Therefore, searching for ideal respiratory care strategies to reduce the morbidity and mortality rates is crucial for caring critical neonates. The main aim of this special issue was focused on the existing and potential strategies or techniques in neonatal respiratory care. In this special issue, we have invited a few papers that address such issues. Meconium aspiration syndrome (MAS) is a common cause of severe respiratory failure in term infants. The associations of persistent pulmonary hypertension of newborn (PPHN), pulmonary air leaks, and other morbidities sometimes make the respiratory care a difficult challenge to neonatologists. Three papers address current respiratory care in MAS. In a paper by K. Swarnam et al. they have a detail review on the epidemiology, pathophysiology, and managements in many different views of MAS. In another paper, P. Dargaville focuses on the application of mechanical respiratory supports in MAS, as well as the role of adjunctive respiratory therapies. In a paper, by C. Fischer et al., they demonstrate the epidemiology of MAS in term neonates using a population-based retrospective study for all births from 2000 to 2007 in a French region (Burgundy). In addition, bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) continues to be a major cause of neonatal morbidity in spite of significant progress in the treatment of preterm neonates. We have two articles discussing the pharmacologic approaches for prevention and treatment of BPD/CLD. S. Gupta et al. focus on the use of corticosteroids in one paper, and K. Tropea reviews all possible medications and the future potential stem cell therapy in another one. Furthermore, research papers discussing other important clinical issues in neonatal respiratory care are included. In a paper by S. Rastogi et al., they report their analysis on the factors associated with the successful weaning from nasal continuous positive airway pressure (NCPAP). In a paper by A. Gentili et al., they report their analysis on the duration of preoperative stabilization in predicting outcome of congenital diaphragmatic hernia. In a paper by K. Hole et al., they report the impact of neonatal resuscitation training in neonatal mortality rates in Malawi, Africa. Mei-Jy Jeng Tsu F. Yeh Peter A. Dargaville Thomas H. Shaffer Jen-Tien Wung

This matched-cohort study was to investigate the role of PP plays in RDS in preterm infants. The medical records of preterm infants ( 30 wk (P< 0.01). Conclusions: preterm infants born to mothers with placenta previa are susceptible to RDS. The mechanisms warrant further investigation. Table

Blunted Serum Erythropoietin (EPO) Response to Anemia in Polytransfusedβ-Thalassemia Major (β-Thal.) 752

This study was to examine whether NIPPV was better than nasal continuous positive airway pressure (NCPAP) in treating AOP. Infants with AOP (cessation of breathing > 20 sec, with frequency >2/hr for 4 hrs and associated with bradycardia) and failed to aminophylline (5 mg/kg, iv) therapy were randomly assigned to have NIPPV (PIP, 12-20 cmH2O; PEEP, 4-5 cmH2O; rate, 20/min; IT, 0.5 sec.) or NCPAP (4-5 cmH2O). NIPPV(n=19) and NCPAP (n=13) groups were comparable in birth weight (955 ± 293 g vs 962 ± 140 g, P=0.47), gestational age (27.2 ± 2.2 wk vs 27.0 ± 1.2 wk, P=0.88), age at study (20.5 ± 12.0 d vs 17.6± 11.0 d, P=0.60), Hb 10.9 ± 2.0 g vs 12.5 ± 2.7 g, P=0.10), serum glucose, Na, K, and Ca levels and blood gas data. There were no differences in pH, PCO2, and PO2 levels during the study. Conclusion: NIPPV is more effective than NCPAP in reducing the frequency of apnea and bradycardia. The mechanisms may relate to intermittently stimulate the nasopharyngx and dilate the upper airway by NIPPV.Table

SUPPRESSION EFFECT OF ERYTHROPOIETIN (EPO) ON THE GROWTH OF MYELOID PROGENITORS IN HUMAN CORD BLOOD. • 1720

Nine infants with early-onset Haemophilus sepsis were seen between January 1973 and July 1977. Of the five isolated strains that were typed, only one was type B. All infants had respiratory distress, metabolic acidosis, and large alveolar-arterial oxygen tension difference gradients. Eight infants weighed less than 1,500 gm and died; one infant weighed 1,701 gm and survived. Roentgenograms in six of eight showed hyaline membrane disease. Pulmonary pathologic specimens in eight infants revealed hyaline membranes in six and polymorphonuclear leukocytes in the alveolar spaces in four. In two infants, small Gram-negative bacilli were noted within proteinaceous exudates in alveolar ducts. The route and time of infection in these infants with early-onset Haemophilus sepsis are unclear. However, the possibility that the infection occurs before birth and that these infants represent septically aborted prematures is suggested by the high incidence of prematurity in infants with early-onset Haemophilus sepsis and early detection of bacteremia in three infants.

