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Clinical Evidence Review

Antenatal Corticosteroids
at 21–23 Weeks

Navigating Periviable Birth with Evidence


Battarbee AN. Obstet Gynecol. 2024;143(1):35–43. PMC10840910
Presented by Chukwuma Onyeije, MD, FACOG · Atlanta Perinatal Associates

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The Clinical Problem

Periviable Birth

Gestational Age
21 wks
Survival <1%
Gestational Age
22 wks
Survival 5–30%
Gestational Age
23 wks
Survival 25–50%
Gestational Age
24 wks
Survival 50–80%

Periviable birth is defined as delivery from 20 0/7 to 25 6/7 weeks. Neonates face extreme risks of death, IVH, BPD, NEC, and neurodevelopmental impairment.

NICHD/SMFM/AAP/ACOG Joint Workshop, 2013
Historical Context

Evolving Guidelines for ACS

1972
First RCT demonstrating ACS reduces neonatal respiratory morbidity
1994
NIH Consensus: ACS indicated 24–34 weeks
2013
NICHD: Consider ACS at 22 wks only if delivery expected ≥23 wks
2017
ACOG/SMFM: ACS not recommended at ≤22 wks
2021
ACOG/SMFM Practice Advisory: ACS should be considered at 22 wks

Key tension: Resuscitation was offered at 22 weeks, but steroids were not recommended — a clinical inconsistency that prompted re-evaluation.

Mechanism

Why ACS May Work at 21–23 Weeks

Lung Development at 21–23 Weeks

  • Canalicular phase: conducting airways and alveoli forming
  • Air-blood barrier being established
  • Surfactant beginning to appear
  • In vitro data: corticosteroids increase epithelial maturation and lamellar bodies in 12–24 wk fetal lung tissue

Observed Neonatal Benefits

  • Reduced early mortality
  • Reduced severe IVH / PVL
  • Reduced NEC
  • Improved survival to discharge
  • Improved survival without major morbidity
Biologic plausibility supported by in vitro studies reviewed at 2013 NICHD Joint Workshop
Key Study · Ehret 2018 · Vermont Oxford Network · N=33,472

Survival to Discharge with ACS

22 Weeks
aRR 2.11
95% CI 1.68–2.65
38.5% vs 17.7% survival to discharge with vs without ACS
23 Weeks
aRR 1.54
95% CI 1.40–1.70
Significant survival benefit confirmed
Morbidity
↑ Survival
without major morbidity
Chronic lung disease rates were unchanged by ACS

Caution  Chorioamnionitis more common in ACS-exposed group (25.5% vs 19.5%)

Ehret DEA et al. Pediatrics 2018; 22-25 wk deliveries at Level 3/4 NICUs
Key Study · Rossi 2021 · NCHS · N=10,627

Infant Survival to 1 Year of Life

22 Weeks — Survival ×1 yr
aRR 1.6
95% CI 1.2–2.1
ACS associated with higher infant survival to 1 year
23 Weeks — Survival ×1 yr
aRR 1.4
95% CI 1.3–1.6
Consistent benefit confirmed at 23 weeks

Maternal Safety Signal

  • 22 wks: Adverse maternal outcomes 7.5% (ACS) vs 3.4% (no ACS)
  • 23 wks: Adverse maternal outcomes 5.5% (ACS) vs 3.0% (no ACS)
  • Composite: transfusion, unplanned surgery, ICU admission

Infection Signal

  • Chorioamnionitis higher at 23 wks in ACS group (11.1% vs 5.9%)
  • Possible mechanism: ACS may delay delivery → prolonged exposure to infection
  • Causality not established in observational data
Rossi RM et al. Am J Perinatol 2021 · Population-based cohort · 22–23 wk neonates receiving resuscitation
Key Study · Travers 2022 · NICHD NRN · N=8,967

Beyond Survival: Intracranial Protection

22 Weeks
↓ ICH/PVL
Statistically significant
ACS reduced severe IVH or PVL even at 22 weeks
Early Mortality
↓ Death
≤12 hours of life
ACS reduced early mortality across all periviable weeks
Mechanism Insight
IVH
Primary mediator
Mortality benefit partially mediated by reduction in intracranial morbidity

Respiratory benefit of ACS at periviable ages remains conflicting across studies. Intracranial protection may be the primary mechanism of survival benefit.

Travers CP et al. Pediatrics 2022 · 22–25 wk deliveries with BW 401–1000g · NICHD NRN 2006–2018
Key Study · Chawla 2022 · NICHD NRN · N=431

ACS Administered at 21–22 Weeks

Survival to Discharge
aOR 1.95
95% CI 1.07–3.56
Complete ACS course vs no ACS
Survival Without Major Morbidity
aOR 2.74
95% CI 1.19–6.30
Complete ACS course vs no ACS
Neonatal Sepsis
↑ Risk
Complete vs partial ACS
No difference in sepsis or death combined (aOR 1.11)

Limitation  Only 17 neonates received ACS at 21 weeks. Data insufficient to draw firm conclusions at 21 weeks.

Chawla S et al. J Pediatr 2022 · Betamethasone administered 21 0/7–22 6/7 wks · Delivery at 22–23 wks
Current Guideline · ACOG/SMFM 2021 Practice Advisory

ACS Recommendations by Gestational Age

Gestational Age ACS Recommendation GRADE Evidence Quality
20 0/7 – 21 6/7 Not Recommended 1A Strong · High-quality evidence
22 0/7 – 22 6/7 Consider 2C Weak · Low-quality evidence
23 0/7 – 23 6/7 Consider 2B Weak · Moderate-quality evidence
24 0/7 – 24 6/7 Recommended 1B Strong · Moderate-quality evidence
25 0/7 – 25 6/7 Recommended 1B Strong · Moderate-quality evidence

Regimen: Betamethasone 12 mg IM × 2 doses, 24 hours apart or Dexamethasone 6 mg IM × 4 doses, every 12 hours

ACOG/SMFM Practice Advisory, September 2021 · GRADE adapted from Norton ME et al. AJOG 2021
Clinical Action

Shared Decision-Making Framework

Step 1
Establish Goals
Determine patient's desire: trial of intensive care vs. comfort-focused care
Step 2
Multidisciplinary Counseling
MFM + Neonatology aligned on prognosis, resuscitation plan, and ACS timing
Step 3
Concordant Management
ACS administration must align with postnatal resuscitation plan — steroids without resuscitation is inconsistent

Factors Favoring ACS at 22–23 wks

  • Neonatal resuscitation is planned
  • Birthweight 500–699g (strongest data)
  • Singleton gestation
  • Delivery anticipated within 7 days

Ongoing Research Needs

  • Efficacy at 21 weeks (very limited data)
  • Optimal timing of ACS relative to delivery
  • Long-term neurodevelopmental outcomes
  • Diverse, non-tertiary-center populations
Battarbee AN. Obstet Gynecol 2024;143(1):35–43 · PMC10840910 · Atlanta Perinatal Associates
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