Index Of Fetal Lung Maturity Research Articles

Microviscosity of amniotic fluid as an index of fetal lung maturity.

Microviscosity of amniotic fluid as an index of fetal lung maturity.

Total surface-active phospholipid/sphingomyelin ratio as an index of fetal lung maturity.

As an index of fetal lung maturity, the ratio of total surface-active phospholipid (phosphatidylethanolamine + phosphatidylinositol + phosphatidyglycerol + lecithin) to sphingomyelin performs as well as or better than any other indicator that we tested, showing 92% sensitivity and 98% specificity. The sensitivity and specificity, respectively, of the other methods were: (a) lecithin/sphingomyelin ratio, 92% and 95%; (b) alkaline phosphatase/glutamyltransferase ratio, 100% and 49%; (c) microviscosity, 75% and 97%; and (d) adsorbance at 650 nm, 50% and 73%. The procedure requires 2 h or less and its simplicity allows it to be offered on a 24 h/day basis without necessitating special training.

Amniotic Fluid Phospholipid Profile Determined by Two-Dimensional Thin-Layer Chromatography as Index of Fetal Lung Maturation

A phospholipid profile, the main features of which were the lecithin/sphingomyelin (L/S) ratio and the presence or absence of phosphatidylglycerol (PG), was determined in amniotic fluid from 188 patients. There was a mature profile (L/S ratio of at least 2 . 0 and detectable PG) in 145 patients, including seven insulin-dependent diabetics, and noe of their babies developed respiratory distress syndrome (RDS). The L/S ratio was less than 2 . 0 and PG absent in 12 patients, nine of whose babies developed RDS, whereas only three small babies (delivered between 28 and 35 weeks because of fulminant pre-eclampsia or severe abruptio placentae) out of 31 developed RDS when the L/S ratio was less than 2 . 0 but PG was present. When amniotic fluid was collected from the vagina only one out of 69 babies developed RDS when PG was present (regardless of the L/S ratio), while all of seven babies developed RDS when PG was absent. It is concluded that the amniotic fluid phospholipid profile, particularly the presence or absence of PG, gives an accurate assessment of fetal lung maturation. The profile may prove a useful adjunct to the management of high-risk pregnancies, especially after premature membrane rupture and perhaps also when the mother is diabetic.

Amniotic fluid absorbance at 650 nm: A comparison with fetal lung maturity characteristics

Using the rhesus monkey as an animal model we measured several indices of fetal lung maturation including pressure-volume characteristics and phospholipid concentrations and correlated them with the absorbance of amniotic fluid at 650 nm (A650). Those parameters, which are indicative of the presence of surfactant (i.e., deflation stability, lecithin-sphingomyelin ratio, lung phosphatidylcholine, as well as disaturated phosphatidylcholine), correlate significantly with the amniotic fluid A650, even after correction for gestational age. Maximal lung volume changes, thought to be reflective of alterations in tissue forces, did not correlate with A650. These data in the rhesus fetus indicate that the A650 reflects pulmonary surfactant characteristics independent of gestational age. Accordingly, this test may prove to be an accurate predictor of the risk of the respiratory distress syndrome.

Amniotic fluid phospholipid profile determined by two-dimensional thin-layer chromatography as index of fetal lung maturation.

A phospholipid profile, the main features of which were the lecithin/sphingomyelin (L/S) ratio and the presence or absence of phosphatidylglycerol (PG), was determined in amniotic fluid from 188 patients. There was a mature profile (L/S ratio of at least 2 . 0 and detectable PG) in 145 patients, including seven insulin-dependent diabetics, and noe of their babies developed respiratory distress syndrome (RDS). The L/S ratio was less than 2 . 0 and PG absent in 12 patients, nine of whose babies developed RDS, whereas only three small babies (delivered between 28 and 35 weeks because of fulminant pre-eclampsia or severe abruptio placentae) out of 31 developed RDS when the L/S ratio was less than 2 . 0 but PG was present. When amniotic fluid was collected from the vagina only one out of 69 babies developed RDS when PG was present (regardless of the L/S ratio), while all of seven babies developed RDS when PG was absent. It is concluded that the amniotic fluid phospholipid profile, particularly the presence or absence of PG, gives an accurate assessment of fetal lung maturation. The profile may prove a useful adjunct to the management of high-risk pregnancies, especially after premature membrane rupture and perhaps also when the mother is diabetic.

A study of the procoagulant properties of amniotic fluid and their correlation with the lecithin/sphingomyelin ratio.

