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Development and validation of a multivariable prediction model of spontaneous preterm delivery and microbial invasion of the amniotic cavity in women with preterm labor

  • Teresa Cobo
    Correspondence
    Corresponding author: Teresa Cobo, MD, PhD.
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain

    Centre for Biomedical Research on Rare Diseases, Barcelona, Spain
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  • Victoria Aldecoa
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Francesc Figueras
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain

    Centre for Biomedical Research on Rare Diseases, Barcelona, Spain
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  • Ana Herranz
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Silvia Ferrero
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Montse Izquierdo
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Clara Murillo
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Raquel Amoedo
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Claudia Rueda
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Jordi Bosch
    Affiliations
    Microbiology, Biomedical Diagnostic Center, Hospital Clínic and ISGlobal (Barcelona Institute for Global Health), University of Barcelona, Barcelona, Spain
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  • Raigam J. Martínez-Portilla
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain
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  • Author Footnotes
    1 These authors contributed equally as last authors of the paper.
    Eduard Gratacós
    Footnotes
    1 These authors contributed equally as last authors of the paper.
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain

    Centre for Biomedical Research on Rare Diseases, Barcelona, Spain
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally as last authors of the paper.
    Montse Palacio
    Footnotes
    1 These authors contributed equally as last authors of the paper.
    Affiliations
    BCNatal–Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clínic de Ginecología, Obstetrícia I Neonatología, Fetal i+D Fetal Medicine Research Center, Institut d’Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain

    Centre for Biomedical Research on Rare Diseases, Barcelona, Spain
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally as last authors of the paper.
Published:March 05, 2020DOI:https://doi.org/10.1016/j.ajog.2020.02.049

      Background

      Early spontaneous preterm delivery is often associated with microbial invasion of the amniotic cavity and/or intraamniotic inflammation.

      Objective

      The objective of the study was to develop and validate clinically feasible multivariable prediction models of spontaneous delivery within 7 days and microbial invasion of the amniotic cavity in women admitted with diagnose of preterm labor and intact membranes below 34 weeks.

      Study Design

      We used data from a cohort of women admitted from 2012 to 2018 with diagnosis of preterm labor below 34 weeks who had undergone amniocentesis to rule out microbial invasion of the amniotic cavity. The main outcome was spontaneous delivery within 7 days from admission. The secondary outcome was microbial invasion of the amniotic cavity, defined by a positive culture and/or 16S ribosomal RNA gene in the amniotic fluid. The sample (n = 358) was divided into derivation (2012–2016) and validation cohorts (2017–2018). Logistic regression models using a stepwise selection of variables were developed for the outcomes evaluated. We explored as predictive variables ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, amniotic fluid glucose, and interleukin-6 (expressed as log units). Models were developed in the derivation cohort and applied to the validation cohort and diagnostic performance was calculated.

      Results

      The derivation cohort included 263 women and the validation cohort 95 women. One hundred five of the women (39%, 105 of 268) spontaneously delivered in the following 7 days and 68 (19%, 68 of 358) had microbial invasion of the amniotic cavity. For spontaneous delivery within 7 days after admission, 4 predictors were identified: cervical length at admission, gestational age, amniotic fluid glucose, and interleukin-6. The diagnostic performance of the model was assessed in the validation cohort using the receiver operating characteristic curve and showed an area under curve of 0.86 (95% confidence interval, 0.77–0.95) with a detection rate of spontaneous delivery within 7 days of 87%, a false-positive rate of 33%, a negative predictive value of 80%, and a negative likelihood ratio of 0.1908. For microbial invasion of the amniotic cavity, 2 independent predictors of the amniotic cavity were identified: amniotic fluid glucose and maternal C-reactive protein. The receiver operating characteristic curve and an area under curve in the validation cohort was 0.83 (95% confidence interval, 0.70–0.96) with a detection rate of 76%, a false-positive rate of 8%, a negative predictive value of 93%, and a negative likelihood ratio of 0.2591.

      Conclusion

      In women with preterm labor, we propose 2 clinically feasible prediction models to classify as low vs high risk of spontaneous delivery within 7 days and of microbial invasion of the amniotic cavity. The models showed a high diagnostic performance and could be of value to optimize clinical management.

      Key words

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