Pre-eclampsia is a pregnancy-specific multisystem disorder occurring after 20 weeks, characterised by new-onset hypertension with end-organ involvement, and may progress to eclampsia.

Pre-eclampsia

2. Epidemiology

3. Risk Factors (Predisposing Factors)

Who is at risk of developing pre-eclampsia? First pregnancy, older maternal age, past obstetric history of pre-eclampsia, pre-existing maternal diseases, obstetric conditions ^[1]

Let me systematically organise these and explain why each is a risk factor:

Risk Factor	Relative Risk	Why? (Pathophysiological Basis)
Nulliparity (first pregnancy)	~2–3×	First-time exposure of the maternal immune system to paternal antigens in the placenta → inadequate immune tolerance → impaired trophoblast invasion. In subsequent pregnancies, the immune system has "learned" to tolerate these antigens
Previous pre-eclampsia	~7×	Demonstrates an underlying maternal predisposition (genetic susceptibility, endothelial dysfunction tendency)
Family history of pre-eclampsia (mother or sister)	2–5×	Genetic component — multiple susceptibility genes involved in angiogenesis, immune regulation, and endothelial function
Older maternal age (> 35 years)	~1.5–2×	Age-related endothelial dysfunction, increased arterial stiffness, and higher prevalence of chronic diseases
Advanced paternal age	Modest increase	Paternally-derived fetal antigens may be more immunogenic
New partner / limited sperm exposure	Increased	Reduced prior exposure to paternal antigens → impaired immune tolerance (same mechanism as nulliparity)
Interval > 10 years since last pregnancy	Increased	Loss of immune "memory" to paternal antigens
Obesity (BMI > 30)	~2–3×	Chronic inflammation, insulin resistance, endothelial dysfunction, oxidative stress
African / South Asian ethnicity	Increased	Genetic predisposition; also confounded by higher rates of chronic hypertension and socioeconomic factors

Condition	Why?
Chronic hypertension	Already-damaged endothelium → reduced capacity to handle the additional vascular stress of pregnancy. Superimposed pre-eclampsia on chronic HTN is common
Diabetes mellitus (Type 1 > Type 2 > GDM)	Hyperglycaemia → advanced glycation end-products → endothelial damage + microvascular disease → impaired placentation
Chronic kidney disease	Impaired renal endothelial function + baseline proteinuria + RAAS dysregulation
Systemic lupus erythematosus (SLE)	Autoimmune-mediated endothelial damage; antiphospholipid antibodies directly damage trophoblasts
Antiphospholipid syndrome (APS)	Antibodies promote thrombosis in placental vasculature → impaired placentation → pre-eclampsia. Also associated with recurrent pregnancy loss ^[5]
Autoimmune conditions	Chronic inflammation → endothelial activation

Condition	Why?
Multiple pregnancy (twins, triplets)	Larger placental mass → greater placenta-derived anti-angiogenic factor release (sFlt-1, sEng) + greater demand on maternal cardiovascular system
Molar pregnancy (hydatidiform mole)	Abnormal trophoblast proliferation → massive release of placental factors. Can cause pre-eclampsia even before 20 weeks (an exception to the rule)
Hydrops fetalis	Large placenta → same mechanism as multiple pregnancy
Triploidy	Abnormal placentation
Donor oocyte / donor insemination	Complete foreign paternal antigen exposure → reduced immune tolerance

4. Anatomy and Function — The Placenta in Normal Pregnancy

To understand pre-eclampsia, you must understand normal placentation. This is the crux of the disease.

5. Etiology and Pathophysiology

The pathogenesis / pathophysiology is related to the placenta ^[1] Placental pre-eclampsia and Maternal pre-eclampsia and Mixed presentations: combining maternal and placental contributions ^[2]

This is a two-stage model (Redman & Sargent), now expanded to incorporate maternal susceptibility:

Stage 2: Maternal Systemic Endothelial Dysfunction (the "Maternal" Stage)

The ischaemic placenta releases a variety of factors into the maternal circulation that cause widespread maternal endothelial dysfunction:

Factor	What it does	Consequence
sFlt-1 (soluble fms-like tyrosine kinase 1)	Decoy receptor that binds and neutralises VEGF and PlGF → anti-angiogenic	Loss of VEGF/PlGF signalling → endothelial damage, loss of fenestrations in glomerular endothelium (→ proteinuria), vasoconstriction
sEng (soluble endoglin)	Binds TGF-β → anti-angiogenic	Potentiates sFlt-1 effects; impairs TGF-β-mediated vasodilation via NO and prostacyclin pathways
PlGF (placental growth factor) — decreased	Pro-angiogenic factor normally produced by placenta	Low PlGF = biomarker of placental dysfunction; loss of its endothelial protective effects
Oxidative stress mediators (ROS, lipid peroxides)	Direct endothelial damage	Activate inflammatory cascades
Syncytiotrophoblast debris (STBMs)	Microparticles shed from damaged placenta	Trigger maternal inflammatory response
Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β)	Systemic inflammatory activation	Endothelial activation → adhesion molecule expression, leukocyte recruitment

	Placental Pre-eclampsia	Maternal Pre-eclampsia
Onset	Early (< 34 weeks)	Late (≥ 34 weeks)
Primary pathology	Defective placentation	Maternal constitutional factors (obesity, metabolic syndrome, chronic HTN)
Placental pathology	Marked — infarcts, abnormal Doppler	Minimal
Fetal effects	Prominent — IUGR, oligohydramnios, abnormal umbilical artery Doppler	Usually mild
Maternal severity	Often severe	Variable
Anti-angiogenic imbalance	Very pronounced (very high sFlt-1, very low PlGF)	Less pronounced
Recurrence risk	Higher	Lower

Mixed presentations: combining maternal and placental contributions are common in clinical practice ^[2].

Why does the placenta cause a systemic maternal disease?

Think of the placenta as a "sensor" — when it is ischaemic, it releases an SOS signal (sFlt-1, sEng, inflammatory cytokines, oxidative stress mediators) into the maternal bloodstream. These signals don't just affect the placenta — they affect every maternal endothelium: brain, kidneys, liver, lungs, vasculature. The mother's body essentially "sacrifices" itself to try to increase blood pressure and perfusion to the ischaemic placenta, but this compensatory mechanism spirals out of control.

Specific Organ Pathophysiology

Classification is a key exam topic ^[2]

Category	Definition	Key Features
Chronic (pre-existing) hypertension	HTN present before pregnancy or diagnosed before 20 weeks gestation, or persisting > 12 weeks postpartum	May be essential or secondary. Need to screen for secondary causes if young
Gestational hypertension	New-onset HTN after 20 weeks without proteinuria or other features of pre-eclampsia	Usually mild; resolves postpartum. ~25% progress to pre-eclampsia
Pre-eclampsia	New-onset HTN after 20 weeks + proteinuria or other end-organ damage (as per NICE 2019 definition above)	Can be non-severe or severe; can be superimposed on chronic HTN
Pre-eclampsia superimposed on chronic hypertension	New-onset proteinuria or sudden worsening of HTN/proteinuria, or development of HELLP/other features in a woman with chronic HTN	Occurs in ~25% of women with chronic HTN; higher risk of adverse outcomes than either condition alone
Eclampsia	Pre-eclampsia + generalised tonic-clonic seizures not attributable to other causes	End-stage; medical emergency
HELLP syndrome	A severe variant of pre-eclampsia: Haemolysis + Elevated Liver enzymes + Low Platelets	Can occur without significant hypertension or proteinuria (diagnostic trap!)

Severity Classification of Pre-eclampsia

Feature	Non-severe	Severe
Blood pressure	≥ 140/90 but < 160/110	≥ 160/110 on two occasions at least 4h apart (or once if treated immediately)
Proteinuria	Present but < 5g/24h	≥ 5g/24h (or 3+ on dipstick) — though this threshold is debated
Symptoms	Usually asymptomatic	Severe persistent headache, visual disturbance, RUQ/epigastric pain, altered mental status
Platelets	≥ 100 × 10⁹/L	< 100 × 10⁹/L
Liver enzymes	Normal or mildly elevated	> 2× upper limit of normal
Renal function	Creatinine < 90 μmol/L	Creatinine > 90 μmol/L (or doubling)
Pulmonary oedema	Absent	Present
Fetal status	Normal growth, reassuring CTG	IUGR, oligohydramnios, abnormal Doppler

Important Distinction

Do NOT confuse gestational hypertension with pre-eclampsia. Gestational hypertension is new-onset HTN after 20 weeks WITHOUT proteinuria or end-organ damage. However, ~25% of women with gestational hypertension will progress to pre-eclampsia, so they need close monitoring.

7. Clinical Features

Pre-eclampsia has many consequences to the mother and child. Think of maternal risk from head to toe → remember the pathophysiology of pre-eclampsia, basically a systemic condition, so can result in many many problems ^[1]

Pre-eclampsia may be asymptomatic and detected only on routine antenatal screening (hence the importance of regular BP and urine checks). When symptoms develop, they often indicate severe disease.

Symptom	Pathophysiological Basis
Severe headache (frontal, throbbing, persistent, not relieved by paracetamol)	Cerebral vasospasm → ischaemia; or vasogenic oedema (PRES) from hypertensive hyperperfusion in posterior circulation. Indicates cerebral involvement and imminent eclampsia risk
Visual disturbance: blurred vision, scotomata (blind spots), photopsia (flashing lights), diplopia, cortical blindness	Occipital lobe oedema/ischaemia (PRES) — the visual cortex is in the occipital lobe which is selectively vulnerable. Retinal vasospasm → retinal oedema/detachment can also occur
RUQ or epigastric pain	Hepatic capsule distension from sinusoidal obstruction and periportal haemorrhage/necrosis. The liver capsule (Glisson's capsule) has pain fibres → distension causes pain. This is a red flag for HELLP syndrome and possible subcapsular haematoma
Nausea and vomiting (in late pregnancy)	Hepatic involvement; also may relate to cerebral oedema (↑ICP)
Sudden facial/hand oedema	↑Capillary permeability from endothelial dysfunction → fluid shifts to interstitial space. Particularly hands and face (not just dependent oedema)
Rapidly progressive generalised oedema	Same mechanism as above, but more severe
Dyspnoea	Pulmonary oedema from ↑capillary permeability + fluid overload (especially if given excessive IV fluids). Can also be from peripartum cardiomyopathy or pleural effusion
Reduced urine output (oliguria)	Renal vasoconstriction + glomerular endotheliosis → ↓GFR → oliguria (< 500 mL/24h)
Hyperreflexia / clonus	Upper motor neuron excitability from cerebral oedema/ischaemia. Clonus (especially sustained ankle clonus) is a warning sign of impending eclampsia
Sudden weight gain (> 1 kg/week)	Fluid retention from endothelial dysfunction → oedema
Seizures (eclampsia)	End-stage: cerebral vasospasm → ischaemia → cortical irritability → generalised tonic-clonic seizure. Or PRES mechanism with vasogenic oedema exceeding autoregulatory capacity

Sign	Pathophysiological Basis
Hypertension (≥ 140/90 mmHg)	↑SVR from vasoconstriction (endothelin-1↑, TXA₂↑, NO↓, PGI₂↓) + ↑sensitivity to angiotensin II. In normal pregnancy, there is relative refractoriness to angiotensin II; in pre-eclampsia, this is lost
Severe hypertension (≥ 160/110 mmHg)	Same mechanism, more severe. Immediate treatment needed to prevent stroke
Proteinuria (≥ 300 mg/24h or ≥ 30 mg/mmol protein:creatinine ratio)	Glomerular endotheliosis → disrupted filtration barrier → protein leak. The podocytes are also damaged (podocyturia can be detected)
Brisk deep tendon reflexes / clonus	Cerebral irritability from oedema and ischaemia → ↑upper motor neuron excitability. Check patellar reflexes and ankle clonus at every assessment
Facial and periorbital oedema	↑Capillary permeability (non-dependent oedema = more specific for pre-eclampsia than ankle oedema which is common in normal pregnancy)
Pulmonary crepitations	Pulmonary oedema from capillary leak ± fluid overload
RUQ tenderness	Hepatomegaly from congestion, subcapsular haematoma, or hepatic capsular distension
Papilloedema (rare)	Severely ↑BP → hypertensive retinopathy grade 4
Retinal changes: arteriolar spasm, exudates, haemorrhages, serous retinal detachment	Retinal arteriolar vasospasm → ischaemia → exudation; severe cases → serous detachment (usually resolves postpartum)
Small-for-gestational-age (SGA) fetus	Placental insufficiency → ↓nutrient/O₂ delivery → IUGR
Oligohydramnios	Fetal renal hypoperfusion (due to redistribution of fetal blood flow away from kidneys to brain — the "brain-sparing effect") → ↓fetal urine output → oligohydramnios
Abnormal fetal heart rate pattern on CTG	Placental insufficiency → fetal hypoxia → late decelerations, reduced variability

