Cardiovascular Journal of Africa: Vol 27 No 2 (March/April 2016)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 2, March/April 2016 AFRICA 71
Pre-eclampsia: its pathogenesis and pathophysiolgy
P Gathiram, J Moodley
Abstract
Pre-eclampsia is a pregnancy-specific disorder that has a
worldwide prevalence of 5–8%. It is one of the main causes of
maternal and perinatal morbidity and mortality globally and
accounts for 50 000–60 00 deaths annually, with a predomi-
nance in the low- and middle-income countries. It is a multi-
systemic disorder however its aetiology, pathogenesis and
pathophysiology are poorly understood. Recently it has been
postulated that it is a two-stage disease with an imbalance
between angiogenic and anti-antigenic factors. This review
covers the latest thoughts on the pathogenesis and pathology
of pre-eclampsia. The central hypothesis is that pre-eclampsia
results from defective spiral artery remodelling, leading to
cellular ischaemia in the placenta, which in turn results in
an imbalance between anti-angiogenic and pro-angiogenic
factors. This imbalance in favour of anti-angiogenic factors
leads to widespread endothelial dysfunction, affecting all the
maternal organ systems. In addition, there is foetal growth
restriction (FGR). The exact aetiology remains elusive.
Keywords: pre-eclampsia, major cause of maternal mortality and
morbidity, placenta
Submitted 6/7/15, accepted 17/2/16
Cardiovasc J Afr 2016; 27: 71–78
DOI: 10.5830/CVJA-2016-009
Pre-eclampsia (PE) is a disorder of pregnancy with a worldwide
prevalence of about 5–8%. It is characterised by new-onset
hypertension with systolic blood pressure ≥ 140mmHg or diastolic
blood pressure ≥ 90 mmHg, measured on two occasions at least
four hours apart, and proteinuria of > 0.3 g per 24 hours or ≥ 1+
proteinuria, detected by urine dipstick after 20weeks of pregnancy,
or in the absence of proteinuria, new-onset hypertension with
new onset of any one of the following: thrombocytopaenia
(platelet count < 100 000/μl), renal insufficiency (serum creatinine
concentration > 1.1 mmg/dl or a doubling of the serum creatinine
concentration in the absence of other renal disease), impaired
liver function (raised concentrations of liver transaminases to
twice normal concentrations), pulmonary oedema, or cerebral or
visual problems.1
PE is one of the main causes of maternal mortality, resulting
in about 50 000–60 000 deaths annually worldwide.1 In addition,
it is associated with an increased risk of the mother and her child
developing cardiovascular complications and diabetes mellitus
later in life.2 Furthermore, PE is a multi-systemic syndrome,
involving genetic and environmental factors in its pathogenesis
and pathophysiology and the only known treatment is delivery
of the foetus and placenta.3
In addition, there are subtypes of PE, which are based on
the time of onset or recognition of the disease. It is generally
divided into two main types, early- and late-onset PE.4 The latter
comprises the majority (> 80%) of pre-eclamptics. In the early-
onset type, the clinical signs appear before 33 gestational weeks,
while in the late-onset type they occur at and after 34 weeks.
However, it is the early-onset type that is responsible for most
of the high maternal and foetal mortality and morbidity rates.
The main pathological feature of early-onset PE is incomplete
transformation of the spiral arteries, resulting in hypoperfusion
of the placenta and reduced nutrient supply to the foetus.
This results in signs of foetal growth restriction (FGR).5 On
the other hand, in late-onset type, the spiral arteries, if at
all, are slightly altered in diameter and there are no signs of
FGR.6 This is because early-onset pre-eclampsia is related to
placental hypoperfusion, while in the late-onset type there is
either no change or a shallow modification of the spiral arteries,
leading in some cases to hyperperfusion of the placenta.7-9
Therefore, it seems that early- and late-onset PE have different
pathophysiological and aetiological pathways.9
In normal pregnancy, the extracellular fluid and plasma
volumes increase by 30–50% and 30–40%, respectively, perhaps
due to a decrease in systemic vascular resistance and increase in
cardiac output. 10 The decreased systemic vascular resistance is
thought to be due the presence of nitric oxide.11 In early-onset
PE, there is a decrease in plasma volume, occurring at 14–17
gestational weeks, 9 before the clinical onset of the disorder.12 This
aspect is discussed more fully later under the role of the renin–
angiotensin–aldosterone system (RAAS).
Despite decades of research, the pathogenesis and
pathophysiology of PE are still poorly or incompletely
understood. 4 The pathogenic process of PE begins during the
first trimester, long before clinical signs are apparent. Hence it
is difficult to identify early biomarkers. The main reason for this
is perhaps ethical in nature, as it is difficult to conduct studies
in early pregnancies, as these may compromise both the mother
Department of Physiology, Women’s Health and HIV
Research Group, Nelson R Mandela School of Medicine,
University of KwaZulu-Natal, Durban, South Africa
P Gathiram, PhD
Department of Obstetrics and Gynaecology and Women’s
Health and HIV Research Group, Nelson R Mandela School of
Medicine, University of KwaZulu-Natal, Durban, South Africa
J Moodley, FCOG,
Review Articles