This document discusses hypertension in pregnancy and preeclampsia. It begins by defining hypertension and preeclampsia and discussing their incidence and complications. It then covers prediction and prevention of preeclampsia, including optimal aspirin dosage and timing. The document recommends tight blood pressure control and lists antihypertensive agents. It provides guidance on managing severe hypertension, including intravenous drugs and magnesium sulfate administration. Throughout, it compares guidelines from ISSHP 2018, NICE 2010, and other sources.

2. WHAT’S NEW
By Dr Kanddy Loo

3.  Definition of hypertension in pregnancy
 Classification of hypertensive disease in pregnancy
 Definition of preeclampsia
 Prediction and prevention of PE
 Optimal dosage and timing of aspirin
 Management of non-severe and severe hypertension in pregnancy

6.  Incidence of hypertension in pregnancy is 2.69 – 3.14% (? Underreporting as
most commonly cite incidence of hypertension in pregnancy 5 – 10%)
 Of which gestational hypertension accounts for 60 – 70% of cases
 Fetal complications
 prematurity – 7.6 – 11.7%
 IUGR – 12 – 15%
 FSB – 6 – 8%
 MSB – 7 – 11%
 Maternal complications
 Abruptio placenta
 PE
 PPH
 DIVC
 APO
 Maternal collapse

8.  Previously – Training manual on hypertension in pregnancy 2014
4 – 6 hours apart

9.  Now
FIGO Textbook of hypertension 2016

10.  Now
ISSHP 2018

11.  Now
Malaysian CPG on Management of hypertension, 5th edition 2018

12. ISSHP 2018

13. White coat hypertension
Should not be
considered as low risk as
there is 50% risk of GH
and 8% risk of PE
Since we do not have facility
for ABPM, any BP reading
≥140/90 in early pregnancy
even though only single
reading require monitoring.
Transient hypertension at
any gestation has 20%
chance of PE and another
20% of gestational
hypertension

14. Resistant
hypertension
 Needing 3
antihypertensives
at high dosage

15. PIH PROTEINURIA PREECLAMPSIA
Traditionally

16. Proteinuria Is No Longer Required To Diagnose
Pre-eclampsia; It’s present in 75% of the case
Others:
Pulmonary Oedema
Placenta Abruption
Oliguria
Epigastric /RHC Pain

17. The term ‘severe preeclampsia’ should
not be used in clinical practice
• PE may become a major threat at any
stage
• Classification into mild or severe
may be misleading/falsely reassuring
• ACOG has eliminated the diagnosis
of severe PE
• ISSHP recommends clinical
approach of PE with/without severe
features (as detailed in the table)

18. Recommendations from ISSHP 2018 For centres without UPCR
MOH HDP
manual

19.  If proteinuria is diagnosed but subsequent dipstick test are negative,
further quantification tests are appropriate to see whether or not true
proteinuria persists
 Gestational proteinuria
 New onset of proteinuria in pregnancy without other obvious features of PE
or primary renal disease
 3 possible outcomes
 No features of PE and proteinuria disappears postpartum
 Proteinuria turns out to be first sign of PE
 Proteinuria persists postpartum and signifies renal disease
 Recommended to monitor these patient more closely and assess proteinuria 3
months postpartum

20.  ISSHP 2018 stated the following for prediction of PE
 No 1st or 2nd trimester test or set of test can reliably predict the development
of all cases of PE
 Combination of maternal risk factors, BP, PIGF and uterine artery doppler
can select women who may benefit from aspirin
 Supports first trimester screening for PE although the cost effectiveness of
this approach remains to be established
 ISSHP 2018 recommends
 Women with established strong clinical risk factors for preeclampsia to be
treated with aspirin, ideally before 16 weeks but DEFINITELY before 20 weeks

21. ISSHP 2018
NICE 2010

22. NICE 2010

23.  Research questions
 Who – will benefit most from aspirin
 What – is optimal dosage of aspirin
 When to start aspirin
 When to take aspirin

