HYPERTENSIVE

DISEASES OF
PREGNANCY
Irene Maria Elena
Departemen Kebidanan dan Kandungan
FK UKRIDA

 More than 80% of maternal

deaths worldwide are due to five
direct causes : hemorrhage,
sepsis, unsafe abortion,
obstructed labour and
hypertensive disease of
pregnancy

HYPERTENSION ???
Is diagnosed when the blood
pressure is at least 140mmHg
systolic or 90mmHg diastolic

PROTEINURIA ???
Is defined as urinary protein of
at least 300mg/24 hours urine
sample, or
At least 1,000mg/random
sample of urine taken 6 hours
apart
Qualitatively, dipstick values of
traces to 1+ signify mild
proteinuria; while 2+ to 4+
signify heavy proteinuria

EDEMA ???
Is such a common finding that
its presence does not validate
the presence of preeclampsia

Risk Factors for Preeclampsia

The basic classification describes 4 types

of hypertensive disease :
1. Gestastional hypertension --evidence for the preeclampsia
syndrome does not develop and
hypertension resolves by 12 weeks
postpartum
2. Preeclampsia and eclampsia
syndrome
3. Chronic hypertension of any etiology
4. Preeclampsia superimposed on
chronic hypertension.

Tabel 1. Diagnostic Criteria for Pregnancy-Associated Hypertension1

Condition

Criteria Required

Gestational hypertension

BP > 140/90 mmHg after 20 weeks in

previously normotensive women

PreeclampsiaHypertension and :
Proteinuria

300 mg/24h, or
Protein : creatinine ratio 0.3 or
Dipstick 1+ presistenta
Or
Platelets < 100,000/L
Creatinine > 1.1 mg/dL or doubling of
baselineb
Serum transaminase levelsc twice normal
Headache,
visual
distrubances,
convulsions
---

Thrombocytopenia
Renal insufficiency
Liver involvement
Cerebral symptoms
Pulmonary edema
a

Recommended only id sole available test

b
No prior renal disease
c
AST (aspartate aminotransferase) or ALT (Alanine aminotransferase)
Williams Obstetrics.24rd ed Chapter 40

Etiology
1. Placental implantation with abnormal
trophoblastic invasion of uterine vessels
2. Immunological maladaptive tolerance
between maternal, paternal (placental), and
fetal tissues
3. Maternal maladaptation to cardiovascular or
inflammatory changes of normal pregnancy
4. Genetic factors inclyding inherited
predisposing genes and epigenetic influences.

Gestational Hypertension
HPN without proteinuria
occuring after 20 weeks AOG or
postpartum
BP returns to normal 12 weeks
postpartum
Without history of chronic
hypertension and without signs
and symptoms of preeclampsia

Preeclampsia
Hypertension with proteinuria
occurring after 20 weeks AOG
With or without edema :
common finding in pregnancy

Severe Preeclampsia
SBP 160 mmHg or
DBP 110 mmHg
Proteinuria :
4 grams / day
+2 on dipstick
Oliguria : < 400 cc / day
*Decreased Renal Blood Flow and Glomerular
Filtration Rate

Severe Headache or Visual Disturbance

* Attributed to Cerebral edema

Pulmonary Edema or Cyanosis

* Due toHemodynamic changes predominantly
increase afterload

Severe Preeclampsia
Intrauterine Growth Restriction
*Decrease uteroplacental blood flow

RUQ or epigastric pain

*Distension of Glissons capsule of the liver

Hemolysis
*Manifests as increase serum
LDH,
hemoglobinuria, hyperbilirubinemia or the
presence of schistocytes

Elevated Liver Enzymes

*Caused by Hepatocellular necrosis

Low Platelet Count : 100,000/mm

*Probably due to Microangiopathic hemolysis
induced by spasm

HELLP Syndrome
Triad of :
Hemolysis
Liver Enzymes elevated
Low Platelet count

Chronic HPN
BP 140/90 mmHg prior to
pregnancy or before 20 weeks
AOG and persists after 12 weeks
postpartum
Multiparity and hypertension in
a previous pregnancy help
support the diagnosis

Chronic HPN
Other causes :
Renal diseases
Interstitial Nephritis
Acute Chronic GN
SLE
Diabetic Glomerulosclerosis
Scleroderma
Polyarteritis Nodosa
Polycystic Kidney Disease
Renovascular Stenosis
Chronic Renal Failure
Renal Transplant

