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Improving the external validity of Antenatal Late Preterm Steroids trial findings
Jennifer A Hutcheon1, Jessica Liauw1
1Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.
Insights
Antenatal corticosteroids for late preterm birth show smaller real-world benefits than in trials. This study adjusts for gestational age differences to provide more accurate estimates for patient counseling regarding respiratory morbidity.
Area of Science:
- Obstetrics and Gynecology
- Neonatal Medicine
- Clinical Trial Methodology
Background:
- Randomized trials may overestimate treatment benefits due to differences between trial participants and real-world populations.
- The Antenatal Late Preterm Steroids (ALPS) trial included participants with younger gestational ages than typically seen in clinical practice.
- This age difference can inflate the perceived benefits of antenatal corticosteroids for neonatal respiratory morbidity.
Purpose of the Study:
- To estimate the real-world absolute risk reduction and number-needed-to-treat (NNT) for antenatal corticosteroids in late preterm infants.
- To account for gestational age discrepancies between the ALPS trial population and the general population.
- To provide more accurate data for patient counseling and clinical decision-making.
Main Methods:
- Individual participant data from the ALPS trial was combined with population-based data from British Columbia, Canada.
- Logistic regression and inverse odds of sampling weights were used to adjust ALPS participants to match the real-world gestational age distribution.
- Treatment effects on neonatal respiratory morbidity were re-estimated using the weighted data.
Main Results:
- The real-world absolute risk reduction for respiratory morbidity was estimated at -2.2 per 100 births (95% CI -4.6, 0.0), compared to -2.8 per 100 in the original trial.
- The number-needed-to-treat (NNT) increased from 35 in the trial to 46 in the real-world setting.
- Benefits were more pronounced at 34 weeks gestation (risk reduction -3.7 per 100) compared to 36 weeks (risk reduction -1.2 per 100).
Conclusions:
- Adjusted estimates of absolute risk reduction and NNT provide a more realistic reflection of antenatal corticosteroid benefits in the real world.
- These findings are valuable for patient counseling regarding the anticipated benefits of antenatal corticosteroids for late preterm infants.
- The study highlights the importance of considering gestational age when evaluating treatment efficacy in diverse populations.
Background:
The external validity of randomised trials can be compromised when trial participants differ from real-world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real-world treatment benefits.
Objectives:
To estimate the real-world absolute risk reduction and number-needed-to-treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real-world populations.
Methods:
Individual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population-based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000-2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re-estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population-based (real-world) sample.
Results:
The real-world absolute risk reduction was estimated to be -2.2 (95% CI -4.6, 0.0) cases of respiratory morbidity per 100, compared with -2.8 (95% CI -5.3, -0.3) in original trial data. Corresponding NNTs were 46 in the real-world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of -3.7 vs. -1.2 per 100 respectively).
Conclusions:
The absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real-world situation.
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