In May I wrote about recommendations made by the International Association of Diabetes in Pregnancy Study Groups (IADPSG) for glucose tolerance testing in pregnancy. Those recommendations advocate for the use of a 75-gram oral glucose tolerance test to detect gestational diabetes mellitus (GDM) in pregnant women between 24 and 28 weeks gestation and were based on findings of the Hyperglycemia and Adverse Outcomes (HAPO) study. That study clearly demonstrated that the risks of adverse maternal and fetal outcomes continually increased as maternal glucose concentrations increased. The American Diabetes Association adopted the IAPDSG criteria and recommends that approach to identifying women with GDM.
In the September 2011 issue of Obstetrics and Gynecology, the American Congress of Obstetricians and Gynecologists (ACOG) opt to stick to their guns. The ACOG continues to recommend the "two-step" approach to screen and diagnose GDM. Step one is a screening test using either patient history, clinical risk factors, or with a 50 gram glucose administered orally followed by the measurement of blood glucose 1 hour later (a result greater than 140 mg/dL is considered abnormal). Those with an abnormal screening test go on to have the diagnostic test: a 100 gram oral glucose tolerance test with blood glucose measured over 3 hours.
The ACOG rightfully acknowledges that while the treatment of mild GDM decreases adverse infant outcomes there is no evidence to indicate that use of the IADPSG recommendations would result in any significant improvements in outcomes. Of course, lack of evidence doesn't mean that there is no benefit, it simply means that any benefits have not yet been demonstrated. The fact that widespread adoption of the IADPSG screening test would double the number of women diagnosed with GDM was also noted by the ACOG. This increase is notable because it would lead to a considerable increase in health care costs and likely overwhelm health care delivery systems.
In contrast to the ACOG, the National Academy of Clinical Biochemistry (NACB) have published guidelines that recommend the approach advocated by the IADPSG. Confused yet? Disagreement among professional groups is not unusual and consensus is not easy to come by. As usual, a lot more research is required before widespread agreement is achieved.
A recent post in the NACB blog titled "Jurassic Lab" invited readers to comment on which laboratory tests they thought should be considered obsolete. I suggested that the Triple Test, a blood test used during the second trimester of pregnancy to screen for Down syndrome, should go the way of the dinosaur.
Labs that offer Down syndrome screening tests should seriously consider taking the Triple Test off of their menus. Why? There are a few reasons:
- It is not a great test. As a screening test for Down syndrome, the Triple test is only okay. If I were grading it, then I would give it a C. It detects about 70-75% of fetuses with Down syndrome and it has a false-positive rate of 5-8%.
- Better tests are available. I've already wrote about the different types of Down syndrome screening tests. Other tests, like the Quad and the Integrated tests perform much better than the Triple test. Given a choice, I imagine most mothers-to-be would prefer to have the best screening test available. It's abundantly clear that of all the tests used to screen for Down syndrome, the Integrated test is best. It has a detection rate of about 90-95% and (importantly) a false-positive rate that is lower than the Triple test. A low false-positive rate is important because it decreases the number of unnecessary invasive diagnostic procedures that are performed due to an abnormal result from a screening test.
- Lack of recommendation. Several national guidelines no longer recommend use of the Triple test and recommend better performing screening tests instead.
Clearly the Triple test is irrelevant. That doesn't mean that all the doctors that order Down syndrome screening tests have gotten the message. A 2009 survey of obstetricians in the US revealed that nearly a quarter of them (23%) continued to use the Triple test. That's lower than it used to be but still rather high for a test that shouldn't be ordered. Until laboratories that offer the Triple test take it off of their menus, it will continue to be (inappropriately) utilized.
This month the National Academy of Clinical Biochemistry (NACB) launched its blog, appropriately 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:
- 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.
- 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.
- 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.
- 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:
- 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.