Gestational Hypertension and PET

Question 1

Definition of gestational hypertension

Answer 1

New onset hypertension (>140/90 mmHg) presenting after 20 weeks of pregnancy without significant proteinuria

Question 2

Incidence and prognosis of GIH

Answer 2

• Incidence: 5-7% of pregnancies
• NOT associated with adverse pregnancy outcomes (aside from risk of developing pre-eclampsia)
• 1/3 of women with GIH will develop pre-eclampsia
• Generally resolves around 1 month following birth

Question 3

Risk factors for GIH which require additional assessment

Answer 3

• Nulliparity, age 40 years or over, pregnancy interval of more than 10 years, FHx of pre-eclampsia, multi-foetal pregnancy, BMI> 35Kg/m2, Hx of PIT or GET, pre-existing vascular or renal disease

Question 4

Management of hypertension of140/90-159/59 mmHg

Answer 4

• DO NOT routinely admit to hospital
• Offer pharmacological treatment if BP remains above 140/90mmHg
• Aim for BP of 135/85 or less
• Perform once or twice weekly BP and once or twice weekly proteinuria
• Measure full blood count, liver function and renal function at presentation and then weekly
• Do Placental Growth Factor (PIGF) testing on one occasion if suspicion of pre-eclampsia
• Offer fetal heart auscultation at every antenatal appointment Carry out ultrasound assessment of the fetus at diagnosis and, if normal, repeat every 2 to 4 weeks

Question 5

Management of severe hypertension (>160 mmHg)

Answer 5

• Admit, but if BP falls below 160/ 110 mmHg then manage as for hypertension
• Offer pharmacological treatment to all women
• Aim for BP < 135/85
• Perform BP monitoring every 15-30 minutes until BP < 160/110 and daily proteinuria testing whilst admitted
• Measure full blood count, liver function and renal function at presentation and then weekly
• Carry out PIGF testing on one occasion
• Same foetal monitoring

Question 6

What antihypertensives can be considered in pregnancy

Answer 6

Consider labetalol (CONTRAINDICATED IN ASTHMA) to treat PI, Consider nifedipine if unsuitable and methyldopa third line

Question 7

How is timing of birth affected by gestational HTN

Answer 7

• DO NOT offer planned early birth before 37 weeks to women with gestational HTN whose BP is lower than 160/110 mmHg, unless there are other medical indications
• After 37 weeks, indications for birth should be discussed with a senior obstetrician

Indications for planned early birth before 37 weeks (add a course of magnesium sulphate or corticosteroids if indicated):
* Inability to control maternal BP despite using 3 or more classes of antihypertensives
* Maternal Sp02 < 90%
* Progressive deterioration in liver function, renal function, haemolysis or platelet count
* Neurological features
* Placenta abruption
* Reversed end-diastolic flow in the umbilical artery doppler, non-reassuring CTG

Question 8

Postnatal management of gestational HTN

Answer 8

• Measure BP: daily for the first 2 days after birth, at least once between day 3 and day 6 after birth, then as clinically indicated if antihypertensive treatment is changed after birth.
• Continue antihypertensive treatment if required (duration will usually be similar to antenatal treatment, but may be prolonged)
• Reduce antihypertensives if BP falls below 130/80
• Stop methyldopa within 2 days after birth and change to an alternative treatment if necessary
• Should have a medical review with the GP or specialist 2 weeks after transfer if they remain on antihypertensives and after 6-8 weeks for all others.

Question 9

Definition of pre-eclampsia

Answer 9

New-onset hypertension of more than 140/90mmHg occurring after 20 weeks gestation, with proteinuria (1+ on urine dipstick and protein:creatinine ratio >30mg/mol or albumin:creatinine ratio >8mg/mmol)
* OR other maternal organ dysfunction- renal insufficiency, liver involvement, neurological complications such as eclampsia, haematological complications (e.g thrombocytopenia)

Question 10

Definition of severe PET

Answer 10

• Severe pre-eclampsia= Pre-eclampsia with severe hypertension that does not respond to treatment or is associated with ongoing or recurring symptoms (or biochemical evidence)

