Diagnosis Of Hyaline Membrane Disease Research Articles

Minimally Invasive Tissue Sampling in Preterm Deaths: A Validation Study.

Uncertainty about the causes of neonatal deaths impedes achieving global health targets to reduce mortality. Complete diagnostic autopsy (CDA) is the gold standard to determine cause of death. However, it is often difficult to perform in high-burden, low-income settings. Validations of more feasible methods to determine cause of death are needed. This prospective, multi-center study in Ethiopia assessed the validity of the minimally invasive tissue sampling (MITS) approach to contribute to causes of death in preterm neonates compared to CDA. The MITS and CDA of 105 cases were reviewed. The MITS sampling success for lungs and liver was 100% and 84%, respectively. The kidney and brain had sampling successes of 58% each. MITS showed good agreement with CDA for the diagnosis of hyaline membrane disease (kappa = 0.78), and moderate to substantial agreement for pneumonia and pulmonary hemorrhage (kappa = 0.59 and 0.68, respectively). Even though CDA is the gold standard in identifying the cause of death, we believe that the MITS method can be a useful alternative method in supporting determination of cause of death in low-resource settings.

Neonatology Specialty Grand Challenge

Neonatology Specialty Grand Challenge

Invasive Mechanical Ventilation in Premature Infants: Where do we Stand Today?

Invasive Mechanical Ventilation in Premature Infants: Where do we Stand Today?

Role of transabdominal ultrasound of lung bases and follow-up in premature neonates with respiratory distress soon after birth

Background:Chest radiography has been the traditional method of diagnostic evaluation of patients of hyaline membrane disease (HMD). Lung sonography (USG) has been lately explored as an alternative modality.Aims:To explore the application of transabdominal USG of lung bases (TASL) in the evaluation of HMD in premature neonates with respiratory distress soon after birth.Settings and Design:Tertiary care institutional setup. Study duration–18 months. Follow-up–variable, up to 1 month. Prospective descriptive study.Materials and Methods:Eighty-eight consecutive patients admitted in the neonatal intensive care unit (NICU) with gestational age <32 weeks having respiratory distress within 6 h of birth were enrolled. The diagnosis of HMD was made if the patient had negative gastric shake test and/or suggestive chest radiograph. TASL was performed in all patients within the first 24 h of life and biweekly subsequently. USG was interpreted as normal, HMD pattern, or broncho-pulmonary dysplasia (BPD) pattern. Biweekly follow-up was done for patients showing HMD till normalization of the sonographic HMD pattern, development of the sonographic BPD pattern, or death/discharge of the neonate from the hospital.Results and Conclusions:TASL showed 85.7% sensitivity, 75% specificity, 88.88% positive predictive value, and 69.2% negative predictive value for the diagnosis of HMD. The abnormal sonographic findings on day 14 had 94.1% accuracy for prediction of eventual occurrence of clinical BPD. TASL is complementary to chest radiograph in the diagnosis of HMD. It is also useful for the early prediction of BPD with the potential of reducing the cumulative radiation dose to these neonates.

Respiratory distress syndrome of the preterm neonate — placenta and necropsy as witnesses

Aim. To assess the agreement between clinical diagnosis of hyaline membrane disease (HMD) and lung necropsy pathological findings of deceased neonates.Material and methods. Review of clinical files and necropsy studies of 40 newborn infants ≤ 37 weeks gestational age.Results. The concordance between clinics and necropsy for the diagnosis of HMD was 43% (n = 17). At the necropsy study of the lungs, 11 cases (28%) of clinically diagnosed HMD were associated to meconium aspiration, pneumonia, or pulmonary hemorrhage; 12 (30%) cases were pneumonia and/or meconium aspiration and pulmonary hemorrhage without hyaline membranes. Of the 17 pneumonias, 15 (88%) were associated to histological chorioamnionitis, RR 3.76 (95%CI: 1.9–4.2) (p < 0.001).Conclusions. The clinical diagnosis of HMD needs a cautious interpretation, as it may be mistaken, or HMD may occur in association with other pathological situations enhancing a more ominous prognosis.

