Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation

BACKGROUND:Preeclampsia (PE) affects about 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. In the last decade extensive research has been devoted to early screening for PE with the aim of reducing the prevalence of the disease through pharmacological intervention in the high-risk group starting from the first-trimester of pregnancy.
OBJECTIVE:To develop a model for PE based on maternal demographic characteristics and medical history (maternal factors) and biomarkers.
STUDY DESIGN:The data for this study were derived from prospective screening for adverse obstetric outcomes in women attending for their routine first hospital visit at 11-13 weeks' gestation in two maternity hospitals in England. We screened 35,948 singleton pregnancies, including 1,058 (2.9%) that developed PE. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index (PI), mean arterial pressure (MAP), serum pregnancy associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) multiple of the median (MoM) values. Five-fold cross validation was used to assess the performance of screening for PE delivering at <37 weeks' gestation (preterm-PE) and >37 weeks (term-PE) by models combining maternal factors with individual biomarkers and their combination with screening by maternal factors alone.
RESULTS:In pregnancies that developed PE the values of uterine artery PI and MAP were increased and the values of serum PAPP-A and PLGF were decreased. For all biomarkers the deviation from normal was greater for early than late PE and therefore the performance of screening was inversely related to the gestational age at which delivery become necessary for maternal and or fetal indications. Combined screening by maternal factors, uterine artery PI, MAP and PLGF predicted 75% (95% confidence interval [CI] 70-80%) of preterm-PE and 47% (95% CI 44-51%) of term-PE, at FPR of 10%; inclusion of PAPP-A did not improve the performance of screening. Such DRs are superior to the respective values of 49% (95% CI 43-55%) and 38% (34-41%) achieved by screening with maternal factors alone.
CONCLUSION:Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-PE.