Topic Name

A	B	C	D	E	F	G	H	I
J	K	L	M	N	O	P	Q	R
S	T	U	V	W	X	Y	Z	#

Disease Categories > Perinatal Disease

Font

Fetal Lung Maturity - FLM

Prematurity is associated with numerous complications, including neonatal respiratory distress syndrome (RDS) and low birth weight; both are major causes of infant morbidity and mortality.

Epidemiology

Risk of RDS is inversely related to gestational age at birth
- >60% at <30 weeks of age
- 20% at 34 weeks of age
- <5% at >36 weeks of age

Pathophysiology

Pulmonary surfactants are synthesized by type II pneumocytes, packaged into storage granules called lamellar bodies, and function to decrease alveolar surface tension
RDS is caused by deficiency of pulmonary surfactant leading to alveoli collapse, hypoxia, hypercapnia and acidosis

Diagnosis

Diagnosis of fetal lung immaturity allows
- Rapid postnatal tracheal instillation of surfactant to reduce risk of RDS
- Delayed birth to permit in utero maturation – mothers can be given betamethasone to induce fetal pulmonary maturation
Laboratory Testing
- Available testing for fetal lung maturity (FLM)
  - Fluorescence polarization (Surfactant-Albumin (S/A) ratio)
    - Test of choice for rapid, accurate results; has widespread availability
    - Sensitivity 99%; specificity 70%; high predictive value for lung maturity
    - Commercially available test (TDx FLM II) reported in units of mg surfactant/g albumin
      - S/A values increase during gestation in parallel with lung maturation
    - ARUP-produced test reported in units of mPol
      - Polarization values decrease during gestation in parallel with lung maturation
    - Blood and meconium contamination can affect result
  - Lamellar body counts
    - Lamellar bodies are similar in size to blood platelets and so can be enumerated using automated cell counter
    - Lung maturity predicted from the number of lamellar bodies within amniotic fluid
    - Sensitivity >95%, specificity of 70%; high predictive value for lung maturity
    - Analyzer-specific cutoffs are required for interpretation
    - Blood and meconium contamination can affect result
  - Phosphatidylglycerol
    - Rapid, qualitative test with moderate availability
    - Sensitivity >95%; specificity 70%; high predictive value for lung maturity
    - Blood and meconium contamination have no effect
    - Detectable in amniotic fluid in late gestation
  - Lecithin-Sphingomyelin ratio
    - Labor intensive test offered by few laboratories
    - Offers no advantage over fluorescence polarization
    - Sensitivity of >95%, specificity of 70%
    - Blood and meconium contamination can affect result
- “Cascade” testing has been advocated by ACOG
  - Utilize rapid test method first (Fluorescence polarization, lamellar body counts)
    - If mature result then stop testing
    - If immature result then consider additional FLM testing (L/S ratio)

Indications for Ordering

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations	Follow Up
Fluorescence Polarization (Fetal Lung Maturity) 0020486 Method: Fluorescence Polarization	Assess fetal lung maturity (FLM) to time delivery of fetus for optimal outcome Assess need for intratracheal administration of exogenous surfactant in premature births Test of choice for urgent clinical situations	Blood contamination can change results, but immature result will not be classified erroneously as mature Evaluate reports of FLM with caution, since no gold standard exists	For immature results, consider another FLM test (cascade testing)
Lamellar Body Counts 0080940 Method: Automated Cell Count	Use in obstetric situations involving premature labor, premature rupture of membranes, management of eclampsia fetal distress and elective delivery at term Test requires less than 10 minutes to determine FLM	Do not apply the reference values for test to other instruments without performing comparison studies Do not use vaginal pool specimens or specimens with >0.5% blood as presence of platelets will artificially inflate count of lamellar bodies Do not use frozen samples	For immature results, consider another FLM test (cascade testing)
Lecithin-Sphingomyelin Ratio 0080200 Method: Chromatography	Traditional test for predicting fetal lung maturity Requires a minimum of 4 hours for results Test of choice for rapid screening is fluorescence polarization	Blood contamination (>0.5%) introduces plasma lipids, which increases low values and decreases high values L/S ratio is slower and less precise than fluorescence polarization
Phosphatidylglycerol 0080275 Method: Immune Agglutination	Often ordered for assessment of FLM when mother has diabetes Positive result indicates maturity Negative result unhelpful	No modern studies exist that show that PG needed for diabetic patients 10% of healthy term infants have no measurable PG	For immature results, consider another FLM test (cascade testing)

