When is an amniocentesis for fetal maturity unnecessary in nondiabetic pregnancies at risk?

For several years standard obstetric practice has been to perform an amniocentesis for evaluation of fetal maturity. In order to provide a more definitive answer as to which pregnancies need an amniocentesis, a group of 294 nondiabetic pregnant women in whom an amniocentesis for the evaluation of fetal maturity had been performed for clinical indications were evaluated. Three predictors of fetal maturity—obstetric estimate of gestational age, fetal biparietal diameter, and ultrasonic determination of placental maturation—were evaluated for their ability to predict three outcomes of fetal maturity, including positive amniotic fluid phosphatidylglycerol, pediatric estimate of gestational age ≥38 weeks, and absence of hyaline membrane disease. A fetal biparietal diameter of ≥90 mm was present in 36% of the total population and was associated with 97% term delivery, 87% positive amniotic fluid phosphatidylglycerol, and 0% hyaline membrane disease. The results associated with an obstetric estimate of gestational age of ≥38 weeks were similar. In the present data set over one third of clinically indicated amniocenteses could potentially be avoided without losing any predictive capability for fetal maturity.     

Critical evaluation of various methods of determining markers of fetal maturity in amniotic fluid

11 methods for investigation of fetal lung maturity, fetal skin maturity and common maturity signs were described. All investigations have been carried out on the base of 61 amniotic fluid samples. A certain declaration of fetal lung maturity is possible by: 1. The absorbance of native amniotic fluid at 650 nm 2. Shake-test (Clements) 3. Average quantities of the keratinocytes of the amniotic fluid cell population. Good results, a small amniotic fluid quantity and a simple procedure characterise these methods. They are usefull in clinical practice.     

Fetal pulmonary maturity in isoimmunized pregnancies

That the lecithin/sphingomyelin (L/S) ratio correlates very closely with fetal gestational age in the uncomplicated pregnancy is well accepted. The presence of fetal or maternal disease has been found to accelerate or retard the development of fetal lung maturity in certain pregnancies. Although only a very small number of isoimmunized pregnancies has been evaluated in the obstetric literature, there is general acceptance that most isoimmunized pregnancies have delayed pulmonary maturation. Our observation has been that, in mild to moderately severe isoimmunized pregnancies, fetal lung maturation is not delayed. This study was designed to compare fetal pulmonary maturation in pregnancies affected by isoimmunization to that in a control group of unaffected but sensitized pregnancies. The results of this study suggest that pulmonary maturation in the mild to moderately affected pregnancy as measured by the L/S ratio is neither delayed nor accelerated but unchanged when comparison is made to the control group.     

Iatrogenic prematurity due to elective termination of the uncomplicated pregnancy: A major perinatal health care problem

In a series of 1,000 newborn infants referred to a regional neonatal center, 32 iatrogenically preterm infants were identified. All had been delivered following elective termination of uncomplicated, apparently term pregnancies, without prior documentation of fetal lung maturity or ultrasonic determination of fetal biparietal diameter. Associated acute morbidity included asphyxia neonatorum in 10, respiratory distress syndrome in 24, and pneumothorax or pneumomediastinum in nine patients. One infant died. Hospital costs totaled $150,643, for a mean of $4,701 per patient. The unexpected premature births were associated with major parental grief reactions and alterations in their daily activities. latrogenic prematurity is a major regional health care problem which, when viewed on a national basis, may affect thousands of newborn infants and their families annually. Our data suggest the need for more accurate assessment of fetal maturity, before elective termination of pregnancy, by well-established techniques.     

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.     

Deficient lung surfactant apoproteins in amniotic fluid with mature phospholipid profile from diabetic pregnancies

An enzyme-linked immunoassay to quantitate lung surfactant apoproteins (15 to 250 ng/ml) in human amniotic fluid is described. The immunoassay was used to quantify lung surfactant in 72 samples of amniotic fluid, for which lecithin/sphingomyelin (L/S) ratios, lecithin and phosphatidylglycerol concentrations, and foam stability indices were also available. The results obtained with the immunoassay were in general agreement with those of the other methods. Measurement of the apoproteins, however, may be a better predictor of fetal lung immaturity and of respiratory distress syndrome than the L/S ratio and the concentration of lecithin. This conclusion is based on the data obtained in the analyses of samples of amniotic fluid from four diabetic and five nondiabetic pregnancies, the infants of which developed respiratory distress. In all cases, the apoprotein concentration was less than 2.1 micrograms/ml, which indicated fetal lung immaturity. In six of these cases (one diabetic and five nondiabetic pregnancies), lung immaturity was also predicted on the basis of other tests. However, in three other cases of diabetic pregnancy, the L/S ratio and lecithin concentration falsely indicated lung maturity. In addition to its being an effective predictor of fetal lung maturity in diabetic, as well as nondiabetic, pregnancies, the immunoassay is better suited for clinical use because of its high specificity, sensitivity, and ease of performance.     

