Hypertension in Pregnancy:

Diagnosis and Management

NICE Guideline NG133

Dr Fran Conti-Ramsden, ST3 O&G, ACF, King’s College London

BACKGROUND

• Hypertensive disorders of pregnancy (HDP) are estimated to affect 1 in 10 pregnancies

• HDP are responsible for approximately 10% of preterm births

• Associated with high rates of maternaland fetal morbidity

GOOD NEWS IN THE UK

Conti-Ramsden et al, Reducing maternal deaths from hypertensive disorders, BMJ, 2019.

CAN WE DO BETTER?

• 2019 MBRRACE report (reporting

period 2015-2017):

• 6 deaths from pre-eclampsia in the UK &

Ireland.

• In 4 out of 6 cases, improvements in

care may have led to a different

outcome

• 4 had indication for aspirin. One

woman was prescribed aspirin appropriately,

one started late, two never.

ABROAD…

• A: Territory according to land area

• B: Territory according to population

• C: Territory according to proportion of

maternal deaths (HDP approx. 10-15%)

• Global burden of disease study estimated

~30,000 maternal deaths due to HDP

in 2013

• 42% Sub-Saharan Africa

• 36% South Asia

Dudley, The Global Impact of eclampsia and pre-eclampsia, Semin. Perinat, 2009.

DEFINITIONS

DEFINITIONS

DEFINITIONS

HYPERTENSION IN PREGNANCY: DIAGNOSIS

AND MANAGEMENT

NICE Guideline NG133 June 2019

HYPERTENSION IN PREGNANCY: DIAGNOSIS

AND MANAGEMENT

1.1 Reducing the risk of hypertensive disorders in pregnancy

1.2 Assessment of proteinuria in hypertensive disorders of pregnancy

1.3 Management of chronic hypertension in pregnancy

1.4 Management of gestational hypertension

1.5 Management of pre-eclampsia

1.6 Fetal monitoring

1.7 Intrapartum care

1.8 Medical management of severe hypertension, severe pre-eclampsia or

eclampsia in a critical care setting

1.9 Antihypertensive treatment during the postnatal period, including

during breastfeeding

1.10 Advice and follow-up at transfer to community care

1.1 REDUCING THE RISK

• Advice: • If any symptoms, advise women to see a Health care

professional immediately • Give the same advice on rest, exercise and work to

women with chronic hypertension or at risk of hypertensive disorders during pregnancy as healthy pregnant women.

• Aspirin: from 12/40 until birth in women with risk factors

• Do not use/recommend:

• Nitric oxide donors / progesterone / diuretics / LMWH / Magnesium / folic acid / antioxidants

• Reducing salt intake (except in chronic HTN)

1.1 REDUCING THE RISK

High Moderate

Previous hypertensive disease

Chronic kidney disease

Autoimmune disease

Type 1 / 2 diabetes

Chronic hypertension

1st baby

Age ≥ 40 years

Pregnancy interval > 10 years

BMI ≥ 35

FHx PET

Multiple pregnancy

Aspirin 75-150mg/day from 12 weeks

for women with:

• 1 high risk factor

• 2 moderate risk factors

1.2 ASSESSING PROTEINURIA

• Use automated machine in secondary care

• Interpret measurements in context of full clinical review

• If dipstick ≥ 1+ protein use PCR or ACR quantification:

PCR: Cut off 30 mg/mmol

ACR: Cut off 8mg / mmol

Repeat PCR / ACR if uncertainty about diagnosis

• Do not use 1st morning void

• Do not not routinely use 24 hour collections

1.6 ADDITIONAL FETALMONITORING

• In women who had previous:

• Severe OR early onset PE requiring delivery <34/40

• PE with birth weight <10th centile

• Intrauterine death

• Placental abruption

Arrange USS for growth, fluid volume and umbilical artery doppler

velocimetry at 28/40 (or at least 2 weeks before gestational age of onset if earlier

than 28/40) and repeat 4 weeks later

1.3 CHRONIC HYPERTENSION

Hypertension that is present at the booking visit, or before 20/40, or if

the woman is already taking antihypertensive medication when referred

to maternity services

1.3 CHRONIC HYPERTENSION

PRE-PREGNANCY ADVICE

• Pre-conception counselling

• Refer to a specialist in HDP to discuss risks / benefits of treatment and decide

on most appropriate treatment

• ↑risk of congenital abnormalities if ACE inhibitors or ARBs are taken

during pregnancy

• Possibly ↑risk of congenital abnormalities and neonatal complications if

thiazide / thiazide-like diuretics are taken during pregnancy

• No evidence of increased risk with antihypertensives other than ACEi, ARBs,

thiazide and thiazide-like diuretic

If pregnant STOP ACEi/ARBs and offer alternatives

1.3 CHRONIC HYPERTENSION

MANAGEMENT

• Lifestyle advice: weight management, exercise, diet, lowering salt intake in line

with non-pregnant advice

• Antihypertensives:

