Hypertensive disorders of pregnancy

DEFINITIONS

• Hypertension = >140 and/or =>90 (SBP =>30 or DBP =>15 above baseline may be significant – Assess for clinical/lab features of pre-eclampsia)
• Moderate HTN = 141-159 and/or 91-109
• Severe HTN =>160 and/or =>110 • Medical emergency =>170 with/without >=110 

DEFINITIONS

• Gestational hypertension = New onset after 20 weeks with no additional features of pre-eclampsia • Resolves within 3 months post-partum

• Pre-eclampsia = Multi-system disorder of hypertension and involvement of one or more organ systems and/or the fetus

• Chronic hypertension occurring in pregnancy = Pre-conception of <20 weeks without known cause

• Pre-eclampsia superimposed on chronic hypertension 

DIAGNOSIS of PRE-ECLAMPSIA

Hypertension arising after 20 weeks* gestation confirmed on 2 or more occasions and accompanied by one or more of organ system features below:

• Proteinuria – Random urine protein:creatinine ratio >=30mg/mmol
• Renal = Plasma creatinine >= 90micromol/L or oliguria
• Haematological = Plt <100, haemolysis (schistocytes, raised bilirubin, raised LDH, decreased haptoglobin), DIC
• Liver = Raised transaminases, severe epigastric or RUQ pain
• Neurological = Severe headache, persistent visual disturbances, hyperreflexia with sustained clonus, convulsions, stroke
• Pulmonary = Pulmonary oedema • Uteroplacental = Foetal growth restriction

*Can occur earlier than 20 weeks in gestational trophoblastic disease 

RISK FACTORS of PRE-ECLAMPSIA

• Antiphospholipid syndrome = 9.72 RR

• Previous pre-eclampsia = 7.19

• Pre-existing diabetes = 3.56

• Twin pregnancy = 2.93

• Nulliparity = 2.91

• FHx of pre-eclampsia = 2.90

• Raised BMI pre-pregnancy = 2.47

• Maternal age >40 

PRESENTATION of PRE-ECLAMPSIA

• Raised BP
• Severe headache
• Altered vision
• Abdominal pain
• Vomiting
• Sudden swelling of face, hands or feet 

ASSESSMENT of PRE-ECLAMPSIA

• Screen for proteinuria

• Dipstick and confirm by laboratory PCR if 2+ proteinuria, persistently 1+ or pre-eclampsia suspected

• 1+ equates to >300mg/24 hours

• FBC, Chem20 including LDH

• Urine MCS

• If bleeding, thrombocytopaenia or falling Hb: • Coags, blood film, LDH, fibrinogen, haemolytic studies

• Foetal assessment

• CTG if >24 weeks

• USS assessment of foetal growth, amniotic fluid volume, umbilical artery flow 

COMPLICATIONS of PRE-ECLAMPSIA

• IUGR
• Premature labour
• Low infant birth weight
• Abruptio placentae
• Future risk of maternal cardiovascular disease
• Complications of disease itself 

TREATMENT OF HYPERTENSION

Moderate Hypertension

• Therapy halves risk of severe hypertension but no evidence of benefit in outcomes otherwise

• Consider therapy if SBP 140-160 and/or DBP 90-100 and/or signs and symptoms of pre-eclampsia

• No evidence of target BP
• Suggested targets of 140 and 90
• Preferred agents
• Methyldopa 125mg BD up to 500mg QID (*most extensively studied)
• Labetalol 100mg BD up to 400mg QID
• Hydralazine 25mg BD up to 100mg BD
• Nifedipine SR 20mg daily up to 120mg daily
• Prazosin 0.5mg BD up to 1mg TDS
• Clonidine 75mcg BD up to 300mcg BD 

Severe Hypertension

• Commence treatment if SBP >=160 or DBP >= 100
• IV agents + concurrent long-acting oral
• Target SBP 130-150 and DBP 80-90
• Aim for gradual and sustained lowering of BP
• Thorough assessment of maternal and foetal condition mandatory
• Continuous foetal heart rate monitoring is recommended
• Drugs not recommended including Magnesium sulfate (unless pending eclampsia), sodium nitroprusside or GTN infusions (unless other treatments failed and birth is imminent)
• Treatment of severe hypertension prevents cerebrovascular complications but not fetal outcome or prolong pregnancy 
• Recommended agents
  • Labetalol 20mg IV over 2 min with increase to 40-80mg boluses every 10 minutes then 20-160mg/hr infusion
  • Hydralazine 10mg IV over 3-10 minutes repeated every 20 minutes then 10-20mg/hr infusion 