Fluctuation of fetal hemoglobin in sickle-cell anemia

A reduction of morbidity and mortality rates in homozygous sickle-cell patients was found in those with high fetal hemoglobin (Hb_F) levels. This factor would lead one to believe that an adequate amount of this substance would be protective to a patient with this hemoglobinopathy. This study utilizing pregnant and nongravid females, as well as males, followed for long periods of time indicates that the Hb_F level fluctuates with crisis. Some patients had low Hb_F levels with many crises and others had high amounts of Hb_F with no crisis. However, many patients with high levels on one occasion demonstrated a decrease in Hb_F levels when crisis occurred. More importantly, no patient had high levels of Hb_F during a crisis although the amount was elevated before and after the episodes. The possible explanation and ramifications of this finding are discussed.     

Absorbance of amniotic fluid at 650 nm as a fetal lung maturity test: A comparison with the lecithin/sphingomyelin ratio and tests for disaturated phosphatidylcholine and phosphatidylglycerol

We compared absorbance of amniotic fluid at 650 nm (A₆₅₀) against the lecithin/sphingomyelin ratio, the quantity of disaturated phosphatidylcholine, and the presence or absence of phosphatidylglycerol in 374 uncontaminated amniotic fluid samples. In addition, we studied these measures of fetal lung maturity in 80 pregnancies where neonatal outcomes were known. Statistical analysis revealed a significant association between increasing absorbance and biochemical indices of lung maturation. Our results indicate that A₆₅₀ of amniotic fluid is useful as a measure of lung maturity but that the greatest utility may be for samples with either low absorbance (<0.10) or high absorbance (>0.20). Because of large false positive and false negative values between these two absorbances, other lung maturity estimates should be used when absorbances fall within this range. Therefore, A₆₅₀ may be most useful as a screen or as part of a battery of lung maturity estimates. We are exploring these possibilities as a means of providing better fetal lung maturity estimates.     

Rapid assessment of fetal pulmonary maturity

The absorbance of amniotic fluid at 653 nm has been measured in 300 specimens and found to have a significant correlation with the L/S ratio. Then 118 patients were further evaluated for neonatal outcome. RDS was absent in 99% of patients with mature absorbance values. This determination has the advantage of rapid performance without specialized equipment or training and represents a significant contribution to the assessment of fetal pulmonary maturity.     

Clinical applications of ultrasound in obstetrics and gynecology

Pulsed echo ultrasound is a valid and reliable procedure and is being employed with increasing frequency in the study of many obstetric and gynecologic problems. Experience with over 3,000 patients indicates a high degree of accuracy in diagnosis of early pregnancy, multiple pregnancy, hydatid mole, and fetal death; in placental localization, and in the measurement of biparietal diameter of the fetal head. Serial measurements of the biparietal diameter are valuable in following growth and development and in determining maturity. This is particularly useful in establishing the time for elective repeat cesarean section. In conjunction with other diagnostic procedures and clinical judgement, ultrasound is helpful in the differential diagnosis of pelvic masses, in following the progress of cancer cases under therapy, and in localization of intrauterine contraceptive devices. Toxicity studies indicate low-intensity ultrasound is safe for both the mother and fetus.     

Amniotic fluid tests for fetal maturity in normal and abnormal pregnancies.

The lecithin-sphingomyelin (L/S) ratio is acknowledged to be superior to most procedures for predictinf fetal lung maturity in normal pregnancy. In complicated gestations, however, errors have been reported. This study involves 686 normal gestations and 389 pregnancies complicated by fetomaternal diseases. The L/S ratio, creatinine level, and percent of fat-staining cells were measured in samples of amniotic fluid from these patients. The results showed good correlation of all three tests with fetal maturity as measured by weight, Dubowitz criteria, and incidence of respiratory distress syndrome in the normal patients. In the complicated pregnancies, however, the creatinine was unacceptable in up to 30% of the cases. The L/S ratio likewise decreased in accuracy for all parameters of fetal maturity measured. The Nile blue staining of the fetal cells appeared to be the most consistent technic in these cases. A fetal maturity battery comprised of these three assays and other methods of assessing fetal health is advocated in pregnancies complicated by certain disease states.     

