Persistent fetal circulation: an evolving clinical and radiographic concept of pulmonary hypertension of the newborn

The roentgenographic presentations of 11 newborn infants with hypoxemia secondary to pulmonary vasospasm and subsequent right-to-left shunting of blood through the foramen ovale and/or ductus arteriosus (persistent fetal circulation) are described (P. F. C. Syndrome). One infant had radiographically normal lungs, while ten had pulmonary parenchymal abnormalities including hyaline membrane disease [4], meconium aspiration syndrome [4], or an ill defined pattern of retained lung fluid [2]. The roentgenographic appearance of the lungs, however, was discordant with the severe hypoxemia observed in most. Heart size was variable but some degree of cardiomegaly was commonly present. Tolazoline, a potent vasodilator, was useful diagnostically and may have resulted in increased survival. An expanded clinical and roentgeonographic concept of the PFC syndrome is suggested.     

Bronchopulmonary dysplasia: correlation of radiographic and clinical findings

BACKGROUND AND PURPOSE: Abnormalities of the chest wall have been described in bronchopulmonary dysplasia (BPD). Clinical, radiographic and pulmonary function variables were evaluated in 1-year-old children ventilated because of neonatal lung disease in order to quantify these thoracic changes and to evaluate the lung disease. METHODS: The pulmonary status of 51 infants with neonatal lung disease requiring artificial ventilation was reevaluated clinically and radiographically at the age of 1 year. Twenty-two of these infants had developed BPD. Thoracic depth and width were measured clinically and on chest X-ray. The Toce score evaluated the presence of cardiomegaly, hyperinflation, emphysema and interstitial lung disease. Lung function was measured after sedation using previously reported methods. In BPD patients, Toce score and lung function were determined and compared at 1 month and at 1 year of age. RESULTS: In BPD patients, chest depth was significantly smaller when measured clinically as well as on chest radiograph (P < 0.05; Mann-Whitney U-test). There was a statistically significant correlation between chest depth measured clinically and on chest X-ray. Toce score was significantly higher in BPD patients (P < 0.05). In BPD patients intersitial abnormalities and decreased lung compliance were more frequent at the age of 1 month than at the age of 1 year. At the age of 1 year, hyperinflation was more frequent and at that time increased airway resistance was still noted. Thus the type of X-ray abnormality reflects the type of lung function disturbance. CONCLUSION: The flatness of the chest is most likely a consequence of the long-standing lung function abnormalities.     

Pathophysiology of chronic obstructive pulmonary disease

Emphysema with bullae is a common feature of patients with chronic obstructive pulmonary disease. Central to the pathophysiology of emphysema is the presence of airflow obstruction and lung and chest hyperinflation. Because of the increased ventilatory demand and the need to maintain gas exchange, patients with emphysema increase their work of breathing. This article reviews the adaptive and maladaptive consequences of these changes. A rationale is given as to the possible mechanism by which surgery aimed at resecting hyperinflated portions of the lungs may be effective.     

Time-dependent effects of antidepressant drugs on the low dose of apomorphine-induced locomotor hypoactivity in rats

Surfactant deficiency in newborn infants with hyaline membrane disease (HMD) reduces peripheral airway stability, leading to lung atelectasis, inhomogeneity of distribution of ventilation, ventilation/perfusion mismatch, and hypoxemia. The aim of this study was to evaluate the immediate effect of exogenous surfactant treatment on ventilation inhomogeneity (VIH) in infants with HMD. Homogeneity of ventilation was measured repeatedly in ten infants (median gestational age 30 weeks and birthweight 1.50 kg) after Exosurf, and in six infants (median gestational age 30 weeks and birthweight 1.42 kg) after Survanta treatment. Lung function was measured before and 0.5, 2, and 6 hours after administration of a single dose of surfactant. The multiple breath nitrogen washout method was used to measure the time pattern of nitrogen elimination from the lungs. VIH was evaluated by using both a compartmental lung model and a model-independent moment analysis. The two-compartment lung model was found to dominate before surfactant treatment, while a single-compartment model (implying homogeneous ventilation) fitted the washout data best 6 hours after Exosurf treatment (P < 0.01). The same pattern occurred 2 hours after Survanta administration. Moment analysis confirmed the reduction in VIH by both surfactants. This study supports the hypothesis that the improved oxygenation after surfactant treatment in infants with HMD results from a reduction in VIH and an increase in functional residual capacity (FRC).     