24.  Aspirin is more effective in high risk women
 NNT 19 compared with women at moderate risk (NNT 119)
 What constitute high risk women
 On the basis of risk factors (as being used in NICE) – poor performance with
detection rate of preterm PE of 39% at a FPR of 10%
 ISSHP 2018 recommends
 Combination of maternal risk factors, BP, PIGF and uterine artery doppler can select
women who may benefit from aspirin
 Based on ASPRE study
 Cost effectiveness unknown

25.  Aspirin is more effective at higher dose
 1/3 of pregnant women are both resistant to the effects of 75 – 80 mg of
aspirin
 ISSHP 2018 and Malaysian CPG on Management of hypertension 2018
 Aspirin should be give at a dose of 100 – 150 mg/day
 Based on ASPRE study that demonstrated the use of 150 mg/day aspirin at
night reduced the incidence of preterm PE from 4.3% to 1.6% in aspirin group

26.  Aspirin is more effective when it is started before 16 weeks
 ISSHP 2018
 Aspirin to be started before 16 weeks and definitely before 20 weeks
 Possibly taken at night based on ASPRE study

27.  ISSHP 2018 (concurred with Malaysian CPG on Management of
hypertension)
 Calcium at the dose of at least 1g/day – reduce the likelihood of PE in women
with low calcium intake
 CAP trial – will further examine preventive benefits of calcium supplementation in
calcium-replete women
 Exercise (aerobic exercise for 50 min, 3x per week) – associated with reduced
gestational hypertension and PE
 Vitamin C and E are not recommended – increase the incidence of low birth
weight
 The role of Vitamin D is not proven

28. MODERATE RISK
(any TWO of the following)
1. Primigravida
2. 40 year-old and above
3. Pregnancy interval > 10 years
4. BMI > 30 at booking
5. Family history of pre-eclampsia
6. Multiple pregnancy
HIGH RISK
(any ONE of the following)
1.Hypertensive disease in previous pregnancy.
2.Chronic renal disease
3. Autoimmune disease such as SLE and APS
4. Chronic hypertension
5. Type 1 or 2 DM
Assessment at booking.
Identifying risk factor
for Pre-eclampsia
Start T. aspirin 100 – 150 mg OD after 12 weeks. Preferably
before 16/52 but definitely before 20 weeks; taken at night
Start T. calcium carbonate 1g bd from 20 weeks.
May be still beneficial if started from up to 34 weeks.

29.  Start treatment when BP ≥
150/100 regardless of type of
hypertension in pregnancy
 Target BP < 150/80 – 100
NICE 2010
 Start treatment when BP ≥
140/90 regardless of type of
hypertension in pregnancy
 Target BP < 160/85
(According to CHIPS trial)
 Antihypertensive should be
reduced if DBP < 80
ISSHP 2018

30.  CHIPS Trial
 Control of Hypertension In Pregnancy Study

31.  CHIPS Trial
 Control of Hypertension In Pregnancy Study
 Compare outcome of less-tight control (target DBP 100 mmHg) and tight
control (target DBP 85 mmHg)
 987 women; 75% had pre-existing hypertension; 25% with gestational
hypertension; 50% developed PE
 Similar primary outcome – pregnancy loss or high-level neonatal care
 Severe hypertension (≥ 160/110) developed in 40.6% of women in the less-tight
control group vs 27.5% in tight-control group (p<0.001)
 Acceptable oral antihypertensive: labetalol, methyldopa, nifedipine;
prazocin and hydralazine as second and third line

