Introduction: Cellular derangements contributing to fetal membrane damage precede spontaneous rupture at term and are even more pronounced in preterm prelabor rupture of membranes. We hypothesized that such pathophysiological processes lead to shedding of fetal membrane-derived cells into maternal blood. This study aimed to identify fetal membrane cells in maternal blood and to examine whether their concentration correlates with membrane rupture.
Methods: Blood samples (30 mL) were collected from pregnant women. Using antibodies targeting proteins highly expressed in the fetal membranes, fetal cells were enriched by magnetic activated cell sorting and isolated by fluorescence activated cell sorting. Their fetal origin was confirmed by short tandem repeat analysis.
Results: Fetal cells were detected in 28% of samples (22 of 78). Detection rates and concentrations varied across groups: (1) spontaneous or iatrogenic term rupture of membranes (≥37 weeks), 50% (10/20), 1-12 cells; (2) term not in labor (≥37 weeks), 27% (4/15), 1 cell; (3) preterm prelabor rupture of membranes (<34 weeks), 17% (3/18), 1 cell; (4) preterm labor with intact membranes (<34 weeks), 10% (1/10), 1 cell; and (5) preterm not in labor (<34 weeks), 27% (4/15), 1-3 cells. After rupture of membranes at term (group 1), the detection rate decreased with time, and no cells were found more than 10 h post-rupture.
Discussion: The protocol successfully isolates fetal cells from maternal blood, potentially originating from the fetal membranes. Their concentration was highest after term rupture of membranes but does not appear to increase after preterm rupture compared with other pregnancies.
Keywords: Biomarkers; Circulating fetal cells; Fetal membranes; Preterm birth; Preterm prelabor rupture of membranes; Rupture of membranes.
Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.