MEDICINE AND OTHER SPECIALTIES
Hypertension in
pregnancy
Paarul Prinja
Catherine Nelson-Piercy
Abstract
As women are becoming pregnant at older ages, hypertension in preg-
nancy is more commonly encountered. Pre-eclampsia affects 5% of
women. Women with known medical problems who become pregnant
can also have pre-existing hypertension. This all requires careful man-
agement, particularly regarding medication review to avoid teratoge-
nicity. These women require a multidisciplinary approach, to monitor
for and reduce the risk of developing pre-eclampsia.
Keywords Aspirin; hypertension; MRCP; pre-eclampsia; pregnancy;
proteinuria
Introduction
Hypertension is the most common medical problem seen during
pregnancy (10e15% of all pregnancies in the UK). It can predate
pregnancy or be diagnosed during pregnancy, when it is
described as pregnancy-induced hypertension. Hypertensive
disorders of pregnancy, such as pre-eclampsia, remain an
important direct cause of maternal death in the UK. Pre-
eclampsia and eclampsia occur in 5% and 0.03% of pregnan-
cies, respectively.1
Definitions
Hypertension in pregnancy is defined as diastolic blood pressure
(DBP) >90 mmHg on two occasions, or one reading >110
mmHg. An increase in systolic blood pressure (SBP) of >30
mmHg or DBP of >15 mmHg above the earliest reading in
pregnancy can also be considered to represent hypertension.2
The different categories of hypertension in pregnancy include
pre-existing hypertension, pregnancy-induced hypertension and
pre-eclampsia.
Pre-existing hypertension
Pre-existing hypertension complicates 1e5% of all pregnancies.3
In these women, the diagnosis of hypertension is made before or
in the early stages of pregnancy.
It is worth noting that, in the first trimester, there is a fall in
blood pressure caused by active vasodilatation, and a drop of 10
mmHg in SBP is usual by 13e20 weeks’ gestation. Thus, women
with near-normal blood pressure measurements in the first
Paarul Prinja MB ChB MRCP UK (Acute Medicine) is a Post-CCT Fellow
in Obstetric Medicine at St Thomas’ Hospital, London, UK.
Competing interests: none declared.
Catherine Nelson-Piercy MA FRCP FRCOG is a Consultant Obstetric
Physician at Guy’s and St Thomas’ NHS Trust and Imperial College
Healthcare NHS Trust, and Professor of Obstetric Medicine at King’s
College, London, UK. Competing interests: none declared.
MEDICINE --:-
Please cite this article in press as: Prinja P, Nelson-Piercy C, Hypertension in pregnancy, Medicine (2018), https://doi.org/10.1016/
j.mpmed.2018.09.010
Key points
C Hypertension is the most common medical problem in
pregnancy
C Labetalol, nifedipine and methyldopa are the drugs of choice
for treating hypertension in pregnancy
C Pre-eclampsia remains an important direct cause of maternal
death in the UK
C Pre-eclampsia is a multisystem disorder that causes wide-
spread effects, not just hypertension and proteinuria
C Delivery is the only cure for pre-eclampsia
trimester can actually have pre-existing hypertension. Risk fac-
tors include increasing maternal age, insulin resistance and
obesity. Secondary causes such as renal disease, cardiac disease,
hyperaldosteronism or neuro-endocrine causes, for example
phaeochromocytoma, should be considered and, if appropriate,
excluded.
The diagnosis of pre-existing hypertension can occasionally
be made retrospectively, i.e. 3e6 months after delivery, when the
blood pressure has not returned to normal.
Women with pre-existing hypertension, regardless of cause,
are at increased risk of superimposed pre-eclampsia (25%),
preterm delivery (28%), birth weight <2500 g (17%), placental
abruption and perinatal death (4%).4
Management of pre-existing hypertension
In women with uncomplicated pre-existing hypertension, the aim
is to keep the blood pressure <150/100 mmHg, but it is impor-
tant to keep DBP >80 mmHg to ensure adequate uteroplacental
blood flow.2 However, if a woman has end-organ damage sec-
ondary to hypertension, such as nephropathy, the aim is to keep
the blood pressure <140/90 mmHg.
Women taking angiotensin-converting enzyme (ACE) in-
hibitors or angiotensin receptor blockers should switch to an
alternative antihypertensive either before or on confirmation of a
pregnancy, as these medications have teratogenic effects.
Antenatally, regular monitoring for proteinuria using auto-
mated reagent strip urinalysis is recommended. If a result of 1þ
or more of protein is detected, the next step is to quantify the
degree of proteinuria by measuring a protein:creatinine ratio or
taking a 24-hour urine collection.