Think of maternal risk from head to toe ^[1]

System	Complications
Brain	Eclampsia (seizures), intracerebral haemorrhage, PRES, cortical blindness, cerebral oedema
Eyes	Retinal vasospasm, papilloedema, serous retinal detachment, cortical blindness
Cardiovascular	Severe hypertension, pulmonary oedema, peripartum cardiomyopathy
Respiratory	Pulmonary oedema, laryngeal oedema (if intubation needed, may be difficult), ARDS (rare)
Liver	HELLP syndrome, hepatic rupture (rare, catastrophic — 60% mortality), subcapsular haematoma
Kidney	AKI (acute tubular necrosis or cortical necrosis), oliguria
Haematological	DIC, MAHA, thrombocytopenia
Placenta	Abruption (2–3% risk in severe pre-eclampsia), infarction
Fetal	IUGR, prematurity, stillbirth, neonatal complications (NEC, IVH, RDS)

8. Prevention of Pre-eclampsia

For those with risk factors / previous history of pre-eclampsia → give low dose aspirin ^[1] Give aspirin before 16 weeks of gestation ^[1] Go back to pathophysiology → pre-eclampsia is failure of good blood supply to placenta in second trimester. So any drug you give, should be given in first trimester to maximize the chance of this happening → if you give it too late, after the inadequate blood supply is formed, there is nothing more that can be done ^[1]

Pathophysiological Event	Clinical Feature	Why?
↑sFlt-1 / ↓PlGF → endothelial dysfunction	Hypertension	Loss of vasodilators (NO, PGI₂) + ↑vasoconstrictors (endothelin, TXA₂) → ↑SVR
Glomerular endotheliosis	Proteinuria	Swollen endothelium + loss of fenestrations → disrupted filtration barrier → protein leak
↑Capillary permeability	Oedema	Protein-poor fluid leaks into interstitium (Starling forces disrupted)
Hepatic sinusoidal obstruction	RUQ pain, ↑LFTs	Fibrin deposition in hepatic sinusoids → periportal necrosis → capsular distension
Cerebral vasospasm / PRES	Headache, visual Sx, seizures	Ischaemia (vasospasm) or vasogenic oedema (PRES) in posterior circulation
Platelet consumption in damaged vessels	Thrombocytopenia	Platelets consumed at sites of endothelial injury
MAHA from fibrin strands	Haemolysis (↑LDH, schistocytes)	RBCs sheared passing through damaged microvasculature
Placental ischaemia	IUGR, oligohydramnios	Reduced nutrient/O₂ delivery; fetal renal hypoperfusion
Coagulation cascade activation	DIC	Widespread endothelial damage → tissue factor exposure → consumption coagulopathy

High Yield Summary

Definition: Pre-eclampsia = new-onset HTN after 20 weeks + proteinuria OR end-organ damage (renal, hepatic, neurological, haematological) OR uteroplacental dysfunction (IUGR, stillbirth). Updated NICE 2019 definition no longer requires proteinuria if other features present.

Pathophysiology (Two-Stage Model):

Stage 1: Failed spiral artery remodelling → placental ischaemia → release of anti-angiogenic factors (↑sFlt-1, ↑sEng, ↓PlGF)
Stage 2: Systemic maternal endothelial dysfunction → vasoconstriction (HTN), capillary leak (oedema), glomerular endotheliosis (proteinuria), hepatic damage (HELLP), cerebral oedema/vasospasm (eclampsia)
Two phenotypes: early-onset "placental" pre-eclampsia (< 34 wk, severe) vs late-onset "maternal" pre-eclampsia (≥ 34 wk, constitutional)

Risk Factors: Nulliparity, previous pre-eclampsia, chronic HTN, CKD, SLE/APS, DM, obesity, older age, multiple pregnancy, molar pregnancy, family history.

Clinical Features: May be asymptomatic. Warning symptoms = severe headache, visual disturbance, RUQ/epigastric pain, brisk reflexes/clonus. HELLP = haemolysis + elevated liver enzymes + low platelets.

Fetal Effects: IUGR, prematurity, oligohydramnios, placental abruption, stillbirth.

Prevention: Low-dose aspirin (150 mg/day) started before 16 weeks in high-risk women. Works by inhibiting COX-1 → ↓TXA₂ → improved uteroplacental perfusion.

Key Concept: Pre-eclampsia is a disease of the placenta manifesting as maternal systemic endothelial dysfunction. Only definitive cure = delivery of the placenta.

Active Recall - Pre-eclampsia (Definition, Epidemiology, Risk Factors, Pathophysiology, Clinical Features)

Differential Diagnosis of Pre-eclampsia

The clinical scenario you are facing is usually this: a woman in the second half of pregnancy presents with hypertension ± proteinuria ± end-organ dysfunction. Your job is to figure out what kind of hypertensive disorder of pregnancy this is — and also to exclude mimics that can masquerade as pre-eclampsia.

Approach to HT: establishment of diagnosis, differentiate between different causes, and assessment of severity of HT ^[1]^[2]

There are two layers of differential diagnosis here:

Differentiating among the hypertensive disorders of pregnancy (the most common clinical task)
Differentiating pre-eclampsia from non-obstetric conditions that mimic it (especially HELLP mimics and seizure mimics)

This is the bread and butter. You see a pregnant woman with high blood pressure — is it chronic HTN, gestational HTN, pre-eclampsia, or superimposed pre-eclampsia?

Chronic HT doesn't mean she cannot develop pre-eclampsia → must continue monitoring patient's BP trend + additional pre-eclampsia features such as proteinuria / end-organ damage ^[1]

Feature	Chronic Hypertension	Gestational Hypertension	Pre-eclampsia	Superimposed Pre-eclampsia on Chronic HTN
Timing of onset	Before pregnancy or < 20 weeks	> 20 weeks	> 20 weeks	Known chronic HTN + new features > 20 weeks
BP	≥ 140/90	≥ 140/90	≥ 140/90	Sudden worsening or previously controlled now uncontrolled
Proteinuria	May have baseline proteinuria (e.g. CKD)	Absent	Present (≥ 300 mg/day) OR absent if other organ dysfunction present	New-onset proteinuria or sudden significant increase from baseline
End-organ damage	May have pre-existing (LVH, retinopathy) — but stable	Absent	Present: renal, hepatic, neurological, haematological, uteroplacental ^[2]^[3]	New organ dysfunction not explained by pre-existing disease
Postpartum course	Persists > 12 weeks postpartum	Resolves by 12 weeks postpartum	Resolves by 12 weeks postpartum (usually within days to weeks)	Chronic HTN component persists
Pathophysiology	Pre-existing vascular disease (essential or secondary HTN)	Unknown; possibly mild endothelial dysfunction that doesn't cross the threshold for organ damage	Failed placentation → anti-angiogenic imbalance → systemic endothelial dysfunction	Pre-existing endothelial disease + superimposed placental dysfunction → the "double hit"

MCQ 1: A pregnant woman was admitted at 38 weeks of gestation for labour. Her blood pressure was persistently elevated > 140/90mmHg. Urine albumin was negative. What is your diagnosis? → Answer: B. Gestational hypertension ^[2]. Why? HTN after 20 weeks, no proteinuria, no end-organ damage = gestational HTN by definition. But remember: ~25% of gestational HTN will progress to pre-eclampsia, so keep monitoring.

The Key Differentiating Questions

When you see a pregnant woman with HTN, ask yourself:

When did it start? Before 20 weeks → chronic HTN. After 20 weeks → gestational HTN or pre-eclampsia.
Is there proteinuria or end-organ damage? No → gestational HTN. Yes → pre-eclampsia.
Did she have HTN before pregnancy? If yes + new proteinuria/organ damage → superimposed pre-eclampsia.
Does the HTN persist > 12 weeks postpartum? If yes → reclassify as chronic HTN.

The tricky scenario is when you don't have pre-pregnancy BP records. If a woman books late (e.g. presents at 22 weeks with HTN), you cannot be sure whether this is chronic HTN or new-onset. Practically, you manage conservatively and reclassify postpartum: if HTN resolves within 12 weeks → it was likely gestational HTN or pre-eclampsia; if it persists → chronic HTN.

B. Conditions That Mimic Pre-eclampsia

This is where it gets clinically dangerous. Several conditions can present with hypertension + thrombocytopenia + liver dysfunction + neurological symptoms + renal dysfunction in pregnancy — and they are NOT pre-eclampsia but require completely different management.

These are the most important mimics because they share the triad of MAHA + thrombocytopenia + organ damage.

MAHA: non-immune haemolysis due to intravascular RBC fragmentation. Causes: TMA (due to microvascular thrombosis), prosthetic heart valve, LVAD, DIC ^[7]

1° TMA: TTP, HUS, drug-induced TMA, complement-mediated TMA 2° TMA: HELLP syndrome, malignant HTN, SLE, scleroderma, antiphospholipid syndrome ^[7]

Condition	Key Distinguishing Features	Why it mimics pre-eclampsia
TTP (Thrombotic Thrombocytopenic Purpura)	Classic pentad: MAHA + thrombocytopenia + neurological features + renal impairment + fever. ADAMTS13 activity < 10% is diagnostic. Platelets typically very low (< 30 × 10⁹/L). LFTs usually normal. Does NOT resolve with delivery	Both have MAHA + thrombocytopenia + neurological symptoms. But TTP has much lower platelets, normal LFTs, and ADAMTS13 deficiency. TTP needs plasma exchange, not delivery
HUS (Haemolytic Uraemic Syndrome)	Renal failure is dominant (much more prominent than in pre-eclampsia). Typical HUS: Shiga toxin-producing E. coli (usually preceded by bloody diarrhoea). Atypical HUS (aHUS): complement-mediated, can be triggered by pregnancy. Does NOT resolve with delivery	Both have MAHA + thrombocytopenia + AKI. But HUS has disproportionate renal failure, diarrhoeal prodrome (typical), and complement abnormalities (atypical). aHUS needs eculizumab (complement C5 inhibitor)
HELLP syndrome	This IS a severe variant of pre-eclampsia. Haemolysis + Elevated Liver enzymes + Low Platelets. Should improve within 48–72h of delivery. If it doesn't → consider TTP or aHUS	HELLP is on the pre-eclampsia spectrum, so it's not truly a "mimic" — but if features persist postpartum, you must reconsider the diagnosis

TTP vs HELLP — The Critical Distinction

If MAHA + thrombocytopenia + organ dysfunction does NOT resolve within 72 hours of delivery, you must urgently consider TTP (check ADAMTS13) or atypical HUS (check complement levels). Missing TTP is fatal — it requires plasma exchange, not just supportive care. Key clue: in TTP, platelets are usually profoundly low (< 30), LFTs are relatively spared, and neurological features predominate over hepatic features.

Feature	AFLP	HELLP/Severe Pre-eclampsia
Primary pathology	Microvesicular fatty infiltration of hepatocytes (defect in mitochondrial fatty acid β-oxidation, often linked to LCHAD deficiency in the fetus)	Endothelial dysfunction → hepatic sinusoidal obstruction → periportal necrosis
Key features	Hypoglycaemia (liver failure → impaired gluconeogenesis), markedly ↑bilirubin (jaundice), coagulopathy (↑PT/INR from impaired hepatic synthesis of clotting factors), DIC, ↑ammonia, ↑uric acid	↑Transaminases, thrombocytopenia, MAHA. Hypoglycaemia and coagulopathy less prominent unless very severe
HTN/proteinuria	May be absent or mild (only ~50% have HTN)	Present by definition
Platelets	Variable (may be low from DIC)	Characteristically low in HELLP
Timing	Usually 3rd trimester (35–36 weeks)	Any time after 20 weeks
Imaging	CT/US may show fatty liver (but sensitivity is low)	Usually unremarkable or shows subcapsular haematoma
Postpartum	Liver function gradually recovers; may need transplant if fulminant	Rapid recovery after delivery (usually within days)

Why the distinction matters: AFLP management includes delivery but also aggressive supportive care for liver failure (IV glucose for hypoglycaemia, FFP/cryoprecipitate for coagulopathy, monitoring for hepatic encephalopathy). Rarely, liver transplant may be needed.