The procoagulant properties of amniotic fluid have been studied in samples taken throughout pregnancy and the results correlated with the lecithin/sphingomyelin ratio: acceleration effects on the prothrombin time. Russell's viper venom test, activated partial thromboplastin time and specific factor VII and X assays and contact acceleration. Although amniotic fluid is shown to function as a complete thromboplastin and to activate factor X directly, none of these tests of procoagulant activity of amniotic fluid is a reliable index of fetal lung maturity.

Formation of acidic phospholipids in rabbit lung during perinatal development.

Summary: Phospholipids were measured in the lamellar bodies and alveolar lavage of perinatal rabbits. Between 28 and 31 fetal days, phosphatidylinositol (PI) increased, and phosphatidylserine decreased. Small amounts of phosphatidylglycerol (PG) appeared at term. After birth, PG markedly increased and PI concomitantly decreased. PG increased prematurely after removal from the uterus of fetuses 29 days gestation or more. Fatty acid analysis of PG and PI revealed the presence of 62 to 63%, and 58 to 59%, of saturated species, respectively. As measured in total lung homogenate, PI increased between 28 and 31 fetal days, and PG increased between term and the first neonatal day. Glycerol incorporation into PG increased at birth, according to the measurement of lung slices. myo-Inositol incorporation into PI increased in the fetus parallel to accumulation of surfactant. The development of the following enzyme activities was studied in subcellular fractions derived from lung homogenates: phosphatidate cytidyltransferase, cytidine 5′-diphosphate (CDP)-diglyceride:inositol transferase, glycerophosphate phosphatidyltransferase, and phosphatidylglycerophosphatase. As measured in the microsomal fraction, all the activities increased between 27 and 30 fetal days. Shortly after birth, phosphatidate cytidyltransferase and glycerophosphate phosphatidyltransferase increased further, whereas the two other enzyme activities decreased somewhat. Cytidine 5′-diphosphate diglyceride:inositol transferase increased after the newborn period. There were only small developmental changes in Km's. In contrast to microsomes, the mitochondrial activities mainly decreased during development. Phosphatidylglycerophosphatase was the only activity that was present in significant amounts in lamellar bodies. It is proposed that the developmental changes in the acidic surfactant phospholipids are due to changes in the biosynthesis rates in type II cell microsomes. This may be controlled both by changes in the enzyme activities (phosphatidate cytidyltransferase, cytidine 5′-diphosphate diglyceride:inositol transferase, and glycerophosphate phosphatidyltransferase) and by changes in substrate concentrations (myo-inositol and sn-glycerol-3-P). Speculation: Besides surfactant lecithin, phosphatidylglycerol is critical to alveolar stability and its absence may precipitate respiratory distress syndrome in the newborn. Surfactant phosphatidylglycerol and phosphatidylinositol serve as indices of fetal lung maturity or help to specify diagnosis of respiratory distress in the neonate. Because several hormones seem to regulate individual surfactant phospholipids, the measurement of these components (lung profile) could be a way to analyze consequences of hormonal or nutritional balance and eventually correct it if necessary.

Amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5’-nucleotidase activity from 13 to 40 weeks’ gestation, and alkaline phosphatase as an index of fetal lung maturity.

Abstract Reference ranges for amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5-nucleotidase are described from 13 to 40 weeks’ gestation. Gamma-glutamyltransferase and 5-nucleotidase activities peak early in the second trimester and then decrease to low values. Alkaline phosphatase shows a similar pattern of activity from 13 to 29 weeks’ gestation, but thereafter activity increases to term; this late increase is mainly related to the heat-labile particulate form of alkaline phosphatase. Total and heat-labile alkaline phosphatase alone or expressed as a ratio with gamma-glutamyltransferase can be used with or as an alternative to lecithin/sphingomyelin ratios in the investigation of fetal lung maturity. A total alkaline phosphatase activity of 0.36 mukat/L and an alkaline phosphatase/gamma-glutamyltransferase ratio greater than 2 indicate pulmonary maturity.

Amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5’-nucleotidase activity from 13 to 40 weeks’ gestation, and alkaline phosphatase as an index of fetal lung maturity.

Reference ranges for amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5-nucleotidase are described from 13 to 40 weeks' gestation. Gamma-glutamyltransferase and 5-nucleotidase activities peak early in the second trimester and then decrease to low values. Alkaline phosphatase shows a similar pattern of activity from 13 to 29 weeks' gestation, but thereafter activity increases to term; this late increase is mainly related to the heat-labile particulate form of alkaline phosphatase. Total and heat-labile alkaline phosphatase alone or expressed as a ratio with gamma-glutamyltransferase can be used with or as an alternative to lecithin/sphingomyelin ratios in the investigation of fetal lung maturity. A total alkaline phosphatase activity of 0.36 mukat/L and an alkaline phosphatase/gamma-glutamyltransferase ratio greater than 2 indicate pulmonary maturity.