Intraoperative and postoperative use of mitomycin-C in the treatment of primary pterygium

OBJECTIVE: This study was conducted to determine the reliability of detecting features and making diagnoses of lower respiratory infections from chest radiograms in young infants. METHODS: Forty chest radiograms of infants younger than 6 months of age admitted with lower respiratory tract infection to a tertiary care pediatric hospital were independently reviewed on two separate occasions by three pediatric radiologists blinded to the patients' clinical diagnoses. For each radiograph the radiologists noted whether a feature was present, absent or equivocal on a standardized form. The features examined were hyperinflation, peribronchial thickening, perihilar linear opacities, atelectasis and consolidation. On the same form each radiologist indicated whether the radiograph was normal or showed airways and/or airspace disease. Within and between observer agreement were calculated by the average weighted kappa statistic. RESULTS: Within observer agreement for the radiologic features of hyperinflation, peribronchial wall thickening, perihilar linear opacities, atelectasis and consolidation were 0.85, 0.76, 0.87, 0.86 and 0.91, respectively. The between observer kappa results for these features were 0.83, 0.55, 0.82, 0.78 and 0.79, respectively. The within and between observer kappa statistics for interpretation of the radiographic features were best for airspace disease (within, 0.92; between, 0.91), and lower for normal (within, 0.80; between, 0.66) radiogram and for airways disease (within, 0.68; between, 0.48). The presence of consolidation was highly correlated with a diagnosis of airspace disease by all three radiologists. CONCLUSIONS: Clinicians basing the diagnosis of lower respiratory infections in young infants on radiographic diagnosis should be aware that there is variation in intraobserver and interobserver agreement among radiologists on the radiographic features used for diagnosis. There is also variation in how specific radiologic features are used in interpreting the radiogram. However, the cardial finding of consolidation for the diagnosis of pneumonia appears to be highly reliable.     

Pulmonary edema in obstetric patients is rapidly resolved except in the presence of infection or of nitroglycerin tocolysis after open fetal surgery

OBJECTIVES: This study was designed to determine the etiology, course, and severity of pulmonary edema in obstetric patients in a tertiary care center. STUDY DESIGN: A retrospective study was carried out on 16,810 deliveries from University of California, San Francisco, 1985-1995. Diagnosis and severity of lung injury were defined by a 4-point system that was based on the chest radiograph, oxygenation, positive end-expiratory pressure, and lung compliance. Resolution of pulmonary edema was defined by improvement in the chest radiograph and hypoxemia (ratio of arterial oxygen tension to inspired oxygen concentration) scores or by extubation. RESULTS: Pulmonary edema developed in 86 patients, or 0.5% of all obstetric cases. It usually showed extensive air space consolidation on the chest radiograph and arterial hypoxemia. Although 43% of the patients had severe pulmonary dysfunction, the average time to resolution of pulmonary edema was 2.4 days. Only 45% of patients required admission to the intensive care unit and only 15% required intubation and positive-pressure ventilation. Patients with infection (mean of 7.2 days) or fetal surgery (mean of 3.8 days) had the most severe, protracted course. CONCLUSION: Although obstetric pulmonary edema is associated with extensive radiographic infiltrates and severe hypoxemia, resolution occurs rapidly in most patients, limiting the need for intensive care support.     

Retinal hemorrhage in newborn infants

The fundi of the 527 infants born within one week were investigated. The results showed that 54 cases (78 eyes) had retinal hemorrhage. Among them, 23 cases (28 eyes) accompanied macular hemorrhage. The retinal hemorrhage in newborn infants was higher in vaginal delivery than in cesarean section, and the incidence of the fetal distress was higher in the newborn infants with macular hemorrhage. The essential causes of the retinal hemorrhage in newborn infants, development of infant macular and the mechanism of amblyopia induced by macular hemorrhage were discussed.     

