Highlights
- The FMF screening strategy integrating maternal factors, MAP, UtA-PI, and PlGF outperforms the current NICE approach in clinical effectiveness and cost-efficiency.
- Cost-effectiveness analysis demonstrates dominant incremental cost-effectiveness ratios favoring FMF screening, with substantial QALY gains and cost savings per 10,000 pregnancies.
- Scenario analyses indicate robustness of FMF strategy across various preterm PE incidence rates and aspirin adherence levels, supporting its wider implementation.
- Early identification of high-risk pregnancies using FMF biomarkers enables targeted aspirin prophylaxis, improving maternal-fetal outcomes.
Background
Preterm preeclampsia (PE) remains a significant contributor to maternal and neonatal morbidity and mortality worldwide, with timely identification and preventive strategies crucial in mitigating adverse outcomes. In the United Kingdom, current antenatal care guidelines by the National Institute for Health and Care Excellence (NICE) recommend screening based primarily on maternal risk factors without systematic integration of specific biomarkers, potentially limiting sensitivity and intervention efficacy. Recognizing this gap, the Fetal Medicine Foundation (FMF) has developed a multifactorial first-trimester screening model incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) to enhance predictive accuracy for preterm PE.
Cost-effectiveness analyses are vital for informing healthcare policy, ensuring that clinical gains translate into sustainable and efficient resource utilization within the National Health Service (NHS). This review examines the evidence surrounding FMF’s first-trimester screening strategy against the NICE framework, emphasizing economic, clinical, and implementation perspectives.
Key Content
Chronological Development of Preterm Preeclampsia Screening
Early recognition of PE risk relied largely on maternal history and clinical observation. Over the past two decades, advances identified circulatory biomarkers and uterine artery Doppler ultrasound as predictors of placental dysfunction underpinning preterm PE. The FMF model, introduced in the early 2010s, was among the first to combine these parameters quantitatively, validated prospectively in diverse populations (e.g., Poon et al., 2013; Akolekar et al., 2011). Subsequent guideline updates have lagged behind, with NICE recommendations still emphasizing maternal risk factors alone.
Evidence by Screening Strategy and Outcomes
The 2026 cost-effectiveness analysis by Ani et al. (PMID: 42383395) modeled 10,000 simulated singleton pregnancies aged 11–13 weeks, comparing NICE and FMF screening strategies through a decision-tree across a lifetime horizon. The FMF screening included maternal factors, MAP, UtA-PI, and PlGF measurement, while the NICE strategy utilized maternal factors only. The model assumed administration of 150 mg aspirin daily to high-risk pregnancies until 36 weeks gestation, consistent with aspirin’s proven efficacy in reducing preterm PE risk (Roberge et al., 2017).
Results demonstrated that the FMF strategy was not only more effective—yielding a gain of 0.92 quality-adjusted life years (QALYs) per 10,000 pregnancies—but also cost-saving by £3191 per 10,000 patients screened compared to the NICE approach, representing a dominant incremental cost-effectiveness ratio (ICER). This corresponded to a £199 cost saving for each preterm PE case avoided. Scenario analyses considering preterm PE incidence (3%, 5%, 7%) and aspirin adherence (75%, 100%) consistently favored the FMF strategy, emphasizing its robustness across clinical variabilities.
Subcomponent analyses validated that including MAP, UtA-PI, and PlGF in the screening model improved detection rates and consequent aspirin prophylaxis targeting, compared to reliance on maternal factors alone. This aligns with prior clinical evidence underscoring the pathophysiological relevance of placental angiogenic factors and uterine artery blood flow measurements in preeclampsia pathogenesis.
Mechanistic and Translational Insights
The FMF screening approach reflects a biomarker-driven precision medicine model in obstetrics, recognizing preterm PE as a disorder of abnormal placentation and maternal systemic response. Elevated UtA-PI and reduced PlGF signal impaired trophoblastic invasion and angiogenic imbalance, triggers for endothelial dysfunction and hypertension characteristic of preeclampsia. By integrating these measurable pathophysiological indices with clinical risk factors and blood pressure assessment, FMF screening enhances early identification, enabling timely aspirin intervention—a mechanism that modulates platelet aggregation, improves placental perfusion, and reduces oxidative stress.
Expert Commentary
The NICe guidelines, while foundational, have demonstrated limitations in screening sensitivity, resulting in missed opportunities for prophylaxis and prevention of adverse outcomes. The evidence synthesized here supports an evolution toward multifactorial biomarker integration as a standard screening paradigm within the UK healthcare framework. The cost-effectiveness findings further reinforce the value of investing in biomarker assays and Doppler assessment, offset by reduced complications, hospitalizations, and long-term morbidity linked to preterm PE.
Clinicians should consider the feasibility of widespread FMF screening deployment, including training for standardized MAP and UtA-PI measurement, laboratory availability for PlGF quantification, and patient adherence to aspirin therapy. Potential barriers include initial setup costs, variability of biomarker levels by maternal characteristics, and the need for quality control in measurements.
Controversies persist regarding the optimal aspirin dosage, adherence challenges, and generalizability to diverse ethnic groups, which warrant further prospective clinical studies. Additionally, integrating these strategies with emerging digital health tools and telemonitoring may enhance scalability and personalized risk assessment.
Conclusion
The integrated FMF first-trimester screening strategy combining maternal factors, MAP, UtA-PI, and PlGF is demonstrably more cost-effective and clinically efficacious than the current NICE guideline-based screening for preterm PE in the UK. Implementation of this model promises improved pregnancy outcomes through targeted aspirin prophylaxis and effective resource allocation within the NHS framework. Future research should focus on real-world effectiveness, patient-centered adherence strategies, and expanding biomarker panels to refine prediction and prevention paradigms further.
References
- Ani MA, Poon LC, Magee LA, Allen AJ, Nicolaides KH. First Trimester Screening for Preterm Preeclampsia in the United Kingdom: A Cost-Effectiveness Analysis. BJOG. 2026 Jul 1;PMID: 42383395.
- Poon LC, Karumanchi SA, Hyett JA, et al. The use of biomarkers in the prediction of preeclampsia. Am J Obstet Gynecol. 2013;208(1):54-64. PMID: 22975342.
- Akolekar R, Syngelaki A, Poon LC, Wright D, Nicolaides KH. Prediction of pre-eclampsia from maternal factors and biomarkers at 11–13 weeks. Prenat Diagn. 2011;31(1):66-74. PMID: 21105293.
- Roberge S, Villa P, Nicolaides KH, et al. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther. 2017;41(3):157-163. PMID: 28278450.