General References

ACOG educational bulletin. Assessment of fetal lung maturity. Number 230, November 1996. Committee on Educational Bulletins of the American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1997;56(2):191-198. (Link to PubMed)

Ashwood ER. Markers of Fetal Lung Maturity. In Gronowski AM, ed. Handbook of Clinical Laboratory Testing During Pregnancy. Totowa, NJ: Humana Press, 2004. pp. 55-70.

Grenache DG, Gronowski AM. Fetal lung maturity. Clin Biochem. 2006;39(1):1-10. (Link to PubMed)

Gronowski AM, Parvin CA. Prediction of risk for respiratory distress syndrome using gestational age and the TDx-FLM II assay. Am J Obstet Gynecol. 2003;189(5):1511-1512. (Link to PubMed)

Haymond S, Luzzi VI, Parvin CA, Gronowski AM. A direct comparison between lamellar body counts and fluorescent polarization methods for predicting respiratory distress syndrome. Am J Clin Pathol. 2006;126(6):894-899. (Link to PubMed)

Kesselman EJ, Figueroa R, Garry D, Maulik D. The usefulness of the TDx/TDxFLx fetal lung maturity II assay in the initial evaluation of fetal lung maturity. Am J Obstet Gynecol. 2003;188(5):1220-1222. (Link to PubMed)

Neerhof MG, Dohnal JC, Ashwood ER, Lee IS, Anceschi MM. Lamellar body counts: a consensus on protocol. Obstet Gynecol. 2001;97(2):318-320. (Link to PubMed)

Parvin CA, Kaplan LA, Chapman JF, McManamon TG, Gronowski AM. Predicting respiratory distress syndrome using gestational age and fetal lung maturity by fluorescent polarization. Am J Obstet Gynecol. 2005;192(1):199-207. (Link to PubMed)

Szallasi A, Gronowski AM, Eby CS. Lamellar body count in amniotic fluid: a comparative study of four different hematology analyzers. Clin Chem. 2003;49(6 Pt 1):994-997. (Link to PubMed)

Tanasijevic M. Predictive model for fetal lung maturity assessment incorporating Abbott FLM S/A II test results and obstetric estimates of gestational age. Clin Chim Acta. 2002;326(1-2):1-2. (Link to PubMed)

Ventolini G, Neiger R, Hood D, Belcastro C. Update on assessment of fetal lung maturity. J Obstet Gynaecol. 2005;25(6):535-538. (Link to PubMed)

Wijnberger LD, Huisjes AJ, Voorbij HA, Franx A, Bruinse HW, Mol BW. The accuracy of lamellar body count and lecithin/sphingomyelin ratio in the prediction of neonatal respiratory distress syndrome: a meta-analysis. BJOG. 2001;108(6):583-588. (Link to PubMed)

References from the ARUP Institute for Clinical and Experimental Pathology®

Chapman JF, Ashwood ER, Feld R, Wu AH. Evaluation of two-dimensional cytometric lamellar body counts on the ADVIA 120 hematology system for estimation of fetal lung maturation. Clin Chim Acta. 2004;340(1-2):85-92. (Link to PubMed)

Reviewed by

Grenache, David G., Ph.D. Medical Director, Special Chemistry at ARUP Laboratories; Assistant Professor, Clinical Pathology, University of Utah

Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah

Comprehensive Review: November 2007
Last Update: March 2008