title: Total plasma fibronectin as a marker of pregnancy-induced hypertensive disorders: a longitudinal study.
abstract: OBJECTIVE
  To determine normal values of total plasma fibronectin in all three gestational trimesters and to examine 1) whether total plasma fibronectin levels differ between normotensive, hypertensive, and preeclamptic women; and 2) whether total plasma fibronectin may serve as an early marker of pregnancy-induced hypertensive disorders.
  
  
  METHODS
  Total plasma fibronectin was measured in 376 nulliparous women once in each trimester of pregnancy. Normotensive controls (n = 222) and subjects with pregnancy-induced hypertensive disorders (n = 154) were identified after delivery. The group with pregnancy-induced hypertensive disorders was subdivided into a gestational hypertensive group (n = 125) and a preeclamptic group (n = 29). A complete total plasma fibronectin data set was obtained from 347 subjects. Trends in total plasma fibronectin values were compared for the different groups and relative risks (RRs) were calculated after optimal cutoff levels had been determined by receiver operating characteristic curves.
  
  
  RESULTS
  Total plasma fibronectin values (+/- standard error of the mean) were 227 +/- 3 mg/L in the first, 219 +/- 3 mg/L in the second, and 260 +/- 5 mg/L in the third trimesters in normotensive pregnancies. In the first trimester and persisting throughout pregnancy, total plasma fibronectin levels were significantly higher in patients with pregnancy-induced hypertensive disorders than in controls and showed a sharper increase throughout pregnancy. Increased first-trimester total plasma fibronectin levels result in an RR of 1.4 (95% confidence interval [CI] 1.1, 1.8) of developing a pregnancy-induced hypertensive disorder in general. The RR for the development of preeclampsia was 1.7 (95% CI 0.9, 3.4), which was not significant, when the first-trimester total plasma fibronectin level was above the cutoff level of 240 mg/L. The RR for developing preeclampsia was 3.8 (95% CI 1.8, 8.0) when the second-trimester total plasma fibronectin level increased above 230 mg/L.
  
  
  CONCLUSIONS
  The findings of the present study confirm those of previous studies that have found increased total plasma fibronectin levels in pregnancy-induced hypertensive disorders. This study discovered that in these women, total plasma fibronectin levels are elevated in the first trimester. Total plasma fibronectin appears to be a poor predictor of preeclampsia when measured in a general pregnant population. Therefore, total plasma fibronectin should not be used as a routine screening test in a low-risk population. However, obstetricians may use total plasma fibronectin values to help determine the relative risk of developing pregnancy-induced hypertensive disorders.
authors.affiliation: Department of Obstetrics and Gynecology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Paarlberg
authors.forename: C L
authors.initials: CL
authors.lastname: de Jong
authors.forename: H P
authors.initials: HP
authors.lastname: van Geijn
authors.forename: G J
authors.initials: GJ
authors.lastname: van Kamp
authors.forename: A G
authors.initials: AG
authors.lastname: Heinen
authors.forename: G A
authors.initials: GA
authors.lastname: Dekker
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008137:Longitudinal Studies; D011237:Predictive Value of Tests; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood*; D012306:Risk; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D005353:Fibronectins