Maladie des membranes hyalines chez le nouveau-né à terme

Objectives. – Evaluation of the consequences of preplanned delivery near term on the neonatal respiratory distress syndrome and its mechanism of occurrence. Patients and methods. – During five years, full-term infants (≥37 weeks gestational age) admitted in the Institut de Puériculture de Paris, with a well characterized hyaline membrane disease, were included in a retrospective study. Results. – During this period, 97 full-term neonates with respiratory distress syndrome were hospitalized in the neonatal intensive care unit. The diagnosis of hyaline membrane disease was made in view of clinical and radiological criteria. The study of mode of delivery has shown a high frequency of pre-planned delivery: 54% caesarean and 24% vaginal delivery. A high-risk of occurrence of hyaline membrane disease was identified around 37 weeks gestational age in the case of preplanned delivery. Conclusion. – Preplanned delivery near 37 weeks gestational age may increase the risk of occurrence of hyaline membrane disease in full-term neonates.

Is the BPD epidemic diminishing?

In a previous study of very low birth weight neonates, < or = 1500 g, admitted to the Vanderbilt University Neonatal Intensive Care Unit (NICU) from 1976-1990, improvements in survival were accompanied by a corresponding increase in the incidence of bronchopulmonary dysplasia (BPD). Since then, certain neonatal and perinatal interventions have been introduced and may influence neonatal outcomes. In this study, we have continued the analysis of the incidence of 3 outcomes: 1) Neonatal death (NEOD), 2) BPD, and 3) NEOD or BPD (NEOD/BPD) for an additional 7 years, 1991-1997. A retrospective study was performed of 3,837 patients with birth weight < or = 1500 g and admitted to the Vanderbilt NICU within 24 hours of birth from 1976 through 1997. The outcomes NEOD, BPD, or NEOD/BPD were modeled by using multiple logistic regression with the following risk factors included as covariates: birth weight, gestational age, Apgar scores at 1 and 5 minutes, gender, race, birth location, diagnosis of hyaline membrane disease, maternal age, maternal diabetes, delivery method, multiple births, duration of ruptured membranes, and biologically relevant interactions among these covariates. To assess time trends in the risk factors and outcomes, patients were divided into time periods (1 = 1976-80, 2 = 1981-85, 3 = 1986-90, 4 = 1991-95, and 5 = 1996-97). For each outcome, only covariates or interactions among covariates found to be significant were retained in the final model. Adjusted odds ratios and 95% confidence intervals were calculated to measure the risk associated with a given time period in comparison to the preceding period. There was a progressive decline in NEOD across all time periods. The previously described increase in BPD from period 1 through period 3 is followed by a decrease in periods 4 and 5. The risk of NEOD/BPD remained fairly constant from period 1 to period 3, but then showed a significant decrease over the two most recent periods. Prior to 1991, the cost of improved survival among very low birth weight infants in this large NICU was an increased incidence of BPD. Since 1991, the risk of BPD has been decreasing even though survival continues to improve. If these findings are also representative of other NICUs, they signify an important reduction in the impact of BPD as one of the costly sequelae of prematurity.

A scoring system to predict the evolution of respiratory distress syndrome into chronic lung disease in preterm infants.

The purpose of this study was to develop and validate an empirical scoring system to predict the evolution of neonatal respiratory distress syndrome (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a more complicated logistic regression model. Clinical study. Neonatal intensive care unit. The retrospective analysis of a 3-year experience showed that a gestational age (GA) of less than 30 weeks, a birth weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD) and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO2) were the highest relative risk factors correlated with the evolution of CLD. On this basis an empirical and a statistical scoring system were defined and prospectively applied at 3 and 5 days of life to 228 neonates with BW less than 1,250 g. The results obtained with both scoring systems were then compared. Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 +/- 2.3 weeks; BW: 1,058 +/- 143 g) were normal and 82 (GA: 27.5 +/- 3.9 weeks: BW: 838 +/- 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system showed a specificity of 97.0% and a sensitivity of 92.7% on the 3rd day of life; on the 5th day of life the specificity was still 95.5%, while sensitivity remained 92.7%. The areas under the ROC curves plotted with both scoring systems tested were similar. The proposed empirical scoring system is easy to use and is highly reliable. The application of this scoring system provides the opportunity to direct aggressive treatment for CLD toward only very high risk patients between the 3rd and 5th days of life.

