The Decline and Fall of a Once-promising Diagnostic Tool

Improved care for premature infants, better understanding of respiratory distress syndrome risks mark clinical exit of fetal lung maturity testing.

Curious about the impact of changing guidelines on fetal lung maturity (FLM) tests, an FLM reference laboratory in Minnesota conducted a retrospective study and discovered very low test volumes among a series of FLM assays. Sharing their study results in Clinical Biochemistry the authors are recommending that clinical lab directors and obstetric providers follow their lead—and stop using these tests to predict respiratory distress syndrome (RDS) in fetuses.
Guidelines from the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal Fetal Medicine (SMFM) had been getting increasingly restrictive over the clinical use of FLM tests, citing its poor reliability in predicting fetal and maternal health outcomes. In 2019, the groups updated their guidelines, advising against using the FLM test to make delivery decisions for the following scenarios: well-dated and suboptimally dated pregnancies, and nonmedically indicated and medically indicated early pregnancies.
The guidelines mirror what was happening in clinical practice “that is, an improved ability to care for premature infants and a simultaneous realization that more than just the fetal lung status is important for determining whether a delivery should occur,” Amy Karger, MD, PhD, assistant professor of laboratory medicine and pathology at the University of Minnesota and the study’s corresponding author, told CLN Stat.
Noticing a steady drop in FLM testing, the reference lab at the University of Minnesota Medical Center (UMMC) decided to retrospectively analyze its own FLM test volumes to assess the impact of ACOG guidelines on ordering practices. Until 2015, the lab had been using thin layer chromatography (TLC) assays to quantify amniotic fluid lecithin/sphingomyelin ratio (L/S), phosphatidylglycerol (PG), and disaturated lecithin (DSL). In 2013 it switched to lamellar body count (LBC) assays, a less laborious method, and phased out the TLC assays over a 2-year period. For the analysis, Karger and her colleagues queried UMMC’s lab information system for FLM testing terms over a 10-year period.
From 2006 to 2016, a significant drop took place in FLM testing. TLC assays had peaked in 2006 with a total volume of 2,665, split across L/S, PG, DSL tests. In contrast, the LBC assays had a peak volume of 29 test results in 2014. “Although we do not have data prior to 2006, our data support the steady downward trend for FLM testing noted in the literature,” according to the authors. UMMC discontinued the test in 2016.
Clinical research has questioned how well FLM testings predict immature (positive predictive value) and mature fetal lungs (negative predictive value). “As ACOG and SMFM addressed in several practice bulletins, studies have found that even with a mature FLM result, the neonate is still at risk for complications related to early term birth,” wrote the authors. One study of the FLM test’s negative predictive value “showed that it changes with gestational age. Additionally, gestational age alone may be the best estimator of risk for RDS,” they continued.
Improved ultrasound practices have made it easier for clinicians to predict due dates and treatment options such as antenatal corticosteroids, ventilators, and artificial surfactants are now available to reduce surface tension in infant lungs. In light of these clinical changes, the authors urged a collaborative effort between labs and obstetricians to eliminate FLM testing.
Karger anticipates a smooth phaseout of the test “given how clearly worded the current ACOG guidelines are … My suspicion is that those few providers still relying on the testing are those who have not kept up on the latest guidelines on this particular topic and are relying on their old practice habits.”