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Preterm Premature Rupture of Membranes (PPROM) and Neurodevelopmental Outcomes

Journal of Perinatology volume 45, pages 1324–1325 (2025)Cite this article

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We appreciate the Author of the Letter to the Editor’s insight and thorough consideration of our findings in the Bhullar et al. study [1]. We are happy to address each point. The first point identified concerns about statistical significance in clinical research. While the absence of statistical significance does not confirm a lack of association, statistical tools are essential for evaluating whether observed outcomes are genuine or due to chance. These methods help quantify effect sizes, account for patient variability, and minimize bias. Post-hoc power calculations indicate that the study had >90% power to detect a clinically meaningful difference of 10% in the incidence of the primary outcome. Although multivariate logistic regression showed a 22% increase in the odds of the primary outcome, this fell within a small effect size range [2]. Furthermore, crude and propensity score–adjusted analyses yielded even smaller effect sizes (odds ratios of 1.09 and 1.08, respectively). Taken together, the lack of statistical significance, the wider confidence intervals including 1.0, and small effect sizes support the conclusion that there is no clinically meaningful association between preterm prelabor rupture of membranes (PPROM) and death or neurodevelopmental impairment (NDI).

The second point addressed concerns regarding the use of a composite outcome combining death and NDI. The authors acknowledge the assumptions underlying composite outcomes but emphasize their widespread use in perinatal epidemiology, particularly in extremely premature infants. Components such as death, low IQ, cerebral palsy, and sensory impairments represent severe adverse outcomes on a shared clinical spectrum. Given the challenges of long-term follow-up and limited sample sizes, using a composite outcome enhances statistical power and provides a more clinically meaningful endpoint—especially as death precludes later neurodevelopmental assessment. Importantly, the individual components of the composite outcome were also reported to allow more granular interpretation. The authors note that varying risks were observed across different components of NDI, which would require larger samples to detect meaningful differences individually.

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References

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Authors and Affiliations

  1. Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    H. Bhullar, A. Stritzke & A. Lodha

  2. Alberta Health Services, Calgary, AB, Canada

    H. Bhullar, A. Stritzke, S. Makarchuk, S. Tang & A. Lodha

  3. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    A. Lodha

  4. Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    A. Lodha

Authors
  1. H. Bhullar
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  2. A. Stritzke
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  3. S. Makarchuk
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  4. S. Tang
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  5. A. Lodha
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Contributions

HB drafted the initial version of the manuscript. AL and AS reviewed the first draft of the manuscript and made the necessary changes. ST was involved in the statistical analysis, and AL was involved in the interpretation of the data and the revision of the manuscript. HB, AS, SM, ST, and AL reviewed the final manuscript before submission and approved it.

Corresponding author

Correspondence to A. Lodha.

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Bhullar, H., Stritzke, A., Makarchuk, S. et al. Preterm Premature Rupture of Membranes (PPROM) and Neurodevelopmental Outcomes. J Perinatol 45, 1324–1325 (2025). https://doi.org/10.1038/s41372-025-02360-8

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  • DOI: https://doi.org/10.1038/s41372-025-02360-8

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