Tests of Fetal Lung Maturity

This month the National Academy of Clinical Biochemistry (NACB) launched its blog, appropriately Slide1 called the NACBlog.  The first post is on the topic of fetal lung maturity tests and how the medical community might respond to the upcoming loss of a popular test of fetal lung maturity that is being discontinued by its manufacturer (disclaimer: I am the author of that post).

Seems like a good reason to talk about FLM tests here!  So, how can a lab test evaluate a fetus' lungs?
First the basics:

  1. The lungs are one of the last organs to mature in a fetus.  In order for them to work properly after birth the alveoli (i.e. air sacs) have to open up and stay open once the baby takes its first few breaths.  This is not as easy as it seems because the inside lining of the alveoli has a thin coating of water and the surface tension of this water promotes their collapse.  A collapsed alveoli doesn't work very well!  Fortunately, our lungs secrete chemicals called surfactants that lower the surface tension of the water that coats the alveoli thus preventing the alveoli from collapsing.
  2. Having enough of these surfactants in the lungs at birth is extremely important because that's when the baby has to make a transition from getting its oxygen from mom to getting it from the air.  If there's not enough surfactant then the alveoli may collapse and the baby may have a difficult time breathing.  When this does happen it's called respiratory distress syndrome of the newborn, or just RDS.
  3. Lung surfactants begin to be made around the 25th week of pregnancy but there's usually not enough of it present to prevent RDS until the 37th week.  That means babies born prematurely are at greater risk of developing RDS than those born at term.
  4. Because the fetus essentially "breathes" amniotic fluid in and out of its lungs, the amount of surfactant in the lungs can be determined by measuring surfactants in the amniotic fluid.  In the lab, there are a few ways we can do just that using a sample of amniotic fluid.

Several fetal lung maturity tests have been developed since the 1970's but only a few are still in use today:

  • AmnioStat-FLM
    • This test looks for the presence of a lung surfactant called phosphatidylglycerol (usually just called PG).
    • This is an agglutination  test that uses antibodies to detect PG in amniotic fluid.  If PG is present then visible agglutinates (clumps of particles) can be seen and the fetal lungs are considered mature.
  • Lamellar Body Count
    • In certain cells of the lungs, surfactants are packaged into granules called lamellar bodies and secreted from the cells into the alveoli.  This test actually counts the number of lamellar bodies in amniotic fluid.
    • The higher the lamellar body count, the more likely it is that the fetal lungs are mature.
  • Lecithin/Sphingomyelin Ratio
    • This was the first test of fetal lung maturity ever developed and is more commonly known as the L/S ratio.  It's a measure of the ratio of two lung surfactants, lecithin and sphingomyeli, that's determined using a technique known as thin-layer chromatography.
    • Lecithin is the most important lung surfactant and provides the greatest surface tension-lowering properties of all the surfactants.  It increases dramatically in the last few weeks of pregnancy.  Sphingomyelin is a minor lung surfactant and that amount of it in the lungs stays about the same throughout pregnancy so it serves as a good baseline against which the increasing amount of lecithin can be compared.  A ratio that is 2.5 or greater is usually used to indicate lung maturity.
    • Many doctors consider this to be the "best" fetal lung maturity test but that is not true.
  • TDx FLM II
    • This test measures the ratio of surfactant to albumin and so is sometimes called the S/A ratio.
    • The test relies on a technique known as fluorescence polarization and is the most widely used fetal lung maturity test; unfortunately it will no longer be available to clinical labs at the end of this year because the manufacturer has decided to stop making it.
    • The effect that the loss of this test will have on patients, doctors, and labs remains to be seen!

There a whole lot more to say about fetal lung maturity tests but those will have to wait for future posts.

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