Eight-epi-PGF2alpha: a possible marker of lipid peroxidation in term infants with severe pulmonary disease.

A prostaglandin F2-like compound, 8-epi-PGF2alpha, formed from oxidation of arachidonate, has been proposed as an indicator of lipid peroxidation. We determined whether tracheal aspirate or urinary 8-epi-PGF2alpha levels would differ over time or between infants in a control group and infants with severe respiratory failure. We correlated tracheal aspirate 8-epi-PGF2alpha levels with the fraction of inspired oxygen and with mean airway pressures at 24 and 48 hours of life. Levels in tracheal aspirates were in the range of 0 to 36 pg/microg of fSC of IgA and were higher in infants with severe pulmonary disorders compared with those in infants in the control group (p < 0.02). Urinary concentrations did not discriminate between sick infants and infants in the control group.

Airway muscle in preterm infants: changes during development.

OBJECTIVE: To quantitate airway muscle changes in infants born at 23 to 41 weeks' gestation (control subjects) and to compare the changes with those in infants with chronic lung disease. METHODS: Fifty-five human lungs (from infants born at 23 to 41 weeks' gestation) were studied: 46 from infants who died of various diseases within 72 hours of birth, and 9 from infants with CLD (infants born at 26.9 +/- 0.5 weeks' gestation, who lived 17 +/- 8 days). All the lungs were perfused via the trachea and pulmonary artery in a standardized protocol. Formalin-fixed tissues in paraffin blocks were cut 5 microns thick. Sections were immunohistochemically stained for alpha-smooth muscle actin. By using computerized image analysis to quantitate images digitized into the computer, we measured the area of muscle, epithelium, airway lumen, and length of basement membrane in 18 airways, from the smallest bronchioles to bronchi, in each infant. RESULTS: Muscle was present at 23 weeks' gestation at all levels of the bronchial tree, and from 25 weeks to term the control lungs had a similar quantity of muscle at any given airway circumference. Relative to airway size, there was more muscle in small airways, less than 1000 microns in circumference, than in larger airways. In airways greater than 1500 microns in circumference, infants with CLD had significantly more muscle than did control lungs. CONCLUSIONS: Airway muscle is present at 23 weeks' gestation at all levels of the conducting airways. The 25-week gestation infants had a quantity of airway muscle relative to airway circumference similar to that of term infants. Preterm infants with CLD who were aged 9 to 29 days have increased airway muscle in airways greater than 1500 microns in circumference. Bronchospasm in very low birth weight infants is possible within the first days of life.

Familial pulmonary lymphatic hypoplasia associated with fetal pleural effusions.

Two siblings born with pleural effusions died of pulmonary insufficiency. The infant born with fetal hydrops at 30 weeks of gestational age lived 45 minutes. The lung weights were mildly hypoplastic on postmortem examination. The sibling, born at 37 weeks of gestational age lived 8 days. Postmortem lung weights were normal, but the infant had a congenital heart anomaly consisting of a complicated vascular ring. Morphometric analysis of both infants indicated relatively normal lungs except for interlobular septal lymphatic hypoplasia, apparently a specific, previously unrecognized cause of fetal pleural effusions.

Neonatal pulmonary insufficiency caused by adenovirus infection successfully treated with extracorporeal membrane oxygenation.

Two infants with fulminant early-onset sepsis syndrome and respiratory failure are described. Adenovirus was isolated from cultures from both patients. Complications during pregnancy and respiratory failure that required tracheal intubation at birth suggested congenital infection. Both infants were successfully treated with extracorporeal membrane oxygenation.

Misalignment of lung vessels and alveolar capillary dysplasia: a cause of persistent pulmonary hypertension.

Two infants with fatal persistent pulmonary hypertension are described. Morphologically there was misalignment of the lung vessels, with the veins and the arterioles anomalously related, often sharing the same adventitial sheet. The capillaries did not make contact with the alveolar epithelium. The arterioles had increased medial muscle, and there was extension of the arteriolar muscularization to the precapillary level. The fraction of the parenchyma that was septal and connective tissue was increased. The acini had a decreased complexity, with immature alveoli and with a decreased radial alveolar count. The cause appeared to be related to abnormal capillary and venous plexus formation and migration. This syndrome seems to be identical with that described in three previous reports and probably represents a specific cause of persistent pulmonary hypertension.

Administration of bovine superoxide dismutase fails to prevent chronic pulmonary sequelae of neonatal oxygen exposure in the rat.

Using a rat model, we assessed the efficacy of varying doses of superoxide dismutase of (SOD) to affect plasma and tissue SOD concentrations and to attenuate dysplastic changes of lung and pulmonary vascular growth, which are chronic sequelae of neonatal oxygen exposure. One hundred forty-three 1-day-old Sprague-Dawley rats were divided into two groups and exposed to hyperoxia (0.96 to 1.0 Fio2) or room air for 8 postnatal days. Each group was subdivided into five treatment groups, which received 6, 20, 100, or 200 mg/kg/d SOD or a placebo, intramuscularly every 12 hours. All rats were then placed in room air; 52 were killed, and lung tissue and blood samples were obtained for measurement of bovine SOD concentration. The remaining rats received routine care until 58 to 60 days of age, when functional and morphologic cardiopulmonary changes were assessed. Bovine SOD concentration of pooled plasma samples increased 26-fold, from 2 to 50 micrograms/mL, between the 6 and 200 mg/kg/d SOD groups, but mean tissue concentration increased only six-fold, from 0.34 to 2.1 micrograms/lung. Cardiovascular and pulmonary changes found in each oxygen group, regardless of SOD dosage, included elevated right ventricular pressure, increased right ventricular weight, decreased number of small pulmonary arteries/mm2, decreased number of alveoli/mm2, and increased volume proportion of lung parenchyma. Thus, high plasma concentrations of bovine SOD failed to prevent the chronic cardiovascular and pulmonary sequelae of neonatal oxygen exposure in the rat, possibly because SOD did not reach the intracellular sites of action.

Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios.

We assessed pulmonary function and compression deformities in 76 preterm infants less than or equal to 34 weeks gestation who had premature rupture of membranes (PROM) for longer than 5 days (mean +/- SD 18.8 +/- 15.4 days, range 6 to 90 days). Twenty-one of the 76 infants had oligohydramnios and positional deformities at birth; however, only two infants met all the criteria for the oligohydramnios tetrad. All 21 required assisted ventilation from the moment of birth. Twenty infants had clinical evidence of pulmonary hypoplasia; 18 of these died. Pulmonary hypoplasia was confirmed by significantly low wet lung weights, low lung DNA content, or low radial alveolar counts in the 13 infants with postmortem examinations. Fifty-five infants with PROM for longer than 5 days did not have positional deformities. Twenty-one required assisted ventilation, of whom 10 had severe oligohydramnios. Eleven of the 21 died; autopsies were performed. All had normal wet lung weights, but seven had significantly decreased radial alveolar counts, implying a less severe but still fatal form of pulmonary hypoplasia. None of the remaining 34 infants had lung disease, and only three had oligohydramnios. We conclude that pulmonary hypoplasia can result from PROM associated with severe oligohydramnios of as short as 6 days duration. Furthermore, fatal pulmonary hypoplasia can occur with little or no external deformation.

Perinatal bacterial infection after prolonged rupture of amniotic membranes: an analysis of risk and management.

Chi-square and logistic stepwise multiple regression analysis of perinatal determinants of infant bacterial infection following prolonged rupture of amniotic membranes for 24 hours or more prior to delivery was applied in 33 infected infants and 66 matched control infants from the NINCDS Collaborative Project. In order of statistical significance, the most important variables were placental inflammation (P = 0.002), gestational age less than 34 weeks (P = 0.008), gestational age 34 to 37 weeks (P = 0.013), male sex (P = 0.015), Apgar score less than 6 at 5 minutes (P = 0.023), and clinical amnionitis (maternal fever, fetal tachycardia, or amniotic or gastric fluid leukocytes or bacteria) (P = 0.044). Duration of labor during PROM, race, and maternal age and parity were insignificant. Using these predictive variables, identification of infected infants for either microbial surveillance (superficial and systemic cultures) or microbial surveillance and anticipatory antibiotic therapy (discontinued after 3 days of negative cultures) was highly significant (P = 0.0001). Incorporating these variables and derived coefficients from multivariate analysis, a mathematical model was used for evaluation and prediction of perinatal bacterial infection with a sensitivity of 82% and specificity of 70%. Analysis of 46 infants prior to and 310 infants after implementation of this process at Harbor-UCLA Medical Center indicated significant improvement in the appropriate management of these infants at risk (from 59% to 87% of the population, P less than 0.05). Inappropriate antibiotic therapy decreased from 35% to 10% (P less than 0.05). In the absence of a shift in the median days of hospitalization of non-PROM infants, determination of the grand median days of PROM infant hospital stay showed a decrease (P less than 0.01) after initiation of this evaluation and management scheme.

Alpha1-antitrypsin in amniotic fluid and cord blood of preterm infants with the respiratory distress syndrome.

Total protein, alpha1-antitrypsin, and alpha2-macroglobulin were measured on amniotic fluid in 125 pregnancies between 11 and 42 weeks' gestation, and on the cord blood of 66 newborn infants. Amniotic fluid surface active material was assessed by the foam stability test. Amniotic fluid alpha1-antitrypsin is linearly and directly related to amniotic fluid total protein (r = 0.703, p less than 0.001). The cord alpha1-antitrypsin is also linearly related to cord total protein. Intrapartum complications are associated with a significant lowering of the cord alpha1-antitrypsin. Infants with a negative foam stability test had RDS regardless of the amniotic fluid alpha1-antitrypsin. The cord blood alpha1-antitrypsin value did not appear to be related to amniotic fluid surface active material. There were 23 infants with cord alpha1-antitrypsin of less than 0.2 gm/dl and with an intermediate or positive foam stability test; 19 of them had respiratory difficulties of varying severity. It is conceivable that infants, in spite of apparent adequate prenatal lung surfactant, develop respiratory disturbances on the basis of pulmonary fluid and protein transudation and/or reduction or inhibition of pulmonary surfactant incident to intrapartum complications.

Patent ductus arteriosus complicating the respiratory distress syndrome in preterm infants.

In 46 preterm infants with RDS the patency of the ductus arteriosus was established by single film aortography or by clinical diagnosis and confirmation at surgery. The estimated left-to-right shunt through the PDA by aortogram correlated well with the heart size and the clinical diagnosis of heart failure. In 14 infants massive cardiomegaly and heart failure with a PDA occurred before the appearance of a heart murmur. Twelve infants had severe RDS and 34 had mild or moderate RDS. Massive cardiomegaly occurred significantly earlier in infants with severe RDS. It is suggested that ductal ligation is indicated when an infant with massive cardiomegaly requires IPPV and whose aortagram shows that all of the contrast material is in the pulmonary arteries and none in the aortic arch. A heart murmur may or may not be present.