Assessment of Fetal Lung Maturity Dr. Ashraf Fawzy Nabhan Assistant Professor of Obstetrics & Gynecology Ain Shams University, Cairo, Egypt Ashraf F I Nabhan

Vision Statement An obstetric practice where the unnecessary tragedy of iatrogenic prematurity no longer exists Ashraf F I Nabhan

Objective This presentation reviews those techniques that enable the obstetrician to predict accurately the risks of respiratory distress syndrome (RDS) for the infant requiring premature delivery and to avoid the unnecessary tragedy of iatrogenic prematurity Ashraf F I Nabhan

How Did We Get Here? Prior to the now common practice of using ultrasound to establish gestational age and amniotic fluid studies to assess fetal pulmonary maturation, iatrogenic prematurity was an important clinical problem. Untimely or unwarranted intervention was responsible for 15 percent of cases of RDS. Ashraf F I Nabhan

Today’s Situation Modern Obstetric practice has shown a decline in iatrogenic prematurity and RDS. Several changes in clinical practice appear to have decreased the incidence of RDS due to iatrogenic prematurity The corner stone of those changes appear to be the increased availability of ultrasound and fetal lung maturity studies and advances in the application and interpretation of these diagnostic procedures Ashraf F I Nabhan

Available Options Quantitation of Pulmonary Surfactant Measurement of Surfactant Function Evaluation of Amniotic Fluid Turbidity Appropriate use of Ultrasonography Ashraf F I Nabhan

Quantitation of Pulmonary Surfactant: L/S Ratio It is the most valuable assay for the assessment of fetal pulmonary maturity. At 32 weeks the L/S ratio reaches 1. Lecithin then rises rapidly, and an L/S ratio of 2.0 is observed at 35 weeks. A ratio of 2.0 or greater has repeatedly been associated with pulmonary maturity. Ashraf F I Nabhan

Quantitation of Pulmonary Surfactant: L/S Ratio A mature L/S ratio predicted the absence of RDS in 98 percent of neonates. With a ratio of 1.5 to 1.9, approximately 50 percent of infants will develop RDS. Below 1.5, the risk of subsequent RDS increases to 73 percent. Thus, the L/S ratio, like most indices of fetal pulmonary maturation, rarely errs when predicting fetal pulmonary maturity, but is frequently incorrect when predicting subsequent RDS. Many neonates with an immature L/S ratio will not develop RDS. Ashraf F I Nabhan

Quantitation of Pulmonary Surfactant: Test for PG A rapid immunologic semiquantitative agglutination test (Amniostat-FLM) can be used to determine the presence of PG. It can detect PG at a concentration >0.5 μg/ml. It takes 20 to 30 minutes to perform and requires only 1.5 ml of amniotic fluid. It is highly sensitive. A positive Amniostat-FLM correlates well with the presence of PG by thin-layer chromatography and the absence of subsequent RDS. It can be applied to samples contaminated by blood and meconium. Ashraf F I Nabhan

Quantitation of Pulmonary Surfactant: Microviscosimeter The relative lipid content of amniotic fluid may be evaluated by fluorescence depolarization analysis. It is an expensive test. Ashraf F I Nabhan

Quantitation of Pulmonary Surfactant: TDx Test The TDx analyzer is an automated fluorescence polarimeter to determine surfactant albumin ratio The test requires 1 ml of amniotic fluid and can be run in less than 1 hour. The surfactant albumin ratio (SAR) is determined with amniotic fluid albumin used as an internal reference. A ratio of 50 to 70 mg surfactant per gram of albumin is considered mature. The TDx test correlates well with the L/S ratio and has few falsely mature results, making it an excellent screening test. Ashraf F I Nabhan

Measurement of Surfactant Function: Shake Test It evaluates the ability of pulmonary surfactant to generate a stable foam in the presence of ethanol. Ethanol, a nonfoaming competitive surfactant, eliminates the contributions of protein, bile salts, and salts of free fatty acids to the formation of a stable foam. At an ethanol concentration of 47.5 percent, stable bubbles that form after shaking are due to amniotic fluid lecithin. Positive tests, a complete ring of bubbles at the meniscus with a 1:2 dilution of amniotic fluid, are rarely associated with neonatal RDS. It is a screening test that gives useful information if mature. Ashraf F I Nabhan

