Good afternoon. I will be talking today about pre-eclampsia and hypertensive disease in pregnancy.
I will first talk about normal blood pressure changes in pregnancy. I will then talk about the differential diagnosis of raised blood pressure in pregnancy. This will be followed by a description of the hypertensive diseases in pregnancy – pre-existing hypertension, pregnancy-induced hypertension and pre-eclampsia. I will then discuss the management of pre-eclampsia from suspicion to after delivery.
In a pregnant lady blood pressure should be measured with the patient semi-recumbent at 45 degrees. The diastolic pressure is measured when the sound disappears. In pregnancy, blood volume increases by 1 litre by week 12. However progesterone, a vasodilator, causes an overall reduction in blood pressure. By the end of the second trimester the blood pressure nadirs. In the third trimester the cardiac output increases and the renin-angiotensin-aldosterone system restores blood pressure to pre-pregnancy levels.
Hypertension in a pregnant lady may be classified into four categories, depending primarily on timing of diagnosis relative to gestation and presence of protein in the urine. The four categories are chronic (pre-existing) hypertension, chronic hypertension with pre-eclampsia superimposed, pregnancy-induced hypertension (gestational hypertension) and pre-eclampsia.
Chronic hypertensive includes patients known to have hypertension; or patients who have high blood pressure less than 20 weeks gestation, when the high blood pressure cannot be thought to be due to the pregnancy and was almost certainly present prior to pregnancy although never measured. The risk factors for chronic hypertension are increasing maternal age, obesity, a family history, medical disorders (e.g. diabetes mellitus, renal disease) and ethnicity (including Asians and Afro-Caribbeans). Hypertension in a young woman not known to have any medical problems should be investigated to exclude more unusual causes such as Conn’s syndrome and phaeochromocytoma. Symptoms are often absent although fundal changes, renal bruits and radiofemoral delay should be excluded in all hypertensives. Proteinuria in patients with renal disease is normally present at booking. Chronic hypertension is not usually associated with proteinuria but there is an increased risk of developing pre-eclampsia, intrauterine growth restriction (due to ischaemia), placental abruption due to increased pressure in placental vessels and stillbirth. It is important to check the mother’s blood pressure and urine regularly, and organise fetal growth scans after 32 weeks’ gestation. Investigations should be to identify secondary hypertension (two 24h urine collections for VMA for phaeochromocytoma), look for coexistent disease (assess renal function and do renal ultrasound) and to identify pre-eclampsia (quantify any proteinuria and serum urate levels at booking and compare in later pregnancy). Methyldopa (acts presynaptically to antagonise adrenaline) and Labetalol are used to treat chronic hypertension in pregnancy. For acute use, Labetalol is the drug of choice.
Pregnancy-induced hypertension is defined as a persistently raised blood pressure first identified after 20 weeks gestation. It is not a disorder of endothelium and is not associated with proteinuria. It probably represents an exaggerated physiological response to pregnancy, and typically resolves within 6 weeks of delivery. It is a diagnosis of exclusion and the clinical sequelae and management are as that of chronic hypertension. It is important to note that you cannot exclude pre-eclampsia until the woman delivers and has not had pre-eclampsia. These are not three distinct categories. Chronic hypertension and pregnancy-induced hypertension can have superimposed pre-eclampsia.
The remainder of this talk will be on pre-eclampsia and its management. It is a multisystem disease that is usually manifest as hypertension and proteinuria in the second half of pregnancy. It may be associated with sudden-onset oedema. It is peculiar to pregnancy, is of placental origin and therefore cured only by delivery. It is relatively common, affecting 6% of all pregnancies.
In pre-eclampsia damage to the blood vessel endothelium causes: vasospasm (and increased vascular resistance), causing reduced organ perfusion; increased capillary permeability (causing proteinuria and oedema); and clotting dysfunction (due to loss of platelets in the urine as well as exposure of tissue factor, which can cause DIC, consuming platelets).