Clinical and economic considerations associated with testing for fetal lung maturity

Performing multiple tests of fetal lung maturity on amniotic fluid samples may not use the individual test results and laboratory personnel most effectively. To determine the best strategy for fetal lung maturity testing, we analyzed our experience with use of a variety of procedures. Clinical usefulness was assessed according to sensitivity, specificity, predictive values, and efficiency. Economic and technical aspects analyzed included time and personnel requirements, availability of tests, and expense of each procedure. Several testing sequence approaches were compared for efficiency and cost. In our laboratory the foam stability index proved to be the most useful initial test of fetal lung maturity, reserving more expensive and time-consuming tests for instances in which the foam stability index is immature. Routine multiple testing did not enhance clinical usefulness and greatly increased costs. Development of a testing strategy using a rapid, inexpensive, and widely available test such as the foam stability index would promote clinical and economic efficiency.     

When betamethasone and dexamethasone are unavailable: hydrocortisone.

OBJECTIVE: To review the literature on alternatives to betamethasone and dexamethasone for enhancement of fetal lung maturity. STUDY DESIGN: A medline search was conducted from 1966 to the present. Trials dealing with enhancement of fetal lung maturity using modalities other than betamethasone or dexamethasone were reviewed. RESULTS: Eight studies met inclusion criteria. Excluding betamethasone and dexamethasone, the most frequently studied glucocorticoids, for fetal lung maturation, are methylprednisolone and hydrocortisone. Methylprednisolone does not cross the placenta. Two grams of hydrocortisone has been shown to improve indices of fetal lung maturity (i.e., L/S ratio) and to improve fetal outcomes compared to no treatment. CONCLUSION: There is limited information about alternatives to betamethasone and dexamethasone for the enhancement of fetal lung maturity in women at risk of preterm delivery. In the absence of these two preferred drugs, hydrocortisone can be given at a dose of 500 mg intravenously every 12 hours for four doses for this indication.     

Need for urgent delivery after third-trimester amniocentesis

OBJECTIVE: To estimate the risk of need for urgent delivery after third-trimester amniocentesis as currently done using ultrasound guidance to assess fetal lung maturity. METHODS: Ultrasound records of women scheduled for third-trimester amniocenteses to assess fetal lung maturity from February 1990 through October 1997 were reviewed for possible complications during or immediately after procedures. Collected data included gestational age, indication for the procedure, number of needle passes, transplacental passage, needle gauge, and fluid color. The primary outcome examined was procedure-related complications that required emergency delivery or the decision to deliver before completion of maturity studies. Infants who developed hyaline membrane disease leading to neonatal intensive care admission were also identified. RESULTS: During the 7 1/2-year study period, 962 amniocenteses were done to assess lung maturity. Complete data were not available for 49 cases. Of the remaining 913 procedures, 15 (1.6%) were unsuccessful (needle pass without collecting fluid). Forty-one infants were delivered spontaneously or by cesarean on the same day as the procedure. However, complications that required delivery were identified in only six cases, an incidence of 0.7% (95% confidence interval = 0.16, 1.24). Complications included fetal heart rate abnormalities (n = 3), placental bleeding (n = 1), abruptio placentae (n = 1), and uterine rupture (n = 1). Only one of six complications had a single needle pass with clear fluid collected. Hyaline membrane disease occurred in 14 neonates, including two with mature indices. CONCLUSION: Although complications that required urgent delivery after third-trimester amniocentesis are rare, the risks of the procedure should be carefully weighed against the benefits.     