Prediction of tumor control in patients with cervical cancer: analysis of combined volume and dynamic enhancement pattern by MR imaging

BACKGROUND: Hypoxemic developing hearts are susceptible to oxygen-mediated damage that occurs after reintroduction of molecular oxygen. This unintended hypoxemic/reoxygenation injury leads to lipid peroxidation and membrane damage and may contribute to postoperative cardiac dysfunction. Biochemical and functional status are improved by delaying reoxygenation on cardiopulmonary bypass (CPB) until cardioplegic arrest. METHODS: Six immature piglets (3 to 5 kg) without hypoxemia underwent 30 minutes of cardioplegic arrest during 1 hour of CPB. Fourteen others underwent 2 hours of hypoxemia on ventilator before reoxygenation on CPB. Reflecting our clinical routine, 9 were reoxygenated on CPB for 5 minutes followed by 30 minutes of cardioplegic arrest and 25 minutes of reperfusion. The other 5 were put on hypoxemic CPB for 5 minutes, before being reoxygenated during cardioplegic arrest for 30 minutes followed by 25 minutes of reperfusion. RESULTS: Cardioplegic arrest (no hypoxemia group) caused no functional or biochemical changes. In contrast, by preceding hypoxemia with subsequent reoxygenation on CPB (no treatment group) we found 39.5% decrease in antioxidant reserve capacity, 1,212% increase in myocardial conjugated diene production, significant increase in coronary sinus blood conjugated dienes, and an 81% reduction of left ventricular contractility, all of which were statistically significant (p < 0.05) when compared with the no hypoxemia group. Conversely, delaying reoxygenation until cardioplegic arrest (treatment group) resulted in 33.1% improvement in antioxidant reserve capacity, 91.7% less conjugated diene production, lower coronary sinus blood conjugated diene levels, and a 95% improved contractility, all of which were significant (p < 0.05) when compared with the no treatment group. CONCLUSIONS: A reoxygenation injury associated with lipid peroxidation and decreased postbypass contractility occurs in cyanotic immature hearts when reoxygenated on CPB. Delaying reoxygenation until cardioplegic arrest by starting CPB with ambient partial pressure of oxygen results in significantly improved myocardial status.     

An autopsy case of extremely immature newborn covered with fetal membrane

We report an autopsy case of extremely immature newborn totally covered with fetal membrane. The infant was a female, 32 cm in length, 662 g in weight, accompanied with the intact umbilical cord and placenta. No remarkable pathological findings for disease or anomalies were observed. Floating tests of the lungs and gastro-intestinal tract were completely negative. In histological examination, the alveoli in the lungs were partially slightly open, filled with amniotic fluid. Pulmonary surfactant was negative immunohistochemically. No evidence was found to confirm a live-born. It was diagnosed that the immaturity has caused the delayed rupture of the fetal membrane and the death during the delivery.     

Spontaneous regression of aneurysmal nonpatent ductus arteriosus: report of a neonate case

We report a newborn baby boy with an aneurysmal ductus arteriosus, that underwent spontaneous regression in the 2 years follow-up. Plain chest films showed the clue. Echocardiography, magnetic resonance imaging and angiocardiography are helpful in the differential diagnosis of other superior mediastinal mass. Perinatal asphyxia and hypoxemia may contribute to the formation of the ductal aneurysm. Intravenous infusion of dopamine and dobutamine may precipitate the nonpatency of the ductal aneurysm.     

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Fetal thrombocytopenia and its relation to maternal thrombocytopenia

BACKGROUND: Neonates with severe thrombocytopenia can have bleeding leading to death or lifelong residual defects. The predictors, frequency, and consequences of fetal thrombocytopenia are not known, nor is it known if there are maternal clinical features that could predict fetal thrombocytopenia. METHODS: We conducted a seven-year cross-sectional study in which platelet counts were determined in newborns' umbilical-cord blood and blood obtained from their mothers at consecutive deliveries in one obstetrical unit. The relations of the umbilical-cord platelet count to maternal risk factors were determined. RESULTS: Platelet counts were determined in blood samples from 15,471 mothers and 15,932 newborn infants. The cord-blood platelet count was less than 50,000 per cubic millimeter in 19 infants (0.12 percent; 95 percent confidence interval, 0.07 to 0.19 percent), whereas the platelet count was less than 150,000 per cubic millimeter in 6.6 percent of the mothers (95 percent confidence interval, 6.2 to 7.0 percent). One infant among those born to 756 mothers with incidental thrombocytopenia, 5 infants among those born to 1414 mothers with hypertension, and 4 infants among those born to 46 mothers with idiopathic thrombocytopenic purpura had cord-blood platelet counts between 20,000 and 50,000 per cubic millimeter. Only 6 infants (0.04 percent; 95 percent confidence interval, 0.01 to 0.08 percent) had cord-blood platelet counts of less than 20,000 per cubic millimeter; all their mothers were among the 18 whose 19 fetuses were at risk for neonatal alloimmune thrombocytopenia. Two of these infants had in utero intracranial hemorrhage. In addition, 3 infants born to these 18 women had cord-blood platelet counts between 20,000 and 50,000 per cubic millimeter; there was 1 stillbirth due to intracranial hemorrhage. CONCLUSIONS: Moderate-to-severe fetal thrombocytopenia is a rare event. The only severely affected neonates with morbidity or mortality due to this condition are those born to mothers with antiplatelet alloantibodies.     