Chronic HPN
Endocrine Diseases :
Cushings Disease
Primary Hyperaldosteronism
Thyrotoxicosis
Pheochromocytoma
Acromegaly
Cardiac Disease :
Coarctation of the Aorta

Chronic HPN with Superimposed

Preeclampsia
Preexisting Chronic HPN with
proteinuria and signs and
symptoms of end-organ
dysfunction

Eclampsia
Presence of convulsions/seizures
in women with underlying
preeclampsia (hypertension and
proteinuria)
Seizures without preeclampsia :
Look for underlying neurologic or
other Central Nervous System
disorder

Pathophysiology
Underlying abnormality is
generalized vasospasm
Renal blood flow and GFR are
significantly lower in
preeclampsia/eclampsia
Afferent vasoconstriction eventually
leads to damage to the glomerular
membranes proteinuria
Cerebral vascular resistance is
always high in patient with
preeclampsia / eclampsia

Pathology
3 Major Pathologic Lesions :
1. Lack of decidualization of the
myometrial segments of the spiral
arteries
2. Glomerular capillary endotheliosis
3. Hemorrhage and necrosis in many
organs, presumably sec to arteriolar
vasoconstriction

PATHOGENESIS

Laboratory Tests
Hematocrit : increased
hemoconsentration
Proteinuria
Serum uric acid
Hemoglobinuria , increase LDH ,
increase SGPT , decdecrease platelet
count HELLP Syndrome

Laboratory Tests
Maternal serum alpha-protein
* levels > 2 multiples of median
Fibronectin
* inc levels vascular disruption
Hypocalciuria , Calcium : Creatinine
ratio
Antithrombin III levels,atrial
natriuretic peptides,
microalbuminuria

Doppler Velocimetry
Preeclampsia : increased afterload
and diminished blood flow in the
uteroplacental unit
Decrease blood flow : diastolic notch
Findings :
increase Systolic/Diastolic (SD)
ratio
Absence or Reverse End
Diastolic
(ARED) Flow : ominous sign

Doppler Velocimetry
Neilson and Alfirevic , 2002
1. Reduction in perinatal deaths
2. Fewer induction of labor and
admissions to hospital
3. No difference found for fetal
distress in labor
Conclusion : Doppler ultrasound in
high risk pregnancies appears to
improve obstetric outcomes and
help reduce perinatal deaths

Prevention
Low Dose Aspirin
High Dose Calcium

Low Dose Aspirin

Mechanism Of Action : inhibits Thromboxane A2 (TXL-A2) and

lipid peroxides

Should low dose ASA be given routinely to pregnant women??

(1) Italian study of ASA in Pregnancy : no difference in
incidence of PIH ;no difference in BW,IUGR,premature births,or
perinatal mortality
(2) Southern USA study : significant decrease in preeclampsia
but did not recommend routine use of ASA in nulliparous women
(3) NICHHD : reduction in incidence of preeclampsia was not
statistically significant ; no difference in incidence of gestational HPN,
IUGR,preterm birth and mean BW ; higher incidence of abruptio
placenta.
(4) CLASP trial : no significant reduction in incidence of
preeclampsia , IUGR ,stillbirths or neonatal deaths

Conclusion : low dose ASA

should not be given routinely
to pregnant women at low
risk for preeclampsia

To Whom is low dose ASA beneficial

???
Patient with identifiable risk
factors :
* previous History of HPN
* previous poor OB outcomes
* (+) MAP or Roll-over tests
* (+) Doppler findings

Dosage
Given : 60-80 mg / day
Platelet count serially monitored
Fetal monitoring :
Ductus arteriosus
urine volume
AFV

High Dose Calcium

Mechanism Of Action :
(1) negative feedback effect on
parathyroid hormone decrease
intracellular Ca smooth muscle
relaxation / decrease response to
pressor stimuli
(2) high levels of Ca increase Ca
excretion inc ion exchange with
Mg inc serum Mg smooth
muscle relaxation blood vessel
dilatation decrease BP

High Dose Calcium

Dosage : 2 gms / day
Study : Atallah,Hofmeyr , and Dulley 2002 :
(1) modest reduction in high BP , risk for
preeclampsia , preterm delivery, and low
birthweight babies
(2) no effect on incidence of stillbirth or
perinatal deaths before hospital discharge
Conclusion : Ca supplementation appears
to be beneficial to women at high risk
for gestl HPN and in communties with
low dietary Ca intake

