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OG12.1 | Hypertensive Disorders of Pregnancy — SDL Guide

Learning Objectives

• Define and classify the hypertensive disorders of pregnancy (chronic hypertension, gestational hypertension, pre-eclampsia, eclampsia, HELLP syndrome, and superimposed pre-eclampsia).
• Describe the aetiology and pathophysiology of pre-eclampsia, including abnormal trophoblast invasion, defective spiral-artery remodelling, and the anti-angiogenic sFlt-1/PlGF axis.
• State the diagnostic criteria and severe-feature thresholds for pre-eclampsia and eclampsia.
• Outline the investigations required in a woman with hypertensive disorders of pregnancy.
• Describe the principles of management: antihypertensive therapy, magnesium sulphate prophylaxis and treatment, timing and mode of delivery, and prevention.

INSTRUCTIONS

Hypertensive disorders of pregnancy (HDP) complicate 5–10% of all pregnancies worldwide and are a leading cause of maternal and perinatal morbidity and mortality in India. This module covers the full spectrum from gestational hypertension through pre-eclampsia to eclampsia and HELLP syndrome, with emphasis on early detection, the pathophysiological basis of organ damage, and evidence-based management including MgSO4 regimens. Mastery is essential for every clinician who will care for pregnant women at any level of the health system.

References

• DC Dutta's Textbook of Obstetrics, 9th ed. — Chapter on Hypertensive Disorders of Pregnancy (textbook)
• Williams Obstetrics, 26th ed. — Chapters 40–41: Hypertensive Disorders (textbook)
• FOGSI/ICMR Good Clinical Practice Recommendations: Hypertensive Disorders of Pregnancy (2024) (guideline)

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Version 2.0 | NMC CBUC 2024

Clinical Presentation and Spectrum of HDP

Hypertensive disorders of pregnancy encompass a heterogeneous spectrum of conditions united by the common feature of elevated blood pressure occurring in the context of pregnancy. The clinical presentation ranges from completely asymptomatic incidental blood-pressure elevation detected at an antenatal visit, through a florid multi-system syndrome of severe pre-eclampsia, to life-threatening convulsions and end-organ failure. Understanding the spectrum as a continuum — rather than as discrete isolated entities — is essential because a woman can move rapidly from one category to a more severe one, and the clinician must recognise the early stages while remaining vigilant for deterioration.

The cardinal symptom triad of pre-eclampsia comprises new-onset hypertension, proteinuria, and — in severe disease — symptoms of end-organ involvement. The neurological warning signs include a persistent, throbbing headache (classically frontal or occipital) that is unresponsive to simple analgesics, visual disturbances such as photophobia, blurred vision, or scotomata (reflecting cerebral and retinal arteriolar spasm), and hyperreflexia. Epigastric pain or right upper quadrant pain signals hepatic capsule distension or hepatic infarction and predicts imminent HELLP or eclampsia. Dependent oedema — particularly facial and hand oedema developing acutely — is clinically significant, though mild pedal oedema is common in normal pregnancy and alone is not diagnostic. Rapid excessive weight gain (more than 0.5 kg per week) may precede overt oedema. Eclampsia is the occurrence of new-onset generalised tonic-clonic convulsions in a woman with pre-eclampsia, in the absence of other explanatory causes; notably, a convulsion can occur without preceding severe hypertension or proteinuria in up to one-third of cases.

The internationally recognised classification of HDP is as follows:

1. Chronic hypertension: Hypertension diagnosed before pregnancy or before 20 completed weeks of gestation, or persisting beyond 12 weeks postpartum. It may be primary (essential) or secondary.

1. Gestational hypertension: New-onset hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) arising after 20 weeks of gestation, without proteinuria or end-organ dysfunction, and resolving within 12 weeks postpartum.

1. Pre-eclampsia: New-onset hypertension (BP ≥140/90 mmHg) after 20 completed weeks of gestation, accompanied by proteinuria (≥300 mg in 24 hours, or PCR ≥30 mg/mmol, or dipstick ≥2+) OR — in the absence of proteinuria — any of the following end-organ features: thrombocytopaenia (<100 × 10⁹/L), renal insufficiency (creatinine >97 µmol/L or doubling of baseline), impaired liver function (transaminases twice normal, with or without severe RUQ/epigastric pain), pulmonary oedema, or new-onset headache or visual disturbance unresponsive to medication. Pre-eclampsia is further classified as without severe features (meeting minimum diagnostic criteria) or with severe features (BP ≥160/110 mmHg on two occasions, or any of the above end-organ criteria met to a severe degree).

1. Eclampsia: The onset of generalised convulsions (not explained by other pathology) in a woman with pre-eclampsia. It is considered a complication and obstetric emergency, not a separate entity.

