Clinical overview
Pre-eclampsia is a multisystem, pregnancy-specific disorder of placental origin that manifests as new-onset hypertension after 20 weeks plus evidence of maternal organ dysfunction or uteroplacental compromise. It is not one disease but a spectrum with at least two phenotypes that share a final common pathway of generalised endothelial dysfunction but differ markedly in their roots: an early-onset form (classically delivery before 34 weeks) driven primarily by defective placentation, and a late-onset form (at or after 34 weeks, the great majority of cases) driven more by maternal cardiovascular and metabolic susceptibility meeting a maturing, ageing placenta. HELLP syndrome — Haemolysis, Elevated Liver enzymes, Low Platelets — is a severe variant on the same continuum, dominated by microangiopathic and hepatic injury, that can occur with only modest hypertension.
For the South African registrar this objective is not academic. Hypertensive disorders of pregnancy are consistently among the leading direct causes of maternal death in the Saving Mothers reports of the National Committee on Confidential Enquiry into Maternal Deaths (NCCEMD), and a large share of those deaths are judged avoidable — failures to measure blood pressure, to give magnesium sulphate, to control severe hypertension, or to deliver in time. Understanding why early- and late-onset disease behave differently sharpens prediction, surveillance and the timing of delivery. This chapter compares their pathophysiology and links it to the management you will be examined on; the clinical thresholds and acute drills overlap heavily with Hypertension in pregnancy.
Core knowledge
Definitions and the diagnostic shift
Pre-eclampsia is new hypertension (≥140/90 mmHg on two occasions, or ≥160/110 once) after 20 weeks, with proteinuria OR maternal organ dysfunction OR uteroplacental dysfunction (e.g. fetal growth restriction). A key conceptual shift, reflected in modern guidance, is that proteinuria is no longer mandatory — renal, hepatic, haematological, neurological or fetal involvement satisfies the diagnosis. The NICE NG133 / ISSHP-aligned position used in the SA NDoH Maternity Guideline (NDoH, 2024) recognises this broadened definition. Eclampsia is pre-eclampsia complicated by generalised tonic–clonic seizures.
The two-stage model — and where the phenotypes diverge
The unifying framework is the two-stage model:
- Stage 1 (preclinical, placental): abnormal spiral-artery remodelling → placental malperfusion → release of antiangiogenic and inflammatory factors into the maternal circulation.
- Stage 2 (clinical, maternal): circulating factors cause systemic endothelial dysfunction → vasospasm, increased capillary permeability, activation of coagulation, and the multi-organ syndrome we recognise.
Both phenotypes pass through Stage 2 (the same endothelium, the same syndrome), but they reach it differently.
Early-onset pre-eclampsia — a placental disease
In normal pregnancy, extravillous trophoblast invades the decidual and inner myometrial segments of the spiral arteries, replacing their muscular walls so they become flaccid, low-resistance conduits delivering high-volume flow to the intervillous space. In early-onset disease this physiological conversion is shallow and incomplete: the arteries retain muscular tone and responsiveness, producing intermittent perfusion, ischaemia–reperfusion injury, and oxidative and endoplasmic-reticulum stress in the syncytiotrophoblast.
The stressed placenta tips the angiogenic balance. It oversecretes soluble fms-like tyrosine kinase-1 (sFlt-1), a decoy receptor that mops up circulating placental growth factor (PlGF) and vascular endothelial growth factor, and secretes soluble endoglin. The net effect is loss of the VEGF/PlGF signalling that maintains healthy endothelium, especially the fenestrated glomerular and hepatic endothelium. A high sFlt-1/PlGF ratio is the biochemical signature, and the foundation of the PlGF-based tests (NICE DG49) used to rule out pre-eclampsia. Because the lesion is placental and early, early-onset disease is tightly associated with placental insufficiency, fetal growth restriction, oligohydramnios and abnormal umbilical-artery Dopplers (see Placental insufficiency response and Intrauterine growth restriction). It is the less common but more dangerous phenotype, carrying higher rates of severe maternal morbidity, HELLP, eclampsia and perinatal loss.
Late-onset pre-eclampsia — a maternal/placental mismatch
Late-onset disease, the majority of cases, often arises in a placenta that was normally implanted. Here the problem is a supply–demand mismatch: as term approaches, a large or senescent placenta outgrows its perfusion, or — more importantly — a maternal constitution predisposed to endothelial and metabolic dysfunction (chronic hypertension, obesity, insulin resistance, dyslipidaemia, pre-existing renal or vascular disease, older age) reaches the threshold at which the normal cardiovascular stress of late pregnancy unmasks disease. The angiogenic imbalance is usually milder (a lower sFlt-1/PlGF rise), fetal growth is more often normal or even large, and umbilical Dopplers are frequently normal. Conceptually: early-onset is placenta failing the mother; late-onset is mother failing the placenta. This distinction is real but a continuum, not a clean dichotomy — overlap is common and should not breed complacency, because late-onset disease still kills.