MANAGEMENT PRE-ECLAMPSIA

• Unpredictable
• HTN and proteinuria may be late and minimal features of pre-eclampsia
• Birth is the definitive management
• Independent risk factor for VTE
• Fluid management
• Large volumes lead to pulmonary oedema
• Strict fluid balance 
• Magnesium sulfate
  • Anticonvulsant of choice to treat and prevent eclampsia •
  • Indications
    • Eclampsia
    • Severe pre-eclampsia as defined: (Magpie trial)
      • SBP >= 170/>= 110 and at least 3+ proteinuria
      • >=150/100 and 2+ proteinuria with at least 2 signs/symptoms of imminent eclampsia
    • Imminent eclampsia (MAGPIE trial)
      • Pre-eclampsia with two or more signs of CNS (imminent eclampsia) 
        • Frontal headache
        • Visual disturbance
        • Altered level of consciousness
        • Hyperreflexia
        • Epigastric tenderness

SUMMARY MAGPIE TRIAL

• 10000 women
• Severe pre-eclampsia, eclampsia or imminent eclampsia
• Mg 4g IV over 20 minutes then 1g/hr for 24 hours
• Halved risk of eclampsia
• Reduces risk of maternal death (not statistically significant)
• Neuroprotective (Cochrane follow-up) 

INDICATIONS FOR DELIVERY PRE-ECLAMPSIA

• Timing of delivery
  • If <23 weeks —> Almost certainly needs termination
• Maternal morbidity 70% and perinatal mortality >80%
• Indications for delivery
  • Maternal
    • Gestational age >= 37 weeks
    • Inability to control HTN
    • Deteriorating platelet count
    • Intravascular haemolysis
    • Deterioration liver/renal function
    • Persistent neurological symptoms
    • Persistent epigastric pain, nausea or vomiting with LFT derangement
    • Pulmonary oedema 
  • Foetal
    • Placental abruption
    • Severe IUGR
    • Non-reassuring fetal status 
• If <34 weeks
  • Delivery should be delayed for 24-48 hours if possible for steroid benefit to be seen (only 60% of women suitable for this though)
• If HELLP syndrome, expectant management is harmful and should not be attempted
• Ideally, control HTN and maternal derangement prior to delivery if >37 weeks 

HELLP syndrome

• Variant of severe pre-eclampsia
• More common in multigravid
• Nulliparity is NOT a risk factor
• 0.1-0.2% of all pregnancies and 20% of those with severe pre-eclampsia
• Hypertension may be absent initially
• 30% of cases occur post-partum, sometimes with no gestational pre-eclampsia (20%)
• Often confused with other causes of RUQ/abdominal pain (assume in any woman >20 weeks with abdo pain)
• Haemolysis, elevated liver enzymes and low platelet count
• MgSO4 may be indicated
• Consider platelet transfusion if risk of operative birth or significant bleeding 

• Most common presentation is RUQ pain and tenderness
• HTN and proteinuria in 80% of cases
• Serious morbidity may occur from DIC, abruptio placentae, acute renal failure, APO, subcapsular haematoma and retinal detachment

Lab criteria
• Microangiopathic haemolytic anaemia with schistocytes
• Plt <100
• Total bili >20micromol/L
• Serum AST >2x ULN 

Complications
• DIC (21%)
• Subcapsular liver haematoma is potentially fatal complication (need CT abdo/pelvis if stable) – seen in 1%
• >50% maternal and foetal mortality even with immediate management
• Spontaneous hepatic or splenic haemorrhage
• End-organ failure
• Abruptio placentae (16%)
• Foetal intracranial bleeding and death
• Segmental hepatic infarction 

Management
• Control HTN like usual
• MgSO4 as usual
• Obstetrics for delivery planning
• Expectant management not advised for anyone except to perhaps get steroids in if <34 weeks
• Platelets if bleeding or <20 for delivery
• Dexamethasone – No evidence of benefit 

Acute fatty liver of pregnancy

• Main DDx of HELLP
• Presents with RUQ pain, nausea/vomiting, malaise, jaundice, encephalopathy and HTN/pre-eclampsia
• Much higher risk of fulminant liver failure and encephalopathy
• More commonly have raised INR, hypoglycaemia and raised creatinine than in HELLP