32. Antihypertensive
agents
Dosage Remarks
Methyldopa 250 – 500 mg twice daily – four times/day
(max dosage – 3000 mg/day; however in view of
potential side effects with higher dose, it is advisable to
give a total dose of 2000 mg/day).
Potential side effects include
depression, hepatitis, positive direct
Coombs test
Labetalol 100 – 400 mg twice daily to four times/day
(usual dose 1200 mg/day; max dose 2400 mg/day)
*in cases where BP is uncontrolled with usual dose of
1200mg/day, discussion should be made with specialist
to increase the dose to max of 2400mg/day
Contraindicated in women with
bronchial asthma, congestive cardiac
failure or heart block
Nifedipine 10 mg three times daily
(max dose is 60 mg/day)
*in cases where BP is uncontrolled with usual dose of 10
mg 3 times daily,, discussion should be made with
specialist to increase the dose to max of 60mg/day
Side effects include maternal
hypotension, tachycardia and
headache

33.  BP monitoring (HBPM as adjunct to monitoring in clinic)
 Monitor for Preeclampsia – urinalysis every visit
 Fetal monitoring – serial ultrasound from 26 weeks onwards; at 4 weeks
interval or 2 weeks interval if there is growth abnormality
 Timing of delivery depends on types of hypertension in pregnancy,
maternal or fetal compromise

34.  SBP ≥ 160 or DBP ≥ 110; surrogate marker for the risk of stroke; reflection of
increased severity of the overall condition of PE; associated with adverse
outcome for both mother and baby
 MAP is not part of definition of severe hypertension – no clinical studies to
relate MAP levels to risk and outcome
 General principles of management of severe hypertension:
 Control of blood pressure
 Prevention/control of eclampsia
 Maternal and fetal monitoring
 Fluid management
 Delivery

35.  The major considerations in controlling blood:
 Oral Nifedipine and parenteral Labetalol are the agents of choice when
BP is  160/110 mmHg as both are equally effective.
 However, when systolic blood pressure is  180 mmHg, it is a medical emergency in
which blood pressure should be controlled more rapidly with parenteral
antihypertensive agents.
 Parenteral hydralazine is an option when labetolol is contraindicated or fails to control
BP.
 Intravenous Glyceryl trinitrate (GTN) can be considered in case of resistant
hypertension.

36.  The goal of blood pressure control - non-severe level instead of
normalization of blood pressure.
 Therefore, target BP should be 140 – 159/90 – 109 mmHg.
 Overzealous control of BP should be avoided as to avoid maternal
hypotension and thus, causing compromise in uteroplacental
perfusion.
 Close fetal monitoring is recommended while trying to control the BP.
 continuous CTG monitoring or if the gestation is less than 28 weeks, fetal
heart rate should be checked at 5 – 10 minutes interval with daptone.
 Algorithm of BP control in severe hypertension

37. 1 vial IV Labetalol contains 25mg/5mls
(1ml = 5 mg IV Labetalol)
Side effects of IV labetalol
Maternal bradycardia
Fetal bradycardia
Contraindications of IV labetalol
Bronchial asthma
Congestive heart failure
Heart block

38. Bolus dose IV Labetalol
Indications BP  160/110 mmHg
Preparation Dilution is not necessary; Use pure form with concentration of 5 mg/ml
Bolus dose (s)  1st dose – 25 mg (5 ml); given in 2 minutes
 2nd dose – 50 mg; given in 2 minutes if BP is  160/110 mmHg 30 minutes after
the 1st bolus
 *3rd dose – 50 mg may be given if SBP is  180 mmHg 30 minutes after the 2nd
bolus and rapid BP controlled is desired
*In hypertensive emergency (SBP  180 mmHg) or in situation where rapid BP controlled is desired,
3rd bolus dose of intravenous labetalol may be given at the discretion of managing specialist.

39. Infusion
dose
IV Labetalol
Indication BP  160/110 mmHg after 2 or 3 boluses of intravenous labetalol
Preparation Dilution is not necessary
Withdraw 10 vials (total of 250 mg) into 50 cc syringe
Titration  Starting dose is 20 mg/H (4 ml/H)
 Titration should be done every 30 minutes to achieve target BP
 Titration of dose:
o 20 mg/H (4 ml/H) 40 mg/H (8 ml/H) 80 mg/H (16 ml/H) 160
mg/H (32 ml/H)
 Target BP: 140 – 150/90 – 109 mmHg
 Maintain the dose if target BP is achieved
 Titrate down the dose if BP is < target BP

