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\title{How sFlt-1 can help after preeclampsia diagnosis. (Mini-commentary on
BJOG-20-0485.R2)}



\author[1]{Daniel Rolnik}%
\author[2]{Aris Papageorghiou}%
\affil[1]{Monash Health}%
\affil[2]{University of Oxford}%


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  \date{May 18, 2024}


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Measurement of maternal serum soluble fms-like tyrosine kinase 1
(sFlt-1) and placental growth factor (PlGF), and the ratio between the
two, has been shown to predict preeclampsia. In women with suspected
preeclampsia, an sFlt-1: PlGF ratio below 38 rules out the need for
delivery in the subsequent week with a negative predictive value of
99.3\% (95\% CI 97.9 to 99.9\%) (Zeisler H \emph{et al.} , N Engl J Med
2016;374:13-22). This test may be of particular benefit for women at low
risk of developing the disease in the short term, as it may reduce
unnecessary follow-up, investigations and admissions (Cerdeira
AS\emph{et al.} , Hypertension 2019;74:983--990).

But do these biomarkers have a potential use in women after preeclampsia
is diagnosed? This has not been studied extensively. In this issue of
BJOG, Peguero and colleagues report the results of a study in which the
changes in sFlt-1 and PlGF levels were examined in 63 women with
early-onset preeclampsia from diagnosis to delivery (Peguero A \emph{et
al.} , BJOG 2020). Whilst no association between the change in PlGF
levels and the development of adverse outcomes was evident, changes in
sFlt-1 levels were significantly more pronounced in women who later
developed complications and negatively associated with interval to
delivery. This change (i.e., the delta sFlt-1) also outperformed a
previously published risk score and the use of sFlt-1 at admission only.

Because prevention is better than cure, identifying high-risk women
early and modifying their risk is desirable. Prediction of preeclampsia
can now be achieved at 11 to 14 weeks of gestational age by calculation
of individual patient risk. The risk calculation is based on a combined
screening test that incorporates maternal characteristics, medical
history and biomarkers (mean arterial pressure, uterine artery Doppler
and PlGF) alongside first trimester combined screening for fetal
aneuploidy. This test is particularly accurate for predicting
early-onset preeclampsia, identifying nine out of ten of these severe
cases (O'Gorman N \emph{et al.} , Am J Obstet Gynecol. 2016;214(1):103
e1- e12). More importantly, when this high-risk group is given
prophylaxis using aspirin 150 mg from the first trimester to 36 weeks,
the rate of preeclampsia before 37 and before 32 weeks is reduced by
more than 60\% and 90\%, respectively (Rolnik DL \emph{et al.} , N Engl
J Med. 2017;377(7):613-22). A recent implementation study demonstrated
that early screening is not only feasible in a public health care
setting, but is also associated with a significant reduction in the rate
of preterm preeclampsia and nearly total physician compliance of aspirin
use (29\% with usual care versus 99\% when combined screening is used)
(Guy GP \emph{et al.} , BJOG 2020).

Nevertheless, not all women will undergo such early screening, and not
all cases will be avoided by aspirin: some women will still develop
preeclampsia, and early-onset disease will remain a significant cause of
morbidity and mortality, disproportionally driving the disease burden.
Hence, the findings of Peguero and colleagues are important and suggest
that serial sFlt-1 measurements following a diagnosis of early-onset
preeclampsia can still allow risk stratification -- identifying women at
lower risk of complications who may be eligible for expectant
management, and those at higher risk who require prompt administration
of steroids and timely transfer to tertiary health care facilities.

\textbf{No disclosures:} Completed disclosure of interest forms are
available to view online as supporting information.

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