Management of Pregnancy Induced

Hypertensive
Guiding Principles :
(1) Prevent / control
convulsions
(2) Control BP
(3) Safe delivery of a viable
fetus

1. Control of Convulsions
Drug Of Choice : Magnesium Sulfate
(MgSO4)
Loading Dose :
4-6 gm slow IV over 15-20min in
100 ml fluid
AND
10 gm deep IM (5 gm IM into
each buttock)

1. Control of Convulsions
Maintenance :
2 gms /hr controlled IV infusion
or
5 gms deep IM q 4 hours
Mechanism Of Action :
(1) cerebral vasodilator
(2) increase uterine blood flow
(3) reduces levels of plasma endotheline-1
and
inc renal excretion of prostacyclin
(4) central anticonvulsant effect
(5) increase EDRF precursors

 Therapeutic plasma levels : 4-7

mEq/L
Discontinued 24 hrs after
delivery
Monitoring :
Adequate patellar reflex
Adequate Urine Output ( 30
cc/hr)
No Respiratory Depression

Clinical Correlates of serum MgSo4

levels (therapeutic range : 4.8-9.6)
Clinical Response
Loss of Patellar Reflex
Somnolence
Slurred Speech
Respiratory Difficulty
Respiratory Arrest
Cardiac Arrest

mEq/Ll
10
10-12
10-12
10
12
30-35

Management of MgSO4 Toxicity

Calcium Gluconate 1 gm IV
Severe Respiratory Depression /
Arrest :
Prompt tracheal intubation
Mechanical ventilation

2. Control of HPN
Emergency parenteral therapy for severe HPN :
(1) Hydralazine : direct vasodilator
* IV boluses of 5- to 10-mg doses at 15- to
20-minute intervals
(2) Labetalol : Non-selective 1 and 1 blocker
* 20 mg initial IV bolus , may give another 40
mg after 10 min if BP response is inadequate
followed by another 40 mg then 80 mg q 10 min
Total dose should not exceed 220 mg
(3) Clonidine IM 75-150 mcg is the next
recommended drug

2. Control of HPN
(3) Nifedipine : 5 or 10 mg orally ,may
be and takes effect within 15-50
minutes ;
Drawback : difficult to control ; May
cause severe hypotension
(4) Na Nitroprusside : seldom used ;
fetal cyanide toxicity
Goal : BP 140 150 / 90 100 mmHg

DRUGS
Prefered agent : Methyldopa
200-500mg BID-QID (max
2g/day)
Second line :
Labetolol 100-400 mg BID-TID
(max 1200mg/day)
Nifedipine PA 10-20mg PO BIDTID (max 180mg/day); XL 2060 mg PO OD (max 120mg/day)

3. Timing and Mode of Delivery

Immediate delivery :

Eclampsia

Severe preeclamptic patient who are at least 34

weeks or with documented fetal lung maturity
and adequate NICU

Severe maternal disease regardless of AOG:

(uncontrolled HPN, oliguria ,severe proteinuria,
thrombocytopenia, pulmonary edema,
impending eclampsia)

Fetal distress (dec fetal movement , poor BPS ,

ARED on Doppler )

3. Timing and Mode of Delivery

Less than 34 weeks :
Temporize and deliver as close to
term if possible ; Deliver
immediately if maternal/fetal
condition starts to deteriorate
Delivery options :
Cervical ripening using
prostaglandins and induction of labor
with amniotomy or oxytocin NSD
Cesarean section if indicated

Mild Preeclampsia
Hospitalization : baseline fetal
monitoring and lab exams
OPD follow up 2x a week : BP
monitoring , fetal surveillance
(NST , BPS , Doppler studies)
Medicantions : Methyldopa , low
dose ASA ,and high dose Ca
Deliver near term as possible

Summary
Delivery is the only definitive cure for
preeclampsia
Mgt of severe preeclampsia is based mainly on :
(1) control of convulsions,(2) control of HPN ,and
(3) best mode and timing of delivery of a viable
fetus
Timing and mode of delivery dictated by : AOG ,
prevailing maternal and fetal conditions , severity
of the disease and adequate NICU facilities

ECLAMPSIA
If MgSO4 is not available, other
options :
Diazepam
A loading dose of 10mg IV over
2 minutes, repeated if
convulsions recurred, followed
by an IV infusion of 40mg in
500ml normal saline for 24
hours

During the next 24hours, an

infusion of 20mg diazepam in
500ml normal is given and
slowly reduced

 Phenytoin
The dose may be varied
according to the patients weight
Is only remommended for the
prevention of seizures
10mg diazepam IV should be
given

