PP054. Predicting preeclampsia at late mid-term pregnancy before occurrence of clinical symptoms: Clinical utility of biomarkers and clinical parameters in a low-risk population.

INTRODUCTION: Despite research efforts and healthcare improvement, preeclampsia (PE) continues to be a leading cause of maternal and fetal morbidity and mortality. Early identification of women at risk of developing PE is the most promising approach to implement preventive measures such as low-dose aspirin to reduce negative outcomes. However, it is still relevant to evaluate pregnant women to detect PE before the occurrence of clinical symptoms and/or to have better tools to assist in its differential diagnosis. Recently, measurements of biomarkers such as soluble fms-like tyrosine kinase-1 (SFLT-1) and placental growth factor (PlGF) have been proposed and some manufacturers are already marketing reagents for this purpose.

OBJECTIVES: To examine in a prospective study the performance of selected clinical and biochemical markers for identifying late mid-term pregnancy women at risk of developing PE within a few weeks.

METHODS: Seven thousand nine hundred and twenty nine pregnant women prospectively recruited at the first routine prenatal visit, provided blood samples, clinical and sociodemographic information. Two hundred and fourteen pregnant women developed hypertensive disorders of pregnancy (HDP) of which 88 had PE (1.2%), including 44 who presented with severe PE (0.6%). We performed a nested case-control study from the whole cohort including for each case of HDP two normal pregnancies after matching for maternal age, gestational age at recruitment, ethnicity, parity, and smoking status. Based on the literature, we selected the most promising clinical and biochemical markers to be included in a multivariate logistic regression model: mean arterial pressure and body mass index (BMI), PlGF, SFLT-1, inhibin A, and PAPP-A. All markers were measured between 20 and 32 weeks of gestation except for BMI (early pregnancy). All biological marker results were transformed in multiples of median. Medians were established for each gestational week. Multivariate logistic regression analyses were performed to develop prediction algorithm.

RESULTS: The resulting regression model discriminated the affected from normal pregnancies as indicated by an area under the receiver operating characteristics (ROC) curve of 0.8. But at a 5% false positive rate, only 28% of the women who have developed HDP would have been detected. Even when the statistical analyses were limited to severe PE, the performance was poor: sensitivity 30%, positive predictive value 2.7%.

CONCLUSION: In our low-risk Caucasian population, neither individual candidate markers nor multivariate risk algorithm using an a priori combination of selected clinical and biochemical markers reached a performance justifying implementation as a screening procedure. These results emphasize the necessity to take into consideration the environment, population and health care settings influencing prevalence and characteristics of HDP before promoting wide implementation of such screening strategies. It is imperative to tailor future recommendations for HDP screening not only according to the individual but also to the population characteristics if clinical utility has to be reached.