Intended for healthcare professionals

Endgames Case Review

Hypertensive disorder of pregnancy

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j285 (Published 02 February 2017) Cite this as: BMJ 2017;356:j285
  1. Robert Charles, ST5 anaesthetics,
  2. Christopher Swales, foundation year 2,
  3. Tess Bonnett, consultant, obstetrics and gynaecology,
  4. Phil Bonnett, consultant, anaesthetics
  1. Sheffield Teaching Hospitals Foundation Trust, Herries Road, Sheffield, South Yorkshire, UK
  1. Correspondence to R Charles robcharles{at}doctors.org.uk

A 41 year old woman (gravida 1 para 0) presented to the antenatal day unit at 32 weeks’ gestation with a blood pressure of 157/93 mm Hg. Her first recorded BMI in pregnancy was 32. She was a non-smoker and had no known drug allergies. Her history included a thoracic spine fracture and two lumbar disc protrusions that had been asymptomatic since 2002. Earlier in the day, she had a headache that was relieved by paracetamol. Urinalysis showed 1+protein and a urinary protein creatinine ratio of 19 mg/mmol. Further measurements found a blood pressure of 163/96 mm Hg. The patient was admitted to the antenatal ward and started on an antihypertensive. Once her blood pressure was stable she was discharged with regular follow-up.

At 34 weeks’ gestation she presented to labour ward triage with a blood pressure of 158/98 m Hg despite antihypertensive treatment. She was admitted to the antenatal ward, her antihypertensive therapy was increased, and a second line agent was started. Urinary protein creatinine ratio was 39 mg/mmol; 24 hour urine collection showed 540 mg/24 hour of protein. An ultrasound scan for growth, liquor volume, and umbilical cord dopplers was normal. Induction of labour was arranged at 37 weeks’ gestation.

Questions

  • 1. What is the most likely diagnosis and what are the risk factors in this case?

  • 2. What is the pathophysiology of this condition?

  • 3. How is this condition managed?

Answers

1. What is the most likely diagnosis and what are the risk factors in this case?

Short answer

Gestational hypertension developing into pre-eclampsia. Risk factors include nulliparity, maternal age >40 years, and body mass index >25.

Discussion

Hypertension can be graded according to severity (box 1).1 The National Institute for Health and Care Excellence (NICE) classifies hypertensive disorder of pregnancy as chronic hypertension, gestational hypertension, or pre-eclampsia.1 Chronic hypertension is defined as pre-existing hypertension or hypertension diagnosed before 20 weeks’ gestation. Gestational hypertension is new onset hypertension without significant proteinuria occurring after 20 weeks pregnancy.1 Pre-eclampsia is new onset hypertension with significant proteinuria occurring after 20 weeks pregnancy.1234 Urinary reagent sticks are used as a screening tool to detect proteinuria. A result of ≥1+should prompt formal quantification of urinary protein. Significant proteinuria is classified as a protein creatinine ratio >30 mg/mmol or a 24 hour urine collection of >300mg protein.1 Severe pre-eclampsia is defined as severe hypertension and/or symptoms and/or biochemical and haematological derangement (box 2).1 The American College of Obstetricians and Gynecologists and the International Society for the Study of Hypertension in Pregnancy define pre-eclampsia as hypertension after 20 weeks pregnancy in the presence of either new onset proteinuria or maternal organ dysfunction.56 The International Society for the Study of Hypertension in Pregnancy definition also includes the presence of uteroplacental dysfunction.6 Pre-eclampsia affects 5%-8% of pregnancies worldwide.237 There is some evidence that the incidence of pre-eclampsia is increasing,6 however the mortality associated with it is in decline.8

Box 1: NICE grading of hypertension1

  • Mild: diastolic blood pressure 90-99 mm Hg, systolic blood pressure 140-149 mm Hg

  • Moderate: diastolic blood pressure 100-109 mm Hg, systolic blood pressure 150-159 mm Hg

  • Severe: diastolic blood pressure >110 mm Hg, systolic blood pressure >160 mm Hg

Box 2: NICE features of severe pre-eclampsia12

  • Severe hypertension and proteinuria or

  • Mild or moderate hypertension and proteinuria with one or more of the following:

    • Severe headache

    • Visual disturbance—eg, blurring, flashing

    • Severe subchondral pain below the ribs or vomiting

    • Papilloedema

    • Signs of clonus (>3 beats)

    • Liver tenderness

    • HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)

    • Thrombocytopenia (<100 × 109/l)

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

NICE has identified risk factors for hypertensive disorders in pregnancy (box 3). Women with a high risk factor or two moderate risk factors are advised to take daily antiplatelet therapy from 12 weeks pregnancy until the baby is delivered.1

Box 3: NICE risk factors for hypertensive disorders of pregnancy1

  • High risk factors:

    • Chronic hypertension

    • Hypertensive disease during a prior pregnancy

    • Chronic kidney disease

    • Autoimmune disease—eg, systemic lupus erythematosus, antiphospholipid syndrome

    • Type 1 or 2 diabetes mellitus

  • Moderate risk factors:

    • Nulliparity

    • First pregnancy

    • Age >40 years

    • Pregnancy interval >10 years

    • BMI >35 kg/m2 on first visit

    • Family history of pre-eclampsia

    • Multiple pregnancy

2. What is the pathophysiology of this condition?

Short answer

Although not fully understood, abnormal placental implantation and uterine spiral artery conversion results in placental ischaemia and an imbalance in pro-angiogenic and anti-angiogenic factors. This results in a cascade of endothelial damage and multisystem end organ effects.

