Hypertensive

Disorders in

PregnancyBy

Agnibho Mondal

Bismoy Mondal

Atrayo Law

Debtanu Banerjee

Debjit Ghosh

Incidence

Hypertensive disorders are among the most

significant & still now unresolving problem

complicating almost one in ten pregnancies

Responsible for 16% of Maternal Mortatlity in

developing countries

Commonest cause of iatrogenic prematurity

accounting 15% of all premature births & 20%

of very LBW births

Hypertension in Pregnancy

Systolic B.P. > 140 mmHg

and/or

Diastolic B.P. > 90 mmHg

Documented on two occasions

At least 6 hours apart

Not more than 7 days apart

Other Criteria (Not part of definition currently)

SBP increased by 30mmHg

DBP increased by 15mmHg

Mean Arterial Pressure increased by 20mmHg

Classification

Hypertension in Pregnancy

Gestational Hypertension

Preeclamsia-Eclampsia

Chronic Hypertension

Preeclamsia superimposed on Chronic Hypertension

Normal Blood Pressure changes in

Pregnancy

What is Significant Proteinuria in

Pregnancy

Total protein in 24 hours urine >

300mg

Protein : Creatinine ratio in random

sample > 0.1

Gestational Hypertension

New onset of hypertension after 20

weeks of gestation without

proteinuria, followed by return of

B.P. to normal within 12 weeks post-

partum.

Preeclamsia

New onset of hypertension after 20

weeks of gestation along with properly

documented proteinuria, followed by

return of B.P. to normal within 12

weeks post-partum.

Preeclamsia Gestational Hypertension Proteinuria

Eclampsia

Generalized tonic-clonic seizure in a

patient with Preeclampsia not attributed

to any other cause.

Eclampsia Preeclampsia

Seizure/

Convulsion/

Coma

Chronic Hypertension in Pregnancy

Hypertension before pregnancy /

Diagnosed before 20 weeks of pregnancy

not due to gestational trophoblastic

disease.

Hypertension diagnosed after 20 weeks but

persistent after 12 weeks postpartum

Chronic HTN & Pregnancy :

Etiology :

1. Essential HTN (Most Common)

2. Secondary HTN :

1. Genetic: Glucocorticoid remediable aldosteronism,

Liddle Syndrome

2. Renal : Parenchymal, Renovascular

3. Endocrine : Primary hyperaldosteronism, cushing

syndrome, Pheochromocytoma

4. Vascular : Aortic coarctation, Estrogen use

5. Others

Superimposed Preeclampsia On

Chronic Hypertension

New onset proteinuria in hypertensive

women but no proteinuria before 20 weeks'

gestation

A sudden increase in proteinuria or blood

pressure or platelet count < 100,000/L in

women with hypertension and proteinuria

before 20 weeks' gestation

Risk Factors

Genetic

Age & parity

Partner factors

Pregnancy Factors

Underlying Medical Conditions

Others

Risk Factors

Risk Factors: Cont.

Genetic

Genetic Predisposition

Family History

Race & Ethnicity

More Common in black & Asians

Pregnancy by ovum donation

Age &Parity

Teenage pregnancy

Age>35 yrs

Long interval between

pregnancy

Nulliparity

Partner Factors

Change of partner

Limited sperm exposure

Pregnancy by donor

insemination

Partner fathered an eclampticpregnancy

Risk Factors: Cont.

Pregnancy Factors

Multiple pregnancy

Hydatiform mole

Hydrops fetalis

Fetal chromosomal anomaly

(trisomy 13)

Underlying Medical Diseae

Chronic hypertension

Diabetes mellitus

Renal Disease

Cardiovascular disease

Hyperthyroidism

Sickle cell disease

Others

Obessity

Psychological stress & strain

Previous history of preeclamsia

PATHOPHYSIOLOGY:

2 stage model for

preeclampsia

Stage 2

Maternal syndrome

(HTN, proteinuria,

Endothelial dysfunction)

Stage1

Reduced placental implantation ???

