Abstract
Objective
A single course of antenatal corticosteroids is standard for women at risk of preterm
birth, including those with ruptured membranes. The benefit of repeat courses in the
setting of preterm premature rupture of membranes (PPROM) remains uncertain. This
study aimed to assess the safety and effectiveness of repeat versus single course
of corticosteroid in women with PPROM.
Study Design
We searched PubMed, Cochrane, and Embase databases from inception to September 17,
2025, with no language restrictions, using the terms related to PPROM and corticosteroids.
Randomized and non-randomized clinical trials enrolling women with PPROM and comparing
repeat with single course were included. Studies without PPROM or comparator group
were excluded. Screening and quality assessment were performed by two authors, with
a third author participation in case of disagreements. Statistical analysis used Review
Manager 5.4 and R studio 4.5.0, with risk ratio (RR), random effects, Cochran Q test
and I-squared statistics, and sensitivity analysis. This study was registered with
PROSPERO (identifier: CRD420251069007).
Results
Six studies comprising 2,434 patients were included. Sensitivity analysis showed that
repeat course of corticosteroids increased the risk of endometritis compared to a
single course (RR = 1.63; 95% CI: 1.10 to 2.43). In the subgroup analysis the mixed
hours corticosteroid favored the outcome of chorioamnionitis (RR = 1.62; 95% CI: 1.12
to 2.36; p = 0.001) with no overall subgroup difference. No difference was observed for the
outcomes of respiratory distress syndrome, neonatal sepsis, necrotizing enterocolitis,
and intraventricular hemorrhage.
Conclusion
Repeat corticosteroid courses in PPROM may increase maternal infections morbidity
without clear neonatal benefit. Further large, well-designed randomized trials are
needed to clarify safety.
Key Points
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Repeat course of corticosteroid might increase maternal infections morbidity.
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A cautious approach due to potential increase in maternal morbidity related to repeat
corticoid use.
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No significant neonatal benefit was observed with repeat courses of antenatal corticosteroids.
Keywords
preterm premature rupture of membranes - corticosteroids - maternal morbidity - neonatal
morbidity
