HYPERTENSIVE DISORDERS IN PREGNANCY

Hypertension in Pregnancy – BP >140/90 ( either systolic or diastolic is raised )

Chronic hypertension Gestational hypertension ( only hypertension +) Chronic hypertension

20wk 12wk PP
Pre-eclampsia ( HTN + proteinuria
or end organ damage )

Eclampsia
• Features of Severe Preeclampsia
+
General Tonic Clonic Seizures / coma

Preeclampsia superimposed on chronic hypertension

• Features of chronic hypertension
+
BP suddenly becomes uncontrollable after 20 weeks, OR
• New onset proteinuria after 20 weeks, OR
• Signs of end organ damage after 20 weeks

PATHOGENESIS - PLACENTA FORMATION

Pre-eclampsia is best described as a pregnancy-specific syndrome that can affect
virtually every organ system.
Before understanding the pathology lets understand about trophoblastic invasion first.

1. Human placental formation begins with the

trophectoderm, which gives rise to a
trophoblast cell layer encircling the blastocyst.
2. By the eighth day postfertilization, after
implantation, trophoblasts differentiate:
• Into an outer layer - syncytiotrophoblasts
• And an inner layer- cytotrophoblasts.
These cytotrophoblasts further divide into:
 • The endovascular trophoblasts replace the cells of the spiral artery lumen and convert
these arteries of high resistance to low resistance, high flow vessels – This process is
known as trophoblastic invasion

Trophoblastic invasion

1st wave of invasion

v
2nd wave of invasion

Trophoblastic Invasion occurs in 2 waves:

• 1st Between 8-10 weeks: up to the Decidual segments of spiral arteries
• 2nd Between 16 -18 weeks: up to Myometrial segments of spiral arteries.
Ø Lets comeback to pathophysiology again.
• Two areas are being affected. 1st is called placental syndrome . This leads to
sequel affecting mother & it is called as maternal syndrome.
• Major factor leading to start of pathology is , “maternal intolerance to paternal
factors

Maternal intolerance to paternal factors

Incomplete trophoblastic invasion

Decreased perfusion , hypoxia & Uteroplacental insufficiency

systemic inflammatory response

Release of antiangiogenic factors , metabolic

factors & inflammatory leucocytes
 These inflammatory mediators leak into maternal blood & give rise to “ Maternal syndrome “.

Antiangiogenic factors , metabolic factors &

s sFLT1
angiog enic factor inflammatory leucocytes in maternal blood
Raised anti
in (Eng)
& endogle

factors –
angiogenic Injure endothelial cells
Decreased
F
VEGF & PIG

Decreased NO production
Vessels become very sensitive
Imbalance in prostaglandins to vasopressor
­TXA2 , ¯PGI2

Now these to effects , injured endothelial cells & vasospasm lead to all manifestations-

INJURED ENDOTHELIAL CELLS (EFFECTS ) VASOSPASM

• Edema • LIVER - Periportal necrosis , rasied AST/ALT

• Haemoconcentration • RENAL - Proteinuria & glomerular
• Proteinuria endotheliosis( ¯ GFR , ­uric acid & creatinine
• Thrombocytopenia (Consumed in forming • CEREBRAL - Headache , visual disturbances,
platelet plugs) convulsions
• Haemolysis • PLACENTA - IUGR , doppler changes
• Pulmonary edema
v PREECLAMPSIA
Hypertension + proteinuria or

+ sign of end organ damage, or

+ Uteroplacental insufficiency

• Proteinuria
ü ³ 300 mg/24 h, or
ü Urine protein: creatinine ratio ³ 0.3, or
ü Dipstick 1+ persistent
• Signs of end organ damage
Thrombocytopenia • Platelet count <100,000/µL
Renal insufficiency • Creatinine level >1.1 mg/dL or doubling of baseline
Liver involvement
Cerebral symptoms
• Serum transaminase levels twice normal
Pulmonary edema • Headache, visual disturbances, convulsions

• Classification of Preeclampsia
NON-severe Severe
> 140/90 mm Hg but
BP > 160/110 mm Hg
< 160/110 mm Hg
or Signs of end organ
Absent Present
damage

