Original Title: Første trimester-screening for utvikling av preeklampsi med bruk av algoritme: en fullstendig metodevurdering

Authors' objectives: In 2020, preeclampsia occurred in 2.6% of pregnancies in Norway. Preeclampsia is associated with an increased risk of premature birth and morbidity and mortality in mother and child. Currently the risk of preeclampsia later in pregnancy is assessed on the basis of maternal factors and pregnancy history. The predictive accuracy of the current assessment is limited and does not provide an optimal basis for identifying women at high risk of preeclampsia later in pregnancy. The Norwegian Institute of Public Health was commissioned by the Ordering Forum, New Methods to perform a health technology assessement of a screening program for pregnant women in gestational week 11-14. The purpose of the program is to estimate the individual risk of preeclampsia later in pregnancy based on an algorithm. Studies indicate that the proposed screening program conducted in weeks 11-14 of pregnancy will have higher predictive accuracy for identifying women at high risk for preeclampsia than current practice. For these women, prevention with acetylsalicylic acid from week 16 or earlier may reduce the incidence of preeclampsia with childbirth before the 37th week of pregnancy, thus contributing to reduced morbidity and mortality in mother and child.

Authors' results and conclusions: RESULTS: We did not find eligible systematic reviews for predictive accuracy, but we included 16 primary studies. Two studies had a case-control-design, two were retrospective cohort studies and the remaining studies were prospective cohort studies. Half of the studies were from Asia, while the other half were conducted in Europe. The included studies had between 291 and 65960 participants. Our meta-analyses showed that at a fixed specificity of 0.9, the sensitivity for predicting delivery with preeclampsia regardless of time in pregnancy was 0.454 with a 95 percent confidence interval from 0.301 to 0.616 (very low confidence in the results). Sensitivity for predicting delivery with preeclampsia before 34 weeks' gestation was 0.880 with a 95 percent confidence interval from 0.755 to 0.946 (low confidence). Sensitivity for predicting pre-discharge with pre-eclampsia before 37 weeks' gestation was 0.728 with a 95 per cent confidence interval from 0.682 to 0.770 (moderate confidence). Studies where no participants received ASA prophylaxis consistently reported higher sensitivity than studies where participants received ASA. We included one study on clinical effect and safety of ASA prophylaxis. Participating women were screened using a similar algorithm as the proposed, but with the addition of the biomarker PAPP-A. However, PAPP-A has not been shown to increase the predictive accuracy of the algorithm. We therefore considered women who were identified as being at high risk of preeclampsia in this study to be representative for women identified as being at high risk based on the proposed algorithm. In the study, 1776 women with an estimated risk of premature preeclampsia of > 1 in 100 were invited to participate in a double-blind study of prevention with ASA (150 mg per day) from 11–14 weeks to 36 weeks of pregnancy compared with placebo. The study showed that compared to placebo, ASA prophylaxis gave a 62 percent reduction in the prevalence of preterm preeclampsia (< week 37), (odds ratio 0.38, 95 % CI 0.20-0,71; P=0.004). ASA prophylaxis did not have significant effect on the prevalence of term preeclampsia. The health economic assessment shows that screening with the algorithm with the recommended prevention of preeclampsia with ASA in women identified at high risk can be cost saving compared to current practice. With the assumptions laid down in the analysis, screening with the algorithm could lead to 173 avoided cases of preterm preeclampsia per year. With a calculated saving of around NOK 97,000 per avoided case, this means a total saving for the health service of ~ NOK 17 million per year. The costs of introducing the screening program together with recommended prevention with ASA are therefore estimated to be lower than the savings resulting from fewer preterm preeclampsia and reduced costs for maternity and neonatal care. CONCLUSION: Screening with the proposed algorithm in the first trimester can probably increase the predictive accuracy of the risk of preeclampsia with delivery before week 37 of pregnancy (preterm preeclampsia) and possibly increase the prediction of preeclampsia with delivery before week 34. Initiation of low-dose ASA prophylaxis in women identified as having a high risk of preeclampsia in weeks 11-14 of pregnancy can probably reduce the prevalence of preeclampsia with delivery before week 37 of pregnancy. Introduction of the proposed screening algorithm plus ASA prophylaxis can result in cost-savings compared to current practice. The expected savings are related to the expected decrease in the number of deliveries due to preterm preeclampsia. Cost reductions related to follow-up, birth and neonatal care/treatment will likely exceed the increased costs related to implementation of the proposed algorithm. Furthermore, long-term health effects and financial consequences of reducing preterm preeclampsia, which are not accounted for in our analysis, will further support the conclusion concerning potential cost savings by introducing screening and ASA prophylaxis. Some of the assumptions in the analysis are uncertain, however sensitivity analyses suggest these uncertainties have limited effect on the overall conclusion that screening plus ASA prophylaxis is likely to be cost saving compared to current practice. A study of the implementation of the proposed screening program can help confirming its usefulness and to identify the need for adjustments that can ensure that the intervention has the desired clinical and economic consequences.

Authors' recommendations: We have assessed the health economic consequences of introducing screening with the proposed algorithm and subsequent prevention with ASA compared to assumed current clinical practice in Norway.

Authors' methods: We carried out a systematic knowledge summary with the purpose of investigating the predictive accuracy of screening with the proposed algorithm as a basis for calculating individual risk of preeclampsia assessing the clinical effect of ASA-prophylaxis on the incidence of preeclampsia for pregnant women identified at high risk of preeclampsia based on the proposed algorithm. We have also assessed financial and organizational aspects of introducing the proposed screening program in the specialist health service. We used PICOS frameworks (population, intervention, comparison, outcome, study design) for the selection of the studies that could be relevant for the HTA, one framework for studies of predictive accuracy and one for the prophylactic effect of ASA. Initially we searched for systematic reviews and thereafter for primary studies that could cover the issues. After inclusion, we assessed methodological quality and the risk of systematic bias in the primary studies. Predictive accuracy was measured as sensitivity to predict high risk of preeclampsia with birth

Project Status: Completed

URL for project: https://www.fhi.no/en/cristin-projects/ongoing/screening-for-preeclampsia-with-use-of-an-algorithm---protocol-for-full-hta/

Year Published: 2022

URL for published report: https://www.fhi.no/en/publ/2022/First-trimester-screening-for-the-development-of-preeclampsia-with-the-use-of-an-algorithm/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo