Hypertension in Pregnancy

Question 1

Baseline % risk of PET in a well woman with no RFs

Answer 1

2-3% low risk multips

Question 2

Risk of PET with antiphosholipid syndrome

Answer 2

8x background risk. 2x9 = 18%

Question 3

Risk of PET with nulliparous women

Answer 3

3-5%

Question 4

List different classes of hypertension in pregnancy

Answer 4

Pre-existing hypertension (white coat, chronic, essential - when ruled out other causes)
Gestational hypertension
Pre-eclampsia

Question 5

Causes of pre-existing hypertension

Answer 5

White coat
Essential - no other cause found
Other medical - renal (renal artery stenosis, glomerulonephritis, polycystic kidneys), cardiac (aortic co-arctation), endocrine (hyperparathyroidism, cushing’s, conn’s, phaeochromocytoma)

Question 6

Investigations for other causes of hypertension (renal, cardiac, endocrine)

Answer 6

Renal - USS, creatinine U+Es, baseline PCR, urine for casts
Cardiac - echocardiogram, L and R arm BPs
Endocrine - hyperparathyroidism (parathyroid hormone, Ca, Phos), Cushing’s (cortisol - early morning/24h), Conn’s (renin/aldosterine ratio - affected by pregnancy however), Phaeo (plasma metanephrines)

Question 7

Definition of hypertension

Answer 7

Systolic BP equal/greater than 140 and/or diastolic BP equal/greater than 90, on 2 or more occasions at least 4h apart …. OR one episode of severe hypertension = systolic equal/greater than 160 or diastolic equal/greater than 110

Question 8

When should gestational HTN resolve by postpartum?

Answer 8

3 months - if elevated at this point then defined as chronic hypertension

Question 9

Can a women be hypertensive with PET 6 weeks postpartum?

Answer 9

Yes

Question 10

When should gestational HTN resolve by postpartum?

Answer 10

3 months - if elevated at this point then defined as chronic hypertension

Question 11

Definition of PET

Answer 11

Gestational HTN: and evidence of end organ dysfunction - haematological Hb Plt DIC, biochemical Creat/LFTs/proteinuria/oliguria, neurological eclampsia/stroke, placental SGA/IUGR/abruption

Pre-existing HTN: and TWO other criteria of end-organ dysfunction

Question 12

Visual/neurological symptoms of PET, and where in the brain does this affect?

Answer 12

Altered mental status, photopsia, persistent visual
scotomata, cortical blindness, retinal vasospasm

Occipital lobe

Question 13

Pre-existing HTN risks

Answer 13

PET - 25%, 46% if severe HTN

Preterm delivery - 15% if no PET, 50% if PET

SGA - 27% if not PET, 48% if PET

CS - 44% if no PET, 70% if PET
Placental abruption

Question 14

Gestational HTN - risk of PET if diagnosed at <30 weeks vs at 38 weeks

Answer 14

a) 40% vs b) 7%

Question 15

Risk factors for PET

Answer 15

Age > 40 - 2 x
BMI > 30 - 2 x
Family history - 3 x
Primip - 2-3 x
Multiple pregnancy -32 x
Previous PET - 7 x
Long birth interval - 2-3 x if > 10 years

Pre-existing HTN , renal disease, diabetes, antiphospholipid syndrome
(10x), connective tissue disease, sickle cell disease

Question 16

Rare presentations of PET <20 weeks include

Answer 16

Consider if hydatidiform mole, tripoloidy,

multiple pregnancy, severe renal disease or antiphospholipid syndrome

Question 17

Timing of eclampsia (ante/intra/postpartum)

Answer 17

Antepartum (45%), intrapartum (20%), postpartum (35%).

Only 1/3 of women with eclampsia have a diagnosis of PET preceding eclapsia

40% of eclamptic fits are after delivery!

Note treat all pregnant women with seizures as though they have eclampsia, however remember it is not the most common cause of seizures

Question 18

Other differentials for a seizure/possible eclamptic fit in a pregnant woman

Answer 18

Epilepsy, pseudoseizure, stroke, intracranial bleed (burst aneurysm, or post assault) intracranial mass, severe electrolyte disturbance (e.g. hyponatraemia)

Question 19

Methyldopa - max dose, onset of action, side effects and contraindications

Answer 19

750mg QID (3g/day), 6h onset, drowsiness and low mood, contraindications depression/concurrent MAOI use/postpartum

Question 20

Labetalol - max dose, onset/peak effect, side effects and contraindications

Answer 20

Varies - 300mg QID, 400mg QID, up to maximum of 2.4g/day - however recommend not to max out to prevent saturation of beta receptors.
Peak effect 2-4h.
SE bronchospasm. Beware in brittle asthma, Raynaud’s disease, phaeo

Question 21

Nifedipine - max dose, onset/peak effect, side effects and contraindications

Answer 21

30mg BD. Long acting onset 3-4h, short acting 30-45 min.
SE - headache
Contraindications/cautions - worsening pre-existing headaches, short acting can cause large drops in BP - recommend to be on CTG

Question 22

Prazosin - max dose, onset/peak effect, side effects and contraindications

Answer 22

4th line - consult with obs med. Start at 0.5mg daily/nocte. Can cause abrupt drop in BP esp postural, sx dizziness

Question 23

IV labetalol - dose, onset of action, repeat dosing

Answer 23

Labetalol - 20mg IV as a bolus over 2 min, 5 min maximal onset of action

Repeat 15 mins. If still > 160/110,
given 40mg IV
Repeat in 15 mins. If still > 160/110, give 80mg IV over 2 mins.

Max 300mg.

Infusion 20-160mg/hr.

Give in ED/HDU/MCA setting, not on ward. Consider arterial line

Question 24

IV hydralazine - dose, onset of action, repeat dosing

Answer 24

5-10mg IV bolus over 3-10min, onset of action 20 min. Repeat every 20 mins if BP remains >160/110. Max 30mg

Give in ED/HDU/MCA setting, not on ward. Consider arterial line

Question 25

Why are ACE-i contraindicated in pregnancy

Answer 25

Second and third trimester - oligohydramnios, renal failure, bony malformations

Question 26

Is an eclamptic fit an indication for immediate delivery?

Answer 26

NO Stabilise the mother (MgSO4, transfer to MCCA/HDU, antihypertensives, bloods) Stabilise the baby (steroids if preterm, MgSO4 if <30 weeks) Discuss with the Obstetric and Obs Med SMOs re: timing of delivery Remember to consider other differentials for seizure

Question 27

MgSO4 dosage

Answer 27

Loading: 4g IV over 20 mins Then infusion 1g/hr (0.5mg/hr in AKI/CKD) for 24h after delivery or after the last seizure, whichever is later. If undelivered or stable after 24h, SMO review if there is still potential for delivery If recurrent seizure given another 2g loading

Question 28

MgSO4 monitoring and antidote

Answer 28

Hourly: UO, BP, HR, reflexes If signs of toxicity: low RR, reduced/absent reflexes, N+V/flushing - send off Mg levels MgSO4 can cause reduced variability on CTG as well Antidote: calcium gluconate 10% - 1g/10mL). Give 10 mL over 10 minutes

Question 29

MgSO4 risk reduction of cerebral palsy for the fetus if <30 weeks

Answer 29

Reduces risk of cerebral | palsy by 31% - RR 0.69.

Question 30

PET <24 weeks - risks of maternal and fetal morbidity/mortality

Answer 30

Discuss TOP | Maternal morbidity 70%, perinatal mortality 80%

Question 31

PET <34 weeks, rates of serious morbidity

Answer 31

25-40% of those managed expectantly will develop severe morbidity (HELLP, abruption, pulmonary oedema, eclampsia)

Question 32

HYPITAT II study - multi centre, unblinded, randomised trial comparing immediate delivery vs expectant management with non severe hypertensive disorders 34-37 weeks gestation

Answer 32

Immediate delivery - reduced incidence of composite maternal morbidity (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death) RR 0.36 but significant increase in neonatal RDS therefore aim for expectant management Follow up study - poorer neurodevelopment outcomes in those with immediate delivery at 2 years but not at 5 years.

Question 33

Should you deliver if a woman has severe PET <36 weeks? Y/N

Answer 33

Yes if maternal deterioration/fetal deterioration, i.e. risks>benefits for expectant management

Question 34

Hypertension in absence of PET - timing of delivery

Answer 34

aim for delivery > 37 weeks, consider | up to 39 weeks if mild and well controlled

Question 35

What do you consider giving if fibrinogen levels are low

Answer 35

Cryoprecipitate

Question 36

Thrombocytopenia in PET - at what level is the risk of PPH increased for delivery?

Answer 36

Not until <50. However anaesthetics would not put in an epidural if <80 Consider platelet transfusion at time of CS or in case of PPH, haematoma, wound bleeding etc

Question 37

Why is regional anaesthesia (if possible) more preferable to GA for severe PET?

Answer 37

Severe HTN usually accompanies intubation - can cause MI, cerebral haemorrhage, pulmonary oedema HOWEVER - GA may be indicated if severe fetal compromise, pulmonary oedema, maternal haemodynamic instability, coagulopathy, severe thrombocytopenia, post eclamptic seizure if persistent neurological deficit

Question 38

What analgesia drug should you withold/use with caution in women with severe PET/those who have had eclampsia?

Answer 38

TRAMADOL - lowers seizure threshold

Question 39

Diazepam dose with eclampsia if prolonged? While MgSO4 being prepared?

Answer 39

Consider IV diazepam 2mg/min to max of 10mg PR for status epilepticus - 10mg PR

Question 40

Risk of recurrent seizure despite MgS04?

Answer 40

10-15%, also control BP - threshold is lower for further seizures after eclampsia

Question 41

Why does BP spike on day 3-6 postpartum?

Answer 41

Previously normotensive women can become transiently hypertensive due to vasomotor instability as non pregnancy vasoregulation is re-established.

Question 42

Pathophysiology - effect of low dose aspirin in preventing PET

Answer 42

Inhibits platelet cycle-oxygensase and TXA2 synthesis, reducing platelet aggregation and dilating blood vessels. Anti-inflammatory effect may also be useful

Question 43

LDA timing of starting and stopping

Answer 43

12-16 weeks ideally, up to 20 weeks. 100mg nocte. 1x trial suggesting increased risk of abruption/mc if taking <12 weeks however not backed up by other studies Stop at 36/40 - studies have not shown benefit at term (effective at preventing preterm PET), also increases bleeding risk if labours

Question 44

Calcium supplementation - indications and dosage

Answer 44

1g elemental Ca daily. Supplement if low levels of dietary calcium - 2-3 servings a day. Until delivery Calcium carbonate 1.25g (500mg elemental ca) = 2 tab a day

Question 45

Renal patients - aim for BP readings of?

Answer 45

130/80

Question 46

PET - yearly check ups with GP for what?

Answer 46

CVD assessment, BP, weight, discuss lifestyle changes e.g. wt loss, smoking cessation. 5 yearly bloods - HbA1c, lipids

Question 47

How does calcium supplementation help to prevent PET?

Answer 47

reducing PTH and renin release, reducing intracellular calcium in vascular smooth muscle, reducing smooth muscle contractility and vasoconstriction

Question 48

Is low vitamin D a risk factor for PET? Dosage?

Answer 48

Yes. Only check levels in those at risk of deficiency (eg Hijab wearing) - don’t retest once commenced treatment. Rx - cholecalciferol 1.25mg monthly for mild-mod deficiency. If severe 1.25mg for 10 days then once monthly

Question 49

Relative risk of developing PET pre-existing conditions: Andrea Patted A Rather Cute Happy Dandy Elephant