Reduced placental

implantation –Stage-1

PREDISPOSING FACTORS:

Abnormal implantation

Association with microvascular diseases (diabetes,

hypertension etc.)

Association with large placentas (hydrops, multiple

gestation, hydatidiform mole)

Net effect

Replacement of endothelial lining & muscular arterial wall by fibrinoid formation

Distended tortuous spiral arteries

Low resistence, low pressure high flow system

uterine artery DOPPLER

In preeclamptic mother:

Showing early diastolic NOTCH

Decreased EDF

(due to high resistance)

In normal mother

ETIOLOGICAL FACTORS

Placental hypoxia

Immunological factors

Placental enzymes

Genetic factors (MTHFR, F5,)

Oxidative stress

???????????????????

What causes maternal

syndrome

Stage 2

Maternal syndrome

(HTN, proteinuria,

Endothelial dysfunction)

Stage1

Reduced placental implantation ???

What gets into maternal circulation??????

Maternal Syndrome

stage-II

not just hypertension and

proteinuria

But also involves different end

organs

Physiology of maintain

uteroplacental flow in Normal

pregnancy

Placenta releases angiotensinase

destruction of angiotensin-II(a potent

vasoconstrictor) BP stabilized

Vascular synthesis of PGI-2 and NO in

excess vasodilation BP stabilized &

uteroplacental flow maintains

Release of VEGF restores

uteroplacental flow

Normal balance of agonist &

anta-gonistic factors:

1.vasodialator &

vasoconstrictor

2. angiogenic and

antiangiogenic factors

1.vasodialator & vasoconstrictor

vasodialator

NO

PGI-2

vasoconstrictor

Angiotensin-II

Endothelin-I

placenta

Syncytiotrophoblast

& endothelium

2. angiogenic and

antiangiogenic factors

Angiogenicfactor

•VEGF

•TFG-beta•PlGF

Antiangiogenicfactor

• sFlt-1

• sEng

Pathophysiology for different

organ damage:

Basic mechanism of different organ

damage:

Increased vasoconstriction

Decreased organ perfusion :

Increased endothelial dysfunction – capillary

leak, oedema, Pulmonary oedema, proteinuria.

Activation of coagulation: DIC, low platelets

Haemoconcentration

Pathophysiology of different

organ damage:

Organ damage

utero-placenta IUGR

Hematological Epistaxis, DIC like features, hemoconcentration

CNS Cerebral edema, cerebral hge seizures

Heart Subendothelial hge , focal necrosis & hge,

cardiomyopathy, heart failure

Lungs Pulmonary edema, hemorrhagic brochopneumonia

Kidneys glomerular endotheliosis, oliguria

liver Subcapsular hge, ischaemiaperiportal necrosis, HELLP

CVS involvement:

• ↑afterload↑ed peripheral

resistance

• ↓preload ↓ed pregnancy induced

hypervolumia

•Pulmonary leak edemaalveolar endothelial

damage & ↓ed plasma oncotic pr

•hemoconcentration & ↑edhematocrit

↓ed blood volume than normal pregnancy(16%

vs 50%):

Heart failure

↓cardiac output

Hematological system

Thrombocytopenia & other PL

abnormality:

• ↑ed PL activation & degranulation,

• ↓ed life span.

• Corelates well wth disease severity.

Intravascular hemolysis

• endothelial damage & altered fluidity of erythrocyte membrane d/t change in serum lipid content →↑ed LDH, spherocytosis, reticulocytosis

• microangiopathic hemolysis

↑ed coagulation & fibrinolysis

• Feature like DIC

• Release of thromboplastin

• ↓fibrinogen

• AT-III

• plasminogen

Renal system involvement:

↓ed renal perfusion :(d/t ↓ed blood volume & ↑ed

afferent arteriolar pr.)

↓ed GFR : d/t

glomerular capillary endotheliosis

Endothelial dysfunction + mesangial swelling + BM

disruption

(but podocyte disruption minimal)

Oliguria

↑ed creatinine level

↑ed uric acid

Hepatic involvement:

Periportalhemorrhage

hematoma formation

Rupture

epigastric pain

Brain involvement:

Acute severe HTN

cerebrovascular overregulation

Vasospasm

Parenchymal ischemia

Cytotoxic edema

sudden ↑↑SBP

exceeds normal range of cerebrovascular autoregulation

Forced vasodilation + hyperperfusion

Vasogenic edema

Lungs involvement:

High SBP

↑ed arteriolar pr

↑ed extravasation of blood into alveoli + rupture of arteriole

Pulmonary edema, hemorrhagic brochopneumonia

Diagnosis

of HDP

Diagnosing Preeclampsia-Eclampsia:

• Blood pressure ≥ 140/90 mm of Hg (at

or after 20 weeks of gestation) on 2

occasions at least 6 hours apart during

bed rest. (≥ 160/90 mm of Hg is

severe disease)

• accompanied by one or more of:

o significant proteinuria

-urinary dipstick 2+

-random urinary

protein/creatinine

ratio ≥ 30 mg/mmol

-24 hour urine excretion ≥300

mg/24 hrs

o renal involvement

-serum creatinine ≥ 90 mmol/L

or

-oliguria (<400 ml in 24 hrs)

o haematological involvement

-platelet count<1 lakh

o liver involvement

-raised AST, ALT (>70 IU/l)

-severe upper abdominal pain

o neurological involvement

-severe headache

-persistent visual disturbances

-hyperreflexia with sustained

clonus

-convulsions (eclampsia)

-stroke

o pulmonary oedema

o fetal growth restriction

o placental abruption

HELLP Syndrome:

-Hemolysis:

● LDH > 600 U per L

● Abnormal PBS showing schistocytes,

burr cells.

● Serum bilirubin ≥ 1.2 mg/dL

-Elevated Liver enzymes:

● AST and ALT >70 IU/l

-Low Platelet count:

● <1 lakh/cubic mm

History -special points• Patient Particulars: Age young or >35 yrs, nulliparity, low SES -

risk factors• Chief Complaints: Swelling of legs or other parts of body (face,

abdominal wall, vulva, or whole body and tightness of the ring on the finger.) Severe disease -Headache, visual changes, nausea, vomiting, abdominal or epigastric pain, and oliguria, insomnia, vaginal bleeding, seizures.

• Present Obstetric History: Onset, Duration, Severity of Htn/Proteinuria and H/o drug intake

• Past Obstetric History: H/o any hypertensive disorder of pregnancy with week of onset. Also note the interval since last pregnancy, gestational age at delivery. Any foetal complications.

• Past History: of pre-existing hypertension, renal disease, diabetes, thrombophilia, or thyroid disorder.

• Family History: of Htn, Preeclampsia, Diabetes, CVD

Physical Examination:● Obesity/BMI>35 kg/m2

● Weight (serial measurements): Gain in wt at the rate of >1 lb a week or

>5 lbs a month in the later months of pregnancy may be the earliest sign

of preeclampsia.

● Oedema (all sites): has to be pathological, meaning visible pitting edema

demonstratable over the ankles after 12 hrs bed rest.

● Pulse (in all 4 limbs)

● B.P.:

○ right arm, sitting/supine, arm at level of heart, cuff length=1.5

times of arm circumference, diastolic BP is the disappearance of

Korotkoff sounds (phase V)

○ taken on 2 occasions at least 6 hrs apart for confirmation of

diagnosis.

● CVS examination: auscultation for heart rate, rhythm, splitting of S2,

murmurs.

