Population Improvement Bias Observed in Estimates of the Impact of Antenatal Steroids to Outcomes in Preterm Birth.

OBJECTIVE: To examine the hypothesis that increasing rates and differential uptake of antenatal steroids would bias estimation of impact of antenatal steroids on neonatal death and severe (grade III-IV) intraventricular hemorrhage (IVH).

STUDY DESIGN: The study population included infants born between 24 and 28 weeks of gestational age in the California Perinatal Quality Care Collaborative. Outcomes were in-hospital mortality and severe IVH. Mixed multivariable logistic regression models estimated the effect of antenatal steroid exposure, one model accounting for individual risk factors as fixed effects, and a second model incorporating a predicted probability factor estimating overall risk status for each time period.

RESULTS: The study cohort included 28 252 infants. Antenatal steroid exposure increased from 80.1% in 2005 to 90.3% in 2016, severe IVH decreased from 14.5% to 9.0%, and mortality decreased from 12.8% to 9.1%. When stratified by group, 3-year observed outcomes improved significantly in infants exposed to antenatal steroids (12.5%-8.6% for IVH, 11.5%-8.8% for death) but not in those not exposed (20.7%-19.1% and 16.6%-15.5%, respectively). Women not receiving antenatal steroids had greater risk profile (such as no prenatal care) and greater predicted probability for severe IVH and mortality. Both outcomes exhibited little change (P > .05) over time for the group without antenatal steroids. In contrast, in women receiving antenatal steroids, observed and adjusted rates for both outcomes decreased (P < .0001).

CONCLUSIONS: As the population's proportion of antenatal steroid use increased, the observed positive effect of antenatal steroids also increased. This apparent increase may be designated as the "population improvement bias."