• Continue existing antihypertensive therapy if safe in pregnancy or switch to

an alternative

• Discontinue antihypertensives if systolic BP <110 or diastolic <70 or

symptomatic hypotension

• Commence treatment if sustained readings above: systolic BP >140 or

diastolic BP > 90

• TARGET: 135/85mmHg

1.3 CHRONIC HYPERTENSION

MANAGEMENT

• Antihypertensives:

• Aspirin 75-150mg from 12/40 until birth

• Placental Growth Factor testing in suspected pre-eclampsia between 20-

35 weeks.

1.3 CHRONIC HYPERTENSION

MANAGEMENT

• Antenatal Appointments

• Individualised plan.

• Weekly if poorly controlled

• 2-4 weekly if well controlled

• Timing of Birth

• Do not offer delivery <37/40 if BP <160/110 with or without

treatment if there are no other medical indications

• Timing of birth after 37/40 should be agreed with the woman and

her obstetrician

• If planned early delivery is necessary offer antenatal corticosteroids

and MgSo4 if indicated in line with guidance on pre term birth

1.3 CHRONIC HYPERTENSION

FETAL MONITORING

• USS for fetal growth, amniotic

fluid volume and Umbilical

artery doppler velocimetry at

28, 32 and 36/40

• CTG only if clinically indicated

1.3 CHRONIC HYPERTENSION

POSTNATAL CARE

• BP measures: BP daily for 2/7 post birth, once between day 3-5

• Target BP: <140/90

• Antihypertensive agent:

• Stop / change methyldopa within 2 days of delivery

• Follow up:

• Review antihypertensive treatment after 2 weeks (GP / Specialist)

• Medical review at 6-8 weeks PN with GP / specialist

1.4 GESTATIONAL HYPERTENSION

New hypertension presenting after 20 weeks of pregnancy without

significant proteinuria

1.4 GESTATIONAL HYPERTENSION

ASSESSMENT

• Full assessment in 2* care by a Healthcare professional trained in HDP

Admit?

Tx?

1.4 GESTATIONAL HYPERTENSION

Mum

Baby

ASSESSMENT

PlGF!

1.4 GESTATIONAL HYPERTENSION

TIMING OF BIRTH

• Do not offer delivery <37/40 if BP lower than 160/110mmHg unless there are

other indications

• Timing of birth after 37/40 should be agreed between the woman and senior

obstetrician

• If planned early delivery is necessary corticosteroids and magnesium sulfate

should be offered in line with NICE guidance

1.4 GESTATIONAL HYPERTENSION

POSTNATAL CARE

• BP measures: BP daily for 2/7 post birth, once between day 3-5

• Target BP: <140/90

• Antihypertensive agent:

• Stop / change methyldopa within 2 days of delivery

• Continue antihypertensives if required, advise duration of Tx

similar to antenatal duration

• Reduce if BP < 130/80

• Start if not on Tx and BP >= 150/100

1.4 GESTATIONAL HYPERTENSION

POSTNATAL CARE

• Follow up:

• Care plan on discharge to community including:

• Who will provide follow up care including medical review if

required

• Frequency of BP checks

• Thresholds for stopping treatment

• Indications for referral to primary care

• If on antihypertensives, review treatment after 2 weeks (GP /

Specialist)

• Medical review at 6-8 weeks PN with GP / specialist

CHOOSING ANTIHYPERTENSIVES

PLACENTAL GROWTH FACTOR

PLACENTAL GROWTH FACTOR

Angiogenic (promotes

formation of new blood

vessels)

PLACENTAL GROWTH FACTOR (PLGF)

PlGF: PARROT study

• 11 maternity centres across the UK, recruited 1035 women with suspected pre-

eclampsia between 20 weeks to 36+6

• Revealed vs concealed testing

• Primary outcome: time from presentation with suspected pre-eclampsia to

documented diagnosis of pre-eclampsia

• Findings:

• Median time to pre-eclampsia diagnosis: 4.1 days with concealed testing

versus 1.9 days with revealed testing (time ratio 0·36, 95% CI 0·15–0·87;

p=0·027).

