Hypertensive Disorders in Pregnancy By Agnibho Mondal Bismoy Mondal Atrayo Law Debtanu Banerjee Debjit Ghosh
Jan 25, 2016
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!!!