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\begin{document}

\title{Performance of a risk score for predicting preterm pre-eclampsia.
(Mini-commentary on BJOG-19-0970.R4)}



\author[1]{Ulla Sovio}%
\affil[1]{University of Cambridge}%


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  \date{June 14, 2024}


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Mini-commentary on BJOG-19-0970.R4: External validation of a simple risk
score based on the ASPRE trial algorithm for preterm preeclampsia
considering maternal characteristics in nulliparous pregnant women: a
multicentric retrospective cohort study

\textbf{Performance of a risk score for predicting preterm
pre-eclampsia}

Ulla Sovio

Cambridge University

The Rosie Hospital

Robinson Way

Cambridge

Email: us253@medschl.cam.ac.uk

Brunelli et al (BJOG 2020) evaluated a previously validated maternal
history -based risk score in a multicentric retrospective cohort from
Italy. The risk score discriminated poorly in this study (AUC=0.659
{[}95\% CI 0.579-0.726{]}) but it discriminated well in the Pregnancy
Outcome Prediction (POP) study (AUC=0.846 {[}95\% CI 0.787-0.906{]})
(Sovio et al, BJOG 2019;126:963-970), although the proportion of women
who developed preterm pre-eclampsia was similar in both studies (1.0\%
and 0.7\%, respectively). What could be the possible reasons for these
differences and what should be the next steps for evaluating such risk
scores?

The prevalence of the maternal risk factors that constitute the risk
score was very low in this study. Chronic hypertension has a major
contribution, i.e. it strongly predicts (superimposed) preterm
pre-eclampsia. Only 0.5\% of all the women in the study and 15\% of the
cases had chronic hypertension, whereas in the POP study, the
prevalences were 5\% and 35\%, respectively (Sovio et al, Hypertension
2017;69(4):731-738). An analysis of the SCOPE study (Myers, Pregnancy
Hypertension 2019;17:S21) illustrated that the performance of the risk
score was similarly poor in a healthy nulliparous population which
excluded all women with chronic hypertension (AUC=0.661 {[}95\% CI
0.596-0.725{]}). This is not surprising.

In this study from Italy, it was not clear how representative the cohort
was of the source population.~In this regard, comparisons between
recruited women and eligible non-recruited women would help in assessing
selection bias, but these are not always possible due to limitations in
data or ethical approvals. Misclassification may also contribute to the
poor performance of the risk score. In the POP study, pre-eclampsia was
ascertained through a careful review of case records and linkage to
electronic databases (Sovio et al, 2017). In the study from Italy,
electronic data were used as a basis of defining pre-eclampsia, and data
quality issues should always be considered and discussed. Moreover,
measurement error or misreporting of risk factors or aspirin use could
have increased random error or bias in the risk score.

Future evaluations of the risk score should be performed in datasets
representative of the underlying population in terms of prior maternal
risk. Only the women undergoing interventions which may alter the risk
of preterm preeclampsia should be excluded. The risk score has already
been validated against the model for predicted gestational age at
preeclampsia (PGAPE) in nulliparous women (Sovio et al, 2019; Myers,
2019). Brunelli et al (2020) did not attempt to validate the risk score
against PGAPE but instead compared it with the full FMF algorithm, and
the latter performed better. The need for additional measurements to
those included in the risk score was expected, given the low prevalence
of prior maternal risk factors (Myers, 2019).

A suggested scoring for maternal risk has been published for parous
women (Sovio et al, 2019). Evaluation of the risk score and validation
against PGAPE in parous women is now needed since this could not be done
in the POP study or in the SCOPE study.

\textbf{Disclosures:} Dr. Sovio reports grants from NIHR Cambridge
Biomedical Research Centre, during the conduct of the study. In
addition, Dr. Sovio has a patent application for a novel predictive test
for fetal growth restriction (FGR) pending. A completed disclosure of
interest form is available to view online as supporting information.

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