Stratification of pregnancy care based on risk of pre-eclampsia derived from biophysical and biochemical markers at 19-24 weeks' gestation.

OBJECTIVE We have previously proposed that all pregnant women should have assessment of risk for preeclampsia (PE) at 20 and 36 weeks' gestation and that the 20 weeks assessment should be used to define subgroups requiring additional monitoring and reassessment at 28 and 32 weeks. The objective of this study is to examine the potential improvement in screening for PE with delivery at <28, <32, <36 and ≥36 weeks' gestation at 19-24 weeks' gestation by the addition of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) to the combination of maternal demographic characteristics and medical history, uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP). METHODS This was a prospective, non-intervention study in women attending for an ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at <36 weeks' gestation were calculated using the competing risks model to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiple of the median (MoM) values of UtA-PI, MAP, PlGF and sFLT-1. Different risk cut-offs were used to vary the proportion of the population stratified into each of four risk categories (very high-risk, high-risk, intermediate-risk and low-risk) with the intention of detecting about 80%, 85%, 90% and 95% of the cases of delivery with PE at <28, <32 and <36 weeks' gestation. The performance of screening was assessed by plotting the detection rate against the screen positive rate and calculating the areas under these curves and by proportion stratified to a given group for fixed detection rates. Model based estimates of screening performance for these various combinations of markers were also produced. RESULTS In the study population of 37886 singleton pregnancies there were 1130 (3.0%) that subsequently developed PE, including 160 (0.4%) that delivered at <36 weeks' gestation. In both the modelled and empirical results there was incremental improvement in the performance of screening with the addition of PlGF and sFLT-1 to the combination of maternal factors, UtA-PI and MAP. If the objective of screening was to identify about 90% of cases of PE with delivery at <28, <32 and <36 weeks and the method of screening was a combination of maternal factors, UtA-PI and MAP, the respective screen positive rates would be 3.1%, 8.5%, and 19.1%. The respective values for screening by maternal factors, UtA-PI, MAP and PlGF were 0.2%, 0.7% and 10.6% and for screening by maternal factors, UtA-PI, MAP, PlGF and sFLT-1 were 0.1%, 0.4% and 9.5%. The empirical results were consistent with the modelled ones. There was good agreement between the predicted risk and observed incidence of PE <36 weeks' gestation with all three strategies of screening. CONCLUSION The performance of screening for PE with delivery at <28, <32 and <36 weeks' gestation at 19-24 weeks' gestation achieved by a combination of maternal demographic characteristics and medical history, UtA-PI and MAP is improved by the addition of serum PlGF and sFLT-1. The performance of screening for PE at ≥36 weeks' gestation is poor irrespective of the method of screening at 19-24 weeks. This article is protected by copyright. All rights reserved.