Surfactant treatment may accelerate epithelial cell regeneration in hyaline membrane disease of the newborn

Previous studies of histologic changes in the lungs of infants with hyaline membrane (HMD) disease of the newborn treated with surfactant have focused on the occurrence of hemorrhage and bronchopulmonary dysplasia (BPD). Observations in autopsied infants with HMD suggested a possible acceleration of epithelial cell regeneration in those receiving surfactant. We studied lungs of the 11 autopsied infants with HMD treated with surfactant, who survived less than 1 week, and compared them to 22 infants with HMD not given surfactant. Epithelial cell regeneration, BPD, and airway and interstitial hemorrhage were graded on a 0-to-3 scale. Treated infants showed significantly more epithelial cell regeneration (p<0.05) and airway hemorrhage (p<0.05). Also, treated infants showed recognizable epithelial regeneration 1 day earlier than the nontreated group. The study supports the observation that regeneration of the necrotic respiratory epithelium of HMD is accelerated in infants treated with surfactant.     

The maternal and fetal levels of human chorionic gonadotropin, human placental lactogen and prolactin during the perinatal period (author's transl)

The levels of human chorionic gonadotropin (HCG), human placental lactogen (human choriosomatomamotropin HCS) and prolactin (PRL) were determined in the serum of 72 maternity patients and the serum of the newborn infants. The determinations were done with radioimmunologic tests (RIA). These three protein hormones were also determined in the amniotic fluid and in the maternal serum from 4-6 days prior to the delivery of the infant. The concentration of HCG or HCS in the serum of the newborn infants was a mean 0.43 or 0.37% of the level in the maternal serum. The concentration of PRL in the serum of the newborn was 118% and slightly higher than in the serum of the mothers. The concentration in the amniotic fluid was 1.5% for HCG, 5.8% for HCS, and 252% for PRL, compared to the corresponding levels in the maternal serum. The fact that the hormone concentrations in the amniotic fluid are significantly higher than in the serum of the newborn suggests excretion of the hormones from the fetal circulation via the fetal liver and the fetal kidney. The high levels of PRL in the maternal and the newborn serum may be caused by the high concentrations of estrogen or progesterone. Increased during the course of the pregnancy there was a significant sex linked difference in the level of HCG in the maternal serum correlated to the sex of the newborn infant.     

The assessment of the severity of pulmonary edema by computed tomography. A comparison between high-resolution computed tomography, objective evaluation with density masks and functional tests

The results of high-resolution computed tomography (HRCT) were correlated with those of pulmonary function tests, chest films and CT expiratory density mask values in the evaluation of pulmonary emphysema in 33 symptomatic subjects. Emphysema was quantitated with both subjective and objective measurements. Conventional chest films were useful to diagnose severe emphysema but its actual extent was more reliably evaluated with CT scoring systems. HRCT and density mask correlated well with function tests, but the former method exhibited stronger correlation with carbon monoxide diffusion capacity. The opposite was true for hyperinflation and expiratory obstruction variables. Subjective CT estimates, which are quick and easy to perform, were seen to correspond more specifically to the pathophysiologic derangement and should therefore be used to evaluate the anatomic extent of disease. The functional severity of emphysema correlated only with the overall extent of disease and not with its regional distribution in the upper or lower lungs. Finally, in 4 cases (12.1%) with low CT scores, FEV1 was reduced but diffusion capacity values were normal. In one of these patients HRCT showed signs of bronchiolitis. In fact, small airway disease might be a more critical factor in determining functional impairment than the actual anatomical emphysema.     

