History and exam

Key diagnostic factors

common

>20 weeks' gestation

Mostly occurs in women after 20 weeks' gestation.[1][16][54]​​

systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg and previously normotensive

Hypertension (defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg) in a previously normotensive woman is diagnostic.[1][16][54]​​

At least two measurements should be made, at least 4 hours apart.[1]

Considered severe if systolic BP ≥160 mmHg and/or diastolic BP ≥110 mmHg.[1][16]

Correct cuff size should be used. The systolic measurement is taken as the first sound heard (K1) and the diastolic measurement is the disappearance of sounds completely (K5). Where K5 is absent, K4 (muffling) should be accepted.

High systolic BP is associated with stroke and placental abruption.[16]

headache

Usually frontal headache. Presence of this symptom classifies pre-eclampsia as severe.[1][16]

Headache occurs in around 40% of women with severe disease, and is one of the few factors that predict an increased risk of eclampsia.[8]​​

upper abdominal pain

Usually right upper quadrant pain. Occurs in around 16% of women with severe disease, and is a clinical symptom of HELLP syndrome.[8]​​

HELLP syndrome is a subtype of severe pre-eclampsia characterised by haemolysis (H), elevated liver enzymes (EL), and low platelets (LP) syndrome.

Presence of this symptom classifies pre-eclampsia as severe.[1][16]

Other diagnostic factors

common

reduced fetal movement

If fetal movements are reduced, there is a need for immediate fetal ultrasound assessment. [ Cochrane Clinical Answers logo ]

fetal growth restriction

Fetal growth restriction is found in around 30% of women.[8]​​

If the uterus is small for dates, this implies that the amniotic fluid volume is reduced, which may signify fetal growth restriction.

Fetal ultrasound assessment is required. [ Cochrane Clinical Answers logo ]

oedema

Very common, but is not discriminatory and so should not be used in diagnosis.

uncommon

visual disturbances

A relatively rare but concerning symptom that may predict an increased risk of eclampsia.[8]​​

Includes photopsia (perceived flashing lights in the visual fields), scotomata, and retinal vasospasm. Cortical blindness is a rare but critical symptom implying cerebral oedema.

Fundoscopy is rarely abnormal, but if it is, underlying chronic hypertension is implied.

Presence of this symptom classifies pre-eclampsia as severe.[1][16]

seizures

Rare but critical symptom that indicates eclampsia and mandates admission to intensive care unit, stabilisation, and delivery.[1]

breathlessness

Rare presentation associated with pulmonary oedema. If pulmonary oedema occurs after delivery, it is one of the main causes of maternal mortality.

Presence of this symptom classifies pre-eclampsia as severe.[1]

oliguria

Defined as <30 mL urine output per hour for >4 consecutive hours.[1] Transient oliguria is commonly observed during labour or the first 24 hours of the postnatal period.

May be associated with increasing oedema. Women are at most risk postnatally when pulmonary oedema is more likely.

Presence of this symptom classifies pre-eclampsia as severe.[1][16]

hyper-reflexia with sustained clonus

Sign of neurological involvement, although does not help predict which women might develop seizures.[54]​​

Risk factors

strong

nulliparity

Pre-eclampsia is strongly associated with nulliparity. The incidence is twice as high in women who are nulliparous compared with multiparous women.[15] This is thought to be because of the development of tolerance to specific immunological factors after the first pregnancy, thereby reducing risk in subsequent pregnancies. These immunological factors are most likely to be associated with placental adaptations, whereby the interaction between maternal and paternal immunological factors is most active. However, some experts believe that pre-eclampsia is driven by systemic circulation of placental debris, which again allows paternal factors to affect the systemic response.[7][10][16][17][18]

pre-eclampsia in a previous pregnancy

The risk of recurrence is around 10% to 50%, although it is thought to be higher in those with previous early onset (i.e., <30 weeks) or severe disease and lower for those with mild to moderate or late-onset disease.[19] Because the risk of recurrence is reduced with a change of partner, the increased risk in these women is likely to be caused by a failure of tolerance to the specific immunological factor.[7][10][16]

family history of pre-eclampsia

If a mother had pre-eclampsia, her daughter has a 25% chance of developing the condition.[20] Similarly, if a sister had pre-eclampsia, there is a 1 in 3 chance of her sibling developing it.[20] These findings suggest a genetic component to the condition. Although some studies have suggested associations with various genetic markers, larger studies are still required.[10][16][21][22]

body mass index (BMI) >30

Raised BMI is associated with an increased risk of pre-eclampsia. The risk increases as BMI increases, becoming more significant when BMI is >35.[10][16][23]