In pre-eclampsia the course of the disease is progressive, but variable and unpredictable. Some women develop life-threatening disease at 24 weeks. Others merely develop mild hypertension at term. Hypertension usually precedes proteinuria. The classification into mild, moderate and severe forms takes into account blood pressure, proteinuria, gestation and complications. Blood pressure below 170/110 and proteinuria indicates the mild form; above 170/110 and proteinuria indicates the moderate form. Elevated blood pressure and proteinuria before 32 weeks gestation or with maternal complications indicates the severe form. The most severe maternal complications are HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) and eclamptic fits (resulting from cerebrovascular vasospasm).
The pathophysiology of pre-eclampsia is not completely understood. It appears to be a two stage process. In the first stage, before 20 weeks gestation, there is incomplete trophoblastic invasion of spiral arterioles, which is necessary for them to dilate. This impaired maternofetal trophoblast interaction may be due to altered immune responses. As a result there is reduced uteroplacental blood flow. In the second stage, in which the disease manifests, the ischaemic placenta reacts, probably via an exaggerated maternal inflammatory response, by inducing widespread endothelial cell damage causing vasospasm, increased capillary permeability and clotting dysfunction. This gives rise to the symptoms and complications of pre-eclampsia.
The diagnosis of pre-eclampsia is made after 20 weeks gestation. Gestational proteinuric hypertension prior to 20 weeks should raise the possibility of an underlying molar pregnancy, drug withdrawal, or (rarely) chromosomal abnormality in the fetus. The criteria for diagnosis of pre-eclampsia are: New-onset hypertension (sustained BP ≥ 140/90 in a previously normotensive woman). Women with new hypertension before 32 weeks have a 50% chance of developing pre-eclampsia. At 24-28 weeks, new hypertension is predictive of severe pre-eclampsia. On average a rise in diastolic blood pressure that does not reach 90mmHg at any time during pregnancy is associated with an uncomplicated pregnancy. New-onset significant proteinuria (&gt;0.3g/24h or ≥1+ on an MSU in the absence of a UTI). New proteinuria with new hypertension is strongly associated with poor fetal and maternal outcome. Quantified protein excretion is independently associated with undiagnosed underlying medical conditions and a poor obstetric outcome. Sudden-onset oedema (of face, hands and legs) may also be present.
Pre-eclampsia is usually asymptomatic, but headache, drowsiness, visual disturbances, nausea/vomiting and epigastric pain may occur at a late stage. On examination hypertension is usually the first sign. In pre-eclampsia oedema is found in most pregnancies. The presence of epigastric tenderness and vomiting are suggestive of impending complications. Urine testing for protein with dipstick should be considered part of the clinical examination. Fetal compromise can be the first clinical indication of pre-eclampsia and should be followed up by an assessment of blood pressure and proteinuria as well as following local management protocols.
Serious morbidity associated with pre-eclampsia can occur from 20 weeks gestation to after delivery. The occurrence of any of the following complications, which may occur together, is an indication for delivery whatever the gestation. They may occur postpartum as it takes at least 24 hours for delivery to ‘cure’ the disease. Eclampsia is grand-mal seizures, probably resulting from vasospasm. It is most common at term. Mortality can result from hypoxia. Treatment is by magnesium sulphate. CVA results from failure of cerebral blood flow autoregulation at mean arterial blood pressures above 140/90mmHg. Treatment of blood pressure reaching 170/110mmHg should prevent this. Due to endothelial cell damage, a consequent rapid fall of platelets due to aggregation on damaged endothelium indicates impending HELLP (haemolysis, elevated liver enzymes and low platelet count: more common before 32 weeks) or disseminated intravascular coagulation. Treatment is by delivery of the baby. Pulmonary oedema is due to fluid overload. ARDS (and mortality) may develop. Treatment is with oxygen and frusemide. Liver failure and liver rupture may occur. In HELLP haemolysis turns the urine dark. Treatment is supportive and includes magnesium sulphate prophylaxis against eclampsia. Intensive care therapy is required in severe cases. High dose steroids are often given although their effects are debated. Renal failure is identified by careful fluid balance monitoring and creatinine measurement. Haemodialysis may be required in severe cases. Perinatal mortality and morbidity of the fetus is greatly increased. In pregnancies affected before 36 weeks the principal problem is IUGR, due to the ischaemic placenta. Preterm delivery is often required. Pre-eclampsia is strongly associated with fetal growth restriction, low birth weight, preterm delivery, respiratory distress syndrome and admission to neonatal intensive care, At all gestations there is an increased risk of placental abruption (more common before 32 weeks).
