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

Sungsam Gong, Carlo Randise-Hinchliff, Suzanne Rohrback, Jing Yin Weng, Komal Singh, Sarah Shultzaberger, Ulla Sovio, Emma Cook, Fiona Kaper, Gordon C. S. Smith and D. Stephen Charnock-Jones ()
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Sungsam Gong: University of Cambridge; NIHR Cambridge Biomedical Research Centre
Carlo Randise-Hinchliff: Illumina Inc.
Suzanne Rohrback: Illumina Inc.
Jing Yin Weng: Illumina Inc.
Komal Singh: Illumina Inc.
Sarah Shultzaberger: Illumina Inc.
Ulla Sovio: University of Cambridge; NIHR Cambridge Biomedical Research Centre
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
D. Stephen Charnock-Jones: University of Cambridge; NIHR Cambridge Biomedical Research Centre

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61931-7

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