Mini-combined test compared with NICE guidelines for early risk-assessment for pre-eclampsia: the SPREE diagnostic accuracy study

Abstract

Background The traditional method of risk assessment for pre-eclampsia recommended by the National Institute for Health and Care Excellence is based on maternal factors and it recommends that high-risk women should be treated with aspirin. An alternative method of screening is based on the competing risk model, which uses Bayes’ theorem to combine maternal factors with mean arterial pressure, the uterine artery pulsatility index, serum placental growth factor and pregnancy-associated plasma protein-A at 11–13 weeks’ gestation. Objective The primary aim was to compare the performance of screening by risks obtained using the competing risk model with risk assessment using the National Institute for Health and Care Excellence guidelines. Design This was a prospective multicentre observational study. Setting The setting was seven NHS maternity hospitals in England. Participants Participants were women with singleton pregnancy attending for a routine hospital visit at 11+0–13+6 weeks’ gestation between April and December 2016. Main outcome measures The performance of screening for pre-eclampsia by the competing risk model was compared with the National Institute for Health and Care Excellence method. Relative reductions in risk with aspirin prophylaxis of 30% and 60% were assumed for all pre-eclampsia and preterm pre-eclampsia, respectively. The primary comparison was the detection rate of the National Institute for Health and Care Excellence method with the detection rate of a mini-combined test (including maternal factors, mean arterial pressure and pregnancy-associated plasma protein-A) in the prediction of all pre-eclampsia for the same screen-positive rate determined by the National Institute for Health and Care Excellence method. Results In 473 (2.8%) of the 16,747 pregnancies there was development of pre-eclampsia, including 142 (0.8%) women with preterm pre-eclampsia. The screen-positive rate by the National Institute for Health and Care Excellence method was 10.3%. For all pre-eclampsia, the false-positive and detection rates by the National Institute for Health and Care Excellence method were 9.7% and 31.6%, respectively. For preterm pre-eclampsia, the false-positive and detection rates were 10.0% and 42.8%, respectively. Compliance with the National Institute for Health and Care Excellence recommendation that high-risk women should be treated with aspirin from the first trimester was 23%. For the same screen-positive rate, the detection rate of the mini-combined test for all pre-eclampsia was 42.8%, which was superior to that of the National Institute for Health and Care Excellence method by 11.2% (95% confidence interval 6.9% to 15.6%). The increase in detection for the same screen-positive rate was accompanied by a reduction in false-positive rate of 0.3%. For the same screen-positive rate as National Institute for Health and Care Excellence, the detection rate for preterm pre-eclampsia by combining maternal factors, mean arterial pressure and placental growth factor was 67.3% compared with 44.1% with the National Institute for Health and Care Excellence method. With the addition of the uterine artery pulsatility index, the detection rate was 78.6%. This was higher than that of the National Institute for Health and Care Excellence method by 35.5% (95% confidence interval 25.2% to 45.8%). Calibration of risks for pre-eclampsia was generally good, with the calibration slope very close to 1.0. The feasibility of incorporating a new biomarker was demonstrated. However, the addition of inhibin A to the full combined test did not improve the detection rates for all pre-eclampsia and preterm pre-eclampsia (61% and 80%, respectively). The same screening model for preterm pre-eclampsia by a combination of maternal factors, mean arterial pressure, the uterine artery pulsatility index and placental growth factor achieved detection rates of 45.8% and 56.3%, respectively, for preterm small for gestational age and early small for gestational age neonates. Limitation The study did not include a health economic assessment. Conclusion The findings suggest that performance of screening for pre-eclampsia provided by a combination of maternal factors and biomarkers is superior to that achieved by current National Institute for Health and Care Excellence guidelines. Future work Future work is required to identify potential biomarkers for further improvement of the competing risk model and to carry out a health economic assessment. Trial registration Current Controlled Trials ISRCTN83611527. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 8. See the NIHR Journals Library website for further project information.