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The amniotic fluid cell-free transcriptome in spontaneous preterm labor.

Gaurav Bhatti1,2, Roberto Romero3,4,5,6,7,8, Nardhy Gomez-Lopez1,2,9

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Summary

Cell-free RNA in amniotic fluid (AF) can predict spontaneous preterm birth. Analysis of AF cell-free RNA identified immune and inflammatory gene expression changes associated with imminent delivery, aiding in the development of new biomarkers.

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Area of Science:

  • Obstetrics and Gynecology
  • Genomics
  • Maternal-Fetal Medicine

Background:

  • Amniotic fluid (AF) cell-free RNA (cfRNA) reflects pregnancy status.
  • The predictive value of AF cfRNA for spontaneous preterm delivery (sPTD) remains unclear.

Purpose of the Study:

  • To investigate the utility of AF cfRNA for predicting imminent spontaneous preterm delivery.
  • To identify specific gene expression signatures in AF cfRNA associated with rapid delivery.

Main Methods:

  • AF samples were collected from women experiencing spontaneous preterm labor.
  • Cell-free RNA expression was profiled and compared between women delivering within 24 hours versus later.
  • Random forest models were used to predict time-to-delivery.

Main Results:

  • 2385 genes were differentially expressed in AF cfRNA between the imminent delivery and later delivery groups.
  • Changes in AF cfRNA were linked to immune and inflammatory processes.
  • Placental immune cell signatures increased with imminent delivery.
  • A transcriptomic prediction model accurately predicted delivery within 24 hours (AUROC = 0.81).

Conclusions:

  • AF cfRNA profiles can predict spontaneous preterm delivery within 24 hours.
  • Immune and inflammatory gene expression in AF cfRNA are key indicators of impending labor.
  • These findings support the development of AF cfRNA-based biomarkers for sPTD risk assessment.