PREDICTION OF PREECLAMPSIA
ü Clinical Risk Factors
ü Biochemical markers
ü Biophysical: Ultrasound (Doppler)
Clinical (Risk Factors) Biophysical
1. Primigravida, Twin/Molar Pregnancy 1. Raised PI in uterine A (11-14 week)
2. P/H : Hypertension, preeclampsia, CKD 2. Notching of uterine A waveform
3. Obesity: BMI>35 (mid-trimester)
4. New Paternity 3. High umbilical A Resistance
5. Thrombophilias (late change – 3rd trimester)
6. APLA, Protein C, S deficiency

ü Biochemical marker
• ­SFLT-1, Endoglin -1
• Decrease VEGF & PIGF

EFFECT ON PREGNANCY
1. Antepartum haemorrhage: (Abruptio Placenta)
2. Postpartum haemorrhage
3. Increased risk of Caesarean section
4. IUGR
5. Prematurity

Preventive management:
ü Low dose aspirin 75mg once daily to be started before 12 weeks of pregnancy
ü Calcium (2g/ day), in case of calcium deficient patient
ü No other method has been proved to be beneficial.

NOTE: SALT RESTRICTION was not proven to be beneficial

EVALUATION OF PATIENT
• History taking
ü Ask for associated clinical features
ü Rule out high risk factors
↓
ü Measure BP
ü If BP > 140 /90mm Hg on 2 occasions 4 hrs apart
↓
ü Measure urine protein by dipstick
ü Classify patient into: Gestational Hypertension (BP > 140 /90mm hg, Proteinuria Absent)
Preeclampsia (BP > 140 /90mm hg, Proteinuria 1+)
↓
ü Do Per/Abdomen examination: Look for Signs of tenderness (? Abruption)
Assess FHS / foetal growth
Assess foetal well-being: USG Doppler / Cardiotocography
• Send following Investigations (maternal)
ü CBC (Esp. Platelet) → (if Thrombocytopenia) → PT/INR
ü LFT: AST/ ALT VALUES (x2 Normal)
ü RFT: Sr. uric acid > 4.5 gm, Sr. creatinine >1mg/dl
ü 24 Hour Urinary Protein
ü Fundus examination

MANAGEMENT
• Main principle: rule out severe features
ü Admit if any severe signs present
ü Treatment threshold , BP >140/90 ( Threshold changed after results of CHAP study)
ü Antihypertensives – labetalol > Nifedipine > Methyldopa ( in decreasing order of preference )
SEVERE NON-SEVERE
Admit Do not admit
Investigations repeated thrice / week Investigations repeated twice /week
USG – repeat every 2wk USG – repeat every 2week
Deliver – 34wk Deliver – 37wk

Early delivery –

• Inability to control BP
• Worsening of organ damage
• Continued neurological sign
• Worsening fetal condition
• Eclampsia & HELLP syndrome
• Abruption or fetal death
v ANTI HYPERTENSIVE DRUGS IN PREGNANCY
Antihypertensives Dosage Comments
Labetalol 100-1200mg BD C/I - Asthma , heart
block , myocardial
Ds

Nifedipine 20-120mg BD Always given oral

Methyldopa 500mg-2g Stop in PP period.
Slow acting drug

• DOC in Chronic / Gestational hypertension/ Pre-eclampsia: Labetalol

• DOC in Hypertensive Crisis: Labetalol > Hydralazine
• Drugs with no adverse effect on breast feeding:
ü Labetalol
ü Nifedipine
ü Captopril/Enalapril
ü Atenolol
ü Metoprolol

v ECLAMPSIA
• Features of Severe Preeclampsia
+
Convulsions ( tonic clonic / partial /multifocal )
Imminent eclampsia
• Symptoms
ü Severe & persistent occipital or frontal headaches
ü Visual disturbance: blurred vision, photophobia
ü Epigastric and/or right upper-quadrant pain
• Signs
ü BP > 160/ 110 mmHg
ü Proteinuria +++ or more
ü Altered mental status
ü Hyper-reflexia
ü Oliguria
• Treatment
ü Resuscitative measures: Airway management
ü MgSO4
ü Anti HTN: IV Labetalol
ü Delivery: Termination of pregnancy irrespective of gestational age

