Hurrell A
Pre-eclampsia is a nebulous term. Literally meaning ‘prior to a seizure
in pregnancy’, the name of the syndrome does not accurately depict the
clinical reality. The disease rarely leads to eclampsia even if
untreated, and this is a rare neurological complication. The definition
has been equally imprecise; it has been recognised for many years there
is a lack of consistency, even in research papers (Chappell et al.BJOG 1999;106(9)983-5). Original definitions were pragmatic,
usually based on consensus, and constructed on blood pressure thresholds
known to equate to increased perinatal mortality. The defining link to
proteinuria and blood pressure was partly driven by ease of measurement,
but clearly there are many other important features of this disease,
including renal, hepatic and haematological abnormalities and fetal
growth restriction. For this reason, some international organisations
have expanded definitions to include evidence of multi-organ and
uteroplacental dysfunction (Brown et al. Pregnancy Hypertens.2018;13:291-310). However, there is little validation of these changes,
in terms of clinical outcomes and impact.
This paper is welcomed as the authors have an important dataset with
well characterised maternal and fetal outcomes, allowing precise
methodology for equating definition to outcome (Magee et al. BJOG2020). A traditional definition based on proteinuria thresholds is
compared with a broader definition, which includes further maternal
symptoms and signs, and is related to important clinical outcomes.
Unsurprisingly, this definition produces a higher proportion of
women classified as “diseased”. This will inevitably improve
sensitivity as in effect it lowers the detection threshold. This might
seem advantageous as fewer women are “missed”, but the trade-off is
lower specificity. However, the slight reduction in specificity is
likely justified. Individual risk equates to predictive values, and the
small change in specificity makes little difference to the positive
predictive value (46.4% compared to 44.6%). The improved sensitivity
equates to a substantial benefit in negative predictive value (81.5%
compared to 75.1%). Overall, this confirms that the broad definition
better distinguishes cases of pre-eclampsia from non-cases and is
therefore a better ‘rule-out test’. We have calculated predictive values
from the authors’ primary outcome.
Clinical features remain dependant on end organ response in mother and
baby, known to be highly variable in pre-eclampsia. For example, a
normal-sized healthy baby is not infrequently found in a severely sick
mother and vice versa. Recently, angiogenic biomarkers have been
introduced into the NHS. These have better prediction than clinical
features and biochemical markers such as urate and liver function when
used in women with suspected pre-eclampsia. Definitions may become more
accurate in both rule-in and rule-out of adverse events if they
incorporate angiogenic markers, as these are likely to reduce false
positive and negative assessments of clinical features. If angiogenic
biomarkers are used in clinical practice, they improve outcomes (Duhig
et al. Lancet 2019;393(10183):1807-1818). When a broader
definition incorporating angiogenic imbalance and uteroplacental
dysfunction is used, this best identifies adverse outcomes (Lai et al.Am J Obstet Gynecol 2020;S0002-9378(20)31286-2). Whether
implementation of a broader definition leads to improved outcomes
remains to be seen.