1. HELLP syndrome: A severe variant characterised by Haemolysis (microangiopathic haemolytic anaemia on peripheral blood film), Elevated Liver enzymes (AST/ALT typically >70 IU/L), and Low Platelets (<100 × 10⁹/L). HELLP may occur in the context of pre-eclampsia but can also present with minimal or absent hypertension and proteinuria.

1. Superimposed pre-eclampsia: Development of pre-eclampsia in a woman with pre-existing chronic hypertension. It carries a higher risk of adverse outcomes than either condition alone.

IMPORTANT NOTE: The 20-week gestational boundary is definitional for gestational hypertension and pre-eclampsia. Hypertension presenting before 20 weeks is almost always chronic or secondary in aetiology (gestational trophoblastic disease is a rare exception that may cause early-onset features); it should not be labelled pre-eclampsia.

Classification of Hypertensive Disorders of Pregnancy

Pathophysiology: From Placental Ischaemia to Endothelial Dysfunction

Pre-eclampsia is fundamentally a placental disorder with systemic maternal consequences. The initiating defect occurs long before clinical symptoms appear — typically in the first trimester when trophoblast cells fail to remodel the uterine spiral arteries adequately. Understanding this two-stage model of pre-eclampsia is essential for interpreting both the clinical syndrome and emerging preventive strategies.

In a normal pregnancy, cytotrophoblast cells invade the decidua basalis and the walls of the maternal spiral arteries in two waves: the first at 8–10 weeks of gestation and the second at 16–20 weeks. This endovascular invasion replaces the muscular wall of the spiral arteries with fibrinoid material, converting them from narrow, high-resistance, vasoconstrictive vessels into wide-bore, low-pressure conduits. The result is an approximately 10-fold increase in blood flow to the intervillous space, securing the metabolic needs of the rapidly growing fetus and placenta. In pre-eclampsia, this transformation is incomplete — defective spiral-artery remodelling leaves vessels in a persistent high-resistance state. The uterine spiral arteries retain their muscular media, remain vasoresponsive, and fail to deliver adequate blood flow to the placenta, resulting in placental ischaemia and intermittent hypoxia-reperfusion injury.

The ischaemic placenta responds by secreting a cascade of factors that enter the maternal circulation and act on the systemic vascular endothelium. The most important of these are the anti-angiogenic factors: sFlt-1 (soluble fms-like tyrosine kinase-1) is a circulating decoy receptor that binds and neutralises two pro-angiogenic vascular growth factors — VEGF (vascular endothelial growth factor) and PlGF (placental growth factor). In pre-eclampsia, maternal serum sFlt-1 is markedly elevated and PlGF is markedly reduced. The resulting VEGF and PlGF deficiency disrupts normal vascular endothelial homeostasis throughout the maternal systemic vasculature.

Endothelial dysfunction is the central mechanism linking placental ischaemia to the clinical syndrome. Dysfunctional endothelium loses its anti-thrombotic, vasodilatory, and barrier properties:

• Vasospasm — reduced nitric oxide production and increased endothelin release cause generalised arteriolar vasoconstriction, raising systemic vascular resistance and blood pressure. This is the haemodynamic basis of hypertension.

• Increased capillary permeability — endothelial barrier breakdown allows protein-rich fluid to leak into the interstitial space (oedema) and into the urine (proteinuria via glomerular endotheliosis — the characteristic renal lesion of pre-eclampsia).

• Platelet activation and consumption — endothelial injury promotes platelet aggregation; in severe disease this leads to the thrombocytopaenia of HELLP syndrome.

• Multi-organ involvement — the same endothelial dysfunction affects every organ bed:
• Kidney: glomerular endotheliosis → proteinuria, elevated creatinine, hyperuricaemia (reduced uric-acid clearance is an early biomarker).
• Liver: hepatic sinusoidal fibrin deposition → elevated transaminases, subcapsular haematoma, RUQ pain; in HELLP syndrome, liver infarction may occur.
• Brain: cerebral arteriolar vasospasm + increased permeability → hypertensive encephalopathy, cerebral oedema, seizures (eclampsia). The mechanism of eclamptic convulsions is multifactorial but cerebral vasospasm and posterior reversible encephalopathy syndrome (PRES) are central.
• Placenta and fetus: chronic ischaemia → fetal growth restriction (FGR), oligohydramnios, placental abruption.
• Coagulation: endothelial injury + thrombocytopaenia → risk of disseminated intravascular coagulation (DIC), especially in HELLP and placental abruption.