ü MgSO4 (Magpie trial – was done to ascertain the efficacy of MgSO4 in Eclampsia Mx)
ü Causes cerebral vasodilatation
ü Blocks calcium channel: therefore, it should be used cautiously with Nifedipine (CCB)
 ü MgSO4 is neuroprotective
ü Maintenance dose has to be adjusted in case of impaired renal function
ü Uses:
§ Severe PE
§ Impending eclampsia
§ Eclampsia
§ Other uses: for neuroprotection in preterm delivery < 30 weeks

• MgSO4 (Two regimes)

PRITCHARD ZUSPAN

LOADING DOSE 4G IV (20%) + 10g IM (5g in each buttock ) 4g IV – 20% solution

Maintenance 5g IM in alternate buttock , every 4hr 1-2g IV/hr

Therapeutic range of MgSO4 – 4 to 7 mEq/L

ü Monitoring for magnesium toxicity is done before giving each maintenance dose:
i. Urine output should be at least 30 mL/hr
ii. Patellar reflex should be present: Disappearance of patellar reflex is the first sign of
MgSO4 Toxicity
iii. Respiration rate should be more than 16/min.:
Blood levels
Loss of DTR >7meq/lt 9mg/dl
Resp depression >10meq/lt 12mg/dl
Resp paralysis & cardiac arrest >25meq/lt 30mg/dl

iv. Best marker of magnesium toxicity is pulse oximetry as oxygen

saturation begins to drop before there is evidence of respiratory
depression.
ü Antidote for MgSO4 toxicity is 10 mL, Injection of 10% calcium gluconate

v HELLP SYNDROME
• It is a complication of severe pre-eclampsia.
• In 10- 15% cases, BP of the patient is normal: (NOTE: Not in all patient of HELLP
syndrome BP is high)
• Most commonly seen in 3rd trimester
• Maternal mortality rate – 1%
• Recurrence rate – 25%
• The mnemonic HELLP stands for:

1. H à HEMOLYSIS
• Its Diagnosis requires any one of the following:
 ü Abnormal peripheral blood smear (schistocytes burr cells)
ü Elevated serum bilirubin (> 1.2 mg/dL)
ü LDH ³ 2x upper limit of normal
ü Low serum haptoglobin
ü Significant drop in Hb level unrelated to blood loss
2. E à Elevated L à Liver Enzymes AST or ALT > 2x upper limit of normal
3. Là Low P à Platelet count < 100,000 /mm3
ALL THREE FEATURES HAVE TO BE PRESENT FOR DIAGNOSIS OF HELPP SYNDROME

• MISSISSIPPI CLASSIFICATION OF HELLP SYNDROME

ü Class I (severe): Platelet count < 50,000/mm3
ü Class II (moderate): Platelet count is between 50 and 100,000/mm3
ü Class III (mild): Platelet count is between 100,000 and 150,000/mm3
• MANAGEMENT
ü If pregnancy is ³ 34 weeks → give prophylactic MgSO4 and immediately deliver.
ü If pregnancy is < 34 weeks → give Corticosteroids and MgSO4 and deliver.

Drug Dose Effects

• 100 mg PO BD up to 800 mg PO every 8 hours
(Max 2400 mg)

Acute Hypertension:
• Iv Labetalol 20 mg • First line
Labetalol
↓ • ↑ risk of IUGR.
• Measure BP after 10 min
↓
If still high
↓
• Iv Labetalol 40mg (Upto 220mg)
• Iv 5-10 mg over 20 min
• Measure BP every 5 min
Hydralazine Postural Hypertension
• Max dose upto 30 mg
• Maintenance: 1-5 mg/ hr
Nifedipine • 10-20mg oral

*sodium nitroprusside is not used in pregnancy , because of risk of cyanide toxicity.

v Postpartum care

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