To confirm the diagnosis, if bedside dipstick analysis is positive for protein, exclude a urinary tract infection cause by taking a mid stream urine specimen. Do a protein-creatinine ratio taken on a single urine sample and if ≥30g/nmol do a 24h urine collection to measure protein. To monitor maternal complications, monitor serum urate, which is elevated in pre-eclampsia (although this predicts complications poorly). Take a platelets measurement – a rapid fall indicates impending HELLP or DIC. LFTs are initially normal, but a rise also suggests liver damage or impending HELLP. A rapidly rising creatinine suggests severe complications and renal failure. To monitor fetal complications, do an ultrasound to assess fetal growth and an umbilical artery doppler to identify reduced flow in the fetal circulation and fetal compromise.
Treatment traditionally focused on treating eclampsia. However, pre-eclampsia is a mixture of diseases and presentations, not just eclampsia. The mainstay of management of pre-eclampsia is appropriate antenatal care, with a low threshold for referral for intervention. A stepwise management scheme is therefore in place.
Input may concern further specialist investigation, clarification of risk or advice on early intervention of pharmacological treatment. The subsequent obstetric care will be determined on an individual basis and may be led by specialists, general practitioners, midwives or by shared care. There are various risk factors predisposing to pre-eclampsia. Older maternal age and obesity are two demographic dispositions. A lady who is nulliparous (or first pregnancy to any partner) or is expecting twins or who has a molar pregnancy, or has a previous history of pre-eclampsia is at higher risk. Having a family history of pre-eclampsia, particularly in a first-degree relative, puts a woman at higher risk. Having a antiphospholipid antibody syndrome or collagen vascular disease predisposes to pre-eclampsia.
All pregnant women, especially those at high risk (see slide on Aetiology) have regular blood pressure and urinalysis checks. Pre-eclampsia is recognised clinically by the presence of pregnancy-induced hypertension and proteinuria. Screening tests are relatively inaccurate. The most commonly used is umbilical artery Doppler as it is more predictive of fetal compromise than a CTG. Scanning for fetal size is not necessary unless other parameters are abnormal. Low-dose Aspirin is used for prevention only if early-onset severe pre-eclampsia in previous pregnancy.
Women with new hypertension &gt; 140/90mmHg are assessed in the outpatient clinic. Referrals are taken directly from midwives, GPs and consultant clinics. The following are criteria for admission: Symptoms; Patients with new proteinuria of 2+ or more should be admitted to hospital, whatever the blood pressure; elevated blood pressure; and suspected fetal compromise. If there is 1+ proteinuria only, patient needs to be reviewed in 2 days but not admitted.
Drugs are used in pre-eclampsia to reduce the incidence of the complications described earlier and to treat eclampsia. Antihypertensives are given if the diastolic blood pressure reaches 110mmHg. Oral labetalol is the drug of choice. Oral labetalol the drug of choice If control not achieved, oral nifedipine given If oral therapy not successful, IV labetalol given. The aim is a blood pressure of about 140/90mmHg. Antihypertensives reduce hospitalisation, and may allow prolongation of a pregnancy affected preterm.
