Landmark Series
The shot that saved preemie lungs
The 1972 Liggins and Howie trial that put antenatal steroids on the map, and what five decades of trials added.
Source: Liggins GC, Howie RN. Pediatrics. 1972;50(4):515–525.
The question
Could a glucocorticoid given to the mother before a preterm birth speed up maturation of the fetal lung and prevent neonatal respiratory distress syndrome (RDS)?
The study
- Controlled trial of betamethasone versus placebo in 282 mothers in whom delivery before 37 weeks was threatened or planned.
- 213 of the mothers were in spontaneous preterm labor. When needed, ethanol or salbutamol infusions were used to delay delivery while treatment was given; a delay of at least 24 hours was achieved in 77%.
What they found
9.0% vs 25.8%RDS, treated vs control
3.2% vs 15.0%Early neonatal mortality in unplanned deliveries
11.8% vs 69.6%RDS in babies under 32 weeks treated ≥24 h before birth
- RDS occurred less often in treated babies (9.0%) than in controls (25.8%).
- The difference was confined to babies born before 32 weeks whose mothers had been treated at least 24 hours before delivery: 11.8% versus 69.6%.
- In unplanned deliveries, early neonatal mortality was 3.2% with betamethasone and 15.0% with placebo.
- No babies of mothers treated for at least 24 hours before delivery died with hyaline membrane disease or intraventricular hemorrhage.
Where the evidence stops
- The authors called their results preliminary and said more work was needed before any new routine was established.
- They flagged a possible increase in fetal death in pregnancies with severe hypertension–edema–proteinuria syndromes treated with betamethasone.
- Benefit depended on timing and gestation; it was not seen across every subgroup.
- It took many more trials to settle the question. A 2020 Cochrane review of 27 trials (11,272 women) found a single course reduces perinatal death (RR 0.85), neonatal death (RR 0.78) and RDS (RR 0.71), and probably reduces IVH (RR 0.58). Its authors still list dosing regimens, multiple pregnancies, the very early and late preterm periods, and long-term effects as open questions.
References
- Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972;50(4):515–525. doi:10.1542/peds.50.4.515 · PubMed 4561295
- McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020;12(12):CD004454. doi:10.1002/14651858.CD004454.pub4 · PubMed 33368142
Independent educational content, not medical advice. Not affiliated with or endorsed by the AAP. Summaries reflect the published papers; read the originals before changing practice.
