Gestational age-specific risks vs benefits of multicourse antenatal corticosteroids for preterm labor

Abstract

Objective: The purpose of this study was to estimate a gestational age threshold at which the benefits of treatment with weekly courses of antenatal corticosteroids (ACS) during preterm labor outweigh the risks.

Study design: Risk-benefit ratios by gestational age were determined with the use of a Markov microsimulation decision-analysis model with a 1-week cycle length. Single course and multiple (weekly to a maximum of 4) courses of ACS by gestational age of entry (23 weeks to 31 weeks 6 days' gestation) were compared. Benefits were composite events (respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, or stillbirth) averted. Risks were small head circumference and small for gestational age.

Results: More composite events are averted (benefits) than risks acquired (ratio, 6:1) when multiple courses of ACS are initiated at 26 weeks' gestation. When multiple courses of ACS are initiated at 29 weeks' gestation, the risk-benefit ratio is 1. Beyond 29 weeks, there is a suggestion of more risk than benefit.

Conclusion: The model suggests that multiple courses of ACS that are initiated at <29 weeks' gestation may have increased benefit compared with risks. Further analyses are needed to determine the long-term clinical significance of these findings.

Keywords: antenatal corticosteroid; decision analysis; preterm labor.

Figure 1

The ovals at the bottom denote the four health states in the model and the arrows denote transitions between health states which the model assumes can occur on a weekly basis. When not delivered the model is re-started weekly and 100,000 microsimulations per treatment arm were performed in the model

Figure 2

Abbreviated decision tree for “risk benefit” of single course versus multiple courses of antenatal corticosteroids for the management of preterm labor

Figure 3

Proportions of small for gestational age and small head circumference (SGA/SHC) in the entire study population. 100,000 trials were performed in the microsimulation. The x-axis has gestational age at entry. The y-axis is the proportion of SGA/SHC events that occurred within each start gestational age group n. An increased proportion of SGA/SHC are seen in multiple courses of ACS versus single course of ACS at each gestational age group of entry.

Figure 4

Number of composite events averted per case of small for gestational age or small head circumference (SGA/SHC). The x-axis is gestational age at entry and the y – axis is number of composite events averted per case of SGA/SHC. A gestational age risk benefit threshold is seen at 29 weeks’ gestation, where the risk equals the benefits.