SLE can flare during pregnancy and mimic pre-eclampsia closely. Both can present with HTN, proteinuria, thrombocytopenia, and renal dysfunction.

Feature	SLE Flare (Lupus Nephritis)	Pre-eclampsia
Timing	Can occur at any gestational age (including < 20 weeks!)	> 20 weeks
Complement levels (C3/C4)	Low (consumed by immune complex deposition)	Normal or high (complement is an acute-phase reactant and increases in normal pregnancy)
Anti-dsDNA antibodies	Rising titres	Not elevated (unless coincidental SLE)
Urine sediment	Active — RBC casts, dysmorphic RBCs (indicates glomerulonephritis)	Typically bland — no active sediment (glomerular endotheliosis, not GN)
Other SLE features	Rash, arthritis, serositis, oral ulcers, alopecia	Absent
sFlt-1/PlGF ratio	Normal (because it's not a placental disease)	Elevated sFlt-1/PlGF ratio
Response to delivery	Does NOT improve with delivery	Improves with delivery

Antiphospholipid syndrome can occur as primary or secondary to SLE ^[5]. It is both a risk factor for pre-eclampsia AND a condition that can independently cause pregnancy complications (thrombosis, pregnancy loss < 10 weeks, premature birth < 34 weeks due to eclampsia) ^[5].

If a pregnant woman seizes, the differential is not just eclampsia:

Condition	Distinguishing Features
Eclampsia	Pre-eclampsia features present (HTN, proteinuria, end-organ damage). Seizures are generalised tonic-clonic. Responds to MgSO₄
Epilepsy	Known history of epilepsy, may have been on anti-epileptic drugs. BP and proteinuria normal. Diagnosed by history and EEG
Cerebral venous sinus thrombosis (CVST)	Pregnancy is a prothrombotic state → risk of CVST. Presents with headache, seizures, focal neurological deficits. CT venogram / MR venogram is diagnostic. May or may not have HTN
Intracranial haemorrhage (ICH)	Sudden severe headache ("thunderclap"), rapid neurological deterioration, focal deficits. CT brain shows haemorrhage. Can coexist with severe pre-eclampsia
Posterior reversible encephalopathy syndrome (PRES)	Actually occurs IN pre-eclampsia/eclampsia but can also occur independently from other causes of severe HTN, immunosuppressants (cyclosporine, tacrolimus). MRI shows characteristic posterior white matter oedema
Meningitis / Encephalitis	Fever, neck stiffness, altered consciousness. LP and neuroimaging diagnostic
Hypoglycaemia	Check glucose! Especially in context of AFLP (impaired gluconeogenesis) or insulin-treated diabetes
Metabolic	Hyponatraemia, hypocalcaemia, uraemia — all can cause seizures. Check electrolytes

If thrombocytopenia is the dominant finding, consider:

Condition	Platelets	Context
Gestational thrombocytopenia	100–150 × 10⁹/L (mild)	Most common cause of thrombocytopenia in pregnancy (~75%). Benign, incidental, no treatment needed. Usually > 70 × 10⁹/L
Pre-eclampsia / HELLP	Can be < 100	HTN + proteinuria + other organ damage
ITP (Immune Thrombocytopenic Purpura)	Can be very low (< 20)	Isolated thrombocytopenia, no MAHA, no HTN, anti-platelet antibodies
TTP	Very low (< 30)	MAHA + neurological features, ADAMTS13 < 10%
DIC	Variable	Consumption coagulopathy — ↑PT, ↑aPTT, ↓fibrinogen, ↑D-dimer ^[7]
SLE	Variable	Other SLE features, ↓C3/C4, ↑anti-dsDNA

When you are faced with a diagnostic dilemma, these tests help discriminate:

Investigation	What it helps differentiate	Interpretation
sFlt-1 / PlGF ratio	Pre-eclampsia vs other causes	Ratio > 38 favours pre-eclampsia; normal ratio effectively rules it out (high NPV). In SLE flare, AFLP, or TTP the ratio is usually normal
ADAMTS13 activity	TTP vs HELLP	< 10% = TTP. Normal (> 20%) in HELLP
Complement levels (C3, C4)	SLE flare vs pre-eclampsia	↓ in SLE flare (consumption); normal/↑ in pre-eclampsia
Anti-dsDNA titres	SLE flare vs pre-eclampsia	Rising in SLE flare; normal in pre-eclampsia
Urine microscopy	Lupus nephritis vs pre-eclampsia	Active sediment (RBC casts, dysmorphic RBCs) in lupus nephritis; bland in pre-eclampsia
Fibrinogen, PT, aPTT	DIC vs pre-eclampsia / HELLP	Markedly ↑PT/aPTT + ↓fibrinogen + ↑D-dimer = DIC ^[7]. HELLP may have mild DIC but fibrinogen is often normal/only mildly low
Blood glucose	AFLP vs HELLP	Hypoglycaemia is a hallmark of AFLP (hepatic synthetic failure); rare in HELLP unless very severe
Ammonia	AFLP vs HELLP	↑ in AFLP (liver failure); normal in HELLP
Bile acids	Intrahepatic cholestasis of pregnancy (ICP) vs HELLP	↑ in ICP; normal in HELLP
24h urine catecholamines / plasma metanephrines	Phaeochromocytoma vs pre-eclampsia	↑ in phaeochromocytoma ^[4]
Antiphospholipid antibodies	APS as underlying cause or co-contributor	Positive in APS; check lupus anticoagulant, anti-cardiolipin, anti-β2-GPI ^[5]

Once you've established the diagnosis of pre-eclampsia, you must determine severity, as this dictates urgency of delivery:

Severe pre-eclampsia or imminent eclampsia:

Symptoms: headache, visual disturbance, epigastric or RUQ pain, nausea and vomiting

Signs: BP ≥ 160/110, proteinuria (3 or 4+ or > 3g/d), gross and rapidly progressive oedema, brisk jerks or clonus, oliguria (< 30 mL/h)

Lab: thrombocytopenia, impaired LFT, RFT, clotting profile ^[1]^[2]

Finding	Mild	Severe
Convulsions (eclampsia)	Absent	Present
Diastolic Blood Pressure	> 90 mmHg but < 110 mmHg	110 mmHg or higher persistently
Generalised oedema (including face and hands)	Absent	Present
Headache	Absent	Present
Visual Disturbances	Absent	Present
Upper Abdominal Pain	Absent	Present
Oliguria	Absent	Present (< 400 mL/24h)
Diminished fetal movement	Absent	Present

^[1]^[2]

Most of these women are asymptomatic → when they complain with symptoms, already severe end of spectrum. How can we catch them early? Via regular antenatal screening (i.e. normal follow up, early pregnancy 4–6 weeks, later pregnancy every 2 weeks). Check BP, proteinuria by dipstick, ultrasound for fetal movement in every visit ^[1]

Important Screening Limitations

Around 1 in 6 will have normal BP and no proteinuria prior to eclampsia ^[1]^[2]. Also remember that even though pre-eclampsia is a placenta problem, the endotoxins can still circulate after delivery, causing pre-eclampsia / eclampsia more than 48 hours after delivery ^[1]. So warn the woman and her family about this possibility.

When you see hypertension + proteinuria + organ dysfunction in pregnancy, run through this mental checklist:

Is it truly after 20 weeks? If not → chronic HTN (or molar pregnancy as the exception)
Is there proteinuria or organ damage? If no → gestational HTN (monitor closely)
Did she have pre-existing HTN? If yes + new features → superimposed pre-eclampsia
Are the liver enzymes and platelets very deranged? → HELLP. Consider AFLP if hypoglycaemia/jaundice/coagulopathy prominent
Is there MAHA + very low platelets + neurological features? → Send ADAMTS13 to rule out TTP
Does it persist after delivery? → Think TTP, aHUS, or reclassify as chronic HTN
Is there active urine sediment + low complement? → Think SLE lupus nephritis flare
Paroxysmal HTN + headache + sweating? → Consider phaeochromocytoma
Isolated mild thrombocytopenia (> 70) + no other features? → Likely gestational thrombocytopenia

High Yield Summary

Differentiating hypertensive disorders of pregnancy:

Chronic HTN = before 20 weeks or persists > 12 weeks postpartum
Gestational HTN = after 20 weeks, no proteinuria, no organ damage
Pre-eclampsia = after 20 weeks + proteinuria or organ dysfunction or uteroplacental dysfunction
Superimposed pre-eclampsia = chronic HTN + new features of pre-eclampsia

Key mimics of pre-eclampsia / HELLP:

TTP: ADAMTS13 < 10%, very low platelets, normal LFTs, neurological features, does NOT resolve with delivery → needs plasma exchange
aHUS: complement-mediated, disproportionate renal failure → needs eculizumab
AFLP: hypoglycaemia, jaundice, coagulopathy, raised ammonia → hepatic synthetic failure
SLE flare: low C3/C4, rising anti-dsDNA, active urine sediment, can occur < 20 weeks, does NOT resolve with delivery
Phaeochromocytoma: paroxysmal HTN + headache + sweating + palpitations

Severity of pre-eclampsia: BP ≥ 160/110, symptoms (headache, visual disturbance, epigastric pain), oliguria, thrombocytopenia, impaired LFT/RFT/clotting → imminent eclampsia.

Screening cannot catch everyone: 1 in 6 have normal BP and no proteinuria before eclampsia. Eclampsia can occur > 48h postpartum.

sFlt-1/PlGF ratio: High NPV — normal ratio effectively rules out pre-eclampsia.

Active Recall - Pre-eclampsia Differential Diagnosis

References

^[1] Lecture slides: Block C - Hypertension and Pregnancy (CFB WCS in 2023_24).pdf ^[2] Lecture slides: GC 224. Hypertension and Pregnancy.pdf ^[3] Lecture slides: GC 115. I am pregnant medical problems complicating pregnancy.pdf ^[4] Senior notes: Maksim Medicine Notes.pdf (p78, Endocrinology — Hypertension DDx) ^[5] Senior notes: Ryan Ho Rheumatology.pdf (p73, Antiphospholipid syndrome) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p137–138, MAHA, TMA, DIC)

Diagnostic Criteria, Diagnostic Algorithm, and Investigations for Pre-eclampsia

A. Diagnostic Criteria

Let's start from first principles. Pre-eclampsia is a clinical diagnosis — there is no single pathognomonic test. You diagnose it by demonstrating: (1) new-onset hypertension after 20 weeks, AND (2) evidence that the disease has affected end-organs or the uteroplacental unit.

How to measure BP in pregnancy:

Patient seated or in left lateral position (to avoid aortocaval compression by the gravid uterus)
Appropriate cuff size (common error: too small cuff → falsely elevated reading)
Use Korotkoff V (disappearance of sounds) for diastolic BP — previously Korotkoff IV was used in pregnancy but current guidelines recommend V
Confirm HT based on 2 measurements 4 hours apart ^[1]

Category	Systolic	Diastolic
Hypertension in pregnancy	≥ 140 mmHg	OR ≥ 90 mmHg
Severe hypertension	≥ 160 mmHg	OR ≥ 110 mmHg ^[1]^[2]

Why the 4-hour interval? Because transient BP elevation (white coat effect, pain, anxiety) is common — you need to confirm it is sustained. However, if BP ≥ 160/110 on a single reading and the clinical picture is consistent, treat immediately — don't wait 4 hours.

