Antenatal Corticosteroids for Prevention of Neonatal Respiratory Distress Syndrome
Antenatal corticosteroids should be administered to all pregnant women at risk of preterm delivery before 37 weeks of gestation to prevent neonatal respiratory distress syndrome (RDS), with betamethasone being the preferred agent. 1
Recommended Regimen and Timing
The standard regimen is 2 doses of 12 mg intramuscular betamethasone given 24 hours apart. 1 This single course should be offered to women who meet specific criteria based on gestational age and risk of imminent delivery.
Gestational Age-Specific Recommendations
Before 34 weeks of gestation:
- Antenatal corticosteroids are strongly recommended for all women at risk of preterm delivery, as this population experiences the greatest benefit in reducing RDS, mortality, intraventricular hemorrhage, and necrotizing enterocolitis 2, 3
- Benefits include a 47% reduction in RDS (OR 0.53,95% CI 0.44-0.63) and a 40% reduction in neonatal mortality (OR 0.60,95% CI 0.48-0.75) 3
Late preterm period (34 0/7 to 36 6/7 weeks):
- Offer corticosteroids to singleton pregnancies at high risk of delivery within 7 days and before 37 weeks 1
- The ALPS trial demonstrated an 20% reduction in need for respiratory support (11.6% vs 14.4%; RR 0.80) and a 33% reduction in severe respiratory morbidity (8.1% vs 12.1%; RR 0.67) 1
- This represents a GRADE 1A recommendation based on high-quality evidence 1
Specific Clinical Scenarios
Preterm Prelabor Rupture of Membranes (PPROM)
Administer antenatal corticosteroids to women with PPROM without concern for increased infection risk. 4 The same benefits for RDS prevention are observed in PPROM without proven increased risk of neonatal or maternal infection 4.
Contraindications and Cautions
Do NOT administer late preterm corticosteroids to women with pregestational diabetes mellitus due to the risk of worsening neonatal hypoglycemia (GRADE 1C recommendation) 1.
Avoid corticosteroids in women with low likelihood of delivery before 37 weeks (GRADE 1B recommendation), as unnecessary exposure may carry uncertain long-term risks 1.
Populations Requiring Individualized Assessment
Consider corticosteroids with caution (GRADE 2C) in: 1
- Multiple gestations reduced to singleton on or after 14 0/7 weeks
- Pregnancies with fetal anomalies
- Women expected to deliver in <12 hours
Alternative Dosing Considerations
Recent evidence suggests that lower doses may be noninferior for late preterm births. A 2024 trial demonstrated that 5 mg dexamethasone every 12 hours for 4 doses was noninferior to 6 mg dosing for preventing RDS in births between 32-36 weeks (RDS rates: 2.2% vs 1.6%, risk difference 0.6%) 5. However, the established guideline-recommended dose remains 12 mg betamethasone 1.
Mechanism and Efficacy
Antenatal corticosteroids work by accelerating fetal lung maturity through enhanced surfactant production and structural lung development 2, 3. The benefits extend across a broad range of gestational ages and are not limited by fetal gender or race 3.
Meta-analysis data demonstrates consistent benefit: 6
- RDS reduction: RR 0.67 (95% CI 0.60-0.75) across 8740 treated participants
- Neonatal death reduction: RR 0.66 (95% CI 0.56-0.78)
- Perinatal death reduction: RR 0.72 (95% CI 0.58-0.89)
Critical Counseling Points
Patients must be counseled that long-term risks of antenatal corticosteroid exposure remain uncertain (GRADE 1C recommendation) 1. While no adverse consequences have been definitively identified in short-term studies 3, ongoing research continues to evaluate potential long-term neurodevelopmental effects 1.
Important Distinction: Postnatal vs. Antenatal Use
Do not confuse antenatal corticosteroids (given to the mother before delivery) with postnatal corticosteroids (given to the infant after birth). Postnatal dexamethasone for bronchopulmonary dysplasia has been associated with adverse neurodevelopmental outcomes and is not routinely recommended 1. In contrast, antenatal corticosteroids have an established safety profile and clear mortality benefit 1, 2, 3.