We studied the pharmacokinetics of indomethacin (0.3 mg/kg) given intravenously in 17 premature infants to promote closure of persistent ductus arteriosus. The decay of indomethacin generally showed an initial rapid distribution (alpha) phase followed by a slower elimination (beta) phase. The mean half-life of elimination (20.7 +/- 8 hours) was three times longer, and the mean clearance rate (13 +/0 9.5 ml/kg/hour) was seven times less than that reported in adults. The indomethacin clearance rate was linearly correlated with postnatal age (r = 0.71, P0.01). There was strong evidence of later re-entry of indomethacin into the plasma, suggesting that enterohepatic recirculation may be common in premature infants and may contribute to the relatively long half-life of elimination. Our data do not clarify the question of target concentration or minimal exposure time above which permanent closure may occur, but the group of infants who had permanent PDA closure after only one dose (8/17) had a significantly higher plasma indomethacin concentration time integral than the group (9/17) who needed more than one dose (P0.01). A 24-hour dosage interval was often sufficient when an iv indomethacin bolus of 0.3 mg/kg was used but, below the age of nonresponsiveness to indomethacin, a shorter interval may be preferable as postnatal age increases.

• Nine infants less than 2 months of age with group B streptococcal (GBS) osteomyelitis or septic arthritis, or both, were seen from January 1975 through January 1978. The infants had local joint signs, usually in the absence of systemic signs. The bones and joints involved were equally distributed between proximal humerus and proximal and distal femur. An infant had involvement of the talus. Treatment consisted of two to three weeks of parenteral antibiotics, arthrotomy in infants with arthritis, and bone decompression in infants with osteomyelitis. Clinical follow-up showed normal growth and function of the affected joint. Of the organisms, five were typed: four were type III and one was type lb. Group B streptococcal osteomyelitis and/or septic arthritis was the second most common late-onset GBS infection, being surpassed only by meningitis. ( Am J Dis Child 133:921-923, 1979)

A loading dose of theophylline produces significant metabolic changes, including increase of plasma glucose concentration and an early rise in serum insulin in some infants. The chronic effects of theophylline on plasma glucose, serum insulin, and glucagon are not known at this time. The potential for development of metabolic derangements must be kept in mind when theophylline is used for protracted periods in premature infants.

Maturational changes in T pharmacokinetics were evaluated in 45 infants; postconceptional age (PCA) 30.9-95.7 wks. After achievement of steady-state on T maintenance therapy, multiple serum and urine samples were obtained over dosing interval and assayed by HPLC for T and metabolites: caffeine (C), 1-methyluric acid (1MU), 3-methylxanthine (3MX), 1,3-dimethyluric acid (1,3MU). Mean(SD) T clearance (Cl) increased significantly (p 50 wks from 21.9(6.3) to 26.6(7.7) and 57.7(17.6). ml/hr/kg, respectively. Concomitant decrease (p 0.10) were found in some infants up to 55 weeks PCA. Stepwise multiple regression analysis showed urinary excretion of 3MX to be the primary parameter explaining the change in both T Cl (r=0.81, p

Previous study has shown that F may prevent the renal side effects of I in infants with PDA. We, therefore, undertook a study to evaluate this effect in infants with PDA and oliguria in whom I therapy has been considered as contraindicated. Six infants (mean±S.D. B.W. 1.3±0.2 kg; G.A. 32±2 wks, Postn. A. 9.6±2.8 days) who had sign. PDA shunt, congestive heart failure, and oliguria due to pre-renal failure were given I, 0.3 mg/kg, followed immediately by F, 1 mg/kg, iv. Pre-renal failure was defined if U/0 was

To evaluate if (F) would prevent the adverse renal effects of I.V.(I), 9 premature infants with PDA were randomized into 2 groups; 4 received 1(0.3mg/kg) alone and 5, I and F (lmg/kg I.V.) simultaneously. There were no slg. differences between the groups in B.W.(mean±S.D, 1179±456 vs 1021±282gm), gest,age(31.3±2.2 vs 29.5±1.9wks), postn. age (9.0±2.9 vs 11.6±0.5d.), clinical cardiovascular status, pH, F102, pO2 and pCO2.