Question 11

Incidence of pre-eclampsia

Answer 11

Occurs in 2-3% of pregnancies

Question 12

PAthophysiology of pre-eclampsia

Answer 12

• Caused by failure of normal invasion of trophoblast cells, leading to maladaption of maternal spiral arteries
• Pre-eclampsia can occur in pregnancies lacking a foetus (molar pregnancies) and in the absence of uterus (abdominal pregnancies)- suggesting that trophoblast tissue provides the stimulus for the disorder
• When the blastocyst implants into the endometrium, the outermost layer, called the syncytiotrophoblast grows into the endometrium
• The synctiotrophoblast forms finger-like projections called chorionic villi- contain foetal blood vessels
• Trophoblast invasion of the endometrium sends signals to the spiral arteries in that area of the endometrium, reducing their vascular resistance and making them more fragile
• Blood flow increases in these arteries, until they break down and leave pools of blood- lacunae
• Maternal blood flows from the uterine arteries, into these lacunae, and back out through the uterine veins. Lacunae form at around 20 weeks gestation
• In normal pregnancy, the spiral arteries dilate to 5-10x their normal size, in pre-eclampsia, these arteries become fibrous causing them to narrow
• This causes high vascular resistance in the spiral arteries and subsequently poor perfusion of the placenta-> uteroplacental ischaemia
• Uteroplacental ischaemia results in oxidative and inflammatory stress-> release of pro-inflammatory cytokines into systemic circulation
• Leads to endothelial dysfunction, vasospasm and activation of the coagulation system

Question 13

What are the three key pathological processes which occur in PET

Answer 13

• Vasospasm-> reduced blood flow to various organs (multi-organ dysfunction)
• Endothelial injury/ coagulation-> formation of thrombi in microvasculature
• Endothelial injury-> increased vascular permeability, peripheral, pulmonary and cerebral oedema (worsened by proteinuria)

Question 14

Examples of organ dysfunction resulting from PET

Answer 14

• Retina- reduced blood flow leads to blurred vision, flashing lights scotoma development
• CV system- marked peripheral vasoconstriction resulting in hypertension (in contrast to normal marked peripheral vasodilation, increased plasma volume and HR)
• Renal system- reduced blood flow to kidney-> glomerular damage + oligouria + proteinuria. Leads to a lesion called glomeruloendotheliosis- associated with impaired GFR and selective protein loss
• Haematological- increased fibrin deposition and a reduced platelet count-> at risk of haemorrhage
• Liver- reduced blood flow can cause liver injury- rise in enzymes- RUQ pain or epigastric pain (symptoms of severe pre-eclampsia). Thrombi build up in vasculature (associated with increase in liver enzymes)
• Neurological- may develop eclampsia-> presence of tonic-clonic convulsions in a woman with pre-eclampsia and in the absence of any other cause (likely due to vasospasm and cerebral oedema)
• FETAL COMPLICATIONS- prematurity, IUGR, oligohydramnios (placental insufficicency)

Question 15

What is HELLP syndrome, how common is it

Answer 15

Haemolysis with elevated liver enzymes and low platelets’ A particularly severe form of pre-eclampsia- presents with RUQ/ epigastric pain, nausea and vomiting, lethargy
* Haemolysis
* Elevated liver enzymes
* Low platelets

• Develops in 10-20% of people with pre-eclampsia and generally occurs at 27-37 weeks of gestation

Question 16

How can HELLP syndrome be diagnosed

Answer 16

• Liver transaminases> 70IU/L
• Serum LDH > 600IU/L
• Platelet count < 100x109/L
• Evidence of haemolysis (raised bilirubin/ raised LDH and AST/ blood smear/ haematuria)
• Severity calculated using the Martin/Mississippi classification

Question 17

Complications of HELLP syndrome

Answer 17

Acute renal failure, placental abruption and stillbirth

Question 18

Management of HELLP syndrome

Answer 18

• Urgent induction of delivery +/- dexamethasone for lung maturation (not indicated in management of maternal disease)
• Magnesium sulphate could be considered for seizure prophylaxis
• If induction not favourable, may continue with conservative management (treatment of PET)

Question 19

Risk factors for pre-eclampsia

Answer 19

High risk:
* Pre-existing hypertension
* Previous PIH (pregnancy induced hypertension)
* Existing autoimmune conditions (e.g SLE)
* Diabetes
* CKD

Moderate risk:
* First pregnancy (nulliparous)
* Aged 40 years or older (advanced maternal age)
* Pregnancy interval of more than 10 years
* BMI> 35kg/m2 on first presentation
* Multi-foetal pregnancy

Question 20

How can pre-eclampsia be prevented

Answer 20

Women with one high risk factor or more than 1 moderate risk factor should be offered 75-150mg aspirin from week 12 until the birth of the baby.
* Aspirin causes remodelling of the spiral arteries and hence should be offered as early as possible (will have no effect if started too late)

BP and urinalysis should be performed at each antenatal visit to screen for pre-eclampsia

Question 21

Presentation of pre-eclampsia

Answer 21

• Severe frontal headache
• Problems with vision, such as blurring or flashing before the eyes
• Severe epigastric or upper abdominal pain
• Nausea and vomiting
• Sudden swelling of the face, hands or feet
• Symptoms of HELLP- RUQ pain, nausea and vomiting, lethargy

Signs include: oedema (oedema of feet common in pregnancy, but this will be rapidly progressing and involve the hands), reduced urine output, brisk reflexes, HTN, papilledema

Question 22

Investigations for pre-eclampsia

Answer 22

Full clinical examination should be carried out at each antenatal appointment for women with pre-eclampsia- offer hospital admission if:
* SBP of 160 mHg or higher, signs of impending eclampsia, pulmonary oedema, fetal compromise, biochemical cause for concern

Assessment should be conducted using validated risk prediction models:
* fullPIERS- intended for use at any time in pregnancy
* PREP-S- intended for use only up to 34 weeks
* These models do not predict outcomes for babies
* Urinalysis for proteinuria
* FBC (look for platelets + haemolysis for HELLP), LFTs (will be elevated), serum creatinine (may be elevated
* CTG+ foetal ultrasound (foetal growth, amniotic fluid assessment)

Question 23

Antenatal management of PET

Answer 23

• The ‘ultimate treatment’ is delivery of the foetus and placenta- however, may not completely resolve in some cases
• (Consider admission)
• Offer labetalol to treat hypertension. Offer nifedipine for women in whom labetalol is not suitable and methyldopa 3rd line.
• Base the choice on any pre-existing treatment, side-effect profiles, risks (including fetal effects) and the woman’s preference
• Should be offered if BP remains above 140/90 mmHg
• Aim for BP of 135/85 mmHg or less (should be measured every 48hrs unless >160- then 4x daily whist the woman is an inpatient
• Bloods (FBC, LFTs, U&Es) should be taken 2x per week
• Consider IV magnesium sulphate in women with features of severe preeclampsia if birth is planned within 24 hours (to prevent eclampsia)

Question 24

Intrapartum management of PET

Answer 24

Record maternal and foetal thresholds for planned early birth before 37 weeks
* Involve senior obstetrician on timing of birth
* Offer IV magnesium sulphate and a short course of antenatal corticosteroids if indicated
* Before 34 weeks: Continue surveillance unless there are indications for early birth (offer IV magnesium sulphate and corticosteroids
* From 34-36+6 weeks: Continue surveillance unless there are indications (take into account the woman’s and baby’s condition, RF, availability of neonatal unit beds)
* 37 weeks onwards: Initiate birth within 24-48 hours
* Mode of delivery- mother’s choice
* During labour, measure BP hourly in women with HTN and every 15-30 until BP < 160/110 if severe (continue antihypertensive medication during labour)
* DO NOT preload women who have severe pre-eclampsia with IV fluid before epidural

Thresholds for early birth could include any of:
* Inability to control BP despite using 3 or more classes of antihypertensives
* Maternal SpO2 < 90%
* Progressive deterioration in liver function, renal function, haemolysis, or platelet count
* Neurological features
* Placental abruption
* Non-reassuring CTG, umbilcal artery doppler

Question 25

Postnatal management of PET

Answer 25

• In women with pre-eclampsia who did not take antihypertensive treatment and have given birth, measure BP at least 4 times a day whilst an inpatient, at least once between day 3-5 after birth and on alternative days until normal
• Start anti-hypertensives if BP 150/100 mmHg or higher
• In women who took antihypertensive treatment and have given birth, measure BP at least 4 times per day as an inpatient and every 1-2 days for 2 weeks after transfer to community
• Continue anti-hypertensive Tx, consider reducing if BP falls below 140/90 mmHg (definitely if < 130/80)
• Stop methyldopa within 2 days after birth and consider an alternative
• Advise that treatment can be adapted to accommodate breastfeeding and that use of anti-HTN does not prevent them from doing so, BUT:
• The antihypertensive can be expressed in breastmilk in very small amounts (not clinically relevant)
• Consider monitoring of baby’s BP- SafetyNet for symptoms