Effects of amygdaloid lesions on exploration by rats

Diagnostic separation of infants with signs of cardiac failure (hypoglycemia, sepsis, myocarditis, hypoxemia) but no congenital cardiocirculatory malformation from those with a large left to right shunt is crucial in newborn management. Echocardiographic studies of 218 infants and children allowed group separation and distinction from normal by the assessment of mean velocity of circumferential fiber shortening (Vcf) and the ratio of left atrial to aortic root diameter at end-systole (LA/Ao). In normal premature and full-term infants, Vcf (1.51 +/- 0.04 [mean +/- standard error]) was significantly lower than in infants with a large shunt (2.12 +/- 0.08, P less than 0.01) and higher than in infants with nonstructural heart disease (1.18 +/- 0.06, P less than 0.001). LA/Ao ratios were comparable in the groups with a large shunt and nonstructural heart disease (1.14 +/- 0.1 and 1.26 +/- 0.2, respectively) and were significantly higher in both groups than in normal subjects (0.77 +/- 0.01, P less than 0.001). Similar echocardiographic distinctions could be made when 10 older children (aged 2 to 10 years) with cardiomyopathy were compared with 45 normal older children. Serial determination of these variables was of major assistance in patient management.     

Decreased sodium ion absorption across nasal epithelium of very premature infants with respiratory distress syndrome

OBJECTIVE AND STUDY DESIGN: Successful adaptation to air breathing at birth depends on rapid absorption of fetal lung liquid that is mediated by activation of amiloride-sensitive sodium ion channels. To test the relationship between respiratory epithelial Na+ transport and development of respiratory distress syndrome (RDS), we measured nasal transepithelial potential difference (PD) in 31 very premature (< or = 30 weeks of gestation) newborn infants. Infants were retrospectively assigned to RDS (22 infants) and non-RDS (9 infants) groups on the basis of clinical and chest x-ray criteria. RESULTS: Maximal nasal epithelial PD increased with birth weight (-1.2 mV/100 gm) and was lower in infants with RDS (-16.5 +/- 0.6 mV) than in those without RDS (-22.0 +/- 1.3 mV). Infants without RDS had PD values similar to normal fullterm infants. Amiloride inhibition of PD, an index of Na+ absorption, was significantly lower, within the first 24 hours of life, in infants in whom RDS developed (3.8 +/- 0.2 mV; 29.5% +/- 0.8% inhibition) than in those without RDS (6.1 +/- 0.6 mV; 38.6% +/- 0.5% inhibition). Maximal and amiloride-sensitive PD returned to normal during the recovery phase of RDS. CONCLUSIONS: We conclude that Na+ absorption across nasal epithelium increases with increasing birth weight and that impairment of Na+ absorption across the respiratory epithelia of very premature infants may contribute to the pathogenesis of RDS.     

Role of nitric oxide in kainic acid-induced elevation of cochlear compound action potential thresholds

PTH-related protein (PTHrP) is found with its receptor in a variety of normal mammalian embryonic tissues where it apparently regulates cellular growth and differentiation. PTHrP stimulates phosphatidylcholine synthesis in rat fetal lung explants, suggesting a role in fetal type II alveolar maturation and surfactant production. We investigated PTHrP levels in tracheal aspirates of newborn infants. We collected tracheal aspirates from 40 intubated newborn infants within the first 24 h of life. PTHrP levels were measured by a RIA using rabbit antisera to PTHrP peptide 38-64. We found significantly lower PTHrP levels in tracheal aspirates from infants born at less than 35 wk of gestation (p = 0.02) and with a birth weight less than 2 kg (p = 0.04). We also found significantly lower PTHrP levels in male preterm (<35 wk of gestation) infants compared with female infants (p = 0.01), and in preterm infants who required multiple doses of surfactant (p = 0.005). Preterm infants exposed to antenatal steroids had significantly higher levels of PTHrP in tracheal aspirates (p = 0.02). PTHrP is associated with various indices of lung maturation and may prove to be a mediator of differentiation and growth.     

Adverse effect of amniofetography on fetal thyroid function

Amniofetography is a valuable tool for the diagnosis of fetal malformations. This technique is being used routinely in pregnancies carrying a high risk of external fetal malformations. There are very few published data concerning the effect of radiopaque dyes, containing large amounts of iodide, on fetal thyroid function. We have performed serial determinations of serum thyrotropin and thyroxine in seven newborn infants to assess the effect of amniofetogrpahy on fetal thyroid function. This work demonstrates that amniofetography induces a transient impairment of fetal thyroid function.