Discussion

During a normal pregnancy, trophoblastic cells derived from the fetus enable implantation. These cells invade the maternal spiral arteries of the uterus and convert them from a high resistance low flow vessel into a low resistance high flow vessel. This change increases blood flow and therefore delivery of nutrients to the feto-placental unit.4

The placenta is central to the pathophysiological changes that occur in pre-eclampsia, although the mechanisms are not fully understood. There is evidence that the pathophysiology of pre-eclampsia depends on the gestation at onset.7 In early onset pre-eclampsia (before 34 weeks’ gestation) abnormal implantation and spiral artery conversion occurs, resulting in hypoperfusion and hypoxia to the feto-placental unit.27 This leads to abnormal placental development and fetal growth restriction.7 In late onset pre-eclampsia (after 34 weeks’ gestation) there is little change in resistance of the spiral arteries. This still results in hypoperfusion of the placenta; however fetal growth restriction is less common.7 In clinical practice, the pathological features of early onset and late onset pre-eclampsia overlap.

Hypoperfusion and ischaemia of the feto-placental unit may result in trophoblast necrosis and apoptosis. It is thought that the resulting debris may cause mechanical obstruction, protease activation, cytokine release, and immune modulation.47 There is believed to be a downregulation of pro-angiogenic factors and upregulation of anti-angiogenic factors, several of which have been identified.79 In contrast with normal pregnancies, peripheral vascular resistance is increased in pre-eclampsia, and plasma volume and cardiac output are both reduced. Although the mechanism is not fully understood, most of the components of the renin-angiotensin-aldosterone system are downregulated, secondary to increased endothelial sensitivity to angiotensin II.47 The overall effect of these pathological changes is endothelial dysfunction, platelet activation, and systemic arterial vasoconstriction. This results in multisystem effects, such as pulmonary oedema, ventricular failure, and thrombocytopenia 249

3. How is this condition managed?

Short answer

The aim of managing pre-eclampsia is blood pressure control. Mild hypertension does not require treatment. Moderate and severe hypertension are treated with antihypertensive medication with a target blood pressure of <150/100 mm Hg.1

Discussion

Women with one high risk factor or two moderate risk factors for a hypertensive disorder of pregnancy (box 3) are advised to take 75 mg aspirin daily from 12 weeks’ gestation until delivery of the baby.1 A diagnosis of pre-eclampsia should be established by serial blood pressure measurement and quantification of urinary protein by urine protein creatinine ratio or 24 hour urine protein measurement. All patients with pre-eclampsia should be admitted to hospital.1 Management of pre-eclampsia is multidisciplinary, involving obstetricians, paediatricians, and anaesthetists.

Mild hypertension does not require drug treatment, but moderate hypertension does. First line treatment is labetalol, aiming to maintain a diastolic blood pressure of 80-100 mm Hg and a systolic blood pressure <150 mm Hg.110 Labetalol can be administered orally at 200-1600 mg in divided doses.10 Nifedipine and methyldopa are alternatives to labetalol, and can also be used as second line agents. Make regular blood pressure checks and take blood tests (full blood count, urea and electrolytes, liver function tests, and clotting studies) at least twice a week to monitor for deterioration in pre-eclampsia.1

Severe hypertension requires close monitoring, drug treatment, and potential escalation to critical care. Invasive blood pressure monitoring via an arterial line may be indicated. First line antihypertensive treatment is labetalol with the aim to keep the systolic blood pressure <150 mm Hg and the diastolic blood pressure at 80-100 mm Hg.1 If the blood pressure does not respond to oral labetalol it can be given intravenously as 50 mg boluses titrated to effect, followed by continuous infusion 20–160 mg/h for treatment resistant hypertension. The consequences of uncontrolled pre-eclampsia include cerebral haemorrhage, maternal death, placental abruption, and intrauterine fetal death.26

Women with pre-eclampsia are often hypovolaemic. If intravenous crystalloid is indicated, it should be administered with care and limited to 80 ml/h (or 1 ml/kg/h), with strict fluid balance monitoring because of the risk of pulmonary oedema.210 Serial blood tests are required to monitor and detect organ dysfunction.1

Magnesium sulphate administration should be considered in severe pre-eclampsia, as it was shown to substantially reduce the risk of developing seizures in the Magpie trial.11 Escalation to critical care should be considered in the presence of complications such as eclampsia, HELLP syndrome, and haemorrhage.

NICE advises that birth should not be offered until after 37 weeks’ gestation if blood pressure is controlled.1 If a clinical deterioration such as uncontrolled hypertension or organ dysfunction occurs before 37 weeks, then early delivery may be indicated. This decision is based upon clinical judgment balancing the risk of continuing the pregnancy to the mother and fetus with the risk of a preterm delivery. The PHOENIX trial is currently investigating the complications of early delivery versus expectant management in women with pre-eclampsia between 34 and 37 weeks’ gestation. The result of this trial may help guide clinical decisions in the future.

Outcome

Induction of labour was commenced with artificial rupture of membranes and oxytocin infusion. An epidural was administered for analgesia. During the course of labour the cardiotocograph became abnormal and the woman was taken to theatre for an urgent caesarean section, performed under epidural top-up. A healthy baby boy was delivered, weighing 3510 g. The woman continued antihypertensive mediation for eight weeks until her blood pressure returned to normal.

Footnotes

  • We have read and understood the BMJ policy on declaration of interests and have no relevant interests to declare.

  • Patient consent obtained.

References

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