HUS/TTP

Major differential if AST/ALT are not elevated but have other features of thrombocytopaenia/microangiopathic haemolytic anaemia + significant AKI more likely in HUS 

MANAGEMENT of ECLAMPSIA

• Defined as occurrence of one or more seizures superimposed on pre-eclampsia
• Seen in 2.6% of pre-eclampsia cases and 8/10 000 births
• <0.1% of all births in Australia
• NOT the most common cause of seizures in pregnancy
• Investigate and treat for this in any woman >20 weeks gestation or <4 weeks post-partum with seizure
• 1/3 of cases occur post-partum (often >48 hours after delivery)
• 15% of cases do NOT have hypertension and 15% do not have proteinuria at time of seizure
• Recurrent convulsions or prolonged ALOC suggests additional cerebral pathology (oedema, ICH, venous thrombosis) and warrants CT head after RSI and delivery 

Treatment
• RESUSCITATE – Seizures, blood pressure and plan birth
Treat seizures
• Magnesium sulphate 4g IV over 20 minutes then 1g/hour for 24 hours
• If seizures recur while on Mg (10% of patients), give another 2g IV over 5 minutes (may be repeated after 2 minutes)
• Midazolam IV if seizure ongoing/recurs while initiating or while on Mg protocol
• MgSO4 is more effective than diazepam and phenytoin in acute management and prevention
• If recurrent seizures despite mag and midaz – phenytoin 10mg/kg load 

Treat BP
• Only treat once seizures controlled with MgSO4 and if remains hypertensive as many will have BP drop with Mg and resolution of seizures • If >160/100 aim for 130-150/80-100
• Nifedipine 10-20mg PO (repeat at 45 minutes) max dose 80mg
• Hydralazine 5-10mg IV over 3-5 minutes q20min (max dose 30mg)
Slow onset of action 10-20 min with duration 6-8 hours
• Labetalol 20mg IV over 2 minutes, repeat dose 40-80mg IV q10min max 300mg
• Plan birth as soon as possible once mother stabilised irrespective of gestation
• Expectant management has 6.3% incidence of maternal death and increased risk of placental disruption
• There is NO role for continuation of pregnancy once eclampsia has occurred, even though many women appear to stabilise 

Monitoring
• Mg therapeutic level 1.7-3.5mmol/L
• Need BP and pulse every 5 minutes until stable then q30min
• Resp rate and patellar reflexes hourly
• Continuous CTG
• Strict fluid balance
• Can safely monitor for clinical signs of toxicity and then measure level if concerned
• Loss of deep tendon reflexes at 5mmol/L, respiratory depression at 10 and cardiac arrest at >10 

Magnesium side effects
• Flushing
• Flaccid paralysis or weakness
• Hyporeflexia
• Diaphoresis
• Hypothermia
• Hypotension
• Respiratory depression
• Coma
• Antidote 10% calcium gluconate 10mL IV over 5 minutes 

ALTERNATE HYPERTENSION RX
• SNP – 0.25mcg/kg/min up to max 5mcg/kg/min infusion reduces BP rapidly but duration should be <4 hours due to risk of fetal cyanide poisoning
• GTN infusion helpful esp. if APO
• Methyldopa not suitable for acute therapy
• Beta-blockers other than labetalol may reduce uteroplacental perfusion, fetal bradycardia 

FLUID THERAPY IN ECLAMPSIA
• Usually reduced circulating volume and oliguria
• Risk of pulmonary oedema with rapid fluid resuscitation
• Maintenance targeting UO >0.5mL/kg/hr
• 250-500mL fluid challenges for oliguria 

POST-PARTUM CARE

• Risk of pulmonary oedema greatest post-delivery and most maternal deaths occur then
• Initial improvement at time of delivery often followed by deterioration over 24 hours
• Continue MgSO4 for 24-48 hours post-partum
• Continue antihypertensives and change to oral preparations as able 

COMPLICATIONS OF ECLAMPSIA

Maternal
• Cerebral oedema (SBP most important predictor)
• PRES
• Intracerebral haemorrhage
Foetal
• Placental abruption
• Prematurity
• Small for gestational age
• Foetal distress 

Last Updated on September 29, 2021 by Andrew Crofton