Pregnancy-induced hypertension
This is defined as hypertension developing in the second half of
pregnancy without proteinuria or any other features of pre-
eclampsia. Pregnancy-induced hypertension usually resolves by
6 weeks after delivery, although blood pressure can remain
elevated for 3 months postpartum. The condition tends to recur
in subsequent pregnancies.
The relative risk of progression to pre-eclampsia is related to
the gestation at presentation of pregnancy-induced hypertension.
1 Ó 2018 Published by Elsevier Ltd.
 MEDICINE AND OTHER SPECIALTIES

With hypertension before 30 weeks the risk is about 40%, but if Postpartum considerations
it presents after 38 weeks the risk is only 7%.4
Blood pressure monitoring for women with pre-existing or
pregnancy-induced hypertension is performed daily for the first 2
Management of pregnancy-induced hypertension
days after birth, and at least once between days 3 and 5. This is
Treatment of pregnancy-induced hypertension depends on the
because postpartum hypertension is common and blood pressure
severity of hypertension:
rises after normal pregnancy, reaching its peak 3e6 days post-
 Mild hypertension (140/90 to 149/99 mmHg) requires no
partum. Therefore, hypertensive women who are normotensive
treatment. However, weekly monitoring of blood pressure
at delivery can become hypertensive again within the first week
and urine dipstick for proteinuria is needed.
postpartum.
 Moderate hypertension (150/100 to 159/109 mmHg) re-
Changes in antihypertensive treatment during the postpartum
quires treatment. Common pharmacological agents used
period require more regular blood pressure monitoring. Treat-
in the treatment of hypertension in pregnancy are sum-
ment can be reduced if blood pressure falls to <140/90 mmHg,
marized in Table 1. Blood pressure and proteinuria
and women who are taking methyldopa can be switched to
monitoring must be undertaken twice-weekly. The target
alternative agents. These include b-adrenoceptor blockers (e.g.
blood pressure is <150/100 mmHg. Blood tests including
atenolol 25e50 mg once a day) with the addition of a calcium
full blood count, renal profile and liver aminotransferases
antagonist (e.g. modified-release nifedipine 10e20 mg twice a
are also recommended to look for evidence of pre-
day, amlodipine 5e10 mg once a day) in the postpartum period.
eclampsia.
ACE inhibitors such as enalapril 5e20 mg twice a day can also be
 Severe hypertension (160/110 mmHg or higher) requires
added.
admission to hospital for blood pressure control and
A detailed care plan that includes thresholds for reducing or
monitoring. Target blood pressure is <150/85 mmHg.
stopping treatment and a 6-week postnatal check must be
Blood pressure is monitored four times daily and protein-
completed for all women with hypertension in pregnancy to
uria daily; blood tests for pre-eclampsia are done weekly.2
ensure a smooth transition to primary care.
Uterine artery Doppler blood flow examination at 20e24
weeks’ gestation, looking particularly for the presence of a pre-
Pre-eclampsia
diastolic notch or persistent high-resistance waveform, is pre-
dictive of subsequent pre-eclampsia, fetal growth restriction Pre-eclampsia is a pregnancy-specific multisystem disorder. It is
and placental abruption. Further fetal monitoring using ultra- characterized by new-onset hypertension and new-onset pro-
sonography is required throughout the rest of pregnancy to teinuria after 20 weeks’ gestation:
assess fetal growth, liquor volume and umbilical artery blood  blood pressure >140/90 mmHg
flow.  proteinuria >300 mg/24 hours, or a spot urinary
All women with the risk factors outlined in Table 2 should be protein:creatinine ratio >30 mg/mmol.