Evidence from twin study implies possible genetic susceptibility to bronchopulmonary dysplasia

To investigate the possibility that susceptibility to bronchopulmonary dysplasia (BPD) is affected by genetic factors, we analyzed risk factors for BPD in 108 twin pairs of infants having birth weight < or = 1,500 g. When BPD occurred in a first born twin (n = 23), it also occurred in 65% (n = 15) of the second born twins, and when BPD did not occur in the first twin (n = 85), it only occurred in 8% (n = 7) of the second twins (crude odds ratio = 20.9). After adjusting for potentially significant risk factors including birth weight, gestational age, gender, diagnosis of hyaline membrane disease, pneumothorax, symptomatic patent ductus arteriosus, and year of admission, using multiple logistic regression on the entire database (1,872 admissions < or = 1,500 g), BPD status of a first twin remained a highly significant predictor of BPD in the second twin (adjusted odds ratio = 12.3, P < .001). Other factors including birth order of twins, twin gestation, inborn/outborn status, cesarean section delivery, 1- and 5-minute Apgar scores, maternal race, maternal diabetes, and antepartum corticosteroid treatment were not significant predictors of BPD. These results are consistent with genetic factors affecting the susceptibility of very low birth weight premature infants to BPD, but we cannot exclude the possibility that factors not included in our analysis are also involved.

Improved Survival Accounts for Most, but Not All, of the Increase in Bronchopulmonary Dysplasia

The incidence of bronchopulmonary dysplasia (BPD) increased from 10.6% in 1976 through 1980, to 21.7% (1981 through 1985), and to 32.9% (1986 through 1990) in very low birth weight neonates (1500 g or less) admitted to the Vanderbilt Neonatal Intensive Care Unit, while there was a concurrent decline in incidence of neonatal death (NEOD) during the same periods (26.4%, 18.3%, and 15.9%, respectively). Population changes in risk factors (birth weight, sex, race, location of birth, gestational age, diagnosis of hyaline membrane disease, and 5-minute Apgar score) over time do not account for this increase. To estimate the proportion of the increase in BPD attributable to the concurrent decline in NEOD during these periods, separate logistic regression models for NEOD and BPD were calculated from patients born during 1976 through 1985. These results were used to predict the expected number of cases of NEOD and BPD during 1986 through 1990, assuming that the adjusted incidence of NEOD and BPD remained constant from 1976 through 1985, to 1986 through 1990. The increase in the combined outcome, NEOD/BPD, over the three time periods (34.2%, 36.1%, and 43.5%) remained statistically significant after adjustment for the risk factors listed above. During 1986 through 1990, the predicted number of NEOD was 83 more than the number observed, while the predicted number with BPD was 115 less than the number observed. If all 83 averted cases of NEOD during 1986 through 1990 had developed BPD, then 83 (72%) of the 115 excess cases of BPD could be attributed to averted NEOD. The approximate 95% confidence interval for this estimate was 58% to 87%.(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphatidylglycerol determination in the amniotic fluid from a PAD placed over the vulva: a method for diagnosis of fetal lung maturity in cases of premature ruptured membranes.

Four hundred and forty seven pregnant women with ruptured membranes, were prospectively studied in order to assess the diagnostic capacity of Phosphatidylglycerol (PhG) determination in amniotic fluid recovered from vulval pads in the diagnosis of Hyaline Membrane Disease (HMD). The identification of PhG was performed using one dimensional silica gel thin layer chromatography. The sensitivity of PhG determination in the diagnosis of HMD in newborns of the total population was found to be 88.2%, with a specificity of 76.9%. In the study population, the incidence of HMD was 7.6%, the negative predictive value was 98.8% and, the positive predictive value was 24.0%. When the 265 newborns of the gestational age group of less than or equal to 34 weeks is considered, we observed an incidence of HMD of 12.1%. The diagnostic capacity of PhG in this group was shown by a sensitivity of 87.5%, a specificity of 76.4%, a positive predictive value of 33.7% and a negative predictive value of 97.8%. This method of assessment of fetal lung maturity has a diagnostic capability similar to that described by other authors, who used amniotic fluid obtained vaginally or transabdominally. The procedure described here of amniotic fluid collection is non-invasive, harmless to the mother and fetus and simple to perform. The characteristics of this method, allow serial studies of the amniotic fluid to be carried out.

Phosphatidylglycerol in tracheal aspirates for diagnosis of hyaline membrane disease.

