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

Related Tests

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 B. 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: January 2016