offered antiplatelet therapy in the form of low-dose aspirin (75 Maternal blood pressure is usually maintained at 140/90
mg daily) from 12 weeks’ gestation throughout pregnancy to mmHg to prevent maternal complications and maintain adequate
reduce the risk of pre-eclampsia. Dipyridamole 100 mg three uteroplacental flow. However, if blood pressure readings are
times a day can be used in women who are allergic to aspirin. >160/110 mmHg, treatment is mandatory to reduce the risk of
Delivery is undertaken between 37 and 40 weeks’ gestation.2 placental abruption and maternal cerebral haemorrhage.2

Common pharmacological treatments for hypertension in pregnancy and the postpartum period2
Agent Dose Common adverse effects Comments

Antenatal
Labetalol 200 mg  2 daily First-line treatment
200e500 mg  3 daily Avoid in women with asthma
Methyldopa 250 mg  2 daily Lethargy, depression First-line treatment
250 mge1 g  3 daily
Nifedipine SR 10 mg  2 daily up to 30 mg  2 daily Headache, flushing, swollen lower limbs First-line treatment
Hydralazine 25e75 mg  3 daily Headache, flushing, tachycardia
Amlodipine 5e10 mg  1 daily
Doxazosin 1 mg  1 daily e 8 mg  2 daily Not safe in breastfeeding
Postpartum
Enalapril 5e20 mg  2 daily Safe in breastfeeding
Nifedipine SR 10e40 mg  2 daily Safe in breastfeeding
Amlodipine 5e10 mg  1 daily Safe in breastfeeding
Atenolol 25e50 mg  1 daily Safe in breastfeeding

Table 1

MEDICINE --:- 2 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: Prinja P, Nelson-Piercy C, Hypertension in pregnancy, Medicine (2018), https://doi.org/10.1016/
j.mpmed.2018.09.010
 MEDICINE AND OTHER SPECIALTIES
Indications for prophylaxis with low-dose aspirin4
Women with the following medical conditions should be commenced
on 75 mg of aspirin from 12 weeks’ gestation until birth:
C Pre-eclampsia in a previous pregnancy
C Chronic hypertension
C Chronic kidney disease
C Autoimmune disease, e.g. systemic lupus erythematosus
C Type 1 or type 2 diabetes mellitus
Women with >1 moderate risk factor for pre-eclampsia should
be commenced on aspirin 75 mg once a day from 12 weeks
gestation until birth. Moderate risk factors include:
C First pregnancy
C Age 40 years or older
C Pregnancy interval >10 years
C Body mass index 35 kg/m2 or more at first visit
C Family history of pre-eclampsia
C Multiple pregnancies
Table 2
Clinical features of pre-eclampsia
Women with pre-eclampsia are usually asymptomatic when the
disease first manifests. Hypertension and proteinuria are the
most common features but can present late and be mild.
Therefore, routine antenatal care involves screening for pre-
eclampsia through regular blood pressure measurements and
urinalysis to detect proteinuria. There is no universal test for pre-
eclampsia, but several clinical features of the diagnosis may be
present (Table 3). Pre-eclampsia is also associated with
increased risks of fetal growth restriction and placental
abruption.
Pathophysiology of pre-eclampsia
There is a genetic predisposition to developing pre-eclampsia:
women who have a mother or sister who have had the condi-
tion have a 3-fold increased risk of developing it. Pre-eclampsia is
a two-stage disorder.
The first stage is abnormal perfusion of the placenta
or placental ischaemia. The invading placenta is unable to opti-
mize blood flow from the maternal uterine vessels as the spiral
arteries in the placental bed do not undergo normal vascular
remodelling. Trophoblast invasion is also abnormal. There is a
failure of adaption of the spiral arteries to become high-
capacitance, low-resistance vessels. This can cause uteropla-
cental ischaemia.
The second stage is the maternal syndrome. A systemic in-
flammatory response is a normal part of pregnancy, and this is
exaggerated in pre-eclampsia, showing higher levels of pro-
inflammatory cytokines associated with endothelial dysfunc-
tion. This leads to increased capillary permeability and pro-
thrombotic factors, platelet activation and increased vascular
tone. These factors in combination can cause the maternal syn-
drome characterized by hypertension, proteinuria and renal or
hepatic disturbance. There is a reduction of placental growth
factor (PlGF) and an increase in soluble fms-like tyrosine kinase
1 (sFlt-1); measurement of these biomarkers can aid in the pre-
diction and diagnosis of pre-eclampsia.4
MEDICINE --:-
Please cite this article in press as: Prinja P, Nelson-Piercy C, Hypertension in pregnancy, Medicine (2018), https://doi.org/10.1016/
j.mpmed.2018.09.010
Clinical features of pre-eclampsia4
Symptoms (may be absent)
C Headaches, flashing lights
C Epigastric or right upper quadrant pain
C Nausea, vomiting
C Rapidly increasing or severe swelling of the face, fingers or legs
Signs
C Pregnancy-induced hypertension
C New-onset proteinuria
C Rapidly progressing oedema
C Epigastric or right upper quadrant tenderness
C Convulsions, mental disorientation
C Fetal growth restriction, intrauterine death
C Placental abruption
Investigations (note that pregnancy-specific reference ranges apply)
C 24-hour urinary protein excretion >0.3 g
C Protein:creatinine ratio >30 mg/mmol
C Thrombocytopenia
C Prolonged clotting times (if concomitant DIC in HELLP syndrome)
C Raised serum creatinine
C Increased haematocrit and haemoglobin
C Anaemia if haemolysis is present, with raised lactate
dehydrogenase and bilirubin
C Raised liver transaminases
C Reduced fetal growth and oligohydramnios
C Abnormal uterine artery Doppler findings (bilateral notches
and increased resistance/pulsatility index at 24 weeks
predicts pre-eclampsia)
C Abnormal umbilical artery Doppler findings (reduced, absent
or reversed end-diastolic flow, indicating fetal compromise)
C Low placental growth factor e reduced in pre-eclampsia
and predictive of delivery for pre-eclampsia within 2 weeks
DIC, disseminated intravascular coagulation; HELLP, haemolysis, elevated liver
enzymes, low platelets.