● Ophthalmic examination: retinal haemorrage, nicking of veins,

arteriole/vein ratio 3:1 from 3:2, papilloedema

● Deep tendon reflexes: hyperreflexia/presence of clonus

How to Measure Blood

Pressure

Sitting Position

Patient Relaxed

Arm well supported

Measured in right arm

Cuff at heart level

Proper cuff size (80% of

arm circumference)

Slow deflation of bladder

(2mmHg/s)

From start of Korotkoff I to

end of Korotkoff V

Obstetric Examination:

Nothing special is found except features of IUGR, oligohydramnios in some cases.

Maternal Investigations:

Tests may be abnormal even when BP elevation is minimal.

• Urine dipstick testing for proteinuria

o Quantitation by laboratory methods if ≥ 2+ on dipstick testing

o Urinary ACR(albumin-creatinine ratio) to detect significant

proteinuria (≥30mg/mmol)

o 24 hour urine collection is not necessary in routine clinical management

• Routine Blood Examination: TLC, DLC, Peripheral Smear, BT, CT, Hb%

• Serum Urea, creatinine, electrolytes including lactate dehydrogenase (LDH)

and uric acid.

• Liver function tests (LFT) -AST, ALT >70 IU/l

• Skiagram of chest –PA view, Pulmonary Capillary Wedge Pressure (PCWP),

Brain Natriuretic Peptide (BNP) for detection of pulmpnary oedema

Foetal Investigations:

• Cardiotocograph (CTG)

• Ultrasound scan (USS) assessment of:

o fetal growth

o amniotic fluid volume (AFV)

o umbilical artery flow (Doppler)

Differential Diagnosis Pre-existing hypertension,

New/gestational hypertension

Pre-eclampsia

Eclampsia

Exacerbation of underlying renal disease/Superimposed pre-eclampsia-eclampsia

SLE

ΔΔ ECLAMPSIA

-Epilepsy,

-Intracranial haemorrhage/thrombosis,

-meningitis,

-cerebral malaria,

-amniotic fluid embolism can mimic eclampsia.

There are several indicators used to

assess the severity of PIH

Blood pressure

Proteinuria

Other associated

abnormalities

N.B: Grades of proteinuria (in g/L): Trace=0.1, 1+=0.3, 2+=1, 3+=3,

4+=10

Pregnancy induced

Hypertension

Gestational HTN

● BP ≥ 140/90mmHg

●No evidence of underlying cause of HTN

●No associated symptoms

●Comes to normal within 6 wks of delivery

Pre-eclampsia

Non Severe Severe

Eclampsia

PreEclamsia

+

Convulsion

±

Coma

N.B: Pre-eclampsia is principally a

syndrome of signs and when symptoms

appear it is usually late.

Assessment of the severity of pre-

eclampsia is given in the next slide.

ABNORMALITIES NONSEVERE (mild) SEVERE

Blood pressure ≥140/90mmHg but

<160/110mmHg

≥160/110mmHg

Proteinuria ≤2+ ≥3+

Oliguria Absent <400ml/day

Headache Absent Present

Visual disturbances Absent Present

Platelet count Normal Thrombocytopenia

(100,000/mm3)

HELLP syndrome Absent May be present

ALT,AST >70 IU/L

LDH>600 IU/L

Bilirubin >1.2g/L

Serum transaminases(AST,ALT) Normal (<40 IU/L) Elevated

Epigastric pain Absent Present

Fetal growth restriction Absent Obvious

Pulmonary oedema Absent present

IMMEDIATE REMOTE

MATERNALFETAL

● IUGR

● IUD

● Asphyxia

●Prematurity

During Pregnancy During Labour During

puerperium●Eclampsia(2%) (more in acute cases)

