Original Title: Cribado de preeclampsia

Authors' objectives: To assess the safety, efficacy, and efficiency of preeclampsia screening and prevention programmes in pregnant women Specific objectives –  To evaluate the efficacy of preeclampsia screening programmes in pregnant women –  To evaluate the efficacy of low-dose aspirin for the prevention of preeclampsia in pregnant women –  To evaluate the cost-effectiveness of preeclampsia screening programmes in pregnant women.

Authors' results and conclusions: What is the efficacy of early, preterm, and term preeclampsia screening programmes based on prediction models for detecting preeclampsia in pregnant women? The literature search retrieved three studies for inclusion in the analysis. None of them showed weaknesses in any of the seven domains considered critical by the Assessment of Multiple Systematic Reviews (AMSTAR)-2 tool. The results of the studies evaluated did not provide sufficient evidence to reliably determine the clinical utility of prediction models. This is because not all of them have been externally validated, and the discrimination and calibration metrics of those that have were inconclusive. Nonetheless, we observed that the models with the highest discriminatory power (> 0.9), that is, those that were superior for classifying pregnant women with preeclampsia as having the condition and those without it as healthy, were the first-trimester models that combined maternal clinical characteristics and biophysical and biochemical markers. Furthermore, these models provided a detection rate of early preeclampsia of over 80 %. What is the efficacy of using low-dose aspirin for the prevention of preeclampsia in pregnant women? Of the publications identified in the literature search, two studies were initially included in the analysis, and one additional study was retrieved from alerts. None of them showed weaknesses in any of the seven domains considered critical by the AMSTAR-2 tool. The evidence retrieved indicated that aspirin led to a statistically significant reduction (15 to 18 %) in the risk of preeclampsia compared to placebo or no treatment. There was no evidence to suggest that the magnitude of this reduction was significantly correlated with the timing of prophylaxisinitiation, the dosage used, or other variables (incidence or assessment of preeclampsia risk). On the other hand, the reduction in risk of preeclampsia associated with taking aspirin was seen to be significantly greater when a higher proportion (≥ 50 %) of women in the group analysed were nulliparous. Are screening programmes based on prediction models and low-dose aspirin prophylaxis in women at high risk of developing preeclampsia cost-effective compared to standard practice? One study retrieved by the literature search was included in the analysis, and one further study was obtained from subsequent alerts. Both were classified as having moderate-to-high quality based on the FLC 3.0 critical appraisal tool. The evidence indicated that, for populations similar to those analysed in the studies, first-trimester preeclampsia screening in pregnant women based on the combined algorithm of the Fetal Medicine Foundation for preeclampsia detection, with low-dose aspirin (150-162 mg/day) prophylaxis for women identified as high risk was more effective than standard practice. It prevented more cases of early-onset or preterm preeclampsia and was also less expensive, thanks to reductions in costs associated with the clinical management of preeclampsia. Conclusion Multivariable prediction models based on clinical characteristics together with biophysical and biochemical markers had the highest discriminatory power. Such models can therefore be considered candidates for use in screening programmes for preeclampsia, given the poor predictive value of standard methods based on the analysis of clinical characteristics alone. Aspirin significantly reduces the risk of developing preeclampsia compared to placebo or no treatment. Adverse effects associated with the use of this drug during pregnancy are rare. Screening for preeclampsia in the first trimester of pregnancy based on the Fetal Medical Foundation combined algorithm followed by low-dose aspirin prophylaxis in women classified as at high risk of preeclampsia by the screening programme was more effective and less expensive than current standard practice. COST ANALYSIS What are the expected healthcare costs associated with an organised screening programme for preeclampsia based on the Fetal Medicine Foundation combined algorithm together with low-dose aspirin (150 mg/day) prophylaxis, started before week 16 and continued until week 36 of pregnancy, in women classified as at high risk of preeclampsia, compared to current standard practice? From the perspective of the national health system’s funding body, and for a short-term horizon, an analysis was carried out to assess the incremental costs associated with an organised screening programme for preeclampsia and subsequent low-dose aspirin prophylaxis for women classified as at high risk of preeclampsia compared to standard practice. We calculated direct healthcare costs and the number of cases of preterm preeclampsia associated with each of the strategies analysed. Taking into account the uncertainty in the variables, we carried out a univariate sensitivity analysis and a scenario analysis considering a screening strategy based on maternal risk factors, mean blood pressure, mean uterine artery pulsatility index and pregnancy-associated plasma protein A level. Compared to current standard practice, the incremental cost associated with an organised screening programme for preeclampsia