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Fibroblast Growth Factor 21 is a Potent Blood-Based Biomarker for the Missed Abortion in Humans
42 Pages Posted: 7 Oct 2020
More...Abstract
Background: Missed abortion (MA) is an asymptomatic embryo death during the early stage of pregnancy affecting 10 to 15% pregnancies worldwide. The lack of prompt diagnostic biomarkers of MA poses a great challenge for current clinical implementation. While the diversified adaptation in hormonal signatures determines outcomes of pregnancy, whether it affects the onset of MA is under-investigated.
Methods: 78 subjects with MA and 86 controls of pregnancies of normal births matching on maternal age and body mass index (BMI), who attended their first prenatal care during gestational age (6-12 weeks), were nested from a prospective cohort to investigate the association between MA and quantified levels of metabolic-related hormones.
Findings: We found the serum fibroblast growth factor 21 (FGF21) and fatty acid-binding protein-4 (FABP4) were significantly and independently elevated in patients with MA compared to the controls. Compared to FABP4, a single measurement of FGF21 level effectively discriminate case of MA from pregnancies of normal births (an area under operating characteristic’s curve (AUROC): 0.81, 95% CI 0.76-0.92). The clinical cutoff of serum FGF21 to identify subjects with MA was determined as 98.73 pg/ml. Association between outcome of MA and serum FGF21 was further evaluated in an external validation cohort consisted of subjects with MA ( n =34) and induced abortion (IA, n =27), yielding a sensitivity of 94.1% (80.9 – 98.9), specificity of 70.4% (51.5 – 84.2), and AUROC of 0.85 (95% CI 0.75-0.96). Meanwhile, the placenta of MA group was characterized by impaired FGF21 signaling aligned with attenuated angiogenesis and villi dysplasia compared to IA group.
Interpretation: The study reveals serum levels of FGF21 may serve as a potential biomarker for the early recognition of MA.
Funding Statement: This study was supported by grants from the Subject Innovation Team of Shannxi University of Chinese Medicine (2019-YS02), NSFC Grant (No. 81770849) and grants of Key Research Program in Department of Education of Guangdong Province (2016KZDXM041).
Declaration of Interests: The authors declared no conflict of interest.
Ethics Approval Statement: Ethical approvals of this study protocol were granted by the Human Research Ethics Committee for Clinical Study of Second Affiliated Hospital of Shaanxi University of Chinese Medicine (IRB Ref. No.: KY201913). All clinical studies were conducted according to Declaration of Helsinki principles. The written informed consent was obtained from all participants before inclusion in this study.
Keywords: Missed abortion, FGF21, FABP4, Biomarkers
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