●Accidental hemorrhage

●Oliguria

●Diminished vision

●HELLP Syndrome

●Cerebral hemorrhage

●ARDS

● Eclampsia

● Postpartum

hemorrhage

●Eclampsia(

in < 48hrs

of delivery)●Shock

●Sepsis

●Residual hypertension

●Recurrent pre-

eclampsia●Chronic Renal Disease

• Abruptio placentae

MATERNAL FETAL

●Asphyxia

●Prematurity

●Hypoxia & IUD

Injuries Systemic

●Tongue bite

●Injuries due

to fall

●Bed sore

●PULMONARY: edema,

pneumonia, ARDS,

embolism

●CARDIAC: acute left

ventricular failure

●RENAL: renal failure

●HEPATIC: necrosis,

subcapsular hematoma

●CNS: cerebral

hemorrhage,

edema(vasogenic)

Vision

●Diminished

vision due to

retinal

detachment or

occipital lobe

ischemia

Hematology

●Low platelet

count

●Disseminated

Intravascular

Coagulation

Postpartum

●Shock

●Sepsis

●Psychosis

HELLP Syndrome

This is an acronym for Hemolysis (H), Elevated Liver

enzymes (EL), and Low Platelet count (LP).

It is a rare multisystem disorder that complicates

pregnancy with lab evidences of micro-angiopathic

hemolysis, hepatic dysfunctioning &

thrombocytopenia.

It is a complication mostly associated with Pre-

eclampsia but can also be diagnosed (rarely though) in

the absence of these disorders.

HEMOLYSIS

(due to passage of

RBCs through partially

obstructed vessel)

s)HEPATIC

DYSFUNCTION(due to

intravascular fibrin

deposition & sinosoidal

obst.)

Decreased Liver blood

flow

HELLP

SyndromeTHROMBO-CYTOPENIA

(due to platelet

aggregation & dipositionin the sites of endothhelial

damage)

Diagnosis

Hemolysis (Hallmark

of the triad)

Elevated Liver

Enzymes

Low Platelet Count

LDH>600IU/L Liver Enzymes (<100,000/cu.mm)

Low serum

haptoglobin

High serum bilirubin

(>1.2 mg/dl)

High ALT & AST

(>70 IU/L)

Abnormal PBS

(Schistocytes, burr

cells)

Later-low Hb%

• ●Epigastric /Right Upper Quadrant pain

• ●Nausea, Vomiting1. Clinical Features:

2. Lab Investigation:

Usual Time of Onset

Relation to delivery Percentage

Antepartum 72

Post_partum 28

≤48 hours 80

>48 hours 20

Gestational Age(Weeks)

21-27 10

28-36 70

>37 20

Treatment

Can we predict whether a pregnancy would be complicated with Hypertensive disorders?

Endothelial Dysfunction/Oxidant Stress

Feto-Placental unit Endocrine Dysfunction

Renal Dysfuntion Misc

Placental Perfusion/ Vascular Resistance related Tests

Uterine Artery Doppler Velocimetry

AT- III

ANPFree fetal DNA

Adapted from Conde-Agudelo and associates (2009)

Indirectly, YES…

How effective are they???

• is most promising, but currently, none of them is completely suitable for clinical use.

• As a result of these trials, some methods to prevent Preeclampsia have been theorized…

Uterine Artery Doppler Velocimetry (abnormal flow resistance/ diastolic notch in

2nd/ 3rd trimester)

Trials of different preventive methods and their outcomes

Sibai et al. Lancet 365:785-99, 2005.

The efficacy of the preventive methods is questionable too…

The investigative procedures are cumbersome, time-consuming and expensive…

MANAGEMENT OF PREECLAMPSIA & PIHAfter early diagnosis, further

management depends on …

Severity of disease

Fetal maturity

Condition of cervix

What is EXPECTANT MANAGEMENT?

NO

YES

Neither forced nor restricted

Treatment proper

For mild - controlled disease :

Thereafter induction may be done at term depending on cervical condition

Can be managed expectantly till term at home/hospital and continued till term.

71

Hospitalisation???

• Gestational HTN : only if severe HTN

• Preeclampsia : If diastolic pressure≥ 100mm of Hg OR, there is proteinuria OR, there is fetal compromise.37 completed weeks of gestation.

