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Am J Perinatol
DOI: 10.1055/a-2708-5314
Original Article

Repeat versus Single Course of Antenatal Corticosteroid in Management of Preterm Premature Rupture of Membranes: A Systematic Review and Meta-analysis

Authors

  • Yosteline Da Costa 

    1   Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique

  • Veena Ramanathan    ‡

    2   Department of Medicine, Davao Medical School, Davao, Philippines

  • Juliana Almeida Oliveira    ‡

    3   Department of Surgery, Federal University of Minas Gerais, Belo Horizonte, Brazil

  • Joaquim Brito 

    4   Department of Medicine, Oeste Paulista University (UNOESTE), São Paulo, Brazil

  • Abdelrahman Yousif

    5   Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, El Paso, Texas, United States
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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

  • Repeat course of corticosteroid might increase maternal infections morbidity.

  • A cautious approach due to potential increase in maternal morbidity related to repeat corticoid use.

  • No significant neonatal benefit was observed with repeat courses of antenatal corticosteroids.

Keywords

preterm premature rupture of membranes - corticosteroids - maternal morbidity - neonatal morbidity

Data Availability Statement

All data used in this meta-analysis were extracted from published studies available in the public domain. The dataset generated during the current study, including extracted variables and statistical code, is available from the corresponding author upon reasonable request. No individual participant data were collected for this analysis.


Contributors' Statement

Y.C.: participated in the conceptualization, formal analysis, and project administration; Y.C. and J.A.O.: contributed in the methodology, validation, visualization, writing—original draft, and writing—review and editing; Y.C., V.R., and J.B.: participated in data curation; Y.C., V.R., and J.A.O.: participated in the investigation; A.Y.: participated in the supervision, validation, and writing—review and editing.


‡ These authors share second authorship.


Supplementary Material



Publication History

Received: 07 September 2025

Accepted: 23 September 2025

Article published online:
09 October 2025

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