Eclampsia is treated by magnesium sulphate, which has a lower re-convulsion rate and rates of maternal death than either diazepam or phenytoin. There is no evidence to suggest that one route is superior to the other. IM route easier to administer. IV route provides better blood levels. Magnesium sulphate is used both for the treatment and, in severe disease, prevention of pre-eclampsia. An intravenous loading dose is followed by an intravenous infusion. It is not an anticonvulsant per se, but treats the pathology underlying eclampsia by increasing cerebral perfusion.
HELLP Syndrome is a syndrome caused by abnormal clotting in which fibrin meshworks are formed in small vessels, in particular the liver. Red blood cells become destroyed by this process, causing anaemia. The liver is the main site of this process, and periportal necrosis may occur. There are several symptoms caused by this. The most severe symptoms are liver rupture causing seizures or coma. I will not be discussing the management of HELLP syndrome in this talk.
Pre-eclampsia is progressive and predictable, and cured only by delivery As a general rule, one or more fetal or maternal complications are likely to occur within 2 weeks of the onset of proteinuria. Mild hypertension without fetal compromise is monitored for deterioration. Induction of labour at term is wise. Modarate or severe pre-eclampsia requires delivery if the gestation exceeds 34-36 weeks, after which time prematurity complications are less of a problem. Hypertension reaching 170/110mmHg must be controlled first. Before 34 weeks, in a specialist unit with full neonatal care facilities, the possible benefits of increasing fetal maturity must be weighed against the risks of disease complications. Steroids are given prophylactically, hypertension is treated and there is intensive surveillance of both mother and fetus (involving daily clinical assessment, CTG and fluid balance and fetal blood testing). Clinical deterioration of mother or fetus will prompt delivery. Severe pre-eclampsia with complications or fetal distress requires delivery regardless of the gestation. The fetus may be previable.
Before 34 weeks, Caesarean section is usual. After 34 weeks, labour can be induced with prostaglandins. Epidural analgesia helps reduce the blood pressure. Antihypertensives can be used throughout labour. Oxytocin rather than ergometrine is used in the third stage as the latter can increase the blood pressure.
It often takes at least 24h post delivery for severe disease to improve and it may worsen during this time. It is important to monitor bloods, fluid balance and blood pressure. Blood investigations are liver enzymes, platelets and renal function. Low platelet levels usually return to normal within a few days. Fluid balance monitoring is essential. If the urine output is low, CVP monitoring will guide management. If high, give Frusemide. If low, give fluid but not albumin. If normal and oliguria, renal failure is likely and a rise in potassium may dictate the need for dialysis. The blood pressure is maintained at around 140/90mmHg. The highest level tends to be reached about 5 days after birth, and continuation admission until then is advised. Postnatal treatment is usually with a beta blocker. Treatment may be needed for several weeks and communication with the GP and community midwives is essential.
In summary: Pregnancy usually associated with a fall in blood pressure, restored during the third trimester Chronic hypertension and pregnancy-induced hypertension associated with risks to both mother and fetus Pre-eclampsia affects 6% of pregnancies. It is a disease of the placenta and affects multiple systems in the body. It resolves after pregnancy. Main concern is eclampsia, HELLP, CVA and pulmonary in the mother; IUGR and stillbirth in the fetus. Pre-eclampsia is treated by antihypertensives, and magnesium sulphate if eclampsia Moderate or severe pre-eclampsia requires delivery; if gestation less than 34 weeks, delay if possible; if complications or fetal distress, deliver regardless Continue monitoring postpartum for blood investigations, fluid balance and blood pressure
Pre-Eclampsia and Hypertensive Disease in Pregnancy
Pre-eclampsia and HypertensivePre-eclampsia and Hypertensive
Plan of PresentationPlan of Presentation
1. Normal blood pressure changes in pregnancy
2. Differential diagnosis
3. Pre-existing hypertension
4. Pregnancy-induced hypertension
6. Stepwise management of pre-eclampsia
1. Normal Blood Pressure Changes In
Measured in semi-
recumbent position at 45o.