The clinical importance of the sFlt-1/PlGF ratio as a predictive biomarker stems directly from this pathophysiology — an elevated ratio (>38 or validated laboratory cut-off) in a symptomatic woman is highly predictive of imminent or confirmed pre-eclampsia, and a low ratio can effectively rule out pre-eclampsia for up to one week in a suspected case. While sFlt-1/PlGF testing is not universally available in Indian settings, its underpinning science helps explain why aspirin (acting partly through thromboxane/prostacyclin balance and trophoblast invasion) and calcium (acting on vascular tone and potentially trophoblast function) reduce pre-eclampsia risk.

Pathophysiology of Pre-eclampsia

Diagnosis and Investigation

The diagnosis of hypertensive disorders of pregnancy rests on accurate blood pressure measurement, detection of proteinuria, and clinical and laboratory assessment for end-organ involvement. Standardised measurement technique is critical because white-coat hypertension, anxiety, and positional artefact are common in pregnancy. BP should be measured in the sitting or semi-recumbent position (never supine, to avoid aortocaval compression), after five minutes of rest, with the arm supported at heart level, using a validated device. Two readings taken at least four hours apart are required for the diagnosis of gestational hypertension or pre-eclampsia, or readings taken two minutes apart if BP is ≥160/110 and rapid treatment is urgently indicated. The importance of accurate technique cannot be overstated: a falsely elevated reading from incorrect positioning or an anxious patient may lead to unnecessary intervention, while a falsely normal reading from poor technique may provide false reassurance in a deteriorating woman. Investigations serve a dual purpose — confirming the diagnosis by quantifying proteinuria and end-organ markers, and monitoring for progression and complications that signal the need for urgent delivery. The full assessment also includes mandatory fetal surveillance because uteroplacental insufficiency may compromise the fetus even before maternal indices reach critical thresholds.

Diagnostic thresholds:

• A systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg on two occasions ≥4 hours apart, arising after 20 completed weeks of gestation, defines hypertension in the context of HDP.

• Proteinuria threshold: ≥300 mg of protein in a 24-hour urine collection, OR a spot urine protein:creatinine ratio (PCR) ≥30 mg/mmol (or equivalently ≥0.3 mg/mg), OR dipstick ≥2+ on a freshly voided, midstream specimen in the absence of urinary infection. Dipstick alone is the least reliable method but remains the screening tool at primary and secondary care levels in India. A 24-hour collection or PCR is required to confirm significant proteinuria before diagnosis. Proteinuria is NOT required for the diagnosis of pre-eclampsia if end-organ features are present.

Severe-feature criteria (any one suffices):

• Systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg on two occasions.
• Thrombocytopaenia: platelets <100 × 10⁹/L.
• Renal insufficiency: serum creatinine >97 µmol/L (>1.1 mg/dL) in the absence of other renal disease, or doubling of baseline creatinine.
• Impaired liver function: elevated transaminases (AST or ALT twice the upper limit of normal) with or without severe right upper quadrant or epigastric pain refractory to medication.
• Pulmonary oedema.
• New-onset headache unresponsive to medication and not accounted for by alternative diagnoses, or new visual symptoms.

Provided image

Laboratory investigations required in all women with suspected or confirmed pre-eclampsia:

Investigation	Rationale / What to look for
Full blood count (CBC) + peripheral blood film	Thrombocytopaenia, microangiopathic haemolytic anaemia (schistocytes) in HELLP
Serum urea, creatinine, uric acid	Renal function; uric acid ≥5.5 mg/dL is an early marker of disease severity
Liver function tests (AST, ALT, LDH, bilirubin)	Hepatic involvement; elevated LDH + haemolysis supports HELLP
Serum albumin	Oedema mechanism; hypoalbuminaemia in severe disease
Urine PCR or 24-hour urine protein	Quantify proteinuria
Coagulation (PT, APTT, fibrinogen, D-dimer)	DIC screen if platelets <100 or clinical suspicion
Blood group and crossmatch	Pre-delivery preparation
sFlt-1/PlGF ratio (where available)	Risk stratification; ratio >38 = high risk of progression

Fetal surveillance:

Because uteroplacental insufficiency may cause fetal compromise before delivery becomes inevitable, continuous fetal monitoring is mandatory in any woman with severe features or in labour:

• Non-stress test (NST) / cardiotocography (CTG): baseline rate, variability, accelerations, decelerations.
• Obstetric ultrasound: fetal biometry (detect FGR — abdominal circumference <10th centile), amniotic fluid index (oligohydramnios), placenta localisation.
• Umbilical artery Doppler: absent or reversed end-diastolic flow indicates severe uteroplacental insufficiency and is an indication for delivery or intensive surveillance depending on gestational age.
• Middle cerebral artery (MCA) Doppler: assess fetal brain-sparing response.
• Biophysical profile (BPP): composite score (NST + ultrasound) ≤4/10 suggests acute fetal compromise.