What are the causes and risk factors for meconium aspiration syndrome?

Causes and Risk Factors for Meconium Aspiration Syndrome

Primary Causative Mechanisms

Meconium aspiration syndrome develops through a combination of fetal meconium passage into amniotic fluid followed by aspiration, with the underlying causes being fetal maturation, intrauterine stress, and systemic inflammation. 1

Three Pathophysiologic Pathways for Meconium Passage

• Gastrointestinal maturation: Meconium passage is related to maturation of the fetal gastrointestinal tract, which explains why it rarely occurs in preterm infants and typically happens at or beyond term gestation. 1

• Pathologic stress triggers: Hypoxia or infection can trigger meconium passage in utero, though the predictive value of meconium-stained amniotic fluid for fetal distress and acidosis remains poor and controversial. 1

• Impaired clearance mechanism: Reduced clearance of defecated meconium may occur due to impaired fetal swallowing or unidentified placental dysfunction, rather than solely increased passage. 1

Major Risk Factors

Gestational Age and Timing

• Post-term pregnancy (≥42 weeks) significantly increases the risk of meconium-stained amniotic fluid, which occurs in approximately 5-15% of all deliveries. 2, 3

• Delivery at <38 weeks gestation paradoxically increases MAS risk among those with meconium-stained fluid (adjusted OR 3.48,95% CI 1.02-11.84). 4

Placental and Amniotic Fluid Abnormalities

• Oligohydramnios (amniotic fluid index <5 cm or maximum vertical pocket <2 cm) is an independent risk factor for meconium-stained amniotic fluid with an odds ratio of 2.6. 2

• Lower amniotic fluid index independently predicts MAS development (adjusted OR 0.99 per unit decrease, 95% CI 0.98-0.99). 4

• Reduced amniotic fluid volume concentrates meconium and reflects chronic placental insufficiency. 2

Inflammatory Processes

• Intraamniotic inflammation (amniotic fluid matrix metalloproteinase-8 >23 ng/mL) substantially increases MAS risk, with 13.0% of exposed newborns developing MAS versus 0% without inflammation. 5

• Funisitis (histologic inflammation of the umbilical cord indicating fetal systemic inflammatory response) increases MAS risk 4.3-fold (95% CI 1.5-12.3). 5

• The combination of intraamniotic inflammation with funisitis produces the highest risk: 28.6% developed MAS versus 0% without either condition. 5

• Mothers whose newborns developed MAS had significantly higher median amniotic fluid matrix metalloproteinase-8 levels (456.8 vs 157.2 ng/mL). 5

Maternal Factors

• Higher maternal body mass index independently predicts MAS (adjusted OR 1.09 per unit increase, 95% CI 1.02-1.16). 4

• Elevated maternal white blood cell count is independently associated with MAS (adjusted OR 1.11 per unit increase, 95% CI 1.02-1.20). 4

Intrapartum and Fetal Factors

• Non-reassuring fetal heart rate tracings increase MAS risk 3-fold (RR 3.0,95% CI 1.2-7.5) and remain significant after multivariate analysis (OR 12.2,95% CI 1.3-111.7). 6

• Presence of meconium below the vocal cords is the strongest predictor, with a 7.3-fold increased risk (95% CI 2.6-20.3) and adjusted OR of 33.4 (95% CI 3.6-303.7). 6

• Apgar score ≤6 at 5 minutes increases risk 3.8-fold (95% CI 1.7-8.4). 6

• Umbilical cord plasma erythropoietin >50 mIU/mL (marker of chronic hypoxia) increases risk 5-fold (95% CI 2.1-12.0). 6

Multifactorial Pathophysiology After Aspiration

Once meconium is aspirated, MAS develops through several mechanisms:

• Mechanical airway obstruction by meconium plugs causes complete obstruction leading to atelectasis and partial obstruction causing air trapping and hyperinflation. 1, 7

• Surfactant inactivation by meconium contributes to areas of atelectasis and impaired gas exchange. 3, 1

• Chemical pneumonitis from meconium's irritant properties causes pulmonary inflammation. 1, 7

• Persistent pulmonary hypertension develops as a result of chronic in utero stress and thickening of pulmonary vessels. 7

• Predisposition to infection: Although meconium is sterile, its presence in airways predisposes to pulmonary infection. 7

Risk Stratification

The presence of multiple risk factors compounds MAS risk:

• One risk factor: 0.8% risk of MAS 4
• Two risk factors: 2.5% risk of MAS 4
• Three risk factors: 100% risk of MAS 4

Critical Clinical Context

Only 3-5% of neonates born through meconium-stained amniotic fluid actually develop MAS, highlighting that meconium exposure alone is insufficient—additional factors (particularly fetal systemic inflammation, hypoxia, and aspiration timing) determine which infants progress to syndrome. 2, 3, 5