Lecithin:sphingomyelin ratio and phosphatidylglycerol were determined by a rapid, simple method in tracheal aspirates obtained from 132 newborn infants with respiratory diseases, sixty five of whom developed hyaline membrane disease. Phosphatidylglycerol determination was more sensitive (97%) than lecithin:sphingomyelin ratio, but their specificities were similar (76%).

Early prediction of symptomatic patent ductus arteriosus from perinatal risk factors: a discriminant analysis model.

A scoring system based on discriminant analysis was devised to predict, within 24 hours after birth, whether or not a premature infant will subsequently develop a symptomatic PDA. Five risk factors including birth weight, the diagnosis of hyaline membrane disease, intrauterine growth retardation, acute perinatal stress, and treatment with distending airway pressure were reduced to a discriminant score which separated infants with symptomatic PDA from infants without symptomatic PDA. Based on this score, the likelihood that an individual infant would later develop symptomatic PDA could be expressed as a probability function. When applied prospectively, this score predicted the correct outcome of 80% of infants in a test population. This predictive model should be useful in clinical trials and other applications requiring a quantitative expression of risk for developing symptomatic ductus shunting.

Lung Development in the Fetal Primate Macaca Nemestrina. III. HMD

Delivery of M. nemestrina at 80% of normal gestation provides a population of neonates at high risk for hyaline membrane disease (HMD). The diagnosis of HMD was made by the presence of reticulogranular densities and air bronchograms on chest radiographs. Patchy atelectasis was seen in the lungs of animals assigned by clinical and radiographic criteria to the HMD group and not in the normal lungs of animals matched for gestational and postnatal age. Total phospholipid and phosphatidylcholine in whole lung, airway lavage fluid, and surface-active materials were lower in animals with HMD. Amniotic fluid L/S ratios were lower in the group that developed HMD. Pressure-volume measurements indicated decreased distensibility and unstable terminal air spaces in the HMD group. Alveolar-arterial oxygen pressure differences were greater in animals with HMD. There were no differences between HMD and normal groups in body weight, lung weight, percent dry lung weight, gestational age, and postnatal age at death. This primate species, subjected to premature delivery, is a suitable animal model of HMD in human neonates.

Serial studies of lung volume and VA-Q in hyaline membrane disease.

Extract: Twenty infants with a clinical and radiologic diagnosis of hyaline membrane disease were studied serially by measurement of functional residual capacity (FRC) and arterial and alveolar gradients for O2, CO2, and N2. Nitrogen washouts were determined as well in nine infants. The FRC, alveolar-arterial O2 gradients (AaDo2) in 100% O2, and true shunt (Qs/Qt), which are different ways of quantitating atelectasis and shunt in hyaline membrane disease, were shown to be statistically related. The FRC was below 1.0 ml/cm in all infants when sick and returned to the usual range for gestational age, generally around 15 days. Extensive cardiopulmonary shunting was recorded both at the height of illness and for a considerable time during recovery. However, during recovery, not all of the venous admixture was due to shunt. As maldistribution of ventilation was excluded, the possibility of a diffusion barrier was raised. Alveoli with a high VA/Q were identified by large arterial-alveolar CO2 gradients (aADCO2) both during illness and recovery. This indicates that maldistribution of pulmonary blood flow is an important physiologic abnormality in hyaline membrane disease. Speculation: The FRC was shown to correlate inversely with AaDo2 and Qs/Qt ratios. As a low FRC is the only true unique characteristic of hyaline membrane disease, it is suggested that in the future the disease be defined in terms of the lung volume as well as in terms of the usual clinical and biochemical parameters which appear in other forms of respiratory distress in neonates. Constant positive airway pressure is an attempt to approach treatment from this point of view.

Amniotic fluid lecithin/sphingomyelin ratio in the diagnosis of hyaline membrane disease

To evaluate fetal lung maturity, lecithin/sphingomyelin (L/S) ratios were determined on 130 amniotic fluid samples obtained from 93 pregnant women between 28 and 43 weeks of gestation. Correlation of these ratios from samples obtained at parturition with the clinical course of the neonate indicated that in 91 of 95 cases the L/S ratio accurately reflected the maturity of the fetal lung. Thus, whether or not hyaline membrane disease will occur at a given time during gestation can be predicted. However, preliminary evidence suggests that the L/S determinations should be viewed with caution in predicting lung maturity of fetuses following intrauterine transfusion and in those pregnancies complicated by maternal diabetes mellitus. A case of triplets born at 28 weeks' gestation, only 2 of whom developed hyaline membrane disease, is also described. All 3 infants had L/S ratios predictive of their individual clinical courses.