Due to atypical presentation of some patients not having proteinuria, the NICE guidelines have new diagnostic criteria → expanded diagnostic criteria, will include more patients just to be safe ^[1]

Still must need new-onset HT after 20 weeks, along with 1 of the following ^[1]:

New-onset hypertension after 20 weeks PLUS one or more of the following new-onset conditions:

Domain	Criteria	Pathophysiological Basis
Proteinuria	≥ 300 mg/day (or protein:creatinine ratio ≥ 30 mg/mmol, or ≥ 2+ on dipstick if quantitative methods unavailable) ^[1]^[2]	Glomerular endotheliosis → disrupted filtration barrier → protein leak
Renal	Creatinine ≥ 90 μmol/L (or doubling from baseline in absence of other renal disease) ^[2]^[3]	Renal cortical vasoconstriction + glomerular endotheliosis → ↓GFR
Hepatic	Elevated transaminases (ALT or AST) ± RUQ or epigastric pain ^[2]^[3]	Hepatic sinusoidal endothelial damage → fibrin deposition → periportal necrosis → capsular distension
Neurological	Eclampsia, altered mental status, blindness, stroke, clonus, severe headache or visual disturbance ^[2]^[3]	Cerebral vasospasm or PRES → ischaemia/vasogenic oedema in posterior circulation
Haematological	Thrombocytopenia (platelets < 150 × 10⁹/L), DIC or haemolysis ^[2]^[3]	Endothelial damage → platelet consumption + coagulation activation + MAHA
Uteroplacental dysfunction	IUGR, abnormal umbilical artery Doppler waveform analysis, or stillbirth ^[2]^[3]	Failed spiral artery remodelling → placental ischaemia → ↓fetal nutrient/O₂ delivery

Meaning that by definition of diagnostic criteria, you can develop pre-eclampsia without proteinuria → but you must have hypertension ^[9]

Why was the definition expanded?

The old definition required proteinuria. But we now know that some women develop severe end-organ damage (liver failure, eclampsia, DIC) BEFORE proteinuria appears — or without proteinuria at all. The expanded criteria capture these women earlier, preventing catastrophic outcomes. The unifying principle is endothelial dysfunction, which can manifest differently in different vascular beds. Some women's glomeruli are relatively spared while their livers or brains bear the brunt.

Severe pre-eclampsia or imminent eclampsia:

Symptoms: headache, visual disturbance, epigastric or RUQ pain, nausea and vomiting

Signs: BP ≥ 160/110, proteinuria (3 or 4+ or > 3g/d), gross and rapidly progressive oedema, brisk jerks or clonus, oliguria (< 30 mL/h)

Lab: thrombocytopenia, impaired LFT, RFT, clotting profile ^[1]^[2]

Finding	Mild	Severe
Convulsions (eclampsia)	Absent	Present
Diastolic Blood Pressure	> 90 mmHg but < 110 mmHg	110 mmHg or higher persistently
Generalised oedema (including face and hands)	Absent	Present
Headache	Absent	Present
Visual Disturbances	Absent	Present
Upper Abdominal Pain	Absent	Present
Oliguria	Absent	Present (< 400 mL/24h)
Diminished fetal movement	Absent	Present

^[1]^[2]

Clinical Pearl

Most of these women are asymptomatic → when they complain with symptoms, already severe end of spectrum ^[1]. The appearance of any symptom (headache, visual changes, epigastric pain) should immediately escalate your level of concern. Don't wait for "textbook" severe pre-eclampsia — a single warning symptom in the context of HTN after 20 weeks demands urgent evaluation.

Since HELLP is a severe variant of pre-eclampsia, it has its own laboratory criteria:

Component	Criterion	What to order
Haemolysis	Abnormal PBS (schistocytes), LDH > 600 IU/L, total bilirubin > 20 μmol/L	PBS, LDH, bilirubin, haptoglobin
Elevated Liver Enzymes	AST or ALT > 70 IU/L (or > 2× ULN)	LFT
Low Platelets	Platelets < 100 × 10⁹/L	CBC

Partial HELLP (only 1–2 of 3 components present) is recognised and still requires close monitoring as it frequently progresses.

C. Investigations — Systematic Approach

Baseline investigations will be ordered to screen for end-organ dysfunction caused by pre-eclampsia ^[1]

The purpose of investigations in pre-eclampsia is threefold:

Confirm the diagnosis (BP + proteinuria/organ damage)
Assess severity and end-organ involvement (is this mild or severe?)
Monitor for progression and guide timing of delivery

I'll organise these by modality, explaining what each test tells you and why you order it.

Modality	Details	Interpretation
Office BP	Seated/left lateral, appropriate cuff, 2 readings 4h apart	≥ 140/90 = HTN; ≥ 160/110 = severe
ABPM (Ambulatory BP Monitoring)	24-hour automated readings	Gold standard for confirming HTN; detects white coat HTN. Indicated when office BP is variable or to confirm diagnosis ^[10]
HBPM (Home BP Monitoring)	Patient self-monitors	Useful for ongoing monitoring; correlates better with prognosis than office BP

Why not just rely on a single office reading? Because anxiety, pain, and the "white coat effect" are common in pregnant women. Ambulatory BP monitoring is indicated when there is increased office BP in pregnant women → to suspect pre-eclampsia ^[10].

Test	Method	Interpretation	Pitfalls
Urine dipstick	Semiquantitative; quick bedside test	≥ 2+ suggests significant proteinuria	High false-positive rate (dehydration, concentrated urine, UTI, exercise). High false-negative rate too. Should be confirmed with quantitative method
Spot urine protein:creatinine ratio (PCR)	Random sample; corrects for urine concentration	≥ 30 mg/mmol = significant proteinuria (equivalent to ~300 mg/day)	Preferred first-line quantitative method — fast and convenient
Spot urine albumin:creatinine ratio (ACR)	More specific for glomerular protein	≥ 8 mg/mmol = significant	Alternative to PCR
24-hour urine protein collection	Gold standard for quantification	≥ 300 mg/day = significant proteinuria; > 3 g/day = severe ^[1]^[2]	Cumbersome, prone to collection errors, delays diagnosis by 24h. Increasingly replaced by spot PCR

Why does proteinuria matter? It reflects glomerular endotheliosis — the pathognomonic renal lesion of pre-eclampsia. The degree of proteinuria roughly (but imperfectly) correlates with disease severity. However, remember: proteinuria is a lagging indicator — organ damage can precede detectable proteinuria.

Urine Dipstick Alone Is Not Enough

A negative dipstick does NOT rule out pre-eclampsia. Around 1 in 6 will have normal BP and no proteinuria prior to eclampsia ^[1]. If clinical suspicion is high (symptoms, lab derangement), proceed with full workup regardless of dipstick result. Always confirm with a quantitative method (PCR or 24h collection).

Bloods: CBC ^[1]

Test	What to look for	Interpretation and Pathophysiology
Full blood count (CBC)	Haemoglobin, platelet count	Thrombocytopenia (platelets < 150 × 10⁹/L) indicates platelet consumption at sites of damaged endothelium ^[2]. Hb may be ↑ (haemoconcentration from reduced plasma volume) or ↓ (haemolysis). A falling platelet trend is as important as the absolute number
Peripheral blood smear (PBS)	Schistocytes (red cell fragments)	Schistocytes = MAHA = red cells being sheared by fibrin strands in damaged microvasculature. Their presence indicates TMA/HELLP. Also look for polychromasia (reticulocyte response to haemolysis) ^[7]
LDH (Lactate Dehydrogenase)	Elevation	↑LDH > 600 IU/L = haemolysis (released from lysed RBCs) and/or tissue necrosis (liver). Non-specific but very useful — a rapidly rising LDH is alarming
Haptoglobin	Depletion	Haptoglobin binds free haemoglobin released from lysed RBCs → consumed → low/undetectable. Low haptoglobin confirms intravascular haemolysis
Indirect bilirubin	Elevation	Haem from lysed RBCs is converted to unconjugated (indirect) bilirubin → ↑ in haemolysis
Coagulation profile (PT, aPTT, fibrinogen, D-dimer)	DIC screen	Impaired clotting profile ^[1]^[2]: ↑PT, ↑aPTT = consumption of clotting factors; ↓fibrinogen = consumed in microthrombi; ↑D-dimer = fibrin degradation. Full DIC = acute decompensated DIC with predominantly bleeding tendency ^[7]

Why check coagulation? Pre-eclampsia/HELLP can trigger DIC (intravascular activation of coagulation from widespread endothelial damage). This is critical to detect before any surgical delivery — you need to know if the patient can clot before you cut.

Test	Finding	Interpretation
Serum creatinine	≥ 90 μmol/L (or doubling from baseline) ^[2]^[3]	Indicates renal involvement. In normal pregnancy, creatinine is lower than non-pregnant values (~50–60 μmol/L) because GFR increases by ~50%. So a creatinine of 90 μmol/L in pregnancy is equivalent to significant renal impairment — don't be fooled by "normal-looking" numbers
Blood urea nitrogen (BUN)	Elevated	Less specific than creatinine; also ↑ in dehydration, GI bleeding
Uric acid (serum urate)	Elevated (> 350 μmol/L)	↑ in pre-eclampsia due to ↓renal excretion (vasoconstriction → ↓GFR) + ↑production from tissue ischaemia. Historically used as a severity marker — rising urate often precedes other derangements. Not diagnostic but a useful trend marker
Electrolytes (Na, K)	Usually normal	Monitor for safety, especially before MgSO₄ administration. Hyperkalaemia may occur in AKI

Normal Creatinine in Pregnancy Is LOW

In normal pregnancy, plasma volume expands ~50% and GFR increases proportionally. So "normal" non-pregnant creatinine (60–110 μmol/L) would actually be abnormally high in pregnancy. A pregnant woman's creatinine should be ~50–60 μmol/L. A value of 90 μmol/L indicates significant renal compromise — this is why the NICE criteria threshold is set at 90 μmol/L, which would seem "normal" outside pregnancy but is clearly abnormal within it.

Test	Finding	Interpretation
ALT and AST	Elevated (> 2× ULN) ^[2]^[3]	Hepatocellular damage from sinusoidal obstruction, fibrin deposition, periportal necrosis. AST may be elevated disproportionately to ALT in HELLP (because LDH is also measured in AST assay, and haemolysis contributes)
Total and direct bilirubin	↑ total bilirubin (predominantly indirect)	Indirect hyperbilirubinaemia = haemolysis. If direct fraction also ↑ → cholestasis or severe hepatocellular damage
Albumin	Low	↓ hepatic synthesis + ↑ capillary leak (protein lost into interstitium → oedema) + dilutional effect of expanded plasma volume
LDH	Elevated (often > 600 IU/L in HELLP)	Dual source: haemolysis + liver necrosis. Very sensitive but non-specific

This is a newer and increasingly important investigation:

Test	Finding in Pre-eclampsia	Clinical Utility
sFlt-1 (soluble fms-like tyrosine kinase 1)	↑↑ (released by ischaemic placenta; binds and neutralises VEGF/PlGF)	Anti-angiogenic factor
PlGF (Placental Growth Factor)	↓↓ (sequestered by sFlt-1 + reduced production by damaged placenta)	Pro-angiogenic factor
sFlt-1/PlGF ratio	Elevated	Ratio > 38 (Elecsys assay): high positive predictive value for pre-eclampsia. Ratio < 38: high negative predictive value — effectively rules out pre-eclampsia developing within the next week. NICE 2019 recommends PlGF-based testing between 20 and 36+6 weeks to help rule out pre-eclampsia

Why is this test useful?