Measurement of Surfactant Function: Foam Stability Index The test is based on the manual foam stability index (FSI), a variation of the shake test. The kit currently available contains test wells with a predispensed volume of ethanol. The addition of 0.5-ml amniotic fluid to each test well in the kit produces final ethanol volumes of 44 to 50 percent. A control well contains sufficient surfactant in 50 percent ethanol to produce an example of the stable foam end point. The amniotic fluid:ethanol mixture is first shaken, and the FSI value is read as the highest value well in which a ring of stable foam persists. Ashraf F I Nabhan

Measurement of Surfactant Function: Foam Stability Index This test appears to be a reliable predictor of fetal lung maturity. Subsequent RDS is very unlikely with an FSI value of 47 or higher. The methodology is simple, and the test can be performed at any time of day by persons who have had only minimal instruction. The assay appears to be extremely sensitive, with a high proportion of immature results being associated with RDS, as well as moderately specific, with a high proportion of mature results predicting the absence of RDS. Contamination of the amniotic fluid specimen by blood or meconium invalidates the FSI results. The FSI can function well as a screening test. Ashraf F I Nabhan

Measurement of Surfactant Function: Tap Test It is a rapid semiquantitative measurement of surfactant function. In amniotic fluid from the mature fetus, the bubbles quickly rise from the bottom layer of the amniotic fluid to the surface and break down, while in amniotic fluid from an immature fetus the bubbles are stable or break down slowly. Note that these end points are opposite those used in the FSI or shake test. The cut-off for maturity is five bubbles. If no more than five bubbles persist in the ether layer, the test is considered mature. The test is read at 2, 5, and 10 minutes. Ashraf F I Nabhan

Measurement of Surfactant Function: Tap Test Fluid obtained from both amniocentesis or a freely flowing vaginal pool may be used. Amniotic fluid contaminated by blood, meconium, or vaginal mucus should be centrifuged before the assay is performed. Fluid contaminated by blood or meconium or obtained from the vaginal pool did not demonstrate an increased incidence of falsely mature tests. The tap test may be a valuable screening test, particularly if a phospholipid profile is not available. Ashraf F I Nabhan

Evaluation of Amniotic Fluid Turbidity: Visual Inspection During the first and second trimesters, amniotic fluid is yellow and clear. It becomes colorless in the third trimester. By 33 to 34 weeks' gestation, cloudiness and flocculation are noted, and, as term approaches, vernix appears. Amniotic fluid with obvious vernix or fluid so turbid will usually have a mature L/S ratio. Ashraf F I Nabhan

Evaluation of Amniotic Fluid Turbidity: Optical Density This method is thought to evaluate the turbidity changes in amniotic fluid that are dependent on the total amniotic fluid phospholipid concentration. An OD of 0.15 or greater at wavelength at 650 nm correlates extremely well with a mature L/S ratio and the absence of RDS. Contamination with blood or meconium invalidates the results. Ashraf F I Nabhan

Evaluation of Amniotic Fluid Turbidity: Lamellar Body Counts Lamellar bodies are the storage form of surfactant. The test requires <1 ml of amniotic fluid and takes 15 minutes to perform. A lamellar body count >30,000/μl is highly predictive of pulmonary maturity, while a count <10,000/μl suggests a risk for RDS. Neither meconium nor lysed blood has an effect on the lamellar body count. Ashraf F I Nabhan

Appropriate use of ultrasound Grade 3 placenta in an uncomplicated pregnancy at term suggests fetal pulmonary maturation. This approach is not reliable in pregnancies complicated by hypertension, DM, IUGR, and Rh isoimmunization BPD of at least 9.2 cm will reliably predict the absence of RDS in uncomplicated pregnancies. This approach should not be used for patients with DM. The most appropriate use of ultrasound in predicting fetal lung maturity is early documentation of gestational age so that elective delivery later in pregnancy can be safely undertaken. Ashraf F I Nabhan

Recommendation An accurate assessment of gestational age and fetal maturity is essential before an elective induction of labor or cesarean delivery before the delivery of a patient whose fetus may not have matured normally such as a growth-restricted fetus or the fetus of a poorly controlled diabetic mother. Ashraf F I Nabhan