Fetal Lung Maturity - Neonatal Respiratory Distress Syndrome

Primary Author: Grenache, David G., PhD.

  • Key Points
  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Fetal lung maturity (FLM) tests have historically been performed to predict whether a fetus’s lungs are developed enough for delivery. However, FLM testing has limited value in light of the most recent ACOG guidelines (2013), which advise against delivery <39 weeks unless medically mandated due to potential serious morbidity when compared to those delivered ≥39 weeks in spite of mature FLM tests.

FLM testing may have value in the following clinical situations:

  • Premature rupture of membranes (≥32 weeks) – if FLM test is mature, delivery is likely safer than “wait and see” approach
  • Assessment of need for NICU – possible only if early delivery has medical mandate and time allows for FLM testing
  • Other selected late preterm and early preterm pregnancy issues where FLM may guide management of at-risk pregnancy
Comparison of FLM Laboratory Testing Options (all testing requires amniotic fluid)

Lamellar body count (LBC)

Phosphatidylglycerol (PG)

Lecithin-sphingomyelin ratio (L/S)

  • Initial FLM of choice
  • Rapid, sensitive
  • New data indicates that one can estimate risk of respiratory distress syndrome (RDS) as a function of gestational age and LBC
  • Unclear whether *ACOG cascade should be followed if LBC is immature
  • Not useful unless gestational age ≥35 weeks
  • Limited availability
  • Sensitive
  • Unclear whether *ACOG cascade should be followed if PG is immature
  • Main role is in adjudication of immature LBC or PG
  • Last test of choice
    • Labor intensive, imprecise
    • Limited availability
    • Results take >24 hrs unless performed at a local laboratory

* Refer to Diagnosis section for ACOG cascade

Note: in general, mature results suggest RDS unlikely

References:

ACOG Practice Bulletin No. 107: Induction of Labor. Obstet Gynecol. 2009; 114 (2) :386-397.

ACOG Practice Bulletin No. 97: Fetal lung maturity. Obstet Gynecol. 2008; 112 (3) :717-726.

Indications for Testing

  • Ruptured membranes ≥32 weeks – if fetal lung maturity (FLM) test is mature, delivery is likely safer than “wait and see” approach
  • Assessment of need for NICU – possible only if early delivery has medical mandate and time allows for FLM testing

Laboratory Testing

  • “Cascade” testing advocated by ACOG
  • Available FLM tests

Prematurity is associated with numerous complications, including neonatal respiratory distress syndrome (RDS), a cause of infant morbidity and mortality.

Epidemiology

  • Incidence – 20/100,000 infant deaths due to RDS
  • Age – more common the younger the gestational age
  • Sex – M>F (minimal)

Pathophysiology

  • Pulmonary surfactants are synthesized by type II pneumocytes and packaged into storage granules called lamellar bodies; these function to decrease alveolar surface tension
    • Lecithin – detected at week 28; surges at week 36
    • Phosphatidylinositol – detected at week 28; peaks at week 35
    • Sphingomyelin – detected at week 28
    • Phosphatidylglycerol – detected at week 36 with increases until delivery
  • RDS is caused by insufficient concentrations of pulmonary surfactants, resulting in collapsed alveoli (alveoli are perfused but hypoventilated)
    • Leads to hypoxia, hypercapnia, and respiratory acidosis
    • Conditions cause vasoconstriction of pulmonary arteries and decreased pulmonary blood flow
      • Pulmonary vasoconstriction causes epithelial cell damage, allowing plasma to leak into alveoli
        • Fibrin accumulation and necrotic cells create a hyaline membrane (RDS previously called hyaline membrane disease)
  • Nearly always associated with preterm birth
    • Risk of RDS is inversely related to gestational age at birth
      • >60% at <30 weeks
      • 20% at 34 weeks
      • <5% at >36 weeks
    • Measurement of fetal lung maturity through biochemical testing of amniotic fluid helps predict risk of RDS

Clinical Presentation

  • Respiratory distress that occurs within the first few hours of life – almost exclusively in preterm infants
  • Hypoxia, hypercapnia, and acidosis ensue with respiratory failure in many neonates
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.

Lamellar Body Counts 0080940
Method: Quantitative Automated Cell Count

Limitations 

Do not apply reference values for test to other instruments without performing comparison studies 

Follow-up 

Unclear whether ACOG cascade should be followed if LBC is immature

Lecithin-Sphingomyelin Ratio 0080200
Method: Quantitative Chromatography

Limitations 

Labor intensive, imprecise

Limited availability

Results take >24 hrs unless performed at a local laboratory

Guidelines

ACOG Committee on Practice Bulletins -- Obstetrics. ACOG Practice Bulletin No. 107: Induction of labor. Obstet Gynecol. 2009; 114(2 Pt 1): 386-97. PubMed

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 97: Fetal lung maturity. Obstet Gynecol. 2008; 112(3): 717-26. PubMed

Grenache D, Beshiri A, Gronowski A, Kyle A, McManamon T, Singer M, Wiet E. Assessment of Fetal Lung Maturity by the Lamellar Body Count; Approved Guideline. Vol 31, No 20, Wayne, PA: Clinical and Laboratory Standards Institute, 2011.

General References

American College of Obstetricians and Gynecologists. ACOG committee opinion no. 560: Medically indicated late-preterm and early-term deliveries. Obstet Gynecol. 2013; 121(4): 908-10. PubMed

Grenache D. Fetal lung maturity testing: what labs need to know now. MLO Med Lab Obs. 2012; 44(2): 8, 10; quiz 16-7. 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): 894-9. PubMed

Leung-Pineda V, Gronowski AM. Biomarker tests for fetal lung maturity. Biomark Med. 2010; 4(6): 849-57. PubMed

Spong CY, Mercer BM, D'alton M, Kilpatrick S, Blackwell S, Saade G. Timing of indicated late-preterm and early-term birth. Obstet Gynecol. 2011; 118(2 Pt 1): 323-33. PubMed

St Clair C, Norwitz ER, Woensdregt K, Cackovic M, Shaw JA, Malkus H, Ehrenkranz RA, Illuzzi JL. The probability of neonatal respiratory distress syndrome as a function of gestational age and lecithin/sphingomyelin ratio. Am J Perinatol. 2008; 25(8): 473-80. PubMed

Zhao Q, Zhao Z, Leung-Pineda V, Wiley CL, Nelson PJ, Grenache DG, Apple FS, Saenger AK, Gronowski AM. Predicting respiratory distress syndrome using gestational age and lamellar body count. Clin Biochem. 2013; 46(13-14): 1228-32. 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. PubMed

Lockwood CM, Crompton C, Riley JK, Landeros K, Dietzen DJ, Grenache DG, Gronowski AM. Validation of lamellar body counts using three hematology analyzers. Am J Clin Pathol. 2010; 134(3): 420-8. PubMed

Yarbrough ML, Grenache DG, Gronowski AM. Fetal lung maturity testing: the end of an era. Biomark Med. 2014; 8(4): 509-15. PubMed

Medical Reviewers

Last Update: August 2016