• Where PlGF was revealed there was lower incidence of adverse outcomes

(adjusted odds ratio 0·32, 95% CI 0·11–0·96; p=0·043)

• Consistent with targeted, increased surveillance

1.5 PRE-ECLAMPSIA

New onset hypertension >140/90 after 20/40 and the coexistence of 1 or

more of the following new onset conditions: proteinuria, other maternal

organ dysfunction, uteroplacental dysfunction

1.5 PRE-ECLAMPSIA

ASSESSMENT

• Full clinical assessment by professional trained in hypertensive disorders of

pregnancy

• Offer admission if concerns for mother or baby e.g.

• Consider using fullPIERS or PREP-S risk prediction models to guide

decisions about appropriate place of care, timing of delivery and

thresholds for intervention

Sustained systolic BP >160mmHg Suspected fetal compromise

Biochemical concern

(creatinine >90, ALT >70, PLTs <150,000)

Signs of impending pulmonary oedema,

eclampsia

Signs of severe pre-eclampsia Any other clinical signs that cause concern

PREP-S PREDICTION MODEL

OVERVIEW

• Aims to predict the risk of MATERNAL (no baby!!) adverse outcomes at 48

hours (PREP-S) and by discharge (PREP-L) in EARLY ONSET PRE-

ECLAMPSIA (up to 34/40)

• Model developed in UK, validated in multi-national and Netherlands cohorts

• Which adverse outcomes?

• Maternal death, neurological (GCS <13, stroke, cortical blindness), hepatic (INR >1.2,

hepatic haematoma, rupture), cardiorespiratory (inotropic support, MI, intubation,

pulmonary oedema), renal (AKI, dialysis) or haematological complications (transfusion,

PPH 1L+), or delivery before 34 weeks

• Factors in the model include: Age, gestational age, medical comorbidities, clinical

features, biochemical measures and treatment

See: https://www.evidencio.com/models/show/1038

FULLPIERS PREDICTION MODEL

OVERVIEW

• Aims to predict the risk of MATERNAL (no

baby!!) adverse outcomes within 48 hours in pre-

eclampsia (any gestational age).

• Model developed and validated in multi-national

cohorts (high income)

• Which adverse outcomes?

• One or more of Maternal death, or serious

nervous system, cardiorespiratory,

hepatic, renal or haematological

morbidity.

See: https://pre-empt.bcchr.ca/evidence/fullpiers

1.5 PRE-ECLAMPSIA

MANAGEMENT

1.5 PRE-ECLAMPSIA

• Repeat CTG if:

• Change in fetal movements

• PV bleeding

• Abdominal pain

• Deterioration in maternal condition

MANAGEMENT

1.5 PRE-ECLAMPSIA

Gestation Timing of Birth

Before 34/40 Continue surveillance unless there are indications for early

delivery

34-36+6/40 As above

When considering option of planned early delivery take into

account woman’s and baby’s condition, risk factors, co morbidities

and the availability of neonatal unit beds

37/40+ Initiate Birth within 24-48 hours

• Involve senior obstetrician in any decisions on timing of birth

• Involve anaesthetists and neonatal teams

• Offer IV Magnesium sulfate and a course of corticosteroids as appropriate

TIMING OF DELIVERY

1.5 PRE-ECLAMPSIA

TIMING OF DELIVERY

Chappell et al, Planned early delivery or expectant management.., Lancet, 2019.

1.5 PRE-ECLAMPSIA

Example maternal and fetal thresholds for

delivery before 37/40Inability to control BP despite using 3 agents (appropriately)

Mat pulse oximetry <90%

Progressive deterioration of LFTS, U&Es, haemolysis or platelets

Ongoing neurological features (eclampsia, intractable headache, repeated

visual scotomata)

Placental abruption

Reversed EDF in umbilical artery, an abnormal CTG or stillbirth

Other features not listed may also be considered

TIMING OF DELIVERY

1.5 PRE-ECLAMPSIA

POSTNATAL CARE: Did not take antihypertensives

• BP measures: QDS whilst I/P, at least once Day 3-5, alternate days until

normal.

