NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By David G. Grenache, PhD, FACB
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Abbott Laboratories recently announced that it was ending production of its widely used fetal lung maturity test, the TDx FLM II, due to the retirement of their TDx and TDxFLx instrument platforms.  The impact of the loss of this test on the obstetrical and clinical laboratory communities remains uncertain but one thing is clear: laboratories that currently perform the TDx FLM II test need to prepare now.  What are some options to consider?

 

Provide an Alternate Test

One obvious option is to provide an alternate test of fetal lung maturity but let’s review the choices.  The lecithin/sphingomyelin (L/S) ratio was the first test of fetal lung maturity developed by Gluck and colleagues in 1971 (1) and, because it was first, everything that came after it was compared to it.  In other words, it became the de facto gold standard test.  Despite numerous studies suggesting otherwise (2), it is still considered to be the best fetal lung maturity test by many obstetricians.  Indeed, a survey of obstetricians revealed that, in the absence of Abbott’s test, 68% would order the L/S ratio (3).  However, only ~20% of laboratories that offer fetal lung maturity testing currently perform the L/S ratio so it has limited availability.  Further, it's unlikely that laboratories that are not currently performing the L/S ratio will begin to offer it.  This is because it’s a labor-intensive test that requires considerable technical expertise to perform and it has poor analytical precision.

 

A commercially available test for the rapid detection of phosphatidylglycerol (PG) is another option.  It’s particularly attractive because it is simple to perform but has some drawbacks.  The test result is somewhat subjective to interpretation and is qualitative (mature or immature) rather than quantitative.  More importantly, PG is a late marker of lung maturity and is often undetectable until 35-36 weeks of gestation.

 

A third option is the lamellar body count (LBC).  Because lamellar bodies are approximately the same size as blood platelets, they can be enumerated using an automated hematology cell counter.  Outcome-based studies have demonstrated that the LBC performs at least as well as the TDx FLM II test (4, 5).  However, unlike the L/S ratio and rapid detection of PG, it is a laboratory-developed test, which can make implementation more challenging.

 

Refer Specimens to Another Laboratory

Rather than replacing the TDx FLM II test with another test, a laboratory may opt to simply send all fetal lung maturity test requests to a laboratory that performs one.  However, physicians typically demand and expect a relatively rapid turn-around-time for fetal lung maturity tests.  Most desire results within 12 hours of sample collection (3), an expectation that may be difficult to meet by referring tests to another laboratory.

 

Stop Offering Fetal Lung Maturity Tests

Due to improvements in gestational age dating, maternal administration of corticosteroids that accelerate fetal lung maturity in at-risk pregnancies, and exogenous surfactant replacement therapies, the number of newborn deaths due to respiratory distress syndrome has declined considerably over the last 15 years.  Most laboratories have noted a decline in the number of fetal lung maturity tests that they perform each year.  This trend reflects their decreased use by obstetricians, many of whom indicate that the tests are no longer needed for patient care (3).  Further, fetal lung maturity testing is predominantly performed in the United States.  Clinical laboratory colleagues in the European Union tell us that they rarely, if ever, perform these tests and yet the rates of infant death due to respiratory distress are no worse than they are in the US.  Has the time come to bid adieu to tests of fetal lung maturity?

 

References

 

1.         Gluck L, Kulovich MV, Borer RC, et al. Diagnosis of respiratory distress by amniocentesis. Am J Obstet Gynecol 1971;109:440-5.

2.         Grenache DG, Gronowski AM. Fetal lung maturity. Clin Biochem 2006;39:1-10.

3.         Grenache DG, Wilson AR, Gross GA, et al. Clinical and laboratory trends in fetal lung maturity testing. Clinica Chimica Acta 2010;411:1746-9.

4.         Ghidini A, Poggi SH, Spong CY, et al. Role of lamellar body count for the prediction of neonatal respiratory distress syndrome in non-diabetic pregnant women. Arch Gynecol Obstet 2005;271:325-8.

5.         Haymond S, Luzzi VI, Parvin CA, et al. A direct comparison between lamellar body counts and fluorescent polarization methods for predicting respiratory distress syndrome. Am J Clin Path 2006;126:894-9.

 

 

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Posted by
On 1/18/2011

Diane, Related to your questions regarding Lab developed tests (LDTs): Briefly, CLIA has a regulation (493.1253(2)) which specifies what parameters need to be validated on tests, and for LDTs that’s pretty much everything. The list includes: Accuracy – (closeness to true, correlation against existing) Precision – (reproducibility) Analytical sensitivity – (Limit Of Detection) Analytical specificity – (interferences) Reportable range – (linearity, AMR) Reference interval – (“normal range”) The parentheses are my comments. These parameters can usually be accomplished with a correlation study, a precision study, a linearity study and if it’s a truly ‘from scratch’ method, you’ll need a study on common interferences (hemolysis, lipemia, icterus) and one to establish a reference interval. Probably what you’ve already done covers most of this, you just need a form to document it. For other help, see: Garber CC, Carey RN. Evaluation of methods. In Kaplan, et al, eds, Clinical chemistry: theory, analysis, correlation, 4th ed, St Louis, 2003, Mosby. Linnet K, Boyd JC. Selection and Analytical Evaluation of Methods – with statistical techniques. In Burtis CA, Ashwood ER, Bruns DE eds, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 4th ed, Philadelphia, 2006, Elsevier Saunders. Regards, Patti Jones Children's Medical Center, Dallas

Posted by
On 1/13/2011

We've been performing LB counts on amniocentesis specimens for over 15 years here in San Diego. We use an algorithm of tests: LBC, FLM(if indicated) and LS(if indicated). We have had tremendous success. Each of our deliveries within 72 hours are reviewed for outcome and we have established a graph which goes out with each LBC or FLM indicating the liklihood of RDS. It's been a lot of work, but with the TDxFLM being retired we will be ammending some testing processes. Darlynn L. San Diego, CA

Posted by
On 1/10/2011

We've been running LBC's for several months now and have had very positive outcomes. It was a long road to implementation but well worth it. Brendon Avera McKennan Hospital South Dakota

Posted by
On 1/10/2011

I have found that Lamellar body counts do not correlate well with FLM results. Timing is a big factor. If the amnionic fluid is not delivered immediately, the counts are vastly different. Debbie Jackson, TN

Posted by
On 1/7/2011

We just got our lamellar body counts up and going live on our hematology instruments. And it was very labor intensive and took us over a year to get enough results. I only hope for all that work, that we see some revenue back! This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!

About the Author
David G. Grenache, PhD, FACB
David G. Grenache, PhD, FACB 
 
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Additional Resources

 

Haymond S, Luzzi VI, Parvin CA, et al.  A direct comparison between Lamellar body counts and the fluorescent polarization methods for predicting respiratory distress syndrome.  Am J Clin Path 2006;126:894-899

 

Lockwood CM, Crompton JC, Riley JK, et al. Validation of lamellar body counts (LBC) using three hematology analyzers. Am J Clin Path. 2010;134:420-8

 

Pineda V, Gronowski AM. Biomarkers for fetal lung maturity. Biomarkers in Medicine

 

Szallasi A, Gronowski AM, Eby CS.  Lamellar body count in amniotic fluid: a comparative study using four different hematology analyzers.  Clin Chem 2003;49:994-997