Hypertensive Disorders in Pregnancy, Pre-Eclampsia

Question 1

Diagnostic criteria for preeclampsia

Answer 1

• Hypertension
• Proteinuria - not mandatory (> = 300mg/24 hours)
  ** * If no proteinuria
  ** Haematological -> low platelets, haemolysis, DIC
  Renal impairment
  Deranged LFTs
  New onset headache, eclampsia, altered mental status, blindness, stroke, clonus
  Pulmonary eoedema
  Uteroplacental dysfunction -> IUGR, abnormal umbilical artery Doppler wave form, stillbirth

Question 2

Cardiovascular changes in pregnancy

Answer 2

**Increase
** Blood volume
Cardiac output and stroke volume
Heart rate
Vascular compliance
Left ventricular mass

** Decrease
** Peripheral vascular resistance -> decreases until 3rd trimester, before slight increase until term
Mean arterial pressure - nadir in 2nd trimester (9% below pre-pregnancy baseline) and gradual return to pre-pregnancy levels near term

Question 3

Renal physiology in pregnancy

Answer 3

**Increase
** Renal plasma flow
GFR, creatinine clearance
Protein excretion

**Decrease
** Urea
Creatinine - should see creatinine in 40s in pregnancy

Question 4

Notes on proteinuria in pregnancy

Answer 4

**Defined as
** > 300mg protein. in24 hour urine sample or
Urine PCR > 30mg/mmol or
Urine A/CR > 8mg.mmol

**Assessment
** Dipstick, if positive -> quantify with PCR

• If 1st half of pregnancy -> probable underlying renal disease
• Develops > 20 weeks gestation -> most often A/W preeclampsia, 50% with isolate proteinuria progress to preeclampsia
• Severity should not be used to guide management

**Gestational proteinuria
** * Normotensive, proteinuria that develops > 20 weeks gestation
Perinatal outcomes favrouable
Isolated proteinuria > 300mg/day can reflect
1. New onset renal disease e.g. primary GN or
2. Unmasked renal disease secondary to systemic disorders e.g. DM, SLE or essential HT

**Investigations
** De novo non-preeclamptic, non-nephrotic proteinuria during pregnancy -> renal US, U&Es, ANA
Renal biopsy if < 24 weeks or nephrotic syndrome/renal impairment
Naturual history -> if due to presclampsia will resolve in postpartum period, usually within 3 months. Needs further investigation if persists > 12 months postpartum or associated with renal impairment

Question 5

Broad classification of hypertensives disorders in pregnancy

Answer 5

1. Chronic hypertension - predates pregnancy or diagnosed before 20 weeks
2. Gestational hypertension (41% of HTN that develops > 20 weeks)
3. Preeclampsia (35% hypertension that develops > 20 weeks)

Question 6

Notes on gestational hypertension

Answer 6

• Usually no foetal growth restriction
• Outcomes generally good though 25% will progress to presclampsia and have poorer outcomes
• Antihypertensives used in pregnancy and side effects - see below

Question 7

Preeclampsia - epidemiology, risk factors

Answer 7

• 2-8% pregnancies
• Highest risk = prior history (15-65% depending on gestation of onset)

** Risk factors
** Maternal obstetric - nulliparity, multiple gestation pregnancy, prior history, GDM
Maternal comorbid conditions - HTN, DM, CKD, BMI > 30, antiphosphokipid antibodies, SLE
Maternal genetic -> thrombolphilia, preclampsia in 1st degree relative
Other - > 40 years, assisted reproductive therapies

Question 8

Pathogenesis of preeclampsia

Answer 8

• Exact aetiology unknown
• Gestational age -> most important clinical variable in predicting both maternal and perinatal outcome
  **Stratified into 2 phenotypes
  ** EOPA (early onset) < 34 weeks
  LOPE (late onset) > 34 weeks

LOPE -> majority of preeclampsia cases
EOPA -> less common, A/W higher rates of neonatal morbidity and a greater degree of maternal morbidity. More often A/W foetal growth restriction

** Both -> increased inflammatory response
** Syncytiotrophoblast oxidative stress and placental hypoxia
EOPE - triggered by dysfunctional perfusion of placenta due to impaired placentation
LOPE - likely caused by increasing mismatch between normal maternal perfusion and metabolic demands of the placenta and foetus, coupled with a maternal prediposition to inflammation, high BMI and or high arterial pressure

Question 9

Notes on sFLT-1 and PIGF in assessment of peeclampsia

Answer 9

• Angiogenic abnormalities most informative for early preeclampsia and now used for prediction and confirmation of preeclampsia
  ** Anti-angiogenic: Pro-angiogenic ratio
  ** sFLT- 1 (soluble VEGF receptor 1): PIGF (placental growth factor)
  Changes in levels of both detected 6-10 weeks before onset of clinical PET, these changes occured earlier in women who developed preterm PET
  **Cut off of 38 -> rule out PET for one week
  85 -> detects the disease as well as adverse outcomes - high sensitivity and specificity

**PIGF
** Can be used as a rule out for preeclampsia - between 20-35 weeks gestation, if women with chronic HTN are suspected of developine PET -> NPV 98%
Confirm suspected PET -> PIGF results reduced time to clinical confirmation, reduced maternal adverse outcomes

**When to use sFLT1/PIGF ratio
**See slide

Question 10

Assessment of preeclampsia

Answer 10

**As inpatient or 3x weekly if stable outpatient
**Foetal growht measurement, CTG, maternal reflexes
Urine dipstick and PCR, no need to repeat once positive
FBC, U&Es, lFTs, uric acid
US assessment of foetal growth, amniotic fluid volume, umbilical artery flow at least every 2 weeks
Monitor and deliver when maternal of foetal abnormalities present

Question 11

Prediction and prevention of PET

Answer 11

**Prediction = foetal medicine foundation model of maternal risk factors and biomarkers

**Prevention
**Moderate exercise > 140 minutes/week
High risk - aspirin before 16 weeks until 10 days before delivery
Supplementary calcium intake

Question 12

Notes on treatment of PET

Answer 12

• Antihypertensives - do not reduce risk or PET, do reduce maternal HTN and associated maternal risks
• Definitive treatment = delivery of placenta
• If preeclampsia worsens several days postpartum -> consider retained placental products

**Indication for delivery
**Progressive maternal organ dysfunction - worsening renal/hepatic function, low platelets, neurological symptoms/signs
Inability to control BP despite 3 anti-HTN at adequate doses
Inadequate foetal growth or non-reassuring foetal status
Reversed end-diastolic flow in UA doppler
Gestational age beyond 37 weeks

All women at risk of delivery before 34 weeks gestation - antenatal corticosteroids

Question 13

Long term consequences of PET

Answer 13

• Chronic HTN, premature atherosclerosis
• Increased risk IHD, stroke, and related death
• Increased risk ESKD
• Hypertension nad metabolic syndrome in about 20% within few years of pregnancy
• Contraception - very high risk of recurrence if pregnant within 1st year of pregnancy with preeclampsia