• Clincal review: Ask about headaches and epigastric pain at every visit

• Antihypertensive agents:

• Start if not on Tx and BP >= 150/100

1.5 PRE-ECLAMPSIA

POSTNATAL CARE: Did take antihypertensives

• BP measures: QDS whilst I/P, every 1-2 days for up to 2 weeks until woman

is off treatment and has no hypertension.

• Clincal review: Ask about headaches and epigastric pain at every visit

• Antihypertensive agents:

• Stop / change methyldopa within 2 days of delivery

• Continue antihypertensive treatment

• Reducing treatment:

• Consider if BP < 140/90

• Reduce if BP < 130/80

1.5 PRE-ECLAMPSIA

POSTNATAL CARE: Biochemistry monitoring

• In women who had pre-eclampsia with hypertension or after step down from

critical care:

• FBC, U&Es & LFTs 48-72 hours after delivery or step down

• DO NOT REPEAT if these results are normal

• If abnormal repeat as clinically indicated until return to normal

• Urine dip for protein at 6-8 weeks after delivery

• If ≥ + protein at 6-8 weeks. Review with U&Es at 3 months and refer to renal

specialist if remain abnormal

1.5 PRE-ECLAMPSIA

POSTNATAL CARE: Transfer to Community

• Criteria:

• No symptoms of pre-eclampsia

• BP with or without treatment is ≤150/100

• Blood tests are stable or improving

• Write a care plan to include

• Frequency of BP checks

• Thresholds for reducing / stopping medication

• Indications for referral to primary care

• Self monitoring for symptoms

• GP / specialist review in 2 weeks and at 6-8 weeks after delivery

1.7 INTRAPARTUM CARE

Blood Pressure Every 15-30 minutes until <160/110 then hourly

Continue antenatal antihypertensives in labour

Haematological &

Biochemical tests

Determine the need for tests using same criteria as in

antenatal period

Care during epidural

analgesia

Do not pre load with IV fluids

Management of 2nd

stage

Do not routinely limit the 2nd stage if BP is controlled

Consider operative or assisted birth for women with

severe hypertension if have not responded to

treatment

1.8 SEVERE HYPERTENSION, SEVERE PRE-ECLAMPSIA,

ECLAMPSIA

- Severe Hypertension: systolic BP >160 or diastolic > 110mmHg

- Severe Pre-eclampsia: Pre-eclampsia with severe hypertension that does not

respond to treatment or is associated with ongoing / recurring severe headaches,

visual scotomata, nausea / vomiting, epigastric pain, oliguria, progressive

deterioration of blood results or failure of fetal growth or abnormal doppler

studies.

- Eclampsia: A convulsive condition associated with pre-eclampsia

1.8 SEVERE DISEASE

ANTICONVULSANTS

• Indication for anticonvulsant therapy (Magnesium Sulfate):

• Give MgSo4 if: Critical care setting and severe hypertension, severe pre-

eclampsia or previously had an eclamptic fit

• Consider MgSo4 if:

• delivery planned within 24 hours OR

• need for MgSo4 if 1 or more of the following:Ongoing / recurring severe

headaches

Epigastric pain

Visual Scotomata Oliguria with severe HTN

Nausea / vomiting Progressive deterioration of

blood tests

1.8 SEVERE DISEASE

ANTIHYPERTENSIVES

• Treat women with severe hypertension (AN/PN) in critical care with:

• Oral / IV labetalol

• Oral nifedipine

• IV hydralazine

• Monitor response to treatment to:

• Ensure BP falls

• Identify adverse effects for mum and baby

• Modify treatment according to response

1.8 SEVERE DISEASE

STEROIDS & FLUID BALANCE

• If early delivery is considered within 7 days offer steroids for fetal lung

maturation in line with preterm birth guidance

• Do not use dex/betamethasone for treatment of HELLP syndrome

• Limit fluids to 80ml/hour unless there are other ongoing fluid losses

• Mode of delivery according to clinical circumstances and woman’s

preference

1.9 POSTNATAL CARE

1.9 POSTNATAL CARE

ANTIHYPERTENSIVE AGENTS (AHA)

• Breastfeeding is okay!

• AHA can cross into breastmilk, but levels likely very low, lack of

testing means we have little data!

• Consider monitoring baby BP, especially preterm, who have

symptoms of low BP

• Monitor babies for drowsiness, lethargy, pallor, cold peripheries

and poor feeding

So which drug?