recorded when sound
Trimester 1-2: blood
volume increases, but
increased SVR due to
progesterone causes drop
Trimester 2-3: Cardiac
output increases and
0 15 40
2. Differential Diagnosis2. Differential Diagnosis
Blood pressure problems in pregnancy can be divided into
1. Chronic hypertension
2. Pregnancy-induced hypertension
3. Chronic Hypertension3. Chronic Hypertension
1. Known hypertensives
2. Patients whose hypertension is diagnosed prior to 20
Increased risk of pre-eclampsia, intrauterine fetal growth
restriction, placental abruption and stillbirth
Investigate to identify secondary hypertension, look for
coexistent disease and identify pre-eclampsia
Use Methyldopa or Labetalol
4. Pregnancy-Induced Hypertension
Persistently raised blood pressure after week 20 in
previously normotensive woman
Not associated with proteinuria
Typically resolves within 6 weeks of delivery
Clinical sequelae and management: as Chronic
A multisystem disorder specific to pregnancy and the
Associated with hypertension and proteinuria in the
second half of pregnancy
May be associated with sudden-onset oedema
Is a disease of the placenta
Affects 6% of all pregnancies
Blood vessel endothelial cell damage, in association
with an exaggerated maternal inflammatory response
leads to vasospasm, increased capillary permeability and
These can affect all the maternal organs to varying
Increased permeability Proteinuria
Reduced placental perfusion IUGR
Reduced cerebral perfusion Eclampsia
Course and degrees of pre-eclampsia
The disease is progressive, but is variable and
Hypertension usually precedes proteinuria
Mild Proteinuria and hypertension
Moderate Proteinuria and hypertension
Severe Proteinuria and hypertension < 32
weeks or with maternal complications
e.g. HELLP, eclamptic fits
Stage 1 (Poor
invasion of spiral
arterioles results in
Stage 2 (Inflammation)
The ischaemic placenta
endothelial cell damage
and maternal systemic
Made after 20 weeks’ gestation
New-onset hypertension (sustained BP ≥ 140/90 in a
previously normotensive woman)
New-onset significant proteinuria (>0.3g/24h or ≥1+ on
an MSU in the absence of a UTI)
Sudden-onset oedema (of face, hands and legs) may also
To confirm the diagnosis
If positive, exclude UTI by MSU
Assess protein:creatinine ratio (≥30g/nmol). If
significant, do 24h urine (≥0.3g/24h)
To monitor maternal complications
Serum urate (elevated)
LFTs (ALT/AST) (elevated)
Serum urea and creatinine (elevated)
To monitor fetal complications
Umbilical artery Doppler
6. Stepwise Management of
Treatment traditionally focused on treating eclampsia
However, pre-eclampsia is a mixture of diseases and
The mainstay of management of pre-eclampsia is
appropriate antenatal care, with a low threshold for
referral for intervention
Risk Assessment early in Pregnancy
Before 20 weeks, offer women specialist input if one of:
Pre-existing hypertension or booking DBP ≥ 90mmHg
Pre-existing renal disease or booking proteinuria
Presence of antiphospholipid antibodies
Or any two of:
First pregnancy or ≥ 10 years since last baby
Age ≥ 40 years
BMI ≥ 35
Family history of pre-eclampsia (mother or sister)
After 20 weeks gestation
At 20 weeks, women should be assessed for the signs and
symptoms of pre-eclampsia
Referred to Maternity Assessment Suite if:
Symptoms of headache or visual disturbance, or both
Epigastric pain or vomiting, or both
Reduced fetal movements, small for gestational age
After 20 weeks gestation – MAS
If proteinuria only, repeat pre-eclampsia assessment in
community within 1 week
Admit if any features in box below
Otherwise refer for hospital step-up assessment, to
confirm the presence of significant hypertension,
distinguish pre-eclampsia from the differentials and
Diastolic ≥110 and ≥1+ protein on dipstick
Systolic ≥170 and ≥1+ protein on dipstick
Diastolic ≥90 and new proteinuria ≥1+ on dipstick with
Hospital Step-Up Assessment
Assessment includes blood pressure readings, urinalysis
for protein, monitoring of symptoms and foetal
movements, fundal height and foetal monitoring for
If SBP < 140 and DBP <90 and protein:creatinine ratio
≥ 30mg/mmol and symptoms/bloods abnormal, admit
If SBP 140-169 and DBP 90-109 and protein:creatinine
ratio ≥ 30mg/mmol or symptoms or bloods abnormal,
Assess blood pressure, urinalysis
Assess signs (oedema, auscultate heart and lung fields,
epigastric tenderness, fundi for papilloedema, tendon
reflexes and clonus)
Assess fetal size, presentation and well-being. Do CTG,
U/S for biometry, umbilical artery Doppler, liquor
volume, biophysical score
Do PET bloods, Group and Save or Cross-match
Monitor observations including fluid balance and urine
Management of blood pressure
Mandatory when systolic blood pressure ≥ 170mmHg
and diastolic blood pressure ≥ 110mmHg
The use of antihypertensives to treat mild to moderate
hypertension reduces the risk of severe hypertension
Early treatment reduces neonatal complications e.g.
