New pathways to diagnose preeclampsia
Ignacio Herraiz
Fetal Medicine Unit, Maternal and Child Health and Development Network
(Red SAMID-RD12/0026/0016). Department of Obstetrics and Gynaecology.
Hospital Universitario 12 de Octubre. Instituto de Investigación
Hospital 12 de Octubre (imas12). Av. de Córdoba, s/n, 28041 Madrid,
Spain.
2 Universidad Complutense de Madrid. Av. Séneca, 2,
28040 Madrid, Spain.
Email:
ignacio.herraiz@salud.madrid.org
The diagnosis of preeclampsia is a major obstetric challenge that we
face daily. In the success differentiating what it is and what it is
not, rests the correct decision making that avoids unnecessary
complications for the mother and the child.
The first step is to always keep this condition in mind. There is no
point in having the most up-to-date guidance if we do not recognize the
palpebral edema of a pregnant woman that enters through our office door
while looking at the computer screen.
The second step is to achieve a diagnostic confirmation as soon as
possible. Rivers of ink have flowed about the inaccuracy of the used
diagnostic criteria that are not based on the etiopathogenic knowledge.
Thus, the definition has been changing over the years. From the classic
triad of “edema, proteinuria, and hypertension”, edema disappeared
more than 20 years ago due to its unspecificity. Nowadays, proteinuria
is no longer considered a sine qua non criterion, due to the
diagnostic delays that its demonstration may cause.
However,
the room for improvement is poor if we still deny the role of the
biomarkers in preeclampsia, as in many other areas of modern medicine.
The pathway was opened with the discovery of the angiogenic imbalance
between anti-angiogenic (e.g. sFlt-1) and pro-angiogenic (e.g. PlGF)
factors in the past decade. They are especially useful for ruling-out
early-onset preeclampsia (Zeisler H et al. NEJM 2016 ;374:13-22). and
its implementation in clinical practice has been shown to translate into
earlier and more accurate diagnosis, with less maternal complications
associated with misdiagnosis (Duhig KE et al. Lancet 2019;393:1807-18).
These biomarkers also have weaknesses as they are less useful in
late-onset forms and its availability depends on the use of expensive
platforms. In this paper (Nagalla SR et al. BJOG 2020), a new biomarker
that should raise our attention is proposed: the glycosylated
fibronectin (GlyFn). This case-control study has obvious weaknesses when
compared with the abovementioned studies on angiogenic-related
biomarkers. In particular, cases and controls slightly differ on
gestational age at sample collection, new criteria for diagnosing
non-proteinuric preeclampsia has not been adopted, fetal growth
restriction has not been analyzed and relevant maternal and perinatal
adverse outcomes are missing. However, the performance of the GlyFn test
shown in this study is impressive, even for late-onset presentations,
with an area under the curve of 0.992 (95% CI 0.988 – 0.997).
The final step is forgoing shortcuts. Immediately after the diagnosis is
made, the patient should be referred to a specialized center with
adequate resources to attend the mother-fetus bionomial. This is of most
relevance in low-resource settings where preeclampsia strikes hardest.
The future availability of this reliable point-of-care test would
facilitate a prompt diagnosis in regions without central laboratory
processing. It will allow timely allocation of these women and hopefully
avoiding severe morbidity and mortality. Therefore, the promising GlyFn
test deserves the development of further studies inspired in those
conducted for PlGF and the sFlt-1/PlGF ratio to validate the results.
Conflict of interest : I have received lecture fees and
consultancy payments from Roche Diagnostics and Thermo-Fisher. A
completed disclosure of interest form is available to view online as
supporting information.