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Reduced circulating NrCAM as a biomarker for fetal growth restriction.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-07-21 DOI:10.1016/j.ebiom.2025.105854

Lucy A Bartho, Susan P Walker, Danica Idzes, Alexander E P Heazell, Lucy E Higgins, Amanda N Sferruzzi-Perri, Natalie J Hannan, Catherine A Cluver, Lina Bergman, Georgia P Wong, Manju Kandel, Ping Cannon, Tuong-Vi Nguyen, Anna Nguyen, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

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引用次数: 0

Abstract

Background: Placental insufficiency underpins pregnancy complications, fetal growth restriction (FGR) and preeclampsia, yet predictive biomarkers are limited. Neuronal Cell Adhesion Molecule (NrCAM) may be a promising biomarker of placental dysfunction. This study investigated whether NrCAM can predict diseases of placental insufficiency.

Methods: Circulating NrCAM was measured across independent cohorts. Plasma NrCAM was assessed at 36 weeks' gestation in women who later delivered FGR infants (<3rd centile birthweight), or developed preeclampsia at term. Circulating NrCAM was also measured in international cohorts: a UK high-risk cohort of women presenting with reduced fetal movements and delivered an FGR infant; a high-risk cohort from South Africa diagnosed with preeclampsia or eclampsia. NrCAM was also assessed in pregnancies with preterm FGR or preeclampsia (<34 weeks gestation). The effect of hypoxia on NrCAM expression was measured in trophoblast stem cells, primary trophoblasts, and a murine FGR model.

Findings: Circulating NrCAM was reduced at 36 weeks' gestation in women who later delivered FGR infants (p = 4.75 x 10^-6, AUC = 0.76, n = 26 FGR, n = 957 controls). In the UK cohort, reduced NrCAM levels were associated with FGR (p = 9.34 × 10^-3, AUC = 0.72, n = 12 FGR, n = 235 control). In the South Africa cohort, circulating NrCAM was reduced with preeclampsia (p = 0.03, AUC = 0.70, n = 27 preeclampsia, n = 15 control). Placental NrCAM expression was lower in FGR (p = 0.0003, n = 23 FGR) and preeclampsia (p = 0.0003, n = 41 preeclampsia, n = 20 controls). Hypoxia reduced NrCAM expression in human trophoblast stem cells (p < 0.01) primary trophoblasts (p < 0.0001) and in a murine FGR model (p < 0.01, n = 9 per group).

Interpretation: Reductions in plasma and placental NrCAM are strongly associated with FGR and may be driven by hypoxia.

Funding: This study was funded by a grant from National Health and Medical Research Council.

查看原文本刊更多论文

减少循环NrCAM作为胎儿生长受限的生物标志物。

背景：胎盘功能不全是妊娠并发症、胎儿生长受限（FGR）和先兆子痫的基础，但预测性生物标志物有限。神经细胞粘附分子（NrCAM）可能是一种有前景的胎盘功能障碍生物标志物。本研究探讨NrCAM对胎盘功能不全疾病的预测作用。方法：在独立队列中测量循环NrCAM。在妊娠36周时，对后来分娩FGR婴儿的妇女进行血浆NrCAM评估(结果：妊娠36周后分娩FGR婴儿的妇女循环NrCAM减少（p = 4.75 x 10-6, AUC = 0.76, n = 26 FGR, n = 957对照）。在英国队列中，NrCAM水平降低与FGR相关（p = 9.34 × 10-3, AUC = 0.72, n = 12 FGR, n = 235对照）。在南非队列中，循环NrCAM随着子痫前期而减少（p = 0.03, AUC = 0.70, n = 27例子痫前期，n = 15例对照组）。胎盘NrCAM表达在FGR （p = 0.0003, n = 23 FGR）和子痫前期（p = 0.0003, n = 41子痫前期，n = 20对照组）均较低。缺氧降低了NrCAM在人滋养层干细胞（p < 0.01）、原代滋养层干细胞（p < 0.0001）和小鼠FGR模型（p < 0.01, n = 9 /组）中的表达。解释：血浆和胎盘NrCAM的减少与FGR密切相关，可能由缺氧驱动。经费：本研究由国家卫生和医学研究委员会资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.

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