Circulating fibroblast growth factor 21 as a potential biomarker for missed abortion in humans.

OBJECTIVE: To investigate whether serum levels of fibroblast growth factor 21 (FGF21) and fatty acid-binding protein-4 (FABP4) are associated with missed abortion (MA) in humans. DESIGN: Cross-sectional study. SETTING: University-affiliated hospital. PATIENT(S): Patients with MA at 8-12 weeks of gestation. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Serum levels of FGF21 and FABP4 were tested by enzyme-linked immunosorbent assay. Placental samples were collected during dilation and curettage surgery, and the expression of FGF21 and its related genes were measured using quantitative polymerase chain reaction. RESULT(S): In the discovery cohort, 78 patients with MA and 79 healthy pregnant women matched for maternal age and body mass index were nested from a prospective cohort. Circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to the levels in the healthy controls. A single measurement of FGF21 serum level effectively discriminated MA with an area under the receiver operating characteristics curve of 0.80 (95% confidence interval: 0.73-0.87). Importantly, in our external validation cohort that comprised subjects with MA (n = 34) or induced abortion (n = 27), the FGF21 serum levels achieved an area under the receiver operating characteristics curve of 0.85 (95% confidence interval: 0.75-0.96) when identifying those with MA. Nevertheless, expression of FGF21 in the placenta was not associated with its serum concentration. Placental tissues from patients with MA exhibited impaired FGF21 signaling. CONCLUSION(S): Our results suggested that serum levels of FGF21 and FABP4 were associated with MA. Circulating FGF21 may serve as a potential biomarker for the recognition of MA.