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100 SECTION 3  Antenatal Care

CHAPTER 27  Pre-eclampsia (PET) and eclampsia

Prevalence and background Risks or complications

• PET – HT presenting after 20 weeks with significant proteinuria (> 0.3 g in 24 hours).
• Severe PET – PET with severe HT and/or with symptoms, and/or biochemical and/or
haematological impairment.
1. There is consensus on severe HT – severe HT (DBP ≥ 110 mmHg or SBP ≥ 170 mmHg
on 2 occasions), together with significant proteinuria (at least 1 g/litre).
2. There is less agreement on degree of moderate HT, which together with other symptoms
or signs constitute severe PET. A DBP ≥ 100 mmHg on 2 occasions and significant
proteinuria with at least two signs or symptoms of imminent eclampsia. (Although some
women who present with eclampsia have no prodromal signs.)
• Eclampsia – the occurrence of one or more convulsions superimposed on PET.
• HELLP syndrome – haemolysis, elevated liver enzymes, and low platelet count.
• Rates for PET – 1.5% to 7.7%.
• The rate depends on parity: the rate for primigravid women is 4.1% and in women in their
second pregnancy 1.7%.
• In the UK – severe PET – 5/1000 maternities; eclampsia – 5/10 000 maternities.
Maternal:
• HT in pregnancy is one of the leading causes of maternal death in the UK.
• One-third of severe maternal morbidity is as a consequence of hypertensive conditions.
• 5% of women with severe PET or eclampsia are admitted to intensive care (UK).
• Case fatality rate – 1.8% and a further 35% of women experience a major complication.
• Long-term consequences for women with a diagnosis of HT during pregnancy – chronic
HT and an increase in lifetime cardiovascular risk.
Fetal:
• 5% of stillbirths in infants without congenital abnormality occur in women with PET.
• PTB rate – 1 in 250 (0.4%) women in their first pregnancy give birth before 34 weeks due
to PET and 8–10% of all PTBs result from hypertensive disorders.
• Half of women with severe PET deliver preterm.
• SGA (FGR arising from placental disease) – 20–25% of PTBs and 14–19% of term births
in women with PET.

Risk factors for pre-eclampsia

Very high High Moderate

History of: • Hypertensive disease during previous pregnancy. • First pregnancy.

• Severe eclampsia. • Chronic kidney disease. • Age ≥ 40 years.
• Pre-eclampsia needing birth before 34 weeks. • Autoimmune disease such as systemic lupus • Pregnancy interval > 10 years.
• PET with baby’s birth weight < 10th centile. erythematosus or antiphospholipid syndrome. • BMI ≥ 35 kg/m2 at first visit.
• Intrauterine death. • Type 1 or type 2 diabetes. • Family history of pre-eclampsia.
• Placental abruption. • Chronic hypertension. • Multiple pregnancy.

• Aspirin 75 mg/day from 12 weeks until birth. • If at least two moderate risk factors, or
• USS – fetal growth and AFV + UmAD: • At least one high risk factor for pre-eclampsia.
* Start at 28–30 weeks, or at least 2 weeks before previous gestational age of onset of
hypertensive disorder if earlier than 28 weeks.
* Repeat at least 4 weeks later. • Aspirin 75 mg/day from 12 weeks until birth.
• If fetal activity abnormal carry out CTG.
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Prevention
• Women at high risk and with more than one moderate risk factor for PET – 75 mg of
aspirin daily from 12 weeks until the birth of the baby.
• Do not use the following solely with the aim of preventing hypertensive disorders
during pregnancy:   *  Nitric oxide donors.  * Progesterone.  * Diuretics.
*  LMWH.   * Magnesium.  *  Folic acid antioxidants (vitamins C and E).  *  Fish oils
or algal oils.  * Garlic.  *  Salt restriction during pregnancy.
• Advice on rest, exercise, and work for women at risk of hypertensive disorders during
pregnancy is the same as for healthy pregnant women.

