In our last two posts we explained the rationale for assessing fetal lung maturity – minimizing the risks for fetal complications related to respiratory distress syndrome (RDS). This has become increasingly important as we try to reduce the morbidity associated with iatrogenic preterm delivery secondary to elective induction of labor and cesarean sections, particularly, when the mother has an uncertain date of conception, late entry to prenatal care, or medical conditions, such as diabetes, that can result in a delay in fetal lung maturation – specifically, in the production of surfactants. The only method currently available for assessing fetal lung maturity is sampling of amniotic fluid by the invasive procedure called amniocentesis. However, there are several different ‘tests’ that can be performed once that fluid is obtained. In this post, let us look at the first two that were introduced in the 1970’s.
In 1971, Gluck and colleagues (Am J Obstet Gynecol 1971;109:440-45) described the first test that became widely used to assess fetal lung maturity – the lecithin/sphingomyelin (L/S) ratio. The rationale for the test is as follows: sphingomyelin is present in amniotic fluid in relatively constant amounts during the third trimester and is not contained in fluids produced by the fetal lungs; whereas, lecithin, which is produced by the lungs, begins to increase in concentration midway through the third trimester. Using a fairly complicated procedure called thin-layer chromatography (TLC), the amounts of both substances can be assessed. The ratio of lecithin to sphingomyelin is used to compare the two because that removes the variable of amniotic fluid volume that can affect the actual concentrations of these substances. Gluck and colleagues found that an L/S ratio of 2.0 or more predicted the absence of RDS in about 98% of neonates; ratios of 1.5 to 1.9 were associated with a 50% risk of RDS; ratios below 1.5 carried a risk of 73%.
It is clear from these results that not all babies with an ‘immature’ L/S ratio will develop RDS, but this test alone does not tell us which babies will not. Furthermore, we have learned through the years that certain pregnancies, particularly those associated with maternal diabetes and/or fetal macrosomia (big babies), may be at greater risk for RDS even with low ‘mature’ L/S ratios – indeed under these clinical circumstances, some providers prefer to see an L/S ratio equal to or greater than 2.5. The presence of maternal blood can falsely lower the L/S ratio and the presence of fetal meconium (feces) in the amniotic fluid can falsely elevate the L/S ratio.
The next test, introduced in the mid-1970’s by Hallman and colleagues (Am J Obstet Gynecol 1976;125:613-17), was assessment of amniotic fluid for the presence of phosphatidylglycerol (PG). These investigators found that PG production by the lungs did not begin to increase until several weeks after the rise in lecithin – and usually was not detectable in significant amounts before 36 weeks’ gestation. PG appears to be involved in the distribution of ‘surfactants’ over the surface of the alveoli. Its presence then, by both timing of production and action, has been found to be associated with a high likelihood of fetal lung maturity. It too was originally assayed by TLC and was simply reported as “present” or “absent” without any quantitative determination.
In recent years, slide agglutination assays have simplified the assessment of PG with a “positive” threshold set at greater than 2%. Like the L/S ratio, the presence of PG also predicts the absence of RDS in 95% or more of cases, but again, its absence does not necessarily indicate the baby will develop RDS. Many providers prefer to see the presence of PG in those conditions associated with delayed fetal lung maturity before proceeding with elective delivery, particularly when there are low ‘mature’ L/S ratios. Furthermore, since detection of PG is not affected by the presence of blood or meconium, it can be used to assess fetal lung maturity on samples of amniotic fluid obtained vaginally in cases of premature rupture of membranes. Measurement of L/S ratios under these circumstances is less reliable unless a very clean specimen is obtained.
These two tests for fetal lung maturity were the first to be widely employed and their value has withstood the test of time. In the next post we will conclude our discussion of fetal lung maturity assessment with several other tests that have been introduced more recently...