title: OS090. Performance of candidate clinical and biochemical markers in screening early in pregnancy to detect women at high risk to develop preeclampsia.
abstract: BACKGROUND
  The advent of early preventive measures, such as low-dose aspirin targeting women at high risk of preeclampsia (PE), emphasizes the need for better detection. Despite the emergence of promising biochemical markers linked to the pathophysiological processes, systematic reviews have shown that, until now, no single tests fulfill the criteria set by WHO for biomarkers to screen for a disease. However, recent literature reveals that by combining various clinical, biophysical and biochemical markers into multivariate algorithms, one can envisage to estimate the risk of PE with a performance that would reach clinical utility and cost-effectiveness, but this remains to be demonstrated in various environments and health care settings.
  
  
  OBJECTIVE
  To investigate, in a prospective study, the clinical utility of candidate biomarkers and clinical data to detect, early in pregnancy, women at risk to develop PE and to propose a multivariate prediction algorithm combining clinical parameters to biochemical markers.
  
  
  METHODS
  7929 pregnant women prospectively recruited at the first prenatal visit, provided blood samples, clinical and sociodemographic information. 214 pregnant women developed hypertensive disorders of pregnancy (HDP) of which 88 had PE (1.2%), including 44 with severe PE (0.6%). A nested case-control study was performed including for each case of HDP two normal pregnancies matched for maternal age, gestational age at recruitment, ethnicity, parity, and smoking status. Based on the literature we selected the most promising markers in a multivariate logistic regression model: mean arterial pressure (MAP), BMI, placental growth factor (PlGF), soluble Flt-1, inhibin A and PAPP-A. Biomarker results measured between 10-18 weeks gestation were expressed as multiples of the median. Medians were determined for each gestational week.
  
  
  RESULTS
  When combined with MAP at the time of blood sampling and BMI at the beginning of pregnancy, the four biochemical markers discriminate normal pregnancies from those with HDP. At a 5% false positive rate, 37% of the affected pregnancies would have been detected. However, considering the prevalence of HDP in our population, the positive predictive value would have been only 15%. If all the predicted positive women would have been proposed a preventive intervention, only one out 6.7 women could have potentially benefited. In the case of severe PE, performance was not improved, sensitivity was the same, but the positive predictive value decreased to 3% (lower prevalence of severe PE).
  
  
  CONCLUSIONS
  In our low-risk Caucasian population, neither individual candidate markers nor multivariate risk algorithm using an a priori combination of selected markers reached a performance justifying implementation. This also emphasizes the necessity to take into consideration characteristics of the population and environment influencing prevalence before promoting wide implementation of such screening strategies. In a perspective of personalized medicine, it appears more than ever mandatory to tailor recommendations for HDP screening according not only to individual but also to population characteristics.
authors.affiliation: CRCHUQ and Université Laval, Canada.
authors.forename: J-C
authors.initials: JC
authors.lastname: Forest
authors.affiliation: CHA, Québec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Massé
authors.affiliation: CRCHUQ and Université Laval, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Bujold
authors.affiliation: CRCHUQ and Université Laval, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Rousseau
authors.affiliation: CRCHUQ and Université Laval, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Charland
authors.affiliation: CRCHUQ and Université Laval, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Thériault
authors.affiliation: Dept. Biol. Sci., UQAM, Montréal, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Lafond
authors.affiliation: CRCHUQ and Université Laval, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Giguère