YL6
Pathologic OB SubModule [Obstetrics]
OUTLINE
I.
Epidemiology
II. Definitions & Modifications
III. Clinical Types
A. Gestational Hypertension
B. Preeclampsia/Eclampsia
C. Chronic Hypertension
D. Chronic Hypertension with superimposed
Preeclampsia/Eclampsia
IV. Pathophysiology
A. Preeclampsia
B. Angiogenetic Factors of Preeclampsia
C. Preeclampsia Physiology
V. Clinical Approach
A. Prediction
B. Prevention
C. Management of Eclampsia & Severe Preeclampsia
I.
II.
06 January 2011
HYPERTENSIVE DISEASE IN PREGNANCY
EPIDEMIOLOGY

43.1 per 100 Pregnancies

Pregnancy Induced Hypertension is the major cause of
maternal mortality in England and Wales

18.42% of maternal deaths were due to PIH

56% of PIH due to eclampsia

2nd Most common medical complication encountered in
pregnancy in the Philippines

It is one of the most common causes of maternal
mortality and an important cause of perinatal mortality
and morbidity
Dr. Sumpaico

Keep in mind other factors that may increase blood pressure:
Arm circumference, type of apparatus, time of BP
measurement, “white-coat” HPN
III.
CLINICAL TYPES
A.
Gestational Hypertension
1. HTN without proteinuria occurring after 20 weeks
gestation or postpartum.
2. It is a temporary diagnosis during pregnancy which
has to be confirmed 12 weeks after delivery.
o If BP becomes normal after 12 weeks, the final
diagnosis is transient hypertension
o If hypertension persists, the final diagnosis is
chronic hypertension.
B.
Preeclampsia/Eclampsia
1. Preeclampsia

The development of hypertension plus
proteinuria, induced by pregnancy after the
20th week of gestation and sometimes earlier
in extensive hydatidiform changes in chorionic
villi.
DEFINITIONS AND MODIFICATIONS
Hypertension

Systolic blood pressure (SBP) of at least 140 mmHg OR
Diastolic blood pressure (DBP) of at least 90 mmHg

Must be manifest on at least 2 occasions taken 6 hours
apart
Proteinuria

Present when 300mg/liter/24 hour collection of urine is
found; OR

More than 1000mg/L/random sample in at least 2
random samples taken 6 hours apart

Qualitatively, dipstick values of traces to 1+ signify mild
while 2+ to 4+ signify heavy proteinuria
Edema

After 12 hours of bed rest, the presence of 1 – pitting
edema; or a weight gain of 5 lbs or more/week
Modifications in Classification and Definition

Eliminate edema as a criterion for diagnosing preeclampsia

As a diagnostic criterion for hypertension, the use of
increased of 30 mmHg systolic or 15 mmHg diastolic above
baseline is no longer recommended since they are not proven
to be good prognostic indicators of outcome.

Use Korotkoff phase V (disappearance of sound) for
determination of diastolic pressure.
Group ##
INSERT. NAMES. OF. ALL. GROUP. MEMBERS. IN. ALPHABETICAL. ORDER.
Criterion for severe preeclampsia
1. SBP ≥ 160
2. DBP ≥ 110
3. Proteinuria
o ≥ 4 grams per day
o ≥ +2 on dipstick
4. Oliguria <400 cc/day due to decreased RBF and GFR
5. Severe Headache or Visual Disturbance
o (+) cerebral edema
6. Pulmonary Edema or cyanosis
o Hemodynamic changes: increased afterload
7. Intrauterine Growth Restriction (IUGR)
o decreased uteroplacental blood flow
8. RUQ or epigastric pain
o Due to abnormal distension of Glisson’s capsule of
the liver
9. Hemolysis
Page 1 of 6
HYPERTENSIVE DISEASE IN PREGNANCY
OBSTETRICS
(endothelial dysfunction)  diverse symptoms of
preeclampsia and eclampsia
o
Manifests as increased serum LDH or
hemoglobunuria
10. Elevated Liver Enzymes
o Hepatocellular necrosis
11. Low Platelet Count
o ≤ 100,000/mm3 (NV: 150,000/ mm3)
o Microangiopathic hemolysis
Picture of the diameter of spiral arteries in normal and abnormal
arteries

Current classification based on Age of Gestation:
Early-onset preeclampsia

Signs and symptoms < 34 weeks
Late-onset preeclampsia

Signs and symptoms ≥ 34 weeks AOG
2.
Pregnant rats exposed to sFlt-1 had distinct clinical and
pathological signs of preeclampsia, including the
characteristics glomerular endotheliosis 
demonstrating for the first time a clear cause and effect
between this protein and this disease
Picture of preeclamptic arteries with proteinacious material (slfit1)
Eclampsia
 The occurrence of convulsions, not caused by
coincidental neurologic disease in a woman
previously fulfilling the criteria for preeclampsia
C.
Chronic Hypertension

BP ≥ 140/90 prior to pregnancy or before 20 weeks
AOG and persists after 12 weeks postpartum OR

Hypertension first diagnosed before 20 weeks
gestation and persistent after 12 weeks postpartum
D.
Chronic HPN with Superimposed Preeclampsia/Eclampsia

Pre-existing Chronic hypertension with new onset
proteinuria and signs and symptoms of various endorgan dysfunction
IV. PATHOPHYSIOLOGY
Graph A
ETIOLOGY OF HYPERTENSIVE DISEASE IN PREGNANCY (APPENDIX)
Graph B
Pro-angiogenetic factors
vs.
Anti-angiogenetic
Placental GF, VEGF
sFlt-1, Endoglin
(dilators)
(constrictors)
 If Pro-angiogