Fetal Lung Maturity - Neonatal Respiratory Distress Syndrome

Key Points

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 (2009), which advise against delivery <39 weeks unless medically mandated. Furthermore, even in the presence of a mature FLM test, infants delivered <39 weeks have serious morbidity when compared to those delivered ≥39 weeks.

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 – only if early delivery has medical mandate and time allows for FLM testing

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
  • Rapid, 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.

Diagnosis

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 – only if early delivery has medical mandate and time allows for FLM testing

 Diagnosis of Fetal Lung Immaturity

  • Rapid postnatal tracheal instillation of surfactant to reduce risk of respiratory distress syndrome (RDS)
  • Delayed birth to permit in utero maturation – mothers can be given betamethasone to induce fetal pulmonary maturation

Laboratory Testing

  • “Cascade” testing advocated by ACOG
      • Fetal Lung Maturity Test Cascade (ACOG)

  • Available FLM tests
    • Fetal Lung Maturity Tests

      Fetal Lung Maturity Tests

      Lamellar body count (LBC)

      Phosphatidyl-glycerol (PG)

      Lecithin/sphingomyelin
      ratio (L/S)

      Method

      Automated
      cell count

      Immune
      agglutination

      Thin layer
      chromatography

      Immaturity cutoff

      None; there is no LBC result below which fetal lung immaturity can be identified with high certainty

      Negative

      ≤1.5

      Maturity cutoff

      ≥50,000/µL

      Positive

      ≥2.5

      Negative (mature) predictive value

      95-100%

      95-100%

      85-100%

      Positive (immature) predictive value

      15-65%

      20-50%

      20-80%

      Effect of blood        

      Decreases count due to trapping of lamellar bodies in clot matrix

      None

      Mature results will be decreased; immature results will be increased
       

      Mature results are still interpretable

      Effect of meconium

      Increases count

      None

      Makes L/S ratio result unreliable

Clinical Background

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

Prevention

  • All attempts should be made to prevent preterm birth
  • Administration of steroids in mother at least 24 hours prior to birth decreases risk of RDS
  • Instillation of exogenous surfactant intratracheally immediately after birth reduces risk of RDS

Indications for Laboratory Testing

  • 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
Lamellar Body Counts 0080940
Method: Quantitative Automated Cell Count

Initial FLM of choice

Rapid, sensitive

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

Evaluate reports of FLM with caution since no gold standard exists

Unclear whether ACOG cascade should be followed if LBC is immature
Phosphatidylglycerol 0080275
Method: Qualitative Immune Agglutination

Not useful unless gestational age ≥35 weeks

Rapid, sensitive

If gestational age of fetus is <35 weeks, results are likely to be negative

10% of healthy term infants have no measurable PG

Evaluate reports of FLM with caution since no gold standard exists

Unclear whether ACOG cascade should be followed if PG is immature

Lecithin-Sphingomyelin Ratio 0080200
Method: Quantitative Chromatography

Main role is in adjudication of immature LBC or PG

Last FLM test of choice

Labor intensive, imprecise

Limited availability

Results take >24 hrs unless performed at a local laboratory

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Fetal Fibronectin 0082024
Method: Semi-Quantitative Immunoassay/Immunosorbent

Assess risk of preterm delivery