Maternal serum glycosylated fibronectin as a short-term predictor of preeclampsia: a prospective cohort study

Abstract

Background: Preeclampsia is a major pregnancy complication that results in significant maternal and infant mortality, most of which occurs in low and middle-income countries. The accurate and timely diagnosis of preeclampsia is critical in management of affected pregnancies to reduce maternal and fetal/neonatal morbidity and mortality, yet difficulties remain in establishing the rigorous diagnosis of preeclampsia based on clinical parameters alone. Biomarkers that detect biochemical disease have been proposed as complements or alternatives to clinical criteria to improve diagnostic accuracy. This cohort study assessed the performance of several biomarkers, including glycosylated fibronectin (GlyFn), to rule-in or rule-out preeclampsia within 4 weeks in a cohort of women at increased risk for preeclampsia. Methods: 151 women with risk factors for or clinical signs and symptoms of preeclampsia were selected from a prospective cohort. Maternal serum samples were collected between 20 and 37 weeks of gestation. Clinical suspicion of preeclampsia was defined as presence of new-onset proteinuria, or clinical symptoms of preeclampsia. Subjects with a clinical diagnosis of preeclampsia at the time of enrollment were excluded. GlyFn, pregnancyassociated plasma protein-A2 (PAPPA2), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured by immunoassay. GlyFn was also determined using a rapid point-of care (POC) test format. Receiver-operating characteristic (ROC) curves derived from logistic regression analysis were used to determine the classification performance for each analyte. Results: 32 of 151 (21%) women developed a clinical diagnosis of preeclampsia within 4 weeks. All biomarkers exhibited good classification performance [GlyFn (area under the curve (AUROC) = 0.

Predictive values of multiple serum biomarkers in women with suspected preeclampsia: a prospective study

“…This distinction may further lead to the differential performance of the GlyFn level in preeclampsia prediction. The glycoprotein PAPP-A2, involved in cleaving insulin-like growth factor binding protein in the placenta, was found to be helpful in diagnosing (12) and predicting preeclampsia (8). In our study, the PAPP-A2/PlGF ratio (p=0.003) was found to be a better marker than PAPP-A2 (p=0.032) alone (Table 2), with an adjusted AUC of 0.72 (Table 3).…”

“…However, the BP elevation standards were not clearly speci ed in Zeisler's study (7); our clinician team decided to take a more cautionary move and had used 120/80 mmHg as the cut-offs. Moreover, the patients on anti-hypertensive treatment were excluded in both Zeisler's (7) and our studies, but were allowed in Huhn's cohort (8). The use of anti-hypertensive medicine could have interfered the pathological development of preeclampsia and potentially compromise the predictive e cacy of the serum markers.…”

“…The use of anti-hypertensive medicine could have interfered the pathological development of preeclampsia and potentially compromise the predictive e cacy of the serum markers. Second, a longer period of time from blood sampling to preeclampsia diagnosis (average 7 weeks in present study) was used compared to other studies with prediction of imminent preeclampsia that took place in 4 weeks or less (7,8) after sampling. Although using delivery as the endpoint in our study seemed reasonable since the appropriate observation window was not wellde ned, the elongated study period may decrease the sensitivities or detection rates of the serum markers.…”

“…Recently, some researchers evaluated preeclampsia predictive markers in patient groups >20 gestational weeks and identi ed high-risk factors or clinical/laboratory signs of preeclampsia (7,8). This type of testing scenario with patients suspected of preeclampsia development has been proven effective, especially in the studies on soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) (7,9).…”

Predictive values of multiple serum biomarkers in women with suspected preeclampsia: a prospective study

“…As an abundant protein with a wide spectrum of functions, serum GlyFn was found to be highly elevated during both the early and late pregnancies of the preeclampsia patients (13,24). More interestingly, in a 2020 study by Huhn et al (8), the GlyFn level in a prospective cohort identi ed with preeclampsia-speci c high-risk factors was reported to show satisfactory preeclampsia prediction with an AUC of 0.94 in the ROC analysis. In our study, GlyFn was also increased, although not signi cantly, in the patient group that developed preeclampsia.…”