Pre-eclampsia/gestational hypertension
Pre-eclampsia/gestational hypertension

Pre-eclampsia/gestational hypertension

In pregnancy, there are major changes to the vascular system in women as well as changes to the haematological system which can result in changes to the pressure within the vasculature of the women. It is normal for the blood pressure to drop until 20-24 weeks of gestation in fact. The blood pressure subsequently rises to the baseline level when the lady reaches term.

However, there are occasions when hypertension begins in pregnancy (gestational hypertension), and more severe cases in which we may get proteinuria associated with the hypertension (pre-eclampsia). Both of these need to be addressed and managed appropriately. It is also important to be aware of the changes to management of a lady with chronic hypertension that subsequently becomes pregnant. All of these shall be discussed in this CCC.

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CHRONIC HYPERTENSION IN PREGNANCY

In pregnancy, chronic hypertension is still an issue that needs to be treated. The management of chronic hypertension in pregnancy is slightly different in certain aspects:

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Management of chronic hypertension in pregnancy:

Women who take ACE inhibitors or ARBs need to be advised on alternative treatments as these are teratogenic. This should ideally be done within 2 days of notification of pregnancy. The same may be true with patients using thiazide/thiazide-like diuretics. All other alternative treatments are totally okay to take.

Existing treatments should be continued unless the woman has symptomatic hypotension or a sustained SBP <110 or a sustained DBP <70.

  1. 🥇 Labetalol is preferred in pregnancy.
  2. 🥈 Nifedipine is a second-line option.
  3. 🥉 Methyldopa is the third-line choice.

If the hypertension is poorly controlled, the woman should have weekly appointments. If it is well-controlled they should have appointments every 2-4 weeks.

  • Aspirin 75-150mg once daily should also be offered from 12 weeks of gestation.
  • Placental Growth Factor (PLGF) testing should be done between 20 - 36+6 weeks to rule out pre-eclampsia.
  • These women can and should give birth at term if there are no other issues with pregnancy.

In the postnatal period, these women should have their blood pressure measured regularly and they should be reviewed by their GP 6-8 weeks after birth.

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GESTATIONAL HYPERTENSION

Gestational hypertension refers to the new onset of hypertension within pregnancy after 20 weeks of gestation but in the absence of proteinuria. The blood pressure readings need to exceed 140/90 on two occasions at least 4 hours apart.

Pathophysiology

Vascular resistance in pregnancy drops along with cardiac output. However, the RAAS system counteracts this and so the drop is not as significant. However, in women who have gestational hypertension, the cardiac output increases. It is not yet certain if gestational hypertension is similar to the disease aetiology seen in pre-eclampsia. We will discuss the pathophysiology on pre-eclampsia in the next section.

⚠️ Risk factors

  • Previous history of gestational hypertension or pre-eclampsia
  • Vascular disease
  • Renal disease
  • Multiple pregnancy
  • Family history of pre-eclampsia
  • Age >40 years old
  • Nulliparity
  • BMI >35
  • Mother being born small for gestational age
  • Diabetes mellitus
  • Migraine
  • Black ethnicity

😷 Presentation

Patients usually are asymptomatic. They should of course be normotensive prior to pregnancy, but if their blood pressure was not previously known then it is indistinguishable from chronic hypertension. Patients often do not have the symptoms suggestive of pre-eclampsia, such as weight gain, peripheral oedema, headaches, abdominal pain.

🔢 Classification

Classification is important to note as it can guide management:

Normal blood pressure
<120/80mmHg
Pre-hypertension
120-139/80-89mmHg
Hypertension
>140/90mmHg - 159/109mmHg
Severe hypertension
>160/100mmHg

🔍 Investigations

The investigations will differ between mothers based on the severity of their hypertension:

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Investigating gestational hypertension:

Blood pressure 140/90 - 159/109mmHg

  • BP measurements once or twice weekly until <135/85mmHg
  • Urine dipstick - done once or twice a week, assessing for proteinuria (i.e. pre-eclampsia)
  • FBC, LFTs and U&Es - at presentation, then every week.
  • PLGF - if suspecting pre-eclampsia.
  • Foetal assessment - check foetal heart rate at every appointment. Ultrasound to be conducted at diagnosis and then every 2-4 weeks if normal.

Blood pressure >160/110mmHg

  • BP measurements every 15-30 minutes until <135/85mmHg
  • Urine dipstick - to be done daily (while admitted to hospital)
  • FBC, LFTs and U&Es - at presentation, then every week.
  • PLGF - if suspecting pre-eclampsia.
  • Foetal assessment - check foetal heart rate at every appointment. Ultrasound to be conducted at diagnosis and then every 2 weeks if normal. CTG to be done at diagnosis too.

Postnatal investigations:

  • Measure BP for first 5 days after birth (once daily for first 2 days and then once more between day 3-5).

🧰 Management

🤰
Management of gestational hypertension:

If severe hypertension → admit to hospital.

  • Placental Growth Factor (PLGF) testing should be done between 20 - 36+6 weeks to rule out pre-eclampsia.

Antihypertensive treatment:

Antihypertensive treatment is only indicated the BP remains above 140/90mmHg.

  1. 🥇 Labetalol is preferred in pregnancy.
  2. 🥈 Nifedipine is a second-line option.
  3. 🥉 Methyldopa is the third-line choice.

Antihypertensive treatment should be continue postnatally and only reduced if the BP drops <130/80mmHg.

If a lady has started antihypertensive treatment, they should be reviewed after 2 weeks postnatally.

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PRE-ECLAMPSIA

Pre-eclampsia refers to hypertension with evidence of end-organ dysfunction, most commonly proteinuria, that occurs after 20 weeks gestation. Pre-eclampsia precedes eclampsia, which is the occurrence of seizures in a woman with pre-eclampsia. There is a subtype of severe pre-eclampsia known as HELLP syndrome which will be discussed at the end of this section.

It is a condition affecting approximately 4% of pregnancies, but more significantly in low-income countries.

Pathophysiology

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Pre-eclampsia is a condition deriving from the placenta. The placenta itself develops around day 8 when the trophoblast cells differentiate into syncytiotrophoblast cells (on the outside) and cytotrophoblast cells (on the inside). The syncytiotrophoblast cells are invasive and erode endometrial tissue to allow for the formation of spiral arteries as well as the lacunae. The cytotrophoblasts form the primary chorionic villi that penetrate into the syncytiotrophoblast with finger-like projections.

Maternal spiral arteries undergo remodelling and become vessels of high blood flow with low resistance. There are endovascular extravillous cytotrophoblast cells invade maternal spiral arteries to replace the endothelial lining of the arteries to make them wider and less resistant. Pre-eclampsia occurs when there is failure of the spiral arteries to be adequately remodelled which causes placental insufficiency. The cause for this insufficient invasion of the spiral arteries remains to be understood entirely.

⚠️ Risk factors

NICE’s guidelines on pre-eclampsia outlines risk factors which are deemed to be high risk and those which are deemed to be moderate risk. This helps guide management on reducing the risk of pre-eclampsia and other hypertensive disorders of pregnancy from 12 weeks onwards:

High risk factors

  1. History of hypertensive disorder in previous pregnancy
  2. CKD
  3. SLE or antiphospholipid syndrome
  4. Diabetes
  5. Chronic hypertension

Women are deemed to be at risk if they have: 1 or more high risk factors

Moderate risk factors

  1. Primiparity
  2. Age >40 years old
  3. Pregnancy interval >10 years
  4. BMI >35
  5. Family history of pre-eclampsia
  6. Multiple pregnancy

Women are deemed to be at risk if they have: 2 or more moderate risk factors

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If women are deemed to be high risk, they should be offered aspirin (75-150mg) from 12 weeks gestation until birth. They should also be placed under consultant-led care.

There are 2 risk prediction models that may guide decision making about adverse outcomes for women:

  1. fullPIERS - identifies women at increased risk of adverse outcomes up to 7 days before complications arise.
  2. PREP-S - a prognostic model predicting the risk of complications in early-onset pre-eclampsia at various timepoints following diagnosis until 34 weeks of pregnancy.

😷 Presentation

The features of pre-eclampsia are hypertension in a previously normotensive lady occurring >20 weeks gestation.

There also needs to be proteinuria or other signs of end-organ dysfunction, such as:

  1. Renal insufficiency - creatinine >90.
  2. Hepatic involvement - elevated transaminases ± RUQ pain/epigastric pain.
  3. Neurological involvement - eclampsia (seizures), altered mental status, blindness, stroke, clonus, headaches, scotoma.
  4. Haematological involvement - thrombocytopenia , DIC, haemolysis.
  5. Uteroplacental dysfunction - foetal growth restriction, abnormal uterine artery doppler, stillbirth.