Amniotic fluid fluorescence polarization value as a predictor of respiratory distress syndrome

Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene in amniotic fluid lipid aggregates was measured to determine the ability of this technique to prospectively predict respiratory distress syndrome. Prior retrospective studies have shown that an FP value of less than or equal to 0.336 correlated best with a lecithin to sphingomyelin ratio of greater than 2.0. Fluorescence polarization values of amniotic fluid samples obtained within 48 hours of birth from 161 pregnancies were correlated with neonatal outcome. Samples from 149 pregnancies had FP values of less than or equal to 0.336 and samples from 12 pregnancies had FP values of greater than or equal to 0.336. No infants delivered from the former group developed RDS and eight of 12 infants from the latter group developed RDS (P less than 0.001). In the entire population the test had a sensitivity of 100% and a specificity of 97%. When 37 infants with birth weights less than 2,500 gm were studied, the FP value remained a highly reliable predictor of the infant at risk for developing RDS (P less than 0.001). In this subset the test had a sensitivity of 100% and a specificity of 90%. L-S ratios were performed on 96 samples and the results correlated well with FP values (P less than 0.001). We conclude that the amniotic fluid FP value is a reliable index of fetal lung maturity and the risk for developing RDS. The FP value also has specific technical and diagnostic advantages over the L-S ratio.

Pulmonary lamellar bodies in human amniotic fluid: Their relationship to fetal age and the lecithin/sphingomyelin ratio

We investigated the appearance of pulmonary lamellar bodies (LBs) in human amniotic fluid as a function of fetal age. We also studied their relationship to the lecithin/sphingomyelin (L/S) ratio and to the results of the rapid surfactant test (RST). LBs observed in amniotic fluid generally ranged in diameter from 1.5 to 2.0 μ and were seen as single structures or in clusters. When patients were grouped by gestational age, there was a significant difference (P < 0.001) in the distribution of amniotic fluid LBs. No LBs were observed in amniotic fluid before 26 weeks' gestation, but 50% of specimens at 28 to 32 weeks' gestation and 85% of specimens at term had LBs. Patients with amniotic fluid LBs had higher L/S ratios and intermediate or mature RST values when compared to patients without LBs, but a statistically significant relationship between the presence of LBs and the L/S ratio or RST was not found. We conclude that qualitative examination of amniotic fluid LB content by conventional electron microscopy is unlikely to reflect fetal lung maturation in a precise manner. However, direct quantification of LBs may provide a more specific index of fetal lung maturity and the risk of respiratory distress syndrome.

Corticosteroids in amniotic fluid and their relationship to fetal lung maturation

Cortisol, progesterone, 11-deoxycortisol and deoxycorticosterone were measured in amniotic fluid from sixty-four subjects. Palmitic acid was measured as an index of fetal lung maturation. The correlation coefficient between cortisol and palmitate levels was 0.46. The ratio of progesterone to deoxycorticoster-one decreased significantly ( P < 0.05) between the 34–35th and 36–37th weeks of gestation, suggesting the induction of the steroid 21-hydroxylase enzyme system. This preceded the significant rise ( P < 0.05) in cortisol levels between the 36–37th weeks and the 38–39th weeks. The greatest rise of palmitic acid did not occur until a week later, and after the period when lung maturation had presumably occurred.

Determination of disaturated lecithin in rhesus monkey amniotic fluid as an index of fetal lung maturity

Although increased concentrations of total lecithin in amniotic fluid allow prenatal assessment of fetal lung maturation, it has become clear that routine use of the L/S index may lead to a substantial number of inaccurate predictions. Since disaturated lecithin (DL) is a more specific marker of pulmonary surfactant than total lecithin, we developed a convenient method for measuring this phospholipid in amniotic fluid, and then evaluated its level in pregnant rhesus monkeys of 120 to 163 days of gestation. The method involves osmic acid destruction of unsaturated lipids, chromatographic isolation of disaturated lecithin, and quantitation by phosphorus assay. It can be performed in approximately 5 hours on 4 ml. of amniotic fluid and yields 67 ± 3 per cent average recovery of added 14C-dipalmitoyl lecithin. The results of analyzing 36 rhesus amniotic fluid specimens showed that disaturated lecithin and the disaturated lecithin/sphingomyelin ratio (DL/S) increase sharply after 150 days of gestation, consistent with the pattern of lung maturation in this species. We conclude that disaturated lecithin can be readily quantitated in primate amniotic fluid and that its concentration, the DL/S ratio, and percentage of disaturated lecithin are potentially useful indices of fetal lung maturity for the clinical laboratory.

The measurement of phosphatidate phosphohydrolase in human amniotic fluid

Phosphatidate phosphohydrolase (EC 3.1.3.4) activity can be found in late gestational human amniotic fluid and is thought to originate in type II alveolar cells of the fetal lungs where it plays an important role in lung surfactant synthesis. In the present study, phosphatidate phosphohydrolase activity was detected and characterized in a 105 000 × g pellet of amniotic fluid using either [ 32P] phosphatidate or a water-soluble analog, 1- O-hexadecyl- rac-[2- 3 H]glycerol 3-phosphate as substrate. With either substrate, enzyme activity was optimal at pH 6.0. The soluble analog was hydrolyzed with a K m value of 163 μM and a V of 30 nmol/min per mg of protein, and offered several advantages over phosphatidate as a substrate for assaying phosphatidate phosphohydrolase in amniotic fluid. Using the synthetic analog, phosphatidate phosphohydrolase activity was measured in the 700 × g supernatant fraction of 30 human amniocentesis samples and compared with another index of fetal lung maturity, the phosphatidylcholine/sphingomyelin ratio. The results suggest that the new phosphohydrolase assay may be clinically useful in the assessment of fetal lung development.

Foam-Stability Test on Gastric Aspirate and the Diagnosis of Respiratory-Distress Syndrome

Gastric aspirate, collected from 79 infants within 30 minutes of birth, was subjected to the foam-stability test. The lecithin/sphingomyelin ratio was determined in 27. The results were compared with the incidence of respiratory-distress syndrome as determined independently by different investigators. Of the 59 infants with a positive foam-stability test on gastric aspirate, three had transient respiratory distress, and one the respiratory-distress syndrome; 17 of 22 had lecithin/sphingomyelin ratios greater than 2.0. Of nine infants who had intermediate test results, three were normal, four had transient respiratory distress, and two had the respiratory-distress syndrome. In all the 11 infants with negative foam-stability tests the respiratory-distress syndrome developed. The three gastric aspirates tested in this group had lecithin/sphingomyelin ratios of less than 1.5. These data indicate that the foam-stability test on gastric aspirate is a reliable index of fetal lung maturity in infants whose amniotic fluid is not available.

Amniotic fluid phospholipids and fetal lung maturity: I. Assessment of various methods of determining lecithin and sphingomyelin

The measurement of the lecithin/sphingomyelin ratio in amniotic fluid as an index of fetal lung maturity has been a controversial and much-discussed topic since the initial report of this procedure appeared in the literature in 1971. Our laboratory has investigated several methods of measuring phospholipid components of amniotic fluid and compared relative reproducibility and accuracy. Correlation of these phospholipid determinations with the clinical presence or absence and relative severity of neonatal respiratory distress syndrome forms the basis of this report. Our findings indicate that careful attention to the biochemical basis of this test results in the ability to predict with great accuracy developmental respiratory distress syndrome. This presentation describes our method of determining lecithin/sphingomyelin ratios in amniotic fluid, compares our results with other tests for determining fetal maturity, and assesses the value of this procedure in clinical situations.

The Lecithin-Sphingomyelin Ratio of Amniotic Fluid: An Index of Fetal Lung Maturity?

The proportion of lecithin (L) to sphingomyelin (S) measured in amniotic fluid has been proposed as an index of fetal lung maturity.1 A ratio of L to S of 1.5 or less has been correlated with hyaline membrane disease in the postnatal period. Therefore, prevention or delay of immediate delivery has been advocated in such circumstances. In our laboratory, the L to S ratio (L/S) was determined immediately before birth in 88 amniotic fluid samples obtained by amniocentesis between the 8th and 46th week of gestation.

PREDICTION OF NEONATAL RESPIRATORY DISTRESS BY ESTIMATION OF AMNIOTIC-FLUID LECITHIN

A simple chemical method for estimating the total lipid, phospholipid, and lecithin content of amniotic fluid is described. It has been used to test the hypothesis that neonatal respiratory function is related to the pre-delivery levels of these substances in amniotic fluid. 171 samples of amniotic fluid taken at different stages of pregnancy from 156 patients were assayed; 110 samples were obtained in the 24 hours before delivery of the infant. Amniotic-fluid lecithin levels of around 3·5 mg. per 100 ml. would seem to be critical, for pre-delivery levels above this value were in every case associated with normal respiratory function, even in 12 infants who were "small for dates " or premature. By contrast the pre-delivery amniotic-fluid lecithin concentration was below 3·5 mg. per 100 ml. (range 0·6-3·4 mg. per 100 ml.) in 12 out of 13 infants who developed respiratory-distress syndrome. The lecithin concentration in the amniotic fluid seems to be a sensitive index of fetal lung maturity and of the potential risk of respiratory distress developing in the baby.