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 (see table below)

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Fetal Fibronectin 0082024 Method: Semi-Quantitative Immunoassay/Immunosorbent	Assess risk of preterm delivery