1.9 POSTNATAL CARE

ANTIHYPERTENSIVE AGENTS

• In line with treatment of non-pregnant hypertensive patients (NICE), or if

breastfeeding:

• Consider Enalapril: MONITOR RENAL FUNCTION + K+

• For black African / Caribbean women consider nifedipine/amlodipine

• Use combination therapy if BP not well controlled:

• Enalapril + nifedipine / amlodipine

• Add on atenolol / labetalol

• Consider choosing once daily dosing if possible.. Adherence is an

issue!

• Involve women in decision making about treatment

• Avoid diuretics and angiotensin receptor blockers

1.10 ADVICE & FOLLOW UP

1.10 ADVICE

RECURRENCE RATES in FUTURE PREGNANCIES

Overall risk is 1 in 5.

1.10 ADVICE

RECURRENCE RATES in FUTURE PREGNANCIES

Overall risk is 1 in 5.

Type of Hypertension current pregnancy

Prevalence of hypertension

in future pregnancy

Any HTN Pre-eclampsia Gestational

Any HTN 21% (1 in 5) 20% (1 in 5) 22% (1 in 5)

Pre-eclampsia 14% (1 in 7) 16% ( 1in 6) 7% (1 in14)

Gestational HTN 9% (1 in 11) 6-12% (up to 1

in 8)

11-15% (up to

1 in 7)

Chronic HTN N/A 2% (1in 50) 3% (up to 1 in

34)

1.10 ADVICE

LONG TERM CARDIOVASCULAR RISK

Type of Hypertension

Risk of

cardiovascular

Disease

Any HTN Pre-eclampsia Gestational Chronic

Major adverse

event

2x 1.5-3x 1.5-3x 1.7x

Cardiovascular

mortality

2x 2x No data No data

Stroke 1.5x 2-3x ? increased 1.8x

Hypertension 2-4x 2-5x 2-4x N/A

1.10 ADVICE

HOW DO WE REDUCE RISK?

• Advise to see GP or specialist to discuss, consider:

• Avoid smoking

• Maintain healthy lifestyle

• Maintain healthy weight (target BMI 18.5-24.9)

• Other considerations:

• Likelihood of recurrence increases if interbirth interval >10 years

• Re. long term risk of end-stage kidney disease, low risk if no HTN or

proteinuria at 6-8 week check

• Pre-pregnancy counselling for women who delivered <34/40 due to HDP

SUMMARY

NICE GUIDELINE

NG133 2019

WHAT HAS CHANGED?

• Definition of Pre-eclampsia

• Lower threshold to initiate treatment: 140/90 mmHg

• Lower Target BP: 135/85 mmHg or less

• Categories of hypertension:

• simplified to hypertension and severe hypertension (vs mild / moderate /severe)

• 24 hour urine collection no longer recommended

• Individualised risk assessment: Place of care

• Pharmacological management now reflects treatment for adults but

adapted for breastfeeding women

• Includes recurrence rates and long term cardiovascular risks

WHAT DO WE NOT KNOW?

• Which Drug (AN)?

• In women who need treatment for chronic hypertension in pregnancy, what is the

effectiveness and safety of antihypertensive agents (compared in head-to-head trials) in

improving maternal and perinatal outcomes?

• In women who need treatment for hypertension in pregnancy, what are the adverse neonatal

outcomes associated with maternal use of beta blockers (or mixed alpha-beta blockers)?

• Which Drug (PN)?

• In women who need treatment for high blood pressure after birth, what is the effectiveness

and safety (including in breastfeeding women) of antihypertensive agents in achieving adequate

blood pressure control?

• Place of care?

• In which women with pre-eclampsia is inpatient management associated with better outcomes

for women and babies?

TO CONCLUDE

• Patient information and involvement

• New thresholds for treatment

• PN follow up and communication

• Appropriate referrals

• Professional education and awareness

FOOTNOTES

Optimal aspirin dosing for preeclampsia prevention

Anna Lene Seidler, MSc, Lisa Askie, PhD

American Journal of Obstetrics & Gynecology

Volume 219, Issue 1, Pages 117-118 (July 2018) DOI: 10.1016/j.ajog.2018.03.018

Copyright © 2018 Elsevier Inc. Terms and Conditions

Figure

American Journal of Obstetrics & Gynecology 2018 219, 117-118DOI: (10.1016/j.ajog.2018.03.018)

Copyright © 2018 Elsevier Inc. Terms and Conditions