Blood pressure (BP)

Symptoms and assessment of proteinuria
Clinical features of severe PET (in addition to HT and proteinuria) are:
• Symptoms – severe headache, problems with vision, such as blurring or flashing before the
eyes, severe pain just below the ribs (epigastric pain), vomiting, sudden swelling of the face,
hands or feet, convulsions, abdominal pain or general malaise.
• Increasing oedema is not in itself a sign to determine management.
• Signs – liver tenderness, clonus, papilloedema.
• Maternal tendon reflexes, although useful to assess magnesium toxicity, are not of value in
assessing the risk of convulsion although the presence of clonus may be.
• Investigations – platelet count falling to < 100 x 109/l; abnormal liver enzymes (ALT or
AST > 70 IU/l); HELLP syndrome.
• When taking BP, the woman should be rested and sitting at a 45° angle. The BP cuff should
be of the appropriate size and placed at the level of the heart. Use multiple readings to
confirm the diagnosis. Korotkoff phase 5 is the appropriate measurement of DBP.
• Automated methods need to be used with caution, as they may give inaccurate BP readings
in PET.
Proteinuria
• Use an automated reagent-strip reading device or a spot urinary protein:creatinine ratio
(uPCR) for estimating proteinuria.
• Automated reagent-strip reading device – if result of 1+ or more, use a spot uPCR or
24-hour urine collection to quantify proteinuria.
• Diagnose significant proteinuria if the uPCR is > 30 mg/mmol or a validated 24-hour urine
collection result shows > 300 mg protein.

Investigations

Maternal
• FBC, LFT, and RFTs. Fetal
• Uric acid – rise confirms the diagnosis of PET and confers an increased risk to the mother
• The main pathology affecting the fetus, apart from prematurity, is placental insufficiency
and baby but do not use the levels in themselves for clinical decision making.
leading to IUGR.
• Renal function is generally maintained in PET until the late stage unless HELLP syndrome
• IUGR occurs in around 30% of PET pregnancies.
develops. If creatinine is elevated early in the disease process, suspect underlying renal
• Ultrasound assessment of fetal size, at the time of the initial presentation to assess fetal
disease. In severe disease, serum creatinine can be seen to rise and is associated with a
growth. Growth restriction is usually asymmetrical so measurement of the abdominal
worsening outcome but renal failure is uncommon in the developed world and when it does
circumference (AC) is the best method of assessment.
occur it is usually associated with haemorrhage, HELLP syndrome or sepsis.
• Reduced liquor volume is also associated with placental insufficiency and FGR. Serial
• A falling platelet count is associated with worsening disease and is itself a risk to the
estimations of liquor volume can detect fetal compromise.
mother. However, it is not until the count is < 100 × 109/l that there may be an associated
• Umbilical artery Doppler assessment (UmAD), using absent or reversed-end diastolic flow,
coagulation abnormality. Consider delivery if platelet count is < 100.
improves neonatal outcome. Serial investigations of this and other fetal vessels can be used
• Clotting studies are not required if the platelet count is > 100 × 109/l.
to follow pregnancies and optimize delivery.
• An AST or ALT level of > 75 IU/l is seen as significant and a level > 150 IU/l is associated
with increased morbidity to the mother.
• A diagnosis of HELLP syndrome needs confirmation of haemolysis, either by LDH levels,
or by blood film to look for fragmented red cells.

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102 SECTION 3  Antenatal Care

Management of PET pregnancy

Mild hypertension Moderate hypertension Severe hypertension

(140/90 to 149/99 mmHg)
• Admit to hospital.
• No antihypertensive treatment.
• Measure BP – at least four times a day.
• Do not repeat quantification of proteinuria.
• Blood tests monitor – twice a week: kidney function,
electrolytes, FBC, transaminases, bilirubin.
(150/100 to 159/109 mmHg)
• Admit to hospital.
• Antihypertensive treatment – with oral labetalol as first-
line treatment to keep: DBP between 80 and 100 mmHg
and SBP < 150 mmHg.
• Measure BP – at least four times a day.
• Do not repeat quantification of proteinuria.
• Blood tests monitor – three times a week: kidney
function, electrolytes, FBC, transaminases, bilirubin.
(160/110 mmHg or higher)
• Admit to hospital.
• Antihypertensive treatment – with oral labetalol as first-
line treatment to keep: DBP between 80–100 mmHg and
SBP < 150 mmHg.
• Measure BP > four times a day.
• Do not repeat quantification of proteinuria.
• Blood tests monitor – three times a week: kidney
function, electrolytes, FBC, transaminases, bilirubin.

