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.