respiratory distress syndrome
Oral methyldopa or labetalol used for mild to moderate
Sustained, markedly elevated blood pressure treated by
Management of complications
Magnesium sulphate (IV or IM)
Used as prevention if sustained SBP >160, DBP >110;
proteinuria > 1g/24h or ≥ 3+ on dipstick; liver and/or
renal impairment; coagulopathy
IM route easier to administer
IV route provides better blood levels
Activation of coagulation cascade destroys red blood
cells, consumes platelets and causes periportal necrosis
Causes headache, blurred vision, malaise, upper
abdominal pain, paraesthesia
May cause liver rupture and seizure or coma
Timing of Delivery
Pre-eclampsia is progressive and cured only by delivery
Complications likely within 2 weeks of proteinuria
Mild hypertension, no fetal
Monitor. Induce at term
Moderate or severe pre-
After 34 weeks: delivery.
Before 34 weeks: Steroids,
treat hypertension and
monitor. Delivery if
Severe pre-eclampsia with
Conduct of Delivery
The ultimate cure for pre-eclampsia, but does not have
an immediate effect
Epidural analgesia helps reduce the blood pressure
Antihypertensives can be used during labour
Oxytocin used in third stage
Induce with prostaglandins
Post-natal care of the pre-eclamptic
It often takes at least 24h post delivery for severe
disease to improve and it may worsen during this time
Blood investigations LFTs, platelets, renal
Fluid balance Urine output
Blood pressure Monitor. Continued
admission advisable until 5
days postpartum. Treat with
beta blocker if raised
Blood pressure falls in early pregnancy, restored during
the third trimester
Chronic hypertension and pregnancy-induced
hypertension associated with risks to mother and fetus.
Pre-eclampsia is a placental disease and affects multiple
systems in the body. It resolves after pregnancy
Main concern is eclampsia, HELLP, CVA, placental
abruption and pulmonary oedema in the mother; IUGR
and stillbirth in the fetus
Blood pressure treated by antihypertensives
Eclampsia treated by magnesium sulphate
Moderate or severe pre-eclampsia requires delivery; if
gestation less than 34 weeks, delay if possible. If
complications or fetal distress, deliver regardless
Continue monitoring postpartum for blood
investigations, fluid balance and blood pressure
1. Impey L, Child C. Obstetrics and Gynaecology. 3rd
Oxford: Wiley-Blackwell; 2008. Chapter 20
2. Parisaei M, Shailendra A, Dutta R, Broadbent JAM.
Obstetrics and Gynaecology (Crash Course Series). 2nd
Ed. Edinburgh: Elsevier; 2008. Chapter 35
3. Walker JJ. Stepwise Management. In: Lyall F, Belfort
M, editors. Pre-eclampsia – Etiology and Clinical
Ed. Cambridge: Cambridge University
Press; 2008. Chapter 24
4. Nottingham University Hospitals NHS Trust