Table 3
Management
Once diagnosed, the only cure is delivery. However, this may
need to be delayed to prolong gestation and improve fetal
outcome. Severe hypertension requires intravenous labetalol or
hydralazine according to local protocols, and these women should
be managed in a high-dependency setting. Once this situation is
reached, it is a medical emergency and a decision on the timing of
delivery is necessary, with senior obstetric input. Early-onset pre-
eclampsia (<34 weeks) has a poorer outcome. Women who have
persistent proteinuria at a 6-week postnatal review must be
referred to a nephrologist to exclude underlying renal disease.
Future implications
The risk of pre-eclampsia in a subsequent pregnancy is 16%, and
this rises to 25% if the first pregnancy was complicated by severe
pre-eclampsia and delivery <34 weeks’ gestation. However,
when delivery is before 28 weeks, the risk of recurrent pre-
eclampsia is 55%.4
Pre-eclampsia can have long-term effects on the mother, with
a 3e4-fold increased risk of developing hypertension later in life.
3 Ó 2018 Published by Elsevier Ltd.
 MEDICINE AND OTHER SPECIALTIES
There is also a 2-fold increase of developing ischaemic heart
disease, stroke and venous thromboembolism. Risk factors for
developing cardiovascular disease, such as smoking, diabetes
mellitus, hypertension, obesity and hyperlipidaemia, must be
assessed on an annual basis.5 A sion and pregnancy outcomes: systematic review and meta-anal-
KEY REFERENCES
1 Centre for Maternal and Child Enquiries. Saving mothers’ lives:
reviewing maternal deaths to make motherhood safer: 2006e2008.
The eighth report on confidential enquiries into maternal deaths in
the United Kingdom. Br J Obstet Gynaecol 2011; 118(suppl 1):
1e203.
TEST YOURSELF
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the
end of the issue or online here.
Question 1
A 34-year-old woman was 13 weeks’ pregnant in her second
pregnancy. She had no symptoms. Her previous pregnancy had
been uneventful. There was a family history of pre-eclampsia.
On clinical examination, her body mass index (BMI) was 25 kg/
m2 and blood pressure 150/100 mmHg. Urine dipstick showed no
proteinuria.
She was advised to take labetalol and prophylactic aspirin.
What is the main indication for commencing aspirin in this
patient?
A Her age
B Her BMI
C Pregnancy-induced hypertension
D Pre-existing hypertension
E Family history of pre-eclampsia
Question 2
A 28-year-old woman was 2 days’ postpartum. She had been
found to have pregnancy-induced hypertension. She also has
asthma. She had been advised to take nifedipine SR 10 mg
twice daily and aspirin 75 mg once daily. She was keen to
breastfeed.
On clinical examination, her blood pressure was 158/96
mmHg.
MEDICINE --:-
Please cite this article in press as: Prinja P, Nelson-Piercy C, Hypertension in pregnancy, Medicine (2018), https://doi.org/10.1016/
j.mpmed.2018.09.010
2 National Institute for Health and Clinical Excellence. Hypertension
in pregnancy: the management of hypertensive disorders during
pregnancy. London: NICE, 2011.
3 Bramham K, Parnell B, Nelson-Piercy C, et al. Chronic hyperten-
ysis. Br Med J 2014; 348: g2301.
4 Nelson-Piercy C. Handbook of obstetric medicine. 5th edn. Lon-
don: CRC Press, 2015.
5 Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia
and risk of cardiovascular disease and cancer in later life: sys-
tematic review and meta-analysis. Br Med J 2007; 335: 974.
After stopping aspirin, what change (if any) to her treatment
should now be made?
A. Monitor her on the same treatment
B. Commence enalapril
C. Change to atenolol 50 mg daily
D. Commence ramipril 2.5 mg daily
E. Increase nifedipine SR to 20 mg 12-hourly
Question 3
A 31-year-old woman was pregnant at 36 weeks’ gestation. She
had no symptoms. She had pregnancy-induced hypertension and
was taking nifedipine SR 20 mg 12-hourly and aspirin 75 mg daily.
On clinical examination, her blood pressure was 140/82 mmHg,
and urine dipstick analysis showed 2þ protein (a new finding).
Investigations
 Fetal growth and umbilical artery Doppler scans were
normal.
What is the next best step?
A. Refer for induction of labour as soon as possible
B. Increase nifedipine SR to 30 mg 12-hourly
C. Request a protein:creatinine ratio
D. Request serum albumin measurement
E. Stop aspirin as delivery is imminent
4 Ó 2018 Published by Elsevier Ltd.