• Only offer antihypertensive treatment other than labetalol after considering side-effect
profiles for the woman, fetus, and newborn baby.
• Alternatives include methyldopa and nifedipine. Consider referral to level 2 critical care.
• Atenolol is associated with an increase in FGR.
• ACE inhibitors and ARBs are contraindicated because of unacceptable fetal adverse effects.
• Diuretics are relatively contraindicated and reserve it for pulmonary oedema.

Fetal monitoring

Pre-eclampsia Women at high risk of pre-eclampsia

• USS for fetal growth and AFV + UmAD at diagnosis – if conservative management is • USS for fetal growth and AFV + UtAD starting at between 28 and 30 weeks (or at least 2
planned, repeat every 2 weeks. weeks before previous gestational age of onset if earlier than 28 weeks) and
• Do not routinely repeat USS more than every 2 weeks. • Repeat 4 weeks later.
• CTG – carry out at diagnosis. If the results of all fetal monitoring are normal, do not • Only carry out CTG if fetal activity is abnormal, in women with previous:
routinely repeat CTG more than weekly. * Severe PET.
• Repeat CTG if – change in fetal movement, vaginal bleeding, abdominal pain, deterioration * PET that needed birth before 34 weeks.
in maternal condition. * PET with a baby whose birth weight was < 10th centile.
* Intrauterine death.
* Placental abruption.
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Timing of birth

Before 34 weeks 34–36 weeks After 37 weeks

• Manage conservatively as it may improve the perinatal outcome at very early • Deliver if PET with severe HT once BP has been • Deliver within 24–48 hours if PET is
gestations but carefully balance with maternal wellbeing. controlled and a course of corticosteroids has been mild or moderate.
• Plan and document the maternal (biochemical, haematological, and clinical) and completed.
fetal thresholds for elective delivery before 34 weeks. • Offer delivery if mild or moderate HT depending
• Offer delivery after discussion with neonatal team and a course of on maternal and fetal condition, risk factors, and
corticosteroids has been given if: availability of NICU.
* Severe HT develops refractory to treatment.
* Maternal or fetal indications develop.

Mode of delivery
• CS versus IOL – choose mode of birth for women with severe HT, severe PET or eclampsia according to the
clinical circumstances and the woman’s preference.
• Decide the mode of delivery after considering the presentation of the fetus and the fetal condition, together Intrapartum care
with the likelihood of success of IOL after assessment of the cervix. Vaginal delivery is generally preferable See Chapter 26 Pregnancy-induced hypertension
but, if gestation is < 32 weeks, CS is more likely as the success of induction is reduced. (PIH) or gestational HT
• After 34 weeks with a cephalic presentation, consider vaginal delivery.
• Manage third stage with 5 units IM Syntocinon or 5 units IV Syntocinon given slowly.
• Do not use Ergometrine or Syntometrine for prevention of PPH as this can further increase the BP.

Postnatal investigation, monitoring, and treatment

Up to 44% of eclampsia occurs postpartum, especially at term, so assess women
with signs or symptoms compatible with PET carefully.

Haematological and biochemical monitoring

Blood pressure
Women who did not take anti-HT treatment
• Measure BP:
* At least 4 times a day while the woman is an inpatient.
* At least once between D 3 and D 5 after birth.
* On alternate days until normal if it was abnormal on
D 3–5.
• Start anti-HT treatment if BP is ≥ 150/100 mmHg.
• Ask women about severe headache and epigastric pain
each time BP is measured.
Women who took anti-HT treatment
• Measure BP:
* At least 4 times a day while the woman is an inpatient.
* Every 1–2 days for up to 2 weeks until the woman is off
treatment and has no HT.
• Continue antenatal anti-HT treatment:
* Consider reducing anti-HT treatment if BP < 140/90 mmHg.
* Reduce anti-HT treatment if BPs < 130/80 mmHg.
• If a woman has taken methyldopa, stop within 2 days of birth.
Women with mild or moderate HT who have given birth, or after
step-down from critical care:
• Measure platelet count, transaminases, and serum creatinine
48–72 hours after.
• Do not repeat if results are normal at 48–72 hours.
• If indices are improving but stay within the abnormal range,
repeat them as clinically indicated and at the postnatal review.
• If indices are not improving relative to pregnancy ranges,
repeat them as clinically indicated.
• In women who have stepped down from critical care level, do not
measure fluid balance if creatinine is within the normal range.