It reflects the underlying pathophysiology (anti-angiogenic imbalance) rather than just downstream manifestations
The negative predictive value is exceptionally high (~99.3%) — if the ratio is normal, you can be very reassured
Helps distinguish pre-eclampsia from other causes of HTN/proteinuria in pregnancy (e.g. chronic HTN, CKD, SLE flare — all of which have a normal ratio)
Helps identify women who will develop pre-eclampsia within the next 1–4 weeks (allows planning)

Uteroplacental dysfunction e.g. IUGR, abnormal umbilical artery Doppler waveform analysis, or stillbirth ^[2]^[3]

Investigation	What it assesses	Key Findings
Ultrasound biometry	Fetal growth (estimated fetal weight, abdominal circumference)	IUGR — EFW or AC < 10th centile for gestational age. Serial measurements (every 2 weeks) show crossing of centile lines (faltering growth)
Umbilical artery Doppler	Placental vascular resistance	Abnormal waveforms: raised pulsatility index → absent end-diastolic flow (AEDF) → reversed end-diastolic flow (REDF) ^[3]. AEDF/REDF indicate severely compromised placental perfusion — imminent fetal danger
Middle cerebral artery (MCA) Doppler	Fetal cerebral redistribution	Low PI (increased diastolic flow) = "brain-sparing effect" — fetus is preferentially shunting blood to the brain at the expense of other organs. Indicates chronic hypoxia
Cerebroplacental ratio (CPR)	MCA PI / UA PI	Low CPR (< 1) indicates fetal compromise even when individual Dopplers are borderline
Amniotic fluid index (AFI)	Amniotic fluid volume	Oligohydramnios (AFI < 5 cm or deepest pocket < 2 cm) — reflects fetal renal hypoperfusion (blood redirected away from kidneys to brain)
Cardiotocography (CTG)	Fetal heart rate pattern	Look for: reduced variability, late decelerations (both indicate fetal hypoxia), absent accelerations. A pathological CTG may mandate emergency delivery
Biophysical profile (BPP)	Composite score: CTG + fetal breathing + fetal movements + fetal tone + AFI	Score 0–8 (or 0–10 with CTG). Low score (≤ 4) = significant fetal compromise
Uterine artery Doppler	Uterine artery resistance (reflects spiral artery remodelling)	High PI with bilateral notching in the 2nd trimester suggests failed spiral artery remodelling — used as a screening/prediction tool rather than diagnostic. Note: most useful at 20–24 weeks as a risk prediction tool

These are ordered when the clinical picture is atypical or a mimic is suspected:

Investigation	Purpose	When to order
ADAMTS13 activity	Rule out TTP	MAHA + very low platelets (< 30) + neurological features. If < 10% → TTP
Complement levels (C3, C4)	Distinguish SLE flare vs pre-eclampsia	Low → SLE flare or aHUS. Normal/high → pre-eclampsia
Anti-dsDNA, ANA	SLE flare	Rising titres suggest active SLE
Antiphospholipid antibodies	APS	Recurrent pregnancy loss, thrombosis history ^[5]
Blood glucose	AFLP	Hypoglycaemia = liver failure (AFLP)
Ammonia	AFLP	Elevated = hepatic encephalopathy
Plasma/urine metanephrines	Phaeochromocytoma	Paroxysmal HTN + headache + sweating + palpitations ^[4]
Bile acids	Intrahepatic cholestasis of pregnancy	Pruritus + ↑bile acids + ↑LFTs; no HTN or proteinuria

Baseline investigations will be ordered to screen for end-organ dysfunction ^[1]:

Domain	Tests
Haematological	CBC ^[1], PBS, coagulation profile (PT, aPTT, fibrinogen), LDH, haptoglobin
Renal	RFT (creatinine, BUN, uric acid), electrolytes
Hepatic	LFT (ALT, AST, bilirubin, albumin, LDH)
Proteinuria	Spot urine PCR (or 24h urine protein if needed)
Angiogenic markers	sFlt-1/PlGF ratio (if available, 20–36+6 weeks)
Fetal	Ultrasound (biometry + AFI + Doppler), CTG

These should be repeated serially (at least twice weekly in severe pre-eclampsia, or more frequently if deteriorating) because the hallmark of pre-eclampsia is progression.

Severity	BP Monitoring	Bloods	Fetal Assessment
Non-severe pre-eclampsia	At least 4× daily	Twice weekly (CBC, LFT, RFT, coag)	Twice weekly CTG; serial USS every 2 weeks
Severe pre-eclampsia	Continuous or every 15–30 min	Daily or more frequently	Continuous CTG; daily umbilical artery Doppler if IUGR
Gestational hypertension	At least 2× weekly	Weekly (to detect progression to pre-eclampsia)	Serial USS every 2–4 weeks

Fluid balance is crucial. Pre-eclampsia is characterised by leaky vessels and endothelial damage → so don't just pump fluids into patient, may cause third spacing and worsen generalised oedema / pulmonary oedema ^[1]

Therefore, strict fluid balance monitoring (input/output chart, consider urinary catheter in severe cases for hourly output) is an essential part of the investigation and monitoring framework.

While not "diagnostic" per se, current practice increasingly incorporates first-trimester combined screening for pre-eclampsia (e.g. the FMF algorithm — Fetal Medicine Foundation):

Component	What it measures
Maternal factors	Age, BMI, ethnicity, medical history, parity, mode of conception
Mean arterial pressure (MAP)	Average of 3 readings at 11–13+6 weeks
Uterine artery pulsatility index (UtA-PI)	Doppler at 11–13+6 weeks; high PI suggests impaired early placentation
Serum PAPP-A	Low PAPP-A = poor placental function
Serum PlGF	Low PlGF in 1st trimester predicts later pre-eclampsia

Combined, these give a patient-specific risk that determines whether prophylactic aspirin should be started. Detection rate for early-onset pre-eclampsia is approximately 90% at a 10% false-positive rate using this combined approach.

High Yield Summary

Diagnostic Criteria (NICE 2019): New-onset HTN (≥ 140/90 on 2 readings 4h apart) after 20 weeks + ONE of: proteinuria ≥ 300 mg/day, renal dysfunction (Cr ≥ 90), hepatic involvement (↑ALT/AST ± RUQ pain), neurological features, haematological features (plt < 150, DIC, haemolysis), or uteroplacental dysfunction (IUGR, abnormal Doppler, stillbirth). Proteinuria is no longer mandatory if other organ dysfunction is present.

Severity Assessment: Severe = BP ≥ 160/110, symptoms (headache, visual disturbance, epigastric pain), oliguria, thrombocytopenia, impaired LFT/RFT/clotting, fetal compromise. Most patients are asymptomatic — symptoms indicate the severe end.

Key Investigations: CBC (platelets!), PBS (schistocytes), LFT (ALT/AST), RFT (creatinine — remember normal in pregnancy is ~50–60 μmol/L), coagulation profile, LDH, haptoglobin, spot urine PCR, sFlt-1/PlGF ratio (< 38 rules out pre-eclampsia with ~99% NPV), and fetal assessment (USS biometry, umbilical artery Doppler, CTG).

HELLP Criteria (Tennessee): Haemolysis (schistocytes, LDH > 600, ↑bilirubin), Elevated Liver enzymes (AST/ALT > 70 or > 2× ULN), Low Platelets (< 100).

Admit ALL pre-eclampsia patients. Monitor BP, bloods, and fetal status serially. Fluid balance is critical — leaky vessels mean IV fluids can cause pulmonary oedema.

sFlt-1/PlGF ratio is the best "rule-out" test: ratio < 38 has ~99% NPV for pre-eclampsia within the next week.

Active Recall - Pre-eclampsia Diagnostic Criteria, Algorithm and Investigations

References

^[1] Lecture slides: Block C - Hypertension and Pregnancy (CFB WCS in 2023_24).pdf ^[2] Lecture slides: GC 224. Hypertension and Pregnancy.pdf ^[3] Lecture slides: GC 115. I am pregnant medical problems complicating pregnancy.pdf ^[4] Senior notes: Maksim Medicine Notes.pdf (p78, Hypertension DDx and investigations) ^[5] Senior notes: Ryan Ho Rheumatology.pdf (p73, Antiphospholipid syndrome) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p137–138, MAHA, TMA, DIC) ^[9] Lecture slides: Block C - I am pregnant_ medical problems complicating pregnancy.pdf ^[10] Senior notes: Ryan Ho Cardiology.pdf (p175, ABPM indications in pregnancy)

Management of Pre-eclampsia

The overarching philosophy is straightforward, but the execution is nuanced. Let me lay it out from first principles.

Definitive treatment of pre-eclampsia is delivery ^[1]^[2] Since the placenta is the problem, basically the only treatment that will really work is delivery ^[1]

But the catch is: delivery is not always in the best interest of the fetus, particularly if preterm. So the entire management framework is a balancing act between maternal safety (worse the longer you wait) and fetal maturity (better the longer you wait).

Pre-eclampsia is a balance between the problems of systemic end organ damage, and prematurity of the baby ^[1]

C. Pillar 1 — Blood Pressure Control

Setting	Target	Rationale
Non-severe pre-eclampsia	< 140/90 mmHg	Prevent progression to severe; maintain perfusion
Severe pre-eclampsia	< 160/110 urgently (within first hour); then aim < 140/90	Prevent stroke. But don't overshoot — maintain uteroplacental flow
Pre-eclampsia/eclampsia — hypertensive emergency	Target SBP < 140 in first hour ^[4]	This is more aggressive than general hypertensive emergency (≤25% drop) because eclampsia/severe pre-eclampsia is a compelling indication for rapid BP control ^[10]

Antihypertensive Agents

IV labetalol / hydralazine ^[1]

Drug	Dose	Mechanism	Advantages	Cautions/Contraindications
IV Labetalol	20 mg IV over 2 min → repeat 40 mg bolus at 15 min if uncontrolled → IV infusion 0.5–2 mg/min → transition to PO ^[4]^[10]	Combined α₁-blocker (peripheral vasodilation) + β-blocker (↓HR, ↓CO). "Labet-" doesn't stand for anything specific, but think Lowers Afterload and Beta-blocks the heart	Smooth, controlled BP reduction. Does not cause reflex tachycardia (unlike hydralazine). Does not raise ICP. First-line in most guidelines	C/I: asthma (β-blockade → bronchospasm), heart block, severe bradycardia, decompensated heart failure. Use with caution in diabetic patients (masks hypoglycaemia symptoms)
IV Hydralazine	5–10 mg slow IV over 20 min, repeat every 30 min, or IV infusion at 200–300 μg/min ^[10]	Direct arteriolar smooth muscle relaxation (mechanism involves NO release and interference with calcium signalling in vascular smooth muscle). "Hydral-" relates to its original discovery as a hydrazine derivative	Very effective vasodilator; long track record in obstetric practice	Causes reflex tachycardia (baroreceptor-mediated) → can be problematic in patients with ischaemic heart disease. Can cause headache (vasodilation → mimics worsening pre-eclampsia symptoms!). C/I: AMI, aortic dissection ^[4]
IV Nicardipine	5–15 mg/h infusion	Dihydropyridine calcium channel blocker → arteriolar vasodilation	Smooth titratable infusion; no reflex tachycardia as pronounced as hydralazine	Avoid with IV MgSO₄ in some protocols (both are vasodilators → risk of profound hypotension — though in practice this combination is used with careful monitoring)

Drug	Dose	Mechanism	Advantages	Cautions/Contraindications
Labetalol PO	100–400 mg BD–TDS	α₁ + β-blocker (see above)	Good first-line oral agent; smooth BP control	Same as IV labetalol — avoid in asthma
Nifedipine MR (modified release)	20–40 mg BD	Dihydropyridine CCB → arteriolar vasodilation. Blocks L-type calcium channels in vascular smooth muscle → ↓intracellular Ca²⁺ → relaxation	Effective second-line; widely available	Use modified release only — short-acting nifedipine can cause precipitous BP drops → fetal distress. Avoid sublingual nifedipine ^[10]
Methyldopa	250 mg BD–TDS (max 3g/day)	Central α₂-agonist → ↓sympathetic outflow from brainstem → ↓SVR and ↓HR	Longest safety track record in pregnancy (used since 1960s). Can be used in first trimester for chronic HTN	Slow onset (6–8h); sedation, depression, dry mouth, hepatotoxicity (rare). Less effective than labetalol/nifedipine for acute control

Drugs CONTRAINDICATED in Pregnancy

Never use the following antihypertensives in pregnancy:

ACE inhibitors (e.g. enalapril, ramipril): teratogenic — renal agenesis, oligohydramnios, pulmonary hypoplasia, fetal death. Mechanism: RAAS is critical for fetal renal development; ACEi blocks angiotensin II → ↓fetal renal perfusion
ARBs (e.g. losartan, valsartan): same mechanism and teratogenic effects as ACEi
Sodium nitroprusside: risk of fetal cyanide toxicity (metabolised to cyanide and thiocyanate) ^[4]^[10]
Atenolol: associated with IUGR (↓uteroplacental perfusion more than labetalol due to β₁-selectivity without α-blockade-mediated vasodilation)
Diuretics: generally avoided — further reduce the already contracted intravascular volume in pre-eclampsia (exception: furosemide for acute pulmonary oedema)