40. 1 vial IV hydralazine contains
20mg/1 ml
Side effects of IV Hydralazine
maternal hypotension
maternal tachycardia
headache and dizziness

41. Bolus dose IV Hydralazine
Indications BP  160/110 mmHg when parenteral Labetalol is contraindicated or parenteral
Labetalol fails to control BP
Preparation Withdraw 1 ampoule (20 mg) of hydralazine + 19 ml of normal saline = 20 mg/20 ml
(1 mg/ml)
Bolus dose (s)  1st dose – 5 mg (5 ml); given in 2 minutes
 2nd dose – 5 mg (5 ml); given in 2 minutes if BP is  160/110 mmHg 30 minutes
after the 1st bolus
 *3rd dose – 5 mg (5 ml) may be given if SBP is  180 mmHg 30 minutes after the
2nd bolus and rapid BP controlled is desired
*In hypertensive emergency (SBP  180 mmHg) or in situation where rapid BP controlled is desired,
3rd bolus dose of intravenous hydralazine may be given at the discretion of managing specialist.

42. Infusion dose IV Hydralazine
Indication BP  160/110 mmHg after 2 or 3 boluses of intravenous hydralazine
Preparation Withdraw 2 ampoules (40 mg) of hydralazine + 38 ml of normal saline = 40 mg/40 ml (1
mg/ml)
Titration  Starting dose is 1 mg/H (1 ml/H)
 Titration should be done at the rate of 1 mg/H (1 ml/H) every 30 minutes up to
maximum rate of 10 mg/H (10 ml/H) to achieve target BP
 Target BP: 140 – 150/90 – 109 mmHg
 Maintain the dose if target BP is achieved
 Titrate down the dose if BP is < target BP
Hydralazine should be considered if BP is uncontrolled after infusion of IV labetalol at
maximum rate of 160 mg/H (32 ml/H)

43.  Magnesium sulphate (MgSO4) – agent of choice
 Associated with almost 50% risk reduction
Indications for Magnesium Sulphate:
1. Eclampsia (as treatment to control seizure)
2. In severe pre-eclampsia as defined by the following (after discussion with O&G specialist):
3. Severe hypertension associated with any of the following;
 Significant proteinuria of ≥ 2+
 Symptoms of impending eclampsia: headache, blurring of vision, epigastric pain, nausea or
vomiting
 Complications from severe pre-eclampsia: HELLP syndrome, acute pulmonary oedema,
placenta abruption, intrauterine death
4. As fetal neuroprotection for woman whose delivery is indicated at ≤ 32 weeks

44. 1 vial MgSO4 contains 2.47g/5ml
(1g MgSO4 = 2 ml MgSO4)
Can be given intravenously or
intramuscularly

45. Loading dose Maintenance dose
Infusion pump Syringe pump
Dose 4g 1g/H 1g/H
Preparation 8ml (4g) of MgSO4 +
12 ml of NS = 20 ml
50ml (24.7g) of MgSO4 +
450ml NS
10ml (5g) of MgSO4 + 40
ml of NS
Administration Give 4g MgSO4 in
slow bolus for15 – 20
min
21ml/H (1g/H) 10ml/H (1g/H)
In cases where seizure occurs after administration of MgSO4, a further bolus of 2 – 4 g MgSO4 can be
given with close monitoring of Mg level. Serum magnesium can be taken before the repeated bolus

46. Loading dose Maintenance dose
Dose Total 10g (5g each buttock) 5g every 4 H in alternate buttock
Preparation 10ml (5g) of MgSO4 + 1 ml of local
anaesthesia = 11 ml
10ml (5g) of MgSO4 + 1 ml of local
anaesthesia = 11 ml
Administration IM injection in each buttock IM injection into alternate buttock every 4
hourly
In cases where seizure occurs after administration of MgSO4, a further bolus of 2 – 4 g MgSO4 can be
given with close monitoring of Mg level. Serum magnesium can be taken before the repeated bolus
MgSO4 if the situation allows.