Severe hypertension may present with the following symptoms:

  • Headaches
  • Visual disturbances - the fundus is usually normal in pre-eclampsia and if it is abnormal then it is most likely suggestive of chronic hypertension.
  • Upper abdominal pain - may be more indicative of HELLP syndrome.
  • Oedema
  • Reduced urine output - <30ml for >4 hours.
  • Hyperreflexia

🔍 Investigations

According to NICE’s 2019 guidance on pre-eclampsia, we can diagnose pre-eclampsia using a blood pressure reading of >140/90 + any of the following:

  1. Proteinuria - seen as 1+ on urine dipstick. We can also do a protein:creatinine ratio or albumin:creatinine ratio to quantify it.
    1. PCR - >30 is significant.
    2. ACR - >8 is significant.
  2. Organ dysfunction:
    1. LFTs - looking for raised transaminases
    2. FBC - thrombocytopenia or haemolytic anaemia.
    3. Serum creatinine - raised creatinine.
  3. Umbilical artery Doppler amniotic fluid assessment and cardiotocography - can help identify severe pre-eclampsia with non-reassuring heart rate and blood flow. It may also guide decision making on timing of birth.
  4. Placental Growth Factor (PlGF) - a protein (deriving from VEGF) that is released by the placenta. It is used between weeks 20-36+6 to rule out pre-eclampsia in women who are suspected of having pre-eclampsia.

If pre-eclampsia is suspected, an urgent secondary care assessment is indicated.

🧰 Management

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Managing pre-eclampsia:

As mentioned, if the woman has 1 or more high risk factors/2 or more moderate risk factors, they should be started on aspirin (75-150mg daily from 12 weeks gestation until birth) as well be placed under consultant-led care.

  • Antihypertensive medication - aiming for a BP of 135/85. They should be continued even during labour.
    1. 🥇 Labetalol is preferred in pregnancy.
    2. 🥈 Nifedipine is a second-line option.
    3. 🥉 Methyldopa is a third-line option but should be stopped within 2 days of birth.
    4. IV hydralazine is used in critical care or with severe pre-eclampsia
  • Fluid restriction - to 80ml/hour.
  • Anticonvulsant medication - IV magnesium sulfate may be given to women with severe pre-eclampsia or if the lady has had an eclamptic fit.

Blood pressure 140/90 - 159/109mmHg

  • BP measurements - every 48 hours at least.
  • FBC, LFTs, U&Es - twice weekly.

Blood pressure >160/110mmHg

  • Admit to hospital
  • BP measurements every 15-30 minutes. Then 4x daily as an inpatient.
  • FBC, LFTs, U&Es - three times weekly.

Timing of birth:

  • Labour should be induced at term (37 weeks), within 24-48 hours.
  • If labour needs to be induced pre-term (<37 weeks) → give antenatal corticosteroids. If before 34 weeks, then also give magnesium sulfate to prevent seizures. Decisions regarding delivery need to be made on a case-by-case basis. We should aim to deliver the baby after 34 weeks if possible, however. The delivery may be vaginal or C-section (once again depending on the case).
  • Delivery of the placenta is ultimately the curative option for pre-eclampsia. However, in the postnatal period women should still take antihypertensives up until 2 weeks after birth. They should also continuously monitor their BP and bloods.

Postnatal management:

  • Continue antihypertensive therapy
    • 🥇 Enalapril - first-line option.
    • 🥇 Nifedipine - if of black/Afro-Caribbean origin.
    • 🥈 + Atenolol/labetalol - if monotherapy doesn’t work.

🚨 Complications

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HELPP syndrome:

HELPP syndrome stands for Haemolysis, Elevated Liver enzymes and Low Platelets. It is a severe form of pre-eclampsia. It is the most severe form of the hypertensive spectrum of disorders in pregnancy. Although it only affects 0.5% of pregnancies, it is a significant cause of maternal mortality and morbidity.

😷 Presentation:

  • Nausea and vomiting
  • Right upper quadrant pain
  • Lethargy
  • Headache
  • Oedema
  • Hyperreflexia

🧰 Management:

  1. Seizure prophylaxis - IV magnesium sulfate
  2. Antenatal corticosteroids - IV dexamethasone
  3. 🏆 Delivery of baby and placenta

🚨 Complications :

Maternal complications:

  • Organ failure
  • Placental abruption
  • Disseminated intravascular coagulopathy (DIC)

Foetal complications:

  • Intrauterine growth restriction
  • Preterm birth
  • Neonatal hypoxia

Other complications of pre-eclampsia include:

  • Foetal growth restriction
  • DIC
  • Placental abruption
  • AKI
  • Pulmonary oedema