D. Pillar 2 — Prevention of Eclampsia (Magnesium Sulphate)

Prevention of eclampsia (for S/S of pending eclampsia / severe PET): Magnesium sulphate (10% risk of second seizure) ^[2] Cannot use conventional anti-epileptics → keep using Magnesium sulphate ^[1] So basically treat the HT, treat the pre-eclampsia and prevent it from turning into eclampsia using magnesium sulphate ^[9]

Phase	Route and Dose	Details
Loading dose	4 g IV over 15–20 min	Dilute in 100 mL saline. Given slowly to avoid cardiovascular side effects
Maintenance dose	1 g/h IV continuous infusion	Typically 20 g MgSO₄ in 500 mL saline at 25 mL/h. Continue for 24 hours after delivery (or 24h after last seizure, whichever is later)
Alternative (IM — Pritchard original)	5 g IM into each buttock (total 10 g IM) after the IV loading	Painful; IV preferred where available
Recurrent seizure despite loading	Additional 2 g IV bolus over 5 min	Maximum one additional bolus. If still seizing → consider intubation + other anticonvulsants (thiopental, diazepam)

Continue MgSO₄ infusion until 24 hours after delivery. And at this juncture, check knee jerk, respiratory rate every hour. Loss of knee jerk is the first sign of magnesium toxicity (10 mEq), from the normal therapeutic level of 4–8 ^[1]

This is critical — MgSO₄ has a narrow therapeutic window:

Serum Mg Level (mmol/L)	Clinical Effect
2.0–4.0	Therapeutic range (anticonvulsant effect)
4.0–5.0	Loss of deep tendon reflexes (patella reflex first to go)
5.0–6.5	Respiratory depression (diaphragmatic paralysis)
> 7.5	Cardiac arrest (asystole from myocardial depression)

Monitoring checklist (before each dose / hourly):

Knee jerk (patellar reflex) — must be present to continue infusion. This is the first clinical sign of toxicity ^[1]^[6]
Respiratory rate — must be > 12/min ^[1]
Urine output — must be > 25 mL/h (Mg²⁺ is renally excreted → oliguria causes accumulation) ^[6]
Serum Mg levels — check if renal function impaired or clinical concern

Antidote for Mg toxicity:

10% Calcium gluconate 10 mL IV over 10 min — directly antagonises Mg²⁺ at the neuromuscular junction and cardiac myocytes
Have this drawn up and available at the bedside whenever MgSO₄ is running

IV MgSO₄ is an important anti-epileptic in eclampsia → important to monitor serum Mg ^[6]

Magnesium Toxicity — The Three-Check Rule

Before every dose or hourly during infusion, check three things:

Reflexes present? (knee jerk) — first sign of toxicity if absent
Respiratory rate > 12? — respiratory depression is life-threatening
Urine output > 25 mL/h? — oliguria causes Mg accumulation

If ANY is abnormal → STOP the infusion and check serum Mg. Have calcium gluconate at the bedside at all times.

Indication	Evidence
Severe pre-eclampsia (seizure prophylaxis)	MgSO₄ for severe pre-eclampsia ^[2]. Magpie Trial: 58% risk reduction in eclampsia
Eclampsia (treatment of seizures + prevention of recurrence)	Magnesium Sulphate (10% risk of second seizure) ^[2]. Collaborative Eclampsia Trial: superior to diazepam and phenytoin
Imminent eclampsia (prodromal symptoms)	Severe headache, visual disturbance, clonus, hyperreflexia — all warrant MgSO₄ even without seizures

F. Pillar 4 — Planning for Delivery

The definitive treatment of pre-eclampsia is delivery ^[2] The timing is a balance between severity of pre-eclampsia and risk of prematurity ^[2]

For pre-eclampsia, all should be delivered by 37 weeks → the cutoff for term pregnancy, after 37 weeks further development of baby does not give further benefit, so delivery at this time will be most beneficial for mother and child health ^[1]

Key gestational age thresholds ^[1]:

37 weeks → defines term and preterm pregnancy

24 weeks → defines viable and non-viable baby (before 24 weeks, no matter what we do, baby cannot be saved)

34 weeks → defines lung viability and non-mature baby lungs (before 34 weeks, give 1 course of steroid)

Gestational Age	Management Approach	Rationale
< 24 weeks (previable)	Counsel regarding termination vs expectant management. Maternal risk is very high with expectant approach. Neonatal survival is negligible	Before 24 weeks, no matter what we do, baby cannot be saved ^[1]. The only indication for continuing is maternal wish — but the risk of maternal complications escalates dramatically
24–34 weeks	If extreme prematurity, can consider conservative treatment (to improve neonatal outcome) with close monitoring of maternal well-being ^[2]. Give corticosteroids (betamethasone 12 mg IM × 2 doses, 24h apart) for fetal lung maturity. Aim to delay delivery by 48h to allow steroids to work. Then deliver	Steroids induce surfactant production in type II pneumocytes → ↓risk of neonatal RDS, IVH, NEC. The 48h window is to allow maximal steroid effect. Steroid: Betamethasone to promote fetal lung maturity (if gestation < 34 weeks) ^[2]
34–37 weeks	Deliver — low benefit of continuing expectant management vs increasing maternal risk ^[2]	After 34 weeks, neonatal outcomes are generally good. Continuing pregnancy risks maternal deterioration with marginal fetal benefit
≥ 37 weeks	Deliver promptly ^[1]^[2]	After 37 weeks, further development of baby does not give further benefit ^[1]. No reason to delay

If mother is asymptomatic / only mild biochemical derangement, monitor closely and hope they can reach 37 weeks ^[1] If mother is symptomatic (e.g. headaches, visual disturbances, epigastric pain): Give panadol first, and start worrying if there is persistent headache. Baby then must be delivered regardless of gestational age ^[1]

Absolute indications for immediate delivery (regardless of gestation):

Uncontrollable severe hypertension despite maximal therapy
Eclampsia (after stabilisation)
Pulmonary oedema
Placental abruption
DIC / rapidly falling platelets
Deteriorating liver function (especially with HELLP)
Persistent severe symptoms despite treatment
Pathological CTG / non-reassuring fetal status

Stabilize patient before delivery → i.e. don't open emergency OT while patient is having a fit in front of you ^[9]

A caesarean is not a must in pre-eclampsia → if patient stable, vaginal delivery is possible, once the placenta is expelled then the condition will be treated. Caesarean indications are the general stuff → IUGR baby, heart rate abnormal, breech baby ^[1]

Factor	Vaginal Delivery	Caesarean Section
Cervical favourability	Favourable cervix (Bishop score ≥ 6) → induce	Unfavourable cervix + urgent need for delivery
Gestational age	More likely achievable at later GA	Early preterm (< 32 wk) — induction less likely to succeed
Fetal status	Reassuring CTG	Non-reassuring fetal heart rate ^[2]
Fetal presentation	Cephalic	Breech, transverse
IUGR severity	Mild	Severe IUGR — baby may not tolerate labour
Platelet count	> 80 × 10⁹/L (for regional anaesthesia)	If < 80 → general anaesthesia often required (epidural contraindicated due to spinal haematoma risk)
Urgency	Can afford time for induction	Immediate delivery needed

Anaesthetic considerations:

Regional anaesthesia (epidural/spinal) is preferred if platelets > 80 (some anaesthetists accept > 75) and coagulation is normal — provides good BP control and analgesia
General anaesthesia if: platelet count too low for regional, eclamptic seizure, need for immediate delivery, patient refusal of regional
- Risk: exaggerated hypertensive response to laryngoscopy/intubation → treat with short-acting agents (remifentanil, alfentanil, or IV labetalol before induction)
- Airway may be difficult due to oedema (laryngeal/pharyngeal)

G. Pillar 5 — Monitoring and Managing Complications

Monitor maternal well-being: BP, Blood tests — CBP, L/RFT, urate, coagulation profile, Urine protein/creatinine ratio or 24-hour urine protein, Symptoms ^[2] Monitor fetal well-being: Cardiotocogram, USG for growth, liquor volume, Doppler studies, Fetal movement ^[2] Thromboprophylaxis — pressure stockings ± LMWH ^[2]

Purpose	Agent and Dose	When
Fetal lung maturity	Betamethasone 12 mg IM × 2 doses, 24h apart ^[2]	If gestation < 34 weeks ^[1]^[2] — induces surfactant production in fetal type II pneumocytes
HELLP syndrome (debated)	Dexamethasone 10 mg IV q12h × 2 then 5 mg IV q12h × 2	Some evidence suggests steroids may improve platelet count and LFTs in HELLP transiently — may buy time for fetal steroid benefit. Not universally recommended

Eclampsia → obstetric emergency ^[1] Pregnant lady with first episode of convulsions at 34 weeks pregnancy → is this eclampsia or epilepsy? We will treat it as eclampsia until proven otherwise, unless patient has a known history of poorly controlled epilepsy ^[1]

Management of eclampsia:

ABC

Prevention of injury and aspiration

Stabilisation of maternal condition:

Magnesium Sulphate (10% risk of second seizure)

Fluid balance

BP control (uteroplacental, cerebral perfusion)

Secondary or associated complications: HELLP, Coagulopathy, pulmonary oedema, renal failure, Stroke (ischaemic/haemorrhage)

Planning for delivery: Mode of delivery (non-reassuring fetal heart rate) ^[2]

Convulsion – usually self-limiting. Start MgSO₄ to prevent recurrence. Stabilise mother then deliver ^[1]

Step-by-step eclampsia management:

Step	Action	Why
1. ABC	Left lateral position (recovery position), secure airway, suction oropharynx, high-flow O₂ by face mask	Seizures → aspiration risk, hypoxia
2. Prevent injury	Side rails up, padded, remove dangerous objects, do NOT restrain or insert anything into mouth	Most eclamptic seizures are self-limiting (60–90 seconds)
3. MgSO₄	Loading dose 4 g IV over 15–20 min → maintenance 1 g/h IV for 24h post-delivery	10% risk of second seizure ^[2] — MgSO₄ prevents this. Superior to diazepam and phenytoin
4. BP control	IV labetalol or IV hydralazine (as above)	Prevent haemorrhagic stroke
5. Fluid restriction	80 mL/h total	Prevent pulmonary oedema
6. Investigations	CBC, LFT, RFT, coag, blood gas, CTG	Assess for HELLP, DIC, fetal distress
7. Stabilise then deliver	Don't rush to OT while patient is fitting ^[9]. Stabilise first (usually within 1–2 hours), then plan delivery	Maternal stabilisation > immediate delivery

Remember postpartum presentation of eclampsia is possible, due to the residual circulating debris ^[1]

I. Postnatal Management and Counselling

Hypertension and proteinuria should resolve by 6 weeks after delivery, if not ? chronic HT / renal disease ^[2]

Component	Management
Delivery	Definitive treatment — same as pre-eclampsia. Deliver once stabilised
BP control	As per severe pre-eclampsia
MgSO₄	Seizure prophylaxis
Blood products	Platelet transfusion if < 20 × 10⁹/L (or < 50 × 10⁹/L if surgical delivery). FFP/cryoprecipitate if active DIC with bleeding
Steroids	Dexamethasone may transiently improve platelet count and LFTs — debated but sometimes used to buy 24–48h for fetal steroid benefit
Postpartum	Expect improvement within 48–72h. If no improvement → reconsider diagnosis (TTP, aHUS, AFLP)

Drug	Route	Indication	Key CI
IV Labetalol	IV → PO	1st-line for acute severe HTN	Asthma, heart block, bradycardia
IV Hydralazine	IV	2nd-line for acute severe HTN	AMI, aortic dissection; causes reflex tachycardia
Nifedipine MR	PO	Maintenance oral BP control	Short-acting formulations (precipitous BP drop)
Methyldopa	PO	Maintenance; chronic HTN in pregnancy	Sedation, depression; switch postpartum
MgSO₄	IV	Seizure prophylaxis and treatment	Renal failure (dose adjust); monitor reflexes/RR/UO
Betamethasone	IM	Fetal lung maturity < 34 weeks	Not a contraindication issue — always give if indicated
Calcium gluconate	IV	MgSO₄ toxicity antidote	—

What You MUST NOT Do

IV sodium nitroprusside is CONTRAINDICATED in pregnancy (cyanide toxicity to fetus) ^[4]
ACEi/ARBs are CONTRAINDICATED antenatally (fetal renal agenesis, oligohydramnios)
Do NOT give excessive IV fluids — leaky endothelium → pulmonary oedema
Do NOT use short-acting nifedipine (sublingual or immediate-release) — precipitous BP drop → fetal distress
Do NOT use diuretics routinely (already volume-depleted intravascularly) — exception: acute pulmonary oedema
Do NOT insert anything into the mouth during an eclamptic seizure — it's self-limiting
Do NOT rush to theatre while the patient is seizing — stabilise first, then deliver

High Yield Summary

Definitive treatment = delivery of the placenta. All else is temporising.