The correlation of ultrasonic placental grading and fetal pulmonary maturation in five hundred sixty-three pregnancies

In a previous study, it was suggested that the presence of a grade III placenta correlates 100% with a mature lecithin/sphingomyelin (L/S) ratio and may replace amniocentesis in confirming fetal lung maturity. In this study that hypothesis was tested in 563 pregnancies. All patients underwent amniocentesis and simultaneously had placental grading. The correlations of placental grade with an L/S ration ≥2 were: grade 0, 17%; grade I, 68%; grade II, 91%; grade III, 93%. The correlations of placental grade with the presence of phosphatidylglycerol (PG) were: grade 0, 17; grade I, 41%; grade II, 79%; grade II, 75%. The false positive rates associated with grade III placenta were, therefore, 7% for mature L/S ratio and 25% for PG present; when combined with a biparietal diameter ≥9.0 cm, a grade III placenta incorrectly predicted lung maturity in 8.5%. We conclude that placental grading is not accurate enough to replace amniocentesis as the standard test of fetal pulmonary maturity.     

Fetal lung maturation in twin gestation

Clear amnionic fluid was collected at cesarean section and the lecithin/sphingomyelin (L/S) ratio was used to evaluate fetal lung maturation in 42 twin gestations. The L/S ratios of twin pairs were usually similar in both numerical value and predictive accuracy except when the greater L/S ratio from one member of a pair indicated borderline lung maturity. Twin fetal lung maturation was found to be independent of sex, zygosity, and birth weight discordance. Comparison of mean L/S ratios in twins to those of uncomplicated singleton pregnancies revealed that fetal lung maturation occurred several weeks earlier in twins.     

Rapid determination of pulmonary surfactant

Although the importance of the lecithin/sphingomyelin ratio in amniotic fluid (Gluck test) has been widely accepted as an accurate means of predicting fetal lung maturity, the test is not widely available. The importance of certain steps in the test as originally described has been ignored in some of the recent rapid tests reported for lecithin/sphingomyelin ratio determination. Modifications of the original test which make it possible for accurate performance of the test in most hospital laboratories are described. Inaccurate results from oversimplification do occur and are illustrated.     

Amniotic fluid lamellar body count and its sensitivity and specificity in evaluating of fetal lung maturity.

This prospective study was designed to perform lamellar body count of amniotic fluid to evaluate fetal lung maturity. Lamellar body counts of 80 amniotic fluid samples from 80 pregnant women (28-40 weeks of gestation) were evaluated. After delivery, each infant was evaluated for any evidence of respiratory distress syndrome. Standard clinical and radiographic criteria were used to diagnose respiratory distress syndrome, and the diagnosis was confirmed by reviewing newborn records. Twenty (25%) infants delivered within 24 hours of sample collection developed RDS. Lamellar body count more than 50,000/microl predicted pulmonary maturity. Seventeen out of 20 respiratory distress syndrome cases had been predicted correctly. The negative predictive value of lamellar body count>50,000/microl was 93% and positive predictive value was 48% and the sensitivity for prediction of RDS was 85% and specificity was 70%. Lamellar body count can be used as a favourable predictor of fetal lung maturity because it is quick, simple and universally available. Also it can be used as an extremely inexpensive, reliable screening test for evaluating fetal lung maturity.     

The utility of the TDx test in the assessment of fetal lung maturity.

Accurate assessment of fetal lung maturity is essential in the management of high-risk obstetric patients. New rapid techniques have been developed to supplement time-consuming chromatographic methods. We compared one of these newer methods, the TDx-FLM, to the standard tests for fetal pulmonary maturity. There was an excellent correlation between the TDx and the lecithin-sphingomyelin ratio (r = 0.78). Although a TDx value of 70 or greater is considered mature, we found a value of 50 or greater predictive of fetal lung maturity in 100% of cases, and have chosen to redefine a mature value as 50 or greater in our institution. This value has greatly enhanced the clinical applicability of the test, allowing use of a large number of specimens from the previously poorly understood and often disregarded borderline category.     

Relationship of placental grade to fetal pulmonary maturity and respiratory distress syndrome

Real-time sonographic placental grading was performed on 215 patients who had amniocentesis for determination of fetal pulmonary maturity between 26 and 42 weeks of gestation. The results of this placental grading were correlated with clinical gestational age and fetal pulmonary maturity, assessed by lecithin-sphingomyelin ratio, phosphatidylglycerol, and the subsequent presence or absence of respiratory distress syndrome. This study showed a statistically significant correlation of placental grade with gestational age, pulmonary maturity, and respiratory distress. Grade 3 placentas were seen in 20% of the cases studied, and in every instance was associated with an absence of subsequent neonatal respiratory distress. Placental grade appeared to be an accurate predictor of fetal pulmonary maturity in the population studied.