Answer 49

``` Antiphospholipid syndrome/SLE = 9 Prev PET = 7 ART = 4 Renal disease = 4 Chronic HTN = 3.6 prev HELLP = 3.7 Diabetes = 3.5 Ethnicity = 3 african, 2.5 indian ```

Question 50

Risk ratio: future risks with next pregnancy of 1) Gest HTN 2) PET 3) Chronic HTN Does the risk change depending on whether you had gest HTN or PET this preg?

Answer 50

Gest HTN in future preg - OR 3 if gest HTN this preg; 6 if PET this preg PET future preg - OR 7 whether gest HTN or PET this preg Chronic HTN outside preg - OR 3

Question 51

Contraindications to MgSO4

Answer 51

Hepatic failure, myasthenia gravis, severe renal failure, cardiac ischemia, heart block and pulmonary edema

Question 52

Magpie trial: purpose, type of trial, number of participants, location, years

Answer 52

To find out if women with PET and their babies benefited from MgSO4 Randomised double blinded RCT - 10,141 women in 33 countries, 1998-2001

Question 53

MAGPIE eligibility, exclusions

Answer 53

Eligibility: all women with PET, uncertainty about whether or not to give MgSO4, antepartum or within 24h of delivery Excluded: MgSO4 hypersensitivity, liver and renal failure, myasthenia gravis

Question 54

MAGPIE primary outcomes results

Answer 54

Primary maternal: decreased risk of eclampsia RR 0.58 - 0.8% in Mg group vs 1.9% in placebo group. NNT=91. Effect consistent regardless of gestations, severity of PET, previous anti-convulsant use, ante/postnatal, parity Primary fetal: no change in rates of perinatal death (incl. at discharge)

Question 55

MAGPIE secondary outcomes

Answer 55

- Serious maternal morbidity – resp depression or arrest, liver/renal failure, cerebral haemorrhage, coagulopathy - MgSO4 toxicity or side effects – need for calcium gluconate, SE’s - Neonatal morbidity/mortality – apgars, intubation, abnormal USS, convulsions, SCBU admission. - Labour and delivery complications – length of IOL, CS, retained placenta, transfusion, gestation - Use of healthcare resources – days of stay, ICU admit, ventilation, dialysis

Question 56

MAGPIE secondary outcomes results

Answer 56

Increased Side Effects reported from Mg group (25% v 5% - Blinding maybe influenced by degree of side effects) IV Mg may be more effected than IM, however not randomised and was at the discretion of the treating team, interpret with care No clear differences between maternal morbidity or composite outcomes, but the trend in decreased maternal mortality favoured MgSO4 group. - No differences in use of healthcare resources, pregnancy outcomes/labour/delivery except lower risk of abruption in MgSO4 group. - No evidence to support MgSO4 as tocolytic or antihypertensive, no evidence that hypotension occurred in women with Mgs04 and nifedipine. - Most maternal deaths were from organ dysfunction as a consequence of severe PET rather than eclampsia. ??suggesting MgSO4 may have more widespread systemic benefits

Question 57

MAGPIE summary

Answer 57

MgSO4 reduces the risk of eclampsia, and may also reduce the risk of maternal death from pre-eclampsia. At the dosage used in this trial there are no significant harmful effects on the mother or child, although 25% of women experience side-effects.

Question 58

HYPITAT 1 - type of study, year, countries, aim of study

Answer 58

Multicentre open-label RCT Published 2009 Whether IOL vs expectant management for gestational HTN or mild PET reduces severe maternal morbidity - evidence for this was scarce

Question 59

HYPITAT I | - Inclusion criteria

Answer 59

INCLUSION 36-41 weeks gestation Singleton fetus Cephalic presentation Gestational HTN with DBP >/= 95 on two occasions at least 6 hours apart PET with DBP >/= 90 on two occasions at least 6 hours apart with proteinuria

Question 60

HYPITAT I - Exclusion criteria

Answer 60

Severe hypertension - BP >/= 170/110 - Severe PET with protein >5g/24 hour (PCR 500) - HELLP - oliguria - Pulmonary oedema - Cyanosis - IV antihypertensives Maternal medical - Pre-existing HTN on meds - Previous caesarean section - DM on insulin - Renal failure, heart disease - HIV Fetal - Congenital abnormality - Suspected IUGR - Abnormal CTG

Question 61

HYPITAT intervention - randomised to IOL or expectant management

Answer 61

756 women in the Netherlands IOL: Start within 24 hours (If BS > 6 – ARM, if BS41 weeks.

Question 62

HYPITAT I - primary outcomes

Answer 62

Composite measure of poor maternal outcomes - death - morbidity - eclampsia - HELLP - pulmonary oedema - VTE - abruption - progression to severe disease - BP >/=170/110 - proteinuria >5g - major PPH (>1,000ml)

Question 63

HYPITAT I - primary outcomes results

Answer 63

Primary maternal composite RR 0.79 in induction group, NNT 8. Mainly by preventing progression to severe disease Progression to severe disease: 23% intervention group, 36% expectant groups RR 0.64 Significantly less antihypertensive use in IOL group Beneficial effect of IOL not present at < 37 weeks (however unreliable as low numbers, not powered to detect significant differences) No difference in PPH

Question 64

HYPITAT I - secondary outcomes and results

Answer 64

Method of delivery Neonatal morbidity and mortality CS rates lower in intervention group, but not significant No difference in instrumental deliveries No difference in composite neonatal outcomes. Significantly lower birthweight in IOL group (understandable as earlier gestation)

Question 65

HYPITAT - final conclusion

Answer 65

Induction of labour recommended for women with gestational hypertension and mild PET at term (>37 weeks) to reduce poor maternal outcome, with no increase in caesarean section rate or neonatal outcomes.

Question 66

HYPITAT I - limitations

Answer 66

- Does not follow WHO criteria for gest HTN or PET - Cross contamination of groups - 50% in expectant management were induced and 30% of these were for maternal request - Progression to severe disease was only single measurement of high BP resulting in broad criteria for primary outcome - Not powered to determine individual maternal outcomes (e.g eclampsia) - No long term follow up - Not clear benefit on neonatal or maternal mortality or morbidity as outcomes measures not associated with worse health outcomes really.