BP Control: Target < 140/90 (don't overshoot). Acute: IV labetalol (1st-line) or IV hydralazine. Maintenance: oral labetalol, nifedipine MR, or methyldopa. ACEi/ARBs CONTRAINDICATED antenatally.

MgSO₄: Drug of choice for BOTH prophylaxis (severe pre-eclampsia) and treatment (eclampsia). Loading 4g IV, maintenance 1g/h for 24h post-delivery. Monitor reflexes, RR, urine output hourly. Antidote: IV calcium gluconate 10%.

Fluid balance: Restrict to ~80 mL/h. Leaky vessels → pulmonary oedema risk.

Timing of delivery: All by 37 weeks. Severe disease → deliver after stabilisation regardless of gestation (except < 24 wk = counsel). 24–34 wk: give betamethasone + aim 48h delay. 34–37 wk: deliver. ≥ 37 wk: deliver promptly.

Mode of delivery: Vaginal delivery is acceptable if stable. Caesarean for standard obstetric indications (fetal distress, breech, unfavourable cervix + urgency).

Eclampsia: ABC → MgSO₄ → BP control → stabilise → deliver. Treat as eclampsia until proven otherwise. 10% risk of second seizure → MgSO₄ prevents this.

Postnatal: Continue monitoring ≥72h. HTN and proteinuria should resolve by 6 weeks (if not → chronic HTN/renal disease). Recurrence 10% (25% if eclampsia). Long-term CVD risk elevated (HT RR 3.7, IHD RR 2.16, stroke RR 1.81).

Active Recall - Pre-eclampsia Management

References

^[1] Lecture slides: Block C - Hypertension and Pregnancy (CFB WCS in 2023_24).pdf ^[2] Lecture slides: GC 224. Hypertension and Pregnancy.pdf ^[4] Senior notes: Maksim Medicine Notes.pdf (p78, Hypertensive crisis management) ^[6] Senior notes: Ryan Ho Urogenital.pdf (p31, Magnesium — IV MgSO4 in eclampsia) ^[9] Lecture slides: Block C - I am pregnant_ medical problems complicating pregnancy.pdf ^[10] Senior notes: Ryan Ho Cardiology.pdf (p182–183, Hypertensive emergency management)

Complications of Pre-eclampsia

Pre-eclampsia is a progressive, multisystem disorder. The complications are the very reason we fear it — they are essentially the clinical manifestations of endothelial dysfunction taken to their extreme. Let me walk through each systematically, organising them by system, and explaining the pathophysiology behind every single one.

Pre-eclampsia has many consequences to the mother and child. Think of maternal risk from head to toe → remember the pathophysiology of pre-eclampsia, basically a systemic condition, so can result in many many problems ^[1] Screening and managing associated complications: HELLP, Coagulopathy, pulmonary oedema, renal failure, Stroke (ischaemic/haemorrhage), Fetal growth ^[2]

A. Maternal Complications — Head to Toe

1. Neurological Complications

3. Cardiovascular Complications

4. Hepatic Complications

5. Renal Complications

6. Haematological Complications

7. Placental Complications

Baby grows less → IUGR, potential preterm delivery. Preterm and low birth weight has many long-term complications (NEC, cardiovascular etc.) ^[1]

Complication	Incidence in PET	Pathophysiology	Management
IUGR (Intrauterine Growth Restriction)	10–25% ^[2]	Failed spiral artery remodelling → placental ischaemia → ↓nutrient/O₂ delivery → fetal growth faltering	Serial USS biometry, umbilical artery Doppler, delivery when risk of staying in utero exceeds risk of prematurity
Preterm delivery	15–67% ^[2]	Mostly iatrogenic (elective preterm delivery for maternal/fetal indications). Less commonly spontaneous	Antenatal corticosteroids if < 34 weeks; neonatal intensive care
Oligohydramnios	Common	Fetal renal hypoperfusion (brain-sparing reflex diverts blood from kidneys to brain) → ↓fetal urine output → ↓amniotic fluid	Serial AFI measurement; consider delivery if severe
Hypoxia — neurological injury	< 1% ^[2]	Placental insufficiency → chronic fetal hypoxia; abruption → acute fetal hypoxia. Severe → hypoxic-ischaemic encephalopathy	Continuous CTG, emergency delivery if non-reassuring
Perinatal death	1–2% ^[2]	Severe placental insufficiency, abruption, or extreme prematurity	Prevention through timely delivery
Stillbirth	Included in above	Acute: massive abruption, cord accident. Chronic: progressive placental failure → fetal hypoxia → death in utero	Serial fetal monitoring; delivery when indicated

Complications of Prematurity (Neonatal)

Complication of prematurity ^[2]

When we deliver preterm for pre-eclampsia, the baby faces its own set of problems:

Complication	Pathophysiology	Why preterm?
Respiratory Distress Syndrome (RDS)	Surfactant deficiency → alveolar collapse → poor gas exchange	Type II pneumocytes not mature enough to produce adequate surfactant until ~34–36 weeks. Betamethasone given if < 34 weeks promotes surfactant production ^[2]
Necrotising Enterocolitis (NEC)	Immature gut barrier + ischaemia → bacterial translocation → bowel wall necrosis and perforation	Premature gut is vulnerable; IUGR babies have redistributed blood flow away from gut ("brain-sparing" → "gut-sacrificing")
Intraventricular Haemorrhage (IVH)	Fragile germinal matrix vessels in premature brain → rupture → bleeding into ventricles	Germinal matrix is richly vascular and involutes by ~32 weeks; very preterm babies still have this vulnerable structure
Bronchopulmonary Dysplasia (BPD)	Lung injury from mechanical ventilation + oxygen toxicity in immature lungs → chronic inflammation and fibrosis	Needed prolonged respiratory support for RDS
Retinopathy of Prematurity (ROP)	Incompletely vascularised retina → exposure to high O₂ → abnormal neovascularisation → retinal detachment	Retinal vascularisation completes by ~40 weeks; preterm birth interrupts this
Sepsis	Immature immune system + invasive lines + prolonged NICU stay	Self-explanatory
Temperature regulation	↓Brown fat, ↑surface area:volume ratio → rapid heat loss	Premature babies cannot thermoregulate

Long term risk of cardiovascular disease after PET:

HT: relative risks were 3.70 after 14.1 years weighted mean follow-up

Ischaemic heart disease 2.16 after 11.7 years

Stroke 1.81 after 10.4 years ^[2]

This is an important emerging concept: pre-eclampsia is not just a pregnancy problem — it is a lifetime cardiovascular risk marker.

Long-term Complication	Relative Risk	Why?
Chronic hypertension	RR 3.70 after ~14 years ^[2]	Pre-eclampsia and chronic HTN share common risk factors (endothelial dysfunction, obesity, insulin resistance, genetic susceptibility). Pre-eclampsia itself may cause lasting vascular damage ("vascular memory"). Or it may unmask a latent vascular phenotype
Ischaemic heart disease	RR 2.16 after ~12 years ^[2]	Same shared pathophysiology — endothelial dysfunction, inflammation, metabolic syndrome. Accelerated atherosclerosis
Stroke	RR 1.81 after ~10 years ^[2]	Vascular damage from pre-eclampsia + subsequent chronic HTN → cerebrovascular disease
Chronic kidney disease	~RR 2–5×	Residual glomerular damage from glomerular endotheliosis. Severe cases (cortical necrosis) → permanent CKD/ESRD
Type 2 diabetes	~RR 2×	Shared metabolic risk factors (obesity, insulin resistance). Pre-eclampsia associated with metabolic syndrome
Venous thromboembolism	Modestly increased	Pre-eclampsia is a prothrombotic state. May have underlying thrombophilia unmasked by pregnancy

Pre-eclampsia as a Cardiovascular Risk Factor

Women who have had pre-eclampsia should be treated as having a cardiovascular risk equivalent. This means lifelong monitoring: annual BP checks, lipid profiles, fasting glucose, and lifestyle counselling. Think of pre-eclampsia as a "stress test" for the cardiovascular system — if the system fails during pregnancy, it is more likely to fail again later in life.

Recurrence

Recurrence of PET: 1 in 10, 1 in 4 (if eclampsia) ^[2]

Overall recurrence rate: ~10% for pre-eclampsia
If eclampsia occurred: ~25% recurrence risk for pre-eclampsia in subsequent pregnancy
Risk higher with: early-onset pre-eclampsia, severe disease, underlying medical conditions, interpregnancy interval > 10 years
Prevention in future pregnancies: aspirin 150 mg/day started before 16 weeks

E. Complications of Treatment

These are iatrogenic complications that arise from our management — important to know:

Magnesium sulfate is a very frequently used drug, but it has a very low therapeutic range → can enter toxic ranges very easily ^[1] Since magnesium cannot be given long term due to toxicity, have to act fast after you administer it ^[1] Magnesium sulfate is excreted by urine → any cause of reduced urinary output, remember to be careful with magnesium dosage ^[1]

Serum Mg (mmol/L)	Clinical Effect
2.0–4.0	Therapeutic (anticonvulsant)
4.0–5.0	Loss of patellar reflexes (first sign of toxicity)
5.0–6.5	Respiratory depression (diaphragmatic weakness)
> 7.5	Cardiac arrest (asystole from myocardial depression)

Also: flushing, nausea, muscle weakness, somnolence, blurred vision
Fetal effects: neonatal hypotonia, respiratory depression (Mg crosses the placenta)
Antidote: Calcium — the lecture states "calcium carbonate" ^[1] but the correct formulation is calcium gluconate 10%, 10 mL IV over 10 min. Calcium directly antagonises Mg²⁺ at ion channels
Risk factors for toxicity: oliguria (Mg is renally excreted → accumulates in AKI), concomitant use of calcium channel blockers (additive vasodilation/hypotension)

Note that IV MgSO₄ can cause hypermagnesaemia ^[6]. D/dx of hypermagnesaemia includes ↑intake (including IV Mg in eclampsia Tx), renal failure, and ↓excretion ^[6].

System	Complications	Frequency
Neurological	Eclampsia, stroke (ischaemic/haemorrhagic), PRES, cortical blindness	Eclampsia < 1%; stroke rare but leading cause of death
Ophthalmic	Retinal vasospasm, serous retinal detachment, cortical blindness	Common (visual symptoms); detachment rare
Cardiovascular	Pulmonary oedema, peripartum cardiomyopathy	Pulmonary oedema ~3% of severe PET
Hepatic	HELLP, subcapsular haematoma, hepatic rupture	HELLP 10–20% of severe PET; rupture < 1%
Renal	AKI (1–5%), cortical necrosis, nephrotic-range proteinuria	AKI 1–5%; cortical necrosis rare
Haematological	DIC, thrombocytopenia, MAHA	DIC ~10% of severe PET
Placental	Placental abruption (1–4%), infarction	Abruption 1–4%
Fetal	IUGR (10–25%), preterm delivery (15–67%), hypoxia-neurological injury (< 1%), perinatal death (1–2%) ^[2]	As listed
Long-term maternal	Chronic HTN (RR 3.70), IHD (RR 2.16), stroke (RR 1.81) ^[2], CKD, T2DM	Lifetime risk
Long-term offspring	Cardiovascular disease, metabolic syndrome, neurodevelopmental	Lifetime risk
Iatrogenic	MgSO₄ toxicity, antihypertensive complications, prematurity, surgical delivery risks	Variable

The Two Killers in Pre-eclampsia

The two most dangerous acute complications — the ones that kill women — are:

Intracranial haemorrhage from uncontrolled severe hypertension → this is why we treat BP ≥ 160/110 urgently
Pulmonary oedema from fluid overload in the context of leaky endothelium → this is why we restrict fluids

Everything else is serious but less immediately lethal. If you remember nothing else about complications, remember these two.

