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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 6, November/December 2018
AFRICA
387
Review Articles
Pre-eclampsia and the foetus: a cardiovascular
perspective
Ismail Bhorat
Abstract
Pre-eclampsia is the leading cause of perinatal morbidity
and mortality. A full understanding of the pathogenesis of
this enigmatic condition is essential if we are to develop
new prophylactic and therapeutic interventions. Central to
our understanding of the pathogenesis of early-onset pre-
eclampsia is absolute utero-placental ischaemia, which is
lack of placental vascular transformation in early pregnancy.
By contrast, relative utero-placental ischaemia, due to a
mismatch between utero-placental blood flow and increased
demand for nutrients occurring later in pregnancy, may be
central to the development of late-onset pre-eclampsia. These
pathogenic mechanisms have advanced our understanding
of this condition, leading to better prediction, screening
and intervention modalities. Screening for pre-eclampsia in
the first and second trimesters by investigating the materno-
placental circulation and placental hormones could identify
a high-risk subgroup. The advantage of screening in the first
trimester is that a prophylactic intervention is available in the
form of low-dose aspirin, if started before 16 weeks’ gestation
in the high-risk group, resulting in a substantial reduction
in severe early-onset pre-eclampsia, while identification of a
high-risk group in the second trimester will lead to focused
management in this group. Using a combination of cardiac
Doppler, multi-vessel Doppler assessment of the foetal circu-
lation and biomarkers in established pre-eclampsia in the
third trimester could predict adverse outcomes and guide
clinicians to timeous delivery. Hopefully, advances in our
understanding of this enigmatic disease will lead to further
prophylactic and new therapeutic interventions.
Keywords:
pre-eclampsia, foetus, cardiac Doppler, utero-placen-
tal ischaemia, Doppler of foetal circulation, placental hormones
Submitted 19/11/16, accepted 12/8/17
Cardiovasc J Afr
2018;
29
: 387–393
www.cvja.co.zaDOI: 10.5830/CVJA-2017-039
Pre-eclampsia (PE) is the leading cause of maternal and foetal/
neonatal morbidity and mortality worldwide.
1
Clinical diagnosis
and definition of PE is commonly based on measurement of
non-specific signs and symptoms, principally hypertension and
proteinuria.
2,3
However due to the recognition that measurement
of proteinuria is prone to inaccuracies and the fact that PE
complications often occur before proteinuria becomes significant,
most recent guidelines support the diagnosis of PE on the basis
of hypertension and signs of maternal organ dysfunction, rather
than proteinuria.
3-5
The clinical presentation and course of PE is variable,
ranging from severe and rapidly progressing early-onset PE,
necessitating pre-term delivery, to late-onset PE at term. There
may be associated intra-uterine growth restriction (IUGR) and
further increasing neonatal morbidity and mortality rates. These
features suggest that classical standards for the diagnosis of PE
are not sufficient to encompass the complexity of the syndrome,
its prediction, and therapeutic intervention. Undoubtedly,
proper management of the pregnant woman at high risk for PE
necessitates early and reliable detection and intensive monitoring,
with referral to specialised perinatal centres, to substantially
reduce maternal, foetal and neonatal morbidity rates.
6,7
Pathogenesis and possible role of the foetus
Recent evidence provides important insights into the role of
chronic utero-placental ischaemia and angiogenic imbalances
in the mechanism of injury of this obstetric syndrome. Recent
observations indicate that angiogenic imbalances, characterised
by an excess of anti-angiogenic factors, including the soluble
form, fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin
(s-Eng), as well as low circulating maternal concentrations
of vascular endothelial growth factor (VEGF) and placental
growth factor (PLGF), are implicated in the mechanisms of
disease in pre-eclampsia.
8,9
Interestingly, changes in maternal/plasma serum
concentrations of angiogenic factors occur before presentation
of pre-eclampsia: elevated levels of anti-angiogenic factors have
been described in the first and second trimesters in patients
who then develop pre-eclampsia in the index pregnancy.
10,11
One
could speculate that in pre-eclamptic patients, chronic utero-
placental ischaemia limits the amount of substrate for foetal
growth. In turn, the foetus may signal the placental release of
anti-angiogenic substances in order to increase maternal blood
pressure in an attempt to compensate for the limited blood flow
to placental and foetal tissues. The magnitude of angiogenic
imbalances, gene–environment interaction and other factors may
College of Health Sciences Durban, University of KwaZulu-
Natal, Durban, South Africa
Ismail Bhorat, MB ChB, FCOG, PhD,
bhorat@worldonline.co.za