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Raised Leptin and Pappalysin2 cell-free RNAs are the hallmarks of pregnancies complicated by preeclampsia with fetal growth restriction

Author

Listed:
  • Sungsam Gong

    (University of Cambridge; NIHR Cambridge Biomedical Research Centre
    University of Cambridge)

  • Carlo Randise-Hinchliff

    (Illumina Inc.)

  • Suzanne Rohrback

    (Illumina Inc.)

  • Jing Yin Weng

    (Illumina Inc.
    Color Health Inc)

  • Komal Singh

    (Illumina Inc.)

  • Sarah Shultzaberger

    (Illumina Inc.
    Pleno Inc)

  • Ulla Sovio

    (University of Cambridge; NIHR Cambridge Biomedical Research Centre
    University of Cambridge)

  • Emma Cook

    (University of Cambridge; NIHR Cambridge Biomedical Research Centre)

  • Fiona Kaper

    (Illumina Inc.)

  • Gordon C. S. Smith

    (University of Cambridge; NIHR Cambridge Biomedical Research Centre
    University of Cambridge)

  • D. Stephen Charnock-Jones

    (University of Cambridge; NIHR Cambridge Biomedical Research Centre
    University of Cambridge)

Abstract

Preeclampsia (PE) and fetal growth restriction (FGR) complicate 5-10% of pregnancies and are major causes of maternal and fetal morbidity and mortality. Here we demonstrate that measuring circulating cell-free RNAs (cfRNAs) from maternal plasma can accurately predict pregnancies complicated by the combination of PE and FGR. We investigated 751 maternal plasma samples from 195 pregnant women (39 cases; 156 non-cases). We developed machine learning models from our discovery cohort (15 cases; 60 non-cases) and evaluated their predictive performances internally (24 cases; 96 controls) and externally (40 cases; 73 non-cases). We found circulating leptin (LEP) and pappalysin2 (PAPPA2) cfRNAs are the strongest cfRNA predictors of complicated pregnancies, each with an area under the receiver operating characteristic curve (AUC) of ~0.82. Using an external validation dataset of women with established PE, the combination of LEP and PAPPA2 had an AUC ~0.951. Our findings show that cfRNAs can predict complications of human pregnancy.

Suggested Citation

  • Sungsam Gong & Carlo Randise-Hinchliff & Suzanne Rohrback & Jing Yin Weng & Komal Singh & Sarah Shultzaberger & Ulla Sovio & Emma Cook & Fiona Kaper & Gordon C. S. Smith & D. Stephen Charnock-Jones, 2025. "Raised Leptin and Pappalysin2 cell-free RNAs are the hallmarks of pregnancies complicated by preeclampsia with fetal growth restriction," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61931-7
    DOI: 10.1038/s41467-025-61931-7
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