Interpretation
The benefit of prophylactic aspirin in women at high risk of PE is well established.4 Using NICE criteria, 12.8% of women in our booking cohort were screen positive. Physician compliance with prescribing aspirin to this high-risk cohort was 75%, approximately three times higher than the rate reported in other UK studies.6, 9 This may be explained by recent changes to the maternity notes at our centre. In 2019, the maternity notes were digitalised at the study site and a mandatory checklist for PE risk assessment was introduced. Despite this improvement, 25% of high-risk women were still not prescribed aspirin. Physician compliance of 96 to 99% has meanwhile been demonstrated with implementation of the FMF algorithm.9, 11
Although we didn’t assess patient compliance in this study, it’s clear that physician compliance with prescribing aspirin does not equate with patient compliance. In an observational cohort study, 44% of women identified as high-risk using maternal characteristics alone, were not compliant with the use of aspirin.15 When compared to those who took aspirin as prescribed, women with low compliance had a higher incidence of early-onset (odds ratio (OR), 1.9 (95% confidence interval (CI), 1.1–8.7); P =0.04) and late-onset PE (OR, 4.2 (95% CI, 1.4–19.8); P =0.04).15
Similarly, in a multicentre randomised controlled trial, the efficacy of aspirin in women identified as high risk using the FMF algorithm in reducing the risk of PE was less in those with lower compliance (OR, 0.24 (95% CI, 0.09-0.65) vs 0.59 (95% CI 0.23-1.53). In research settings, patient compliance with aspirin prescribed based on FMF criteria is favourable compared to when NICE screening is employed. In one recent study, 71% of trial participants were compliant with the use of aspirin when screened using the FMF algorithm.16Therefore, improving the robustness of the screening process is likely to not only improve physician compliance but also patient concordance with aspirin prophylaxis.
Several studies have compared the cost-effectiveness of implementing the FMF algorithm for first trimester prediction of PE to the current method that involves maternal characteristics alone.17-21Only one of these studies included the UK. In contrast to our study that modelled cost on real data, this study used a theoretical population of 100,000 pregnancies and compared the two screening methods using input data from published literature. The authors demonstrated that the FMF algorithm, independent of the sensitivity and specificity of the new test, was associated with lower total costs and more PE cases averted.19 Similarly, in Belgium and Switzerland, cost savings of \euro28.67 (£24.74)17 and CHF42 (£33.32)18, respectively, per patient screened using the FMF algorithm have been reported. In contrast, in other European countries that include Sweden, Ireland, and Germany implementation of the FMF algorithm has incurred higher costs.18, 19These inconsistencies in the literature are the result of variations both in PE prevalence and healthcare costs across different countries. For example, in Sweden, where the prevalence of PE is 1.7%, and in Ireland where healthcare costs are comparatively less than the UK, use of the FMF algorithm was more expensive.19
Implications of the findings on clinical practice and future research
The largest study to date on the clinical effectiveness of first trimester PE using the FMF algorithm, showed that screen positive women were significantly more likely to develop PE at any gestation (5.7% vs 2.4%, risk ratio (RR) 2.33, 95% CI 2.05-2.65, p<0.001), preterm PE (2.1% vs. 0.7%, RR 3.04, 95% CI 2.46–3.77, P < 0.001) and other adverse pregnancy outcomes that include birthweight <3rd centile when compared to the general population (4.5% vs. 2.1%, RR 2.10, 95% CI 1.82–2.42, P < 0.001). Conversely, screen negative women had comparatively lower rates of the reported outcomes.22 Finally, the potential benefit of the FMF algorithm has been demonstrated to result in relative effect reductions of 80% (p=0.025) and 45% (p=0.004) in preterm PE and delivery of an SGA infant <10th centile, respectively.9, 10
Despite these studies demonstrating clinical superiority of the FMF algorithm in comparison to maternal characteristic based screening for PE, barriers to its more widespread implementation persist. Most notably, these include concerns regarding the cost of not only the test but also the package of care it involves, such as training to measure 1st trimester uterine Doppler indices and additional growth scans for screen positive women. The findings of our study do not support this. The cost-savings demonstrated here are modest, but we have adopted a conservative approach and, nonetheless, confirmed that even when higher rates of physician compliance are achieved, FMF screening algorithms can be implemented without additional cost to the healthcare system. This would ultimately enable greater individualisation of antenatal care through the identification of a high-risk cohort that require not just aspirin prophylaxis but also evidence-based third trimester fetal growth surveillance and earlier induction of labour.
To enable re-evaluation of the current national recommendations of maternal characteristic based screening, larger prospective studies are clearly needed to further demonstrate the cost-effectiveness of the FMF algorithm.