Assessing Fetal Lung Maturity - 4 - TDx-FLM, Lamellar Body Count, and Foam Stability Index
Sunday, August 10, 2008
Kenneth F. Trofatter, Jr., MD, PhD
The next test that saw a rise in use in the early 1990’s was the TDx-FLM assay. This test employs fluorescence polarization to measure the ratio of surfactant to albumin (S/A) in uncentrifuged amniotic fluid. It is simple, quantitative, can be performed in 60 minutes or less and is highly reproducible (Steinfeld, et al., Obstet Gynecol 1992;79:460-4) . The threshold for fetal lung maturity using the most recent version of the test is set at > 55mg surfactant/gram albumin. TDx-FLM results correlate well with the L/S ratio and PG and with clinical outcomes (Obstet Gynecol 1993;82:1004-8). Blood or meconium in the amniotic fluid can interfere with the accuracy of the test results but, generally, will not result in immature results being erroneously reported as ‘mature’. PG can be used under these conditions as a back-up study. As in L/S ratio determinations, the standard threshold may not be quite as reliable in the woman who is diabetic, particularly, if she has a large baby. Livingston and colleagues (Obstet Gynecol. 1995;86:826-9) have shown that values > 70mg/g were not associated with respiratory distress syndrome in infants of diabetic mothers, even if PG was absent.
Another simple, rapid, and accurate test that can be performed on amniotic fluid to assess fetal lung maturity is the lamellar body (LB) count. LB are made by the type II cells in the alveoli that produce surfactant and, indeed, they are the packages in which surfactant is stored. They are released into the amniotic fluid from the lungs in increasing quantities that parallel surfactant production. LB are about the size of blood platelets so they can be quickly counted in the same laboratory machines that are used to perform a complete blood count (Dubin, Am J Clin Pathol 1992;97:836-49). It is recommended that the assay be done on uncentrifuged amniotic fluid and LB counts in the range of 30,000-40,000/microliter correlate well with fetal lung maturity (Ghidini, et al., Arch Gynecol Obstet 2005;271:325-8). There is evidence to support using a higher threshold of 50,000 in diabetic women. Because of their similarity in size to platelets, amniotic fluid contaminated with blood may interfere with the accuracy of the LB count, resulting in both falsely elevated LB counts, initially, and lower counts over time.
The final test I want to mention is one that actually measures the functional capacity of the surfactants that are present in the amniotic fluid. This test is called the foam stability index (FSI). It too is simple, inexpensive, and can be rapidly performed. I believe it is elegant in terms of both its relative simplicity and its predictive value. If you recall from our first post on this subject, I described alveoli as little “bubbles” that were at the mercy of the physics of surface tension and surfactants as chemicals that helped reduce surface tension so that the alveoli would not so readily collapse. The FSI assay takes advantage of this principle.
The FSI assay takes centrifuged amniotic fluid and adds a fixed volume (0.5 mL) to tubes containing serial concentrations of ethanol to produce final ethanol concentrations ranging between 44 and 50%. The tubes are then shaken for 30 seconds and the tube with the highest ethanol concentration that is able to retain a stable ring of bubbles at the air/fluid interface is read as the FSI result. RDS rarely occurs when the FSI is 47 or greater. Again, the simple beauty of the test is in its ability to measure the function, not the individual components, of the surfactants present in the amniotic fluid.
There are other approaches to the assessment of fetal lung maturity, but these are the most commonly available and widely used. It is generally accepted that in the nondiabetic pregnancy, any of these amniotic fluid tests that meets its threshold for ‘maturity’ meets the current standard of care for assessment of fetal lung maturity. Rather than performing several of these studies, most providers will now first perform a rapid test (e.g., TDx-FLM, FSI, or LB count) and only resort to the L/S ratio and/or PG studies if the initial test is immature. Another option would be to perform a second rapid test before doing the L/S ratio or PG since these studies may need to be sent off to an outside laboratory, delaying the final result.
Labels: fetal lung maturity, FSI, lamellar body count, LB, TDx-FLM
8 Comments:
At Sun Aug 10, 09:53:00 PM 2008,
D. Lafler said…
Dear Dr.,
I would like to mention that the lamellar body counts are instrument/manufacturer dependent. As the lamellar bodies are enumerated through the platelet channel, some instruments use impedance methodology, while others use optical methods for quantifying platelets(lamellar bodies) and some use both. It's important that with each lamellar body result reported, the lamellar body count range for "the low incidence of RDS" be stated for that institution based upon their data and neonatal outcomes.
At Mon Aug 11, 11:14:00 AM 2008,
Anonymous said…
Dr. T, I have had two pregnancies induced at 38 weeks for medical reasons related to thrombophilia risk. For both pregnancies, no one did any sort of fetal lung maturity testing nor was this even mentioned to me. I was only told that after 37 weeks, the baby is fully formed and able to survive outside the womb. Both babies were born very healthy and have no problems. There were no other complicating factors in my pregnancies. The gestational dates were practically certain and were monitored from conception. Does a high degree of certainty as to gestational age make a difference as to whether fetal lung maturity testing is needed? Thanks for any information!
At Tue Aug 12, 05:51:00 AM 2008,
Anonymous said…
Dr. Trofatter,
I have an anterior placenta. Does this pose any particular risk if I need a c-section? Also, my practitioners tell me this is why I don't feel the baby move very often (I'm 32 weeks). Is this true or should I be concerned about the sporadic movement?
Thank you!
At Tue Aug 12, 05:57:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To d lafler: Thanks for the comments. I left out much of the specific details on these posts, intentionaly, but we have readers with a wide range of backgrounds and your observations are much appreciated. Thanks again! Dr T
At Tue Aug 12, 07:53:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Aug 11: MOST, but not all babies beyond 37 weeks will be "mature' from the respiratory standpoint. That "but not all" is very important because I can give you many examples of 38 week babies, with dating as accurate as yours, who developed severe RDS and complications requiring NICU admissions. This occurs most often when elective cesarean sections are performed for delivery before the onset of labor. That is why the American College of Obstetricians and Gynecologists has adopted the stance of encouraging documentation of fetal lung maturity in elective deliveries prior to 39 weeks. "Elective deliveries" means that there is not an urgent maternal or fetal problem indicating that delivery is necessary. Dr T
At Wed Aug 13, 03:32:00 PM 2008,
Katrina said…
Dr. T, First time writing. I am currently 24wks pregnant with #4 and for the 1st time while pregnant on 40mg once daily of lovenox. I once had a DVT-PE while pregnant so this is just a precaution after having all the clinical signs of a DVT at around 14wks pregnant. I also have vertigo and I am feeling it badly right now. It just started today with the vertigo problems. I normally just take Dramamine for it because it is not all that bad to deal with. However I can not reach my doctors right now and the local pharamacist (spelling is wrong im sure) isnt being too helpful. I try to avoid any other drugs because of the lovenox. How much would it hurt if i took one dramamine to kind of make the spinning sensation stop. Thanks for your help. You also seem to have good advice.
At Thu Aug 14, 12:48:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Katrina: The dramamine should be fine. Take it if you need it and get in touch with your doctor as soon as you can if the symptoms persist. Good luck! Dr T
At Sat Aug 16, 05:38:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Aug 12: Anterior placentas can (but not invariably, increase your risk for bleeding, particularly if your doctor has to cut across it to get to the baby. Also, if you have previiously had a c/section, and the anterior placenta is sitting under that old scar, you are at increased risk for a placenta accreta, which could certainly increase the risk of hemorrhage. Best wishes! Dr T
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