An initial phenytoin loading

dose of 1g slow IV (over 20
minutes) is given with
continuous cardiac monitoring
Succeeding doses of 100mg
every 6hours for the next
24hours

DELIVERY in ECLAMPSIA

After control of seizures

The pregnancy should be terminated
The uterus is sensitive to axytocine
CS is reserved if :
Vaginal delivery does not appear
easy and imminent
There is failure of progress after
induction
There is fetal compromise
Anticonvulsion therapy should be
continued for at least 24h after
delivery

Pencegahan dan Tatalaksana Kejang

Bila terjadi kejang perhatikan jalan napas,
pernapasan (O2) dan sirkulasi (cairan intravena)
MgSO4 diberikan secara intravena kepada ibu
dengan eklampsia (sebagai tatalaksa kejang) dan
preeklampsia berat (sebagai pencegahan kejang)
Pada kondisi dimana MgSO4 tidak dapat diberikan
seluruhnya, berikan dosis awal (loading dose),lalu
segera rujuk ibu ke fasilitas kesehatan yang
memadai
Lakukan intubasi jika terjadi kejang berulang dan
segera kirim ibu ke ICU (apabila tersedia) yang
sudah siap dengan fasilitas ventilator

Cara Pemberian MgSO4

antihipertensi
Ibu dengan hipertensi berat selama kehamilan
perlu mendapat terapi antihipertensi
Pilihan antihipertensi didasarkan terutama pada
pengalaman dokter dan ketersediaan obat
Ibu yang mendapatkan terapi antihipertensi
dimasa antenatal dianjurkan untuk melanjutkan
terapi antihipertensi hingga persalinan
Antihipertensi golongan ACE Inhibitor, ARB dan
Klorotiazid dikontraindikasikan pada ibu hamil

Beberapa jenis antihipertensi yang dapat

digunakan :
Nama Obat

Dosis

Keterangan

Nifedipin

4x10-30 mg per oral

(short acting)
1x20-30 mg per oral
(long acting/Adalat
Oros)

Dapat menyebabkan
hipoperfusi pada ibu
dan janin apabila
diberikan sublingual

Nikardipin

5mg/jam, dapat
ditritasi 2,5 mg/jam
tiap 5 menit hingga
max 10 mg/jam

metildopa

2x250-500 mg per oral

(dosis max 2000
mg/hari)

Pemeriksaan Penunjang
DPL
ABO dan Rh; uji pencocokan
silang
LDH, SGOT, SGPT
Serum ureum dan kreatinin
PT, APTT, Fibrinogen
USG terutama jika ada gawat
janin dan pertumbuhan janin
terhambat

Pertimbangan Persalianan/Terminasi
Kehamilan
Pada ibu dengan eklampsia, bayi harus
segera dilahirkan dalam 12 jam sejak
terjadinya kejang
Induksi persalinan dianjurkan bagi ibu
dengan PEB dengan janin yang belum viabel
atau tidak akan viabel dalam 1-2 minggu
Pada ibu dengan PEB, dimana janin sudah
viabel namun usia kehamilan belum
mencapai 34 minggu, manajemen ekspektan
dianjurkan, asalkan tidak terdapat
kontraindikasi

 Pada ibu dengan PEB, dimana usia kehamilan

antara 34-37 minggu, manajemen ekspektan
boleh dianjurkan, asalkan tidak terdapat
hipertensi yang tidak terkontrol, disfunsi
organ ibu, dan gawat janin lakukan
pengawasan ketat
Pada ibu dengan PEB yang kehamilannya
sudah aterm, persalinan dini dianjurkan
Pada ibu dengan PER atau Hipertensi
Gestasional ringan yang sudah aterm, induksi
persalinan dianjurkan

HELLP SYNDROME
The Tennesse Classification
(1) mod to severe
thrombocytopenia with platelets
100,000/ml or less
(2) AST 70 IU/L or greater
(3) LDH 600 IU/L or greater or
bilirubin 1.2 mg/dL or greater

 The Mississippi Triple Class

System
Class 1 : platelets 50,000/ml;
AST and or ALT 70 IU/L; LDH
600 IU/L
Class 2 : platelets > 50,000 to
100,000/ml
Class 3 : platelets >100,000 but
150,000/ml /ml; AST and or
ALT 40 IU/L; LDH 600 IU/L

THANK YOU
GOD BLESS US