When should we use antihypertensive to control the BP???

• Acute management of severe hypertension (BP > 160/110: to

prevent stroke)

which may require parenteral therapy.

What are the options???

Acute

Hydralazine inj.: now available

LabetalolInjection

Nifedipinecapsule/Tablet

Long term

Methyl Dopa250 mg Tab.

Labetalol Tablet 100 mg

Nifedipine5,10,20 mg

But wait…can antihypertensives be used in expectant management???

• In non-severe Pregnancy hypertension– No clear Evidence of benefit other than to reduce The

Frequency of Episodes of Severe hypertension

• May Adversely Effect Fetal Growth velocity

For severe-uncontrolled disease:

LUCS OR In case of very severe uncontrolled disease elective LUCSmay be done without induction

Preinduction

Cervical ripening with prostaglandin/osmotic dilators followed by induction

Termination is considered

76

If failed

For early onset severe preeclampsia:

• Controversy regarding termination in early onset disease

• But there is no beneficial role for mother, as well as perinatal mortality is also high instead of conservative management

• So…

77

termination is seriously considered

Fetalconsiderations

Prematurity

Stillbirth

Newborn asphyxia

Maternal considerations

– Worsening of disease

Complications

DELIVERY CARE

• For any HDP, vaginal delivery should be considered unless a CS is required for the usual obstetric indications.

• Antihypertensives : continued throughout labour to maintain BP < 160/110 mmHg .

• 3rd Stage : actively managed with oxytocin 5 units IV or 10 units IM, particularly in the presence of thrombocytopenia or coagulopathy. (I-A)

• Ergometrine should NOT be given

Management of Eclampsia :

Prompt delivery of fetus to achieve cure

Avoidance of diuretics & hyper osmotic agents

Limitation of I.V fluid

Intermittent antihypertensive to control BP judiciously

Control of convulsion by MgSO4 (IM/IV route)

Protection & supporting care during convulsionProtection in a railed cot

Protection of airway & prevention of tongue bite

Correction of hypoxia & acidosis

Managed in Eclampsia room.

80

to control convulsion

“It is the most effective drug to

control even recurrent seizures

without any central nervous

system depression to mother &

fetus”

81

Magnesium

sulphate

Dosages

→Paralysing agent & Intubation

→Amobarbital 250mg I.V over 3 min

In case of uncontrolled recurrent seizure (10-15%) : →additional 2-4g of 20% solution IV @ <1g/min

→4gm of 20% solution IV slowly(@ <1g/min) + 10g of 50% solution deep IM in upper & outer quadrant of buttock by a wide bore needle then 5g

of 50% solution IM 4hrly similarly

IM regime (Pritchard protocol):1955

→4 gm loading in 100ml of IVF over 15-20 min followed by 2-3g/hr in 100 ml IVF as maintenance

I.V regime (Sibai protocol):1990

IM doses are as active as IV doses in controlling seizures

82

Some more about Magnesium• Duration : 24 hrs from last convulsion or from delivery which one is

longer.(This is called Magnesium sulphate prophylaxis in severe preeclampsia.)

• Features of toxicity:i> Impaired breathing(@8-10meq/L)ii>Arrythmia and Asystole ( @10-13 mEq/L)iii>Decreased/absent deep tendon reflex

(Hyporeflexia at 4 mEq/L, loss of patellar reflex at 7-10 mEq/L)iv> Shock (>13 mEq/L)

• For a maintenance dose following must be present -

Serum Mg level 4-7meq/l(twice daily)

Having Patellar reflex

Urine output >30ml/hr

RR>12/min

83

WHAT If magnesium toxicity is suspected???

Administration of 10mL of 10% calcium gluconate (1 g in total) as a slow intravenous push.

Serum magnesium level obtained.

Magnesium infusion should be discontinued, supplemental oxygen administered,

Thank You!!!