The reasons for this are multifactorial, but may include overdiagnosis due to difficulties in measuring blood pressure, and the fact that adipose tissue is a potent supplier of inflammatory mediators, thereby making obese women more likely to mount an exaggerated inflammatory response.[10][24]

maternal age >40 years

Women >40 years of age have a 1.5-fold greater risk of pre-eclampsia compared with women aged <35 years.[25][26] This is probably due to altered physiological adaptation to pregnancy, and an increase in comorbidities.[10][16]

multiple gestations

The association between pre-eclampsia and multiple gestations is well documented.[27]​ The data are most compelling in twin pregnancies and show increased morbidity and mortality from pre-eclampsia in these women.[10][15][16]

sub-fertility

Women with sub-fertility are at higher risk of adverse pregnancy outcomes, including pre-eclampsia.[28] This association is independent of maternal age and multiple pregnancy. The incidence of pre-eclampsia is significantly higher for pregnancies in which there is a donor embryo.[29]

gestational hypertension

Up to 50% of women with gestational hypertension (hypertension after 20 weeks' gestation in the absence of both proteinuria and systemic symptoms) go on to develop pre-eclampsia and the progression is more likely if hypertension is diagnosed before 32 weeks’ gestation.[1] These women should, therefore, be monitored closely.

pre-existing diabetes

Pre-eclampsia is associated with hyperplacentation disorders such as diabetes.[8]​ Diabetes is associated with a larger than average placenta and an increase in inflammatory vascular disease, so there is a potential risk of both the placental trigger and a strong maternal systemic response.[7][8]​​[9]

migraine

Pregnant women with a history of migraine are at increased risk of hypertensive disorders of pregnancy, including pre-eclampsia.[30][31][32]

polycystic ovary syndrome (PCOS)

Women with PCOS may be more likely to develop pre-eclampsia because of their increased risk of obesity, type 2 diabetes, and treatment for sub-fertility.[10][16][33]

autoimmune disease

Women with an autoimmune disease, especially those with antiphospholipid antibody syndrome, have an increased risk of pre-eclampsia, although it can be difficult to distinguish the two conditions.[10][15][16]

Women with an autoimmune disease may have pre-existing vascular disease that worsens pre-eclampsia, resulting in severe illness.

An acute postnatal exacerbation of the autoimmune disease can occur, but this is most likely to be due to the underlying disorder.

renal disease

Women with renal disease may already have hypertension and proteinuria, thereby making the diagnosis of pre-eclampsia difficult.[34] However, women with chronic kidney disease who have proteinuria in early pregnancy are at higher risk of superimposed pre-eclampsia.[35] The presence of any autoimmune disease can further increase the incidence.[36]

pre-existing cardiovascular disease and chronic hypertension

The incidence of pre-eclampsia in women with chronic hypertension of any type is around 25%.[37] The presence of any autoimmune disease can further increase the incidence.[36]

weak

interval of ≥10 years since previous pregnancy

Women with a long interval between pregnancies have an increased risk of pre-eclampsia, but factors such as age, obesity, and comorbidities may contribute to the risk.[15][16][17]

high-altitude residence

The incidence of pre-eclampsia may be increased at high altitudes.[38]

hypothyroidism

There may be an association between hypothyroidism and pre-eclampsia, but high-quality studies are lacking. Globally, iodine deficiency is the commonest cause of hypothyroidism. Long-standing iodine deficiency plus the demands of pregnancy may increase the risk of pre-eclampsia.[39][40]​

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