Can discharge to community if:
* There are no symptoms of pre-eclampsia
* BP with or without treatment, is 150/100 mmHg or less
* Blood test results are stable or improving
* Measure platelet count, transaminases and serum creatinine 48–72 hours after birth or step-down
* If they remain on antihypertensives, need a GP or specialist review 2 weeks after transfer to community
* HTN in postnatal period- Enalapril or if black African or Caribbean- nifedipine/amlodipine (combination of enalapril and nifedipine 2nd line)
* All women with pre-eclampsia require GP or specialist review 6-8 weeks after birth (urine dip, BP)

Question 26

Maternal complications of pre-eclampsia

Answer 26

• Eclampsia- grand mal seizures
• Cerebrovascular haemorrhage- failure of cerebral blood flow autoregulation at MAP above 140 mmHg
• Liver and coagulation problems: HELLP syndrome, DIC, liver failure and liver rupture, Epigastric pain and haemolysis
• Renal failure
• Pulmonary oedema
• ARDS-> highest risk of maternal mortality
• Risk of recurrence of any hypertensive disorders in future pregnancy: 1 in 5 (risk of future pre-eclampsia 1 in 6)
• Risk of CVD- increased roughly 3x depending on type of CVD

Question 27

Foetal complications of PET

Answer 27

• Stillbirth- 5% of stillbirths are due to pre-eclampsia
• Preterm deliveries- 10% of all preterm deliveries are due to pre-eclampsia
• If presented under 34 weeks: Principal problem= IUGR, Pre-term delivery is often required
• If presented at term: Pre-eclampsia affects growth less but is associated with foetal morbidity and mortality
• Risk of placental abruption at all gestations

Question 28

Foetal monitoring required in pre-eclampsia

Answer 28

• Cary out CTG at diagnosis of pre-eclampsia or severe PIH

If conservative management is planned, carry out the following:
* USS for foetal growth and amniotic fluid volume assessment
* Umbilical artery doppler velocimetry

DO not routinely repeat CTG unless indicated by:
* Change in foetal movement, vaginal bleeding, abdominal pain deterioration in maternal condition

Question 29

Definition and aetiology of eclampsia

Answer 29

A complication of pre-eclampsia, defined as new onset of generalised tonic-clonic seizures in women with pre-eclampsia. Eclamptic seizures can occur antepartum, 20 weeks after gestation, intrapartum and postpartum.
* The exact aetiology of eclampsia is still unclear, but its proposed that there is increased permeability of the blood-brain-barrier during pre-eclampsia, which causes an alteration to cerebral blood flow due to impaired autoregulation

Question 30

Management of eclampsia

Answer 30

• ABCDE approach
• If a woman in a critical care setting who has severe hypertension or severe pre-eclampsia has or previously had an eclamptic fit, give IV magnesium sulfate.
• Can also be considered in woman with severe pre-eclampsia who are in a critical care setting and have a birth planned within 24 hours
• Consider the need for magnesium sulphate if one or more of the following is present:
• Ongoing or recurring severe headaches, visual scotomata, nausea or vomiting, epigastric pain, pregressive deterioration in blood markers
• A loading dose of 4 g should be given intravenously over 5 to 15 minutes, followed by an infusion of 1 g/hour maintained for 24 hours. If the woman has had an eclamptic fit, the infusion should be continued for 24 hours after the last fit
• Recurrent fits should be treated with a further dose of 2–4 g given intravenously over 5 to 15 minutes
• DO NOT use diazepam, phenytoin or other anticonvulsants as an alternative to magnesium sulphate
• BEWARE: Toxicity can result in respiratory depression and arrythmias-monitor for signs of toxicity every 4 hours (HR, BP, RR, deep tendon reflexes)
  o Antidote= 10ml 10% calcium gluconate over 10 mins
• Continue antihypertensives (IV/oral labetalol, nifedipine, hydralazine)
• If early birth is considered likely within 7 days- offer a course of antenatal corticosteroids for foetal lung maturation
• In women with severe pre-eclampsia, limit maintenance fluids to 80 ml/hour unless there are other ongoing fluid losses