based on the Fetal Medicine Foundation combined algorithm together with low-dose aspirin (150 mg/day) prophylaxis, started before week 16 and continued until week 36 of pregnancy, in women classified as at high risk of preeclampsia, was -€4,635,517. The cost of €17,684,788 associated with the screening programme for preeclampsia plus aspirin prophylaxis, for pregnant women at high risk of preterm preeclampsia, was compensated for by reductions in healthcare expenditure, estimated at €22,320,305, associated with the avoidance of 1,023 cases of preterm preeclampsia. The univariate sensitivity analysis indicated that the rates of prevention, detection and incidence of preterm preeclampsia are the sources of the greatest uncertainty in the cost analysis. In the scenario analysis, for the screening strategy analysed, an increase was observed in the number of women with preterm preeclampsia compared to the baseline scenario, the incremental cost being negative compared to standard practice. Conclusions Compared to current standard practice, an organised screening programme developed using the combined algorithm proposed by the Fetal Medicine Foundation together with low-dose aspirin prophylaxis (150 mg/day), started before week 16 and continued until week 36 of pregnancy, in women classified as at a high risk of preterm preeclampsia had a negative incremental cost. Specifically, the cost associated with the screening programme for preeclampsia together with aspirin prophylaxis was €17,495,476; and this was more than compensated for by less use of maternal and newborn healthcare resources associated with preeclampsia. The cost of the preeclampsia screening programme is related to the number of women classified as at high risk of developing preterm preeclampsia, the prescribing of low-dose aspirin prophylaxis, and the level of adherence of these women to the treatment prescribed, as well as the appropriate measurement of the biochemical and biophysical markers considered in the screening and the associated costs. ETHICAL IMPLICATIONS The possibility of implementing preeclampsia screening in clinical practice raises ethical questions that go beyond the scope of the technology itself, given that principles such as beneficence, nonmaleficence, and respect for personal autonomy may conflict with population health goals. The goals of current antenatal care are based on the moral principles of beneficence and autonomy. According to the principle of beneficence, healthcare professionals are obliged to improve the physical and psychological health of pregnant women, maintaining a favourable balance between benefit and harm. The evidence available to date, summarized in this report, indicates that the benefits of preeclampsia screening together with aspirin prophylaxis (reduction in preeclampsia resulting from increased detection and prevention of preeclampsia, preterm births, small-for-gestational-age infants, and foetal deaths) outweigh its few adverse effects (concern or anxiety in healthy women identified as at high risk of preeclampsia, and the potential risk of vaginal bleeding, antepartum, intrapartum, or postpartum haemorrhage, postpartum haematoma, and/or neonatal intracranial haemorrhage related to aspirin use), yielding a benefit-risk ratio in favour of the introduction of preeclampsia screening. On the other hand, in accordance with the principle of autonomy, there is an obligation to respect the opinions of pregnant women in relation to antenatal care. To this end, women must not be coerced or manipulated to achieve adherence, and hence, the question arises of whether we should require formal informed consent, which enables patients to participate in decision-making. We should reflect on whether it would be necessary to ask women to give informed consent before preeclampsia screening or whether there are reasons for adopting an opt-out policy for this screening, and if so, whether this would compromise personal autonomy to the point of counteracting the benefits obtained. Given that the risk of harm associated with preeclampsia screening is low, while the risk of harm associated with developing this condition and/or not receiving the appropriate care at the beginning of the pregnancy can be high, it may be justifiable to offer preeclampsia screening as part of general antenatal care, giving women the possibility of opting out of the procedures if they wish. Whether women agree or decline to participate in the screening should be documented in the health record.

Authors' methods: To assess the efficacy of preeclampsia screening programmes based on prediction models and the efficacy of low-dose aspirin for preeclampsia prevention in pregnant women compared to standard practice, we conducted a review of the evidence published in systematic reviews. To assess the cost-effectiveness of screening programmes based on prediction models together with prescribing low-dose aspirin to women at high risk of developing preeclampsia compared to standard practice, we analysed economic evaluation studies found in a literature search.

Project Status: Completed

Year Published: 2024

URL for published report: https://www.euskadi.eus/contenidos/informacion/2024_osteba_publicacion/eu_def/adjuntos/E-24-07-Cribado_de_preeclampsia.pdf

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Basque Office for Health Technology Assessment

Contact Address: C/ Donostia – San Sebastián, 1 (Edificio Lakua II, 4ª planta) 01010 Vitoria - Gasteiz

Contact Name: Lorea Galnares-Cordero

Contact Email: lgalnares@bioef.eus

Copyright: <p>Osteba (Basque Office for Health Technology Assessment) Health Department of the Basque Government</p>