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104 SECTION 3  Antenatal Care

Postnatal care

Community care Breastfeeding

• Transfer to community care if all of the following criteria are met:
* No symptoms of PET.
* BP with or without treatment is ≤ 149/99 mmHg.
* Blood test results are stable or improving.
• Write a care plan for women who are being transferred to community care: who will
provide follow-up care, including medical review if needed, frequency of BP monitoring,
thresholds for reducing or stopping treatment, indications for referral to primary care for
BP review, self-monitoring for symptoms.
• Women who are still on anti-HT treatment 2 weeks after transfer to community care –
offer a medical review.
• In women who still need anti-HT treatment in the postnatal period, avoid diuretics if the
woman is breastfeeding or expressing milk.
• These anti-HT drugs have no known adverse effects on babies receiving breast milk:
labetalol, nifedipine, enalapril, captopril, atenolol, metoprolol.
• There is insufficient evidence on the safety of breastfeeding with ARBs, amlodipine, ACE
inhibitors other than enalapril and captopril.
• Assess the clinical wellbeing of the baby, especially adequacy of feeding, at least daily for
the first 2 days after the birth.

Postnatal review (6–8 weeks after the birth)

• Offer all women a medical review.

• Offer women who still need anti-HT treatment a specialist assessment of their HT.
• Urinary reagent-strip test. Offer women who still have proteinuria ( ≥ 1+) a further review at 3 months to
assess kidney function and consider referral for specialist kidney assessment.
• Up to 13% of women with PET will have underlying chronic or essential HT that was not suspected
antenatally.

Follow-up care

Long-term risk Risk of recurrence

• Long-term risk of cardiovascular disease – an increased risk of developing high BP and its • Women with PIH – risk in future pregnancy:
complications in later life. * PIH – 1 in 6 (16%) to 1 in 2 (47%) pregnancies.
• Long-term risk of end-stage kidney disease – women who have no proteinuria and no HT * PET – 1 in 50 (2%) to 1 in 14 (7%) pregnancies.
at the postnatal review have a low absolute risk and no further follow-up is necessary. • Women with PET – risk of developing in future pregnancy:
• Thrombophilia and the risk of PET – do not routinely perform screening for thrombophilia * PIH – 1 in 8 (13%) to 1 in 2 (53%) pregnancies.
in women who have had PET. * PE T – up to 1 in 6 (16%) pregnancies.
* No additional risk if interval before next pregnancy < 10 years.
• Women with severe PET, HELLP syndrome or eclampsia:
* And if led to birth < 34 weeks – PET in a future pregnancy is about 1 in 4 (25%)
pregnancies.
* And if led to birth < 28 weeks – 1 in 2 (55%) pregnancies.
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Medical management of severe HT, severe PET or

eclampsia in a critical care setting

Anticonvulsants Antihypertensives Corticosteroids

• Give IV magnesium sulphate – if a woman has severe HT or severe PET, has or • Treat with – labetalol (oral or IV); hydralazine • For fetal lung maturation –if delivery is likely
previously had an eclamptic fit. (IV); nifedipine (oral). within 7 days:
• Consider IV magnesium sulphate to women with severe PET who are in a • Aim to keep SBP < 150 mmHg and DBP between * Give 2 doses of betamethasone 12 mg IM,
critical care setting if birth is planned within 24 hours. 80 and 100 mmHg. 24 hours apart in women between 24 and 34
• Features of severe PET: • Measure BP continually. weeks.
1. Severe HT and proteinuria or • Monitor response: to ensure that BP falls, to * Consider giving 2 doses of betamethasone
2. Mild or moderate HT and proteinuria with one or more of: identify adverse effects for both the woman 12 mg IM, 24 hours apart in women between
* Severe headache. and the fetus, to modify treatment according to 35 and 36 weeks.
* Problems with vision – blurring or flashing before the eyes. response. • Do not use dexamethasone or betamethasone for
* Severe pain just below the ribs or vomiting. • Consider using up to 500 ml crystalloid fluid the treatment of HELLP syndrome.
* Papilloedema. *  Clonus (3 beats). before or at the same time as the first dose of IV
* Liver tenderness. *  HELLP syndrome. hydralazine in the antenatal period.
* Platelet count < 100 × 10 /l.
9

* Abnormal liver enzymes (ALT or AST > 70 IU/l).