High Yield Summary

Maternal complications (head to toe): Eclampsia (< 1%), stroke (ICH > ischaemic; leading cause of death), PRES, cortical blindness, pulmonary oedema (~3%), HELLP (10–20% of severe PET), hepatic rupture (rare, 60% mortality), AKI (1–5%), DIC (~10%), MAHA, placental abruption (1–4%).

Fetal complications: IUGR (10–25%), preterm delivery (15–67%), hypoxia/neurological injury (< 1%), perinatal death (1–2%). Prematurity complications: RDS, NEC, IVH, BPD, ROP.

Long-term maternal risk: Pre-eclampsia = lifetime CVD risk marker. HT RR 3.70 after 14y, IHD RR 2.16 after 12y, Stroke RR 1.81 after 10y. Annual CV screening recommended.

Long-term offspring risk: Barker hypothesis — IUGR programmes for adult metabolic syndrome, HTN, IHD, T2DM.

Recurrence: 10% for pre-eclampsia, 25% if eclampsia occurred.

Iatrogenic: MgSO₄ toxicity (loss of reflexes → respiratory depression → cardiac arrest; antidote = calcium gluconate). Excessive BP lowering → fetal distress. Fluid overload → pulmonary oedema.

Two big killers: ICH from uncontrolled HTN + pulmonary oedema from fluid overload. Prevent both through BP control and fluid restriction.

Active Recall - Pre-eclampsia Complications

References

^[1] Lecture slides: Block C - Hypertension and Pregnancy (CFB WCS in 2023_24).pdf ^[2] Lecture slides: GC 224. Hypertension and Pregnancy.pdf ^[3] Lecture slides: GC 115. I am pregnant medical problems complicating pregnancy.pdf ^[4] Senior notes: Maksim Medicine Notes.pdf (p78, Hypertensive crisis management) ^[6] Senior notes: Ryan Ho Chemical Path.pdf (p28, Hypermagnesaemia) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p137–140, MAHA, TMA, DIC) ^[10] Senior notes: Ryan Ho Cardiology.pdf (p182–183, Hypertensive emergency — compelling indications) ^[11] Senior notes: Maksim Surgery Notes.pdf (p298, Obstetric anaesthesia — difficult intubation)

High Yield Summary

Definition: Pregnancy-specific multisystem disorder with new-onset hypertension after 20 weeks plus at least one of: proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Proteinuria is not mandatory if there is end-organ or placental dysfunction.

BP thresholds: Hypertension in pregnancy = >= 140/90 mmHg. Severe hypertension = >= 160/110 mmHg. Confirm with 2 readings at least 4 hours apart unless severe, where treatment should not wait.

Diagnostic criteria: Hypertension after 20 weeks plus proteinuria (>= 300 mg/day, PCR >= 30 mg/mmol, or dipstick >= 2+) OR renal dysfunction (creatinine >= 90 umol/L), elevated LFTs/RUQ pain, neurological features, thrombocytopenia/DIC/haemolysis, or uteroplacental dysfunction such as IUGR or abnormal Doppler.

Pathophysiology: Defective trophoblast invasion -> poor spiral artery remodelling -> placental ischaemia -> anti-angiogenic factors (especially sFlt-1) -> systemic maternal endothelial dysfunction. Delivery of the placenta is the definitive cure.

Risk factors: Nulliparity, previous pre-eclampsia, chronic hypertension, diabetes, CKD, SLE/APS, thrombophilia, obesity, age > 35, family history, multiple pregnancy, molar pregnancy, IVF, and long inter-pregnancy interval.

High Yield Summary

Differentiate hypertensive disorders of pregnancy:

Chronic hypertension: BP elevated before pregnancy or before 20 weeks, or persists > 12 weeks postpartum.
Gestational hypertension: New hypertension after 20 weeks without proteinuria or organ dysfunction.
Pre-eclampsia: New hypertension after 20 weeks with proteinuria, organ dysfunction, or uteroplacental dysfunction.
Superimposed pre-eclampsia: Chronic hypertension with new proteinuria, worsening BP control, or new organ dysfunction after 20 weeks.
Eclampsia: Generalised tonic-clonic seizures in the setting of pre-eclampsia.
HELLP: Haemolysis, elevated liver enzymes, low platelets. Can occur without marked hypertension or proteinuria.

Important mimics: TTP, HUS, DIC, acute fatty liver of pregnancy, SLE flare/lupus nephritis, epilepsy, CVST, intracranial haemorrhage, meningitis/encephalitis, and metabolic seizures.

Exam traps: HELLP has liver involvement and resolves with delivery; TTP has ADAMTS13 < 10% with normal PT/APTT; DIC has deranged PT/APTT and low fibrinogen. SLE flare favours low complement, rising anti-dsDNA, and active urinary sediment.

High Yield Summary

Investigations:

Confirm diagnosis: Serial BP, urine dipstick, urine PCR or 24-hour urine protein.
Maternal end-organ assessment: CBC/platelets, peripheral smear, LDH/haptoglobin/bilirubin if haemolysis suspected, LFT, RFT/creatinine, uric acid, clotting profile, group and crossmatch.
Fetal assessment: Ultrasound for growth and liquor volume, umbilical artery Doppler, CTG, and biophysical profile if needed.
Biomarkers: Low PlGF or high sFlt-1/PlGF ratio supports pre-eclampsia; low ratio has strong rule-out value in suspected cases.
Exclude mimics when atypical: C3/C4 and anti-dsDNA for SLE flare, ADAMTS13 for TTP, brain imaging for focal neurological signs or atypical seizures.

Severe features: BP >= 160/110, severe headache, visual disturbance, clonus, epigastric/RUQ pain, oliguria, thrombocytopenia, impaired LFT/RFT, deranged clotting, pulmonary oedema, eclampsia, or non-reassuring fetal status.

High Yield Summary

Management principles: Admit all pre-eclampsia. Management balances maternal end-organ risk against fetal prematurity. The five priorities are admission, BP control, convulsion prevention, delivery planning, and fluid balance.

Mild pre-eclampsia: Inpatient monitoring, serial BP, twice-weekly bloods, urine monitoring, fetal surveillance, antihypertensives if needed, steroids if preterm delivery likely, and delivery by 37 weeks.

Severe pre-eclampsia/eclampsia: Obstetric emergency. Stabilise mother first: left lateral position, IV access, control BP with IV labetalol or hydralazine, give MgSO4, restrict fluids, monitor urine output, check bloods, continuous fetal monitoring, and plan delivery once stabilised.

Antihypertensives: Labetalol, nifedipine MR, and methyldopa are used in pregnancy. Avoid ACE inhibitors, ARBs, sodium nitroprusside, and aggressive BP drops that compromise uteroplacental perfusion.

MgSO4: First-line for treatment of eclampsia and prophylaxis in severe pre-eclampsia. Monitor hourly reflexes, respiratory rate, and urine output. First toxicity sign is loss of knee jerk. Antidote is 10% calcium gluconate 10 mL IV.

Delivery timing: Deliver at >= 37 weeks for mild disease, generally deliver at >= 34 weeks for severe disease, and consider expectant management before 34 weeks only if mother and fetus can be stabilised in a tertiary centre.

High Yield Summary

Maternal complications:

Eclampsia, PRES, cortical blindness, ischaemic or haemorrhagic stroke.
Pulmonary oedema, cardiac failure, severe hypertension.
HELLP, hepatic subcapsular haematoma, hepatic rupture, liver failure.
Acute kidney injury, cortical necrosis, oliguria.
DIC, thrombocytopenia, MAHA, venous thromboembolism.
Placental abruption and anaesthetic difficulties.
Long-term increased risk of chronic hypertension, ischaemic heart disease, stroke, CKD, diabetes, and recurrent pre-eclampsia.

Fetal/neonatal complications: IUGR, oligohydramnios, fetal distress, stillbirth, preterm delivery, perinatal death, and prematurity complications such as RDS, IVH, NEC, ROP, sepsis, and neurodevelopmental delay.

Treatment-related complications: MgSO4 toxicity, iatrogenic pulmonary oedema from overhydration, fetal compromise from over-aggressive BP lowering, and complications of early delivery.

Pre-eclampsia

1. Definition

2. Epidemiology

Global Burden

Hong Kong Context

Timing

3. Risk Factors (Predisposing Factors)

A. Maternal Factors

B. Pre-existing Maternal Diseases

C. Obstetric Conditions

D. Other Factors

4. Anatomy and Function — The Placenta in Normal Pregnancy

Normal Placental Development

Normal Spiral Artery Remodelling

Uteroplacental Circulation

5. Etiology and Pathophysiology

Stage 1: Abnormal Placentation (the "Placental" Stage)

Stage 2: Maternal Systemic Endothelial Dysfunction (the "Maternal" Stage)

Key Circulating Factors

The Anti-angiogenic Imbalance

Downstream Consequences of Endothelial Dysfunction

The Two Phenotypes [2]

Specific Organ Pathophysiology

1. Vascular System → Hypertension

2. Kidney → Proteinuria and Renal Dysfunction

3. Liver → HELLP Syndrome

4. Brain → Eclampsia

5. Haematological System → DIC, Thrombocytopenia

6. Placenta → Fetal Compromise

6. Classification of Hypertensive Disorders of Pregnancy

7. Clinical Features

A. Symptoms

B. Signs

C. HELLP Syndrome — A Special Severe Variant

D. Maternal Risks — Head to Toe

E. Fetal Risks

8. Prevention of Pre-eclampsia

Low-Dose Aspirin

Other Preventive Measures

9. Connecting Pathophysiology to Clinical Features — A Summary Table

Active Recall - Pre-eclampsia (Definition, Epidemiology, Risk Factors, Pathophysiology, Clinical Features)

References

A. Differentiating Among Hypertensive Disorders of Pregnancy

B. Conditions That Mimic Pre-eclampsia

1. Thrombotic Microangiopathies (TMAs)

2. Acute Fatty Liver of Pregnancy (AFLP)

3. Systemic Lupus Erythematosus (SLE) — Lupus Nephritis Flare

4. Other Causes of Seizures in Pregnancy (Eclampsia Mimics)

5. Other Causes of Hypertension in Pregnancy

6. Other Causes of Thrombocytopenia in Pregnancy

C. Diagnostic Differentiation Algorithm

D. Key Differentiating Investigations

E. Severity Assessment Once Pre-eclampsia Is Diagnosed

F. Summary — Differential Diagnosis Decision Framework

Active Recall - Pre-eclampsia Differential Diagnosis

A. Diagnostic Criteria

1. Blood Pressure Criteria

2. Updated NICE 2019 Diagnostic Criteria [2][3][9]

3. Severity Criteria

4. HELLP Syndrome Diagnostic Criteria (Tennessee Classification)

B. Diagnostic Algorithm

C. Investigations — Systematic Approach

1. Blood Pressure Assessment

2. Urine Assessment — Quantifying Proteinuria

3. Haematological Investigations

4. Biochemistry — Renal Function

5. Biochemistry — Liver Function

6. Angiogenic Biomarkers — sFlt-1/PlGF Ratio

7. Fetal Assessment — Uteroplacental Dysfunction

8. Additional Investigations for Differential Diagnosis

9. Summary — The "Baseline Investigation Panel" for Pre-eclampsia

D. Monitoring and Frequency

E. First-Trimester Screening / Prediction (Brief Note)

Active Recall - Pre-eclampsia Diagnostic Criteria, Algorithm and Investigations

A. The Five Pillars of Pre-eclampsia Management

B. Overall Management Algorithm

C. Pillar 1 — Blood Pressure Control

Why treat hypertension?

BP Targets

Antihypertensive Agents