47. Parameters Interval of monitoring Target
Blood Pressure 15 minutes 140 – 150/90 – 109 mmHg
Pulse rate 15 minutes  60 bpm
Respiratory rate Hourly  16 breaths per minute
Urine output Hourly  30 ml/H or  100 ml/4 hours
Deep tendon reflex of
knee
Hourly Presence of reflexes
*Monitoring of magnesium level is NOT routine in women receiving MgSO4.
However, if there is suspicion of magnesium toxicity, the Mg level should be checked

48. Loss of deep tendon (patella) reflex
Respiratory rate - <16 breaths per min
Pulse rate - <60 bpm
STOP MGSO4; CHECK MG LEVEL; MAY RESUME MGSO4 IF MG
LEVEL IS NORMAL OR REFLEXES RETURN

49. Cardiorespiratory arrest
 STOP MgSO4 immediately
 Resuscitation – DR ABC; intubation and ventilation
 Intravenous calcium gluconate as antidote
10% Calcium Gluconate 10ml IV over 10 minutes

50. Urine output < 100 ml/4H @ < 30 ml/H
Reduced urine output is NOT a sign of MgS04
toxicity
Assessment – hydration status, serum BUSE/creat,
serum Mg level (if available)
Check reflexes and respiratory rate to ensure no
signs of toxicity

51. Urine output < 100 ml/4H @ < 30 ml/H
 If serum creatinine is normal and Mg level is within therapeutic range then
continue MgSO4 at 1 g/H.
 If serum creatinine is normal and Mg level is raised above therapeutic range,
reduce the dose by half to 0.5 g/H
 If serum creatinine is raised or serum Mg level is above the therapeutic range then
STOP the infusion
 If unable to do serum Mg level, reduce the maintenance dose to 0.5mg/H
 May consider fluid challenge with 500ml NS/H after discussion with
 Once urine output improves, the maintenance dose should be resumed at 1g/H

52.  Algorithm of management of severe hypertension

53.  Definition of hypertension – persistent BP ≥ 140/90 mmHg AT LEAST 15
minutes apart; especially BP ≥ 160/110 mmHg.
 Be aware of white coat hypertension, masked hypertension and transient
hypertension.
 Be familiar with conditions that define preeclampsia and the severe
features of preeclampsia
 Start T. Aspirin 100 – 150 mg/day; to be taken at night before 16 weeks (12
– 16 weeks); definitely before 20 weeks; T calcium lactate 1 g BD from
20 weeks onwards.

54.  Start antihypertensive when BP persistently ≥ 140/90 mmHg with target
BP <160/80 – 85 mmHg
 There’s urgency to reduce BP of ≥ 160/110 mmHg to non-severe
hypertension.
 Be familiar with the suitable type of antihypertensives as well as the
dosage and dilution of drugs involved in the management of severe
hypertension

55. 1. NICE clinical guideline. Hypertension in pregnancy: the management of
hypertensive disorders during pregnancy. RCOG. The Royal College of
Midwives. 2011
2. Zahra Hoodbhoy. The FIGO textbook of pregnancy hypertension.
October 2016.
3. Brown et al. Hypertensive Disorders of Pregnancy: ISSHP Classification,
Diagnosis, and Management Recommendations for International
Practice. ISSHP.2018;72:24 – 43.
4. Malaysian Clinical Practice Guidelines: Management of hypertension.
5th Edition (2018)

56. 5. Rolnik et al. ASPRE trial: performance of screening for preterm
preeclampsia. Ultrasound Obstet Gynaecol 2017;50:492 – 495.
6. Rolnik et al. Aspirin versus Placebo in Pregnancies at High Risk for
Preterm Preeclampsia. N Engl J Med 2017;377:613 – 22.
7. Magee et al. Less-Tight versus Tight Control of Hypertension in
Pregnancy. N Engl J Med 2015;372:407 – 17.