Glycosylated fibronectin point‐of‐care test for diagnosis of pre‐eclampsia in a low‐resource setting: a prospective Southeast Asian population study

Abstract

Objective To determine the performance of a glycosylated fibronectin (GlyFn) point‐of‐care (POC) test for pre‐eclampsia (PE) in a large Southeast Asian cohort (India) in comparison to previously described biomarkers. Design A total of 798 pregnant women at ≥20 weeks of gestation were enrolled in a prospective case‐control study. Study participants included 469 normotensive women with urinary mg protein/mmol creatinine ratio <0.3, 135 with PE (hypertension with urinary mg protein/mmol creatinine ratio ≥0.3) and 194 with gestational hypertension (hypertension with urinary mg protein/mmol creatinine ratio <0.3). Methods GlyFn levels were determined using a POC device and PIGF, sFlt‐1 and PAPPA2 levels were determined by immunoassay. Performance was assessed using logistic regression modelling and receiver‐operating characteristic (ROC) curves. Classification performance and positive and negative predictive values are reported at specific thresholds. Results Increased levels of GlyFn, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and pregnancy‐associated placental protein A2 (PAPPA2), and decreased levels of placental growth factor (PlGF) were significantly associated (P < 0.01) with clinically defined PE. Area under the ROC (AUROC) values with 95% confidence intervals were: GlyFn, 0.99 (0.98–0.99); PlGF, 0.96 (0.94–0.98); sFlt‐1, 0.86 (0.83–0.89); and PAPPA2, 0.96 (0.94–0.97). Of subjects with GH, 48% were positive for more than two PE biomarkers, and 70% of these delivered preterm. Conclusions The Lumella™ GlyFn POC test has been validated in a low/middle‐income country setting for PE diagnosis and may be a useful adjunctive tool for early identification, appropriate triage, and improved outcomes. Tweetable abstract The Lumella™ point‐of‐care test had excellent performance in diagnosing PE in a large Southeast Asian cohort.

Glycosylated fibronectin positivity in the spectrum of hypertensive disorders of pregnancy in relation to the severity and adverse outcomes

“…17 Overall biomarker performance was not different between early-versus late onset PE, or between non-severe and severe PE. 25 A significant proportion of subjects clinically stratified as GH were positive for PE biomarkers and also exhibited a higher frequency of preterm birth than control patients. 25…”

“…24 The LumellaTM GlyFn POC test, (GlyFn point-of-care test for diagnosis of PE) has been validated in a low/middle-income country setting for PE diagnosis. 25 It has been concluded in the study that this may be a useful diagnostic tool for early identification, and appropriate early institution of treatment, so as to reduce adverse maternal and fetal outcomes. 25 Alternative forms of fibronectin have been demonstrated to play a role in acute inflammation and ischemia, vascular remodeling and placental insufficiency and oxygen levels may contribute to altered glycosylation of glycoproteins like fibronectin.…”

Glycosylated fibronectin improves first‐trimester prediction of pre‐eclampsia

“…PE pregnancies compared with non-PE pregnancies is consistent with that of a longitudinal and cross-sectional combined cohort study in Finnish women (n = 107), which reported significantly higher GlyFn in PE vs non-PE pregnancies in the first as well as later trimesters 11 . More recently, elevated GlyFn at ≥ 20 weeks' gestation was shown to be a short-term predictor for development of PE in Swiss and Indian cohort studies 12,13 . The association between serum levels of fibronectin and PE was reported as early as the 1980s 25 .…”

“…One potential alternative biomarker for PE is the glycosylated form of fibronectin (GlyFn). Raised GlyFn level was reported in pregnant women of differing ethnic backgrounds who developed PE after 20 weeks' gestation 11–13 . In addition, GlyFn was found to be elevated between 6 and 14 weeks' gestation in pregnancies that subsequently developed PE compared with those that did not 11 .…”

Two Great Intricate Gestational Syndromes. New Screening and Treatment Strategies

“…According to ACOG, preeclampsia has an incidence of about 2-8%, 5-7% are nulliparous and 2% of patients will develop eclampsia. (3,4) Preeclampsia along with the other subcategories of this hypersensitive disease spectrum are responsible annually for approximately 400,000 maternal deaths and six million perinatal fetal deaths while being considered risk factors for premature birth and underweight newborns.…”