Steroids in Hyaline Membrane Disease

A relationship between the adrenal and hyaline membrane disease has been suggested by the report of Naeye, Harcke, and Blanc in the April issue of Pediatrics.1 A few years ago, while active on the newborn service at the Guyan Valley Hospital, I treated a 5 lb Caucasian male premature with dyspnea, marked sternal retraction, and cyanosis. A diagnosis of hyaline membrane disease was confirmed by x-ray. Treatment with oxygen and moisture in an Isolette did not help.

INDICATIONS FOR MECHANICAL VENTILATION IN INFANTS WITH HYALINE MEMBRANE DISEASE

One hundred and four infants with a diagnosis of hyaline membrane disease who weighed more than 1,000 gm at birth were admitted to the Neonatal Unit of University College Hospital during a period of 3 years. The management of the infants is described. Seventy-two infants survived without mechanical ventilation. The remaining 32 infants became apneic or collapsed with a heart rate of less than 80/minute, did not respond to simple resuscitative measures, and were mechanically ventilated; 7 of these 32 infants survived. Only one infant survived out of a total of 22 infants who became apneic within 24 hours of delivery. Six out of 10 infants survived when apnea occurred later than 24 hours after delivery. It is concluded that mechanical ventilation is unlikely to lead to the survival of the most severely affected infants, and that controlled trials of this form of treatment are both justifiable and desirable so that its effectiveness can be properly assessed. Many infants with very severe abnormalities of gas exchange survived intact without needing mechanical ventilation. Therefore, it may be dangerous to select infants for mechanical ventilation on the basis of blood gas criteria because they may then be unnecessarily subjected to a potentially hazardous procedure.

Radiographic Diagnosis of Hyaline Membrane Disease

Radiographic Diagnosis of Hyaline Membrane Disease

“Hyaline membrane disease” in newborn infants: Macroscopic, Radiographic, and Light and Electron Microscopic Studies

Abstract o 1. This paper reviews the pathology of hyaline membrane disease using light and electron microscopy together with vascular injection experiments. Particular emphasis is placed on the ultrastructure of developing and neonatal lungs as compared to adult lungs. A sharp distinction is made between the air-blood barrier, the interalveolar septum, and the alveolar wall. 2. The appearance of the lungs differs in hyaline membrane disease depending on the postmortem interval. The classic radiologic appearance of the lungs is not present unless the lungs are re-expanded; increasing the postmortem interval produces a variable and uneven air expansion pattern and more prominent pulmonary edema. In addition, reparative and reactive changes occur if the children live any significant length of time. 3. Hyaline membranes are still the most reliable criterion for the diagnosis of hyaline membrane disease. These membranes are the result of increased plasma transudation, epithelial necrosis, and inhaled amniotic fluid. Fibrin is only exceptionally observed. 4. Pulmonary lymphatics are enlarged and distended in hyaline membrane disease. This study provided a unique opportunity to investigate the structure and function of human pulmonary lymphatics. 5. Postmortem vascular injection experiments show a filling defect involving the small muscular pulmonary arteries and the pulmonary arterioles although the pulmonary veins and venules are normal. 6. Lamellar bodies, considered to be related to the secretion of pulmonary surfactant, are present in the type II alveolar epithelial cells in hyaline membrane disease. Typical lamellar bodies and multivesicular bodies were also observed in the terminal air spaces of a fetus of 20 weeks' gestation. 7. There are multiple, apparently related mechanisms involved in the pathogenesis and outcome of the idiopathic respiratory distress syndrome, and it is not as yet certain which is primary. Important factors seem to be high pulmonary vascular resistance; impaired or deficient surfactant activity; increased alveolar wall permeability and transudation; and inhaled amniotic fluid. Secondary phenomena seem to be epithelial necrosis and hyaline membrane formation, lymphangiectasis and lymphatic congestion, interstitial and reparative phenomena, and pulmonary edema and pulmonary hemorrhage. 8. More data should be available about, and investigations directed toward, gestation, intrauterine development, and birth of infants with hyaline membrane disease as the disease seems not to start after birth but be induced before it.