循环中NrCAM减少作为胎儿生长受限的生物标志物。
Reduced circulating NrCAM as a biomarker for fetal growth restriction.
作者信息
Bartho Lucy A, Walker Susan P, Idzes Danica, Heazell Alexander E P, Higgins Lucy E, Sferruzzi-Perri Amanda N, Hannan Natalie J, Cluver Catherine A, Bergman Lina, Wong Georgia P, Kandel Manju, Cannon Ping, Nguyen Tuong-Vi, Nguyen Anna, Tong Stephen, Kaitu'u-Lino Tu'uhevaha J
机构信息
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, 3084, VIC, Australia; Mercy Perinatal, Mercy Hospital for Women, VIC, Australia.
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, 3084, VIC, Australia; Mercy Perinatal, Mercy Hospital for Women, VIC, Australia.
出版信息
EBioMedicine. 2025 Jul 21;118:105854. doi: 10.1016/j.ebiom.2025.105854.
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, AUC = 0.76, n = 26 FGR, n = 957 controls). In the UK cohort, reduced NrCAM levels were associated with FGR (p = 9.34 × 10, 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.
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。神经元细胞粘附分子（NrCAM）可能是胎盘功能障碍的一个有前景的生物标志物。本研究调查了NrCAM是否能预测胎盘功能不全相关疾病。
方法
在独立队列中测量循环中的NrCAM。在妊娠36周时，对后来分娩FGR婴儿（出生体重低于第3百分位数）或足月发生先兆子痫的女性进行血浆NrCAM评估。还在国际队列中测量循环中的NrCAM：一个英国高危队列，该队列中的女性出现胎动减少并分娩了FGR婴儿；一个来自南非的高危队列，该队列被诊断为先兆子痫或子痫。还对早产FGR或先兆子痫（妊娠<34周）的孕妇进行了NrCAM评估。在滋养层干细胞、原代滋养层细胞和小鼠FGR模型中测量缺氧对NrCAM表达的影响。
研究结果
后来分娩FGR婴儿的女性在妊娠36周时循环中的NrCAM降低（p = 4.75×10，AUC = 0.76，FGR组n = 26，对照组n = 957）。在英国队列中，NrCAM水平降低与FGR相关（p = 9.34×10，AUC = 0.72，FGR组n = 12，对照组n = 235）。在南非队列中，先兆子痫患者循环中的NrCAM降低（p = 0.03，AUC = 0.70，先兆子痫组n = 27，对照组n = 15）。FGR（p = 0.0003，n = 23例FGR）和先兆子痫（p = 0.0003，先兆子痫组n = 41，对照组n = 20）患者的胎盘NrCAM表达较低。缺氧降低了人滋养层干细胞（p < 0.01）、原代滋养层细胞（p < 0.0001）和小鼠FGR模型（p < 0.01，每组n = 9）中的NrCAM表达。
解读
血浆和胎盘NrCAM的降低与FGR密切相关，可能是由缺氧驱动的。
资金来源
本研究由澳大利亚国家卫生与医学研究委员会的一项拨款资助。
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