• Regimen for administration of magnesium sulphate – loading dose of 4 g IV
over 5 minutes, followed by an infusion of 1 g/hour maintained for 24 hours.
Treat recurrent seizures with a further dose of 2–4 g given over 5 minutes.
• Do not use diazepam, phenytoin or lytic cocktail as an alternative to
magnesium sulphate in women with eclampsia.
• Administration of magnesium sulphate reduces the risk of an eclamptic seizure
with a 58% lower risk of an eclamptic seizure.
• More women need to be treated when PET is not severe (109) to prevent one
seizure when compared with severe PET (60).
• If magnesium sulphate is given, continue for 24 hours following delivery or 24
hours after the last seizure, whichever is the later.
• Monitor urine output, maternal reflexes, respiratory rate, and oxygen saturation.
Fluid balance and volume expansion
• Pulmonary oedema has been a significant cause of maternal death.
• This is associated with inappropriate fluid management. Limit maintenance
fluids to 80 ml/hour unless there are other ongoing fluid losses (for example,
haemorrhage).
• Maintain the regime of fluid restriction until there is a postpartum diuresis, as
oliguria is common with severe PET.
• Do not use volume expansion unless hydralazine is the antenatal
antihypertensive.

Indications for referral to critical care levels women with severe HT or severe PET

Level 3 Level 2 Level 1

• Severe PET needing ventilation. Step-down from level 3 or severe PET with: • PET with mild or moderate HT.
• Eclampsia. • Ongoing conservative antenatal management of
• HELLP syndrome. severe preterm HT.
• Haemorrhage. • Step-down treatment after the birth.
• Hyperkalaemia.
• Severe oliguria.
• Coagulation support.
• IV antihypertensive treatment.
• Initial stabilization of severe HT.
• Evidence of cardiac failure.
• Abnormal neurology.

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106 SECTION 3  Antenatal Care

Management of eclampsia

• Call for help (anaesthetist and senior obstetrician).

• Aim to prevent maternal injury during the convulsion.
Basic principles of airway, breathing, and circulation
• Place the woman in the left lateral position and administer oxygen.
• Assess the airway and breathing and check pulse and BP.
• Pulse oximetry is helpful.

• Magnesium sulphate is the therapy of choice

• Do not use diazepam and phenytoin as first-line drugs.
Anticonvulsants • Magnesium toxicity is unlikely with standard regimens so do not measure levels routinely. Magnesium
sulphate is mostly excreted in the urine. Monitor urine output closely observed and if it becomes reduced
< 20 ml/hour, stop magnesium infusion.
• Magnesium toxicity can be assessed by clinical assessment as it causes a loss of deep tendon reflexes and
respiratory depression. If there is loss of deep tendon reflexes, stop magnesium sulphate infusion.
• Calcium gluconate 1 g (10 ml) over 10 minutes can be given if there is concern over respiratory depression.

Antihypertensives • Treat with – labetalol (oral or IV); hydralazine (IV); nifedipine (oral).
• Aim to keep SBP < 150 mmHg and DBP between 80 and 100 mmHg.
• Up to 500 ml crystalloid fluid before or at the same time as the first dose of IV hydralazine.
• Measure BP continually. Monitor response: to ensure that BP falls; to identify adverse effects for both the
woman and the fetus; to modify treatment according to response.

Repeated seizures • Repeat magnesium sulphate.

• Alternative agents such as diazepam or thiopentone may be used, but only as single doses, since prolonged
use of diazepam is associated with an increase in maternal death.
• If convulsions persist, intubation is necessary to protect the airway and maintain oxygenation.
• Transfer to intensive care facilities with intermittent positive pressure ventilation is appropriate in these
circumstances.
Delivery

• Once stabilized, plan to deliver; however there is no particular hurry and a delay of several hours to make
sure the correct care is in hand is acceptable, assuming that there is no acute fetal concern such as a fetal
bradycardia.

The Management of Severe Pre-Eclampsia/Eclampsia. RCOG Guideline No. 10(A); March 2006.
Hypertension in Pregnancy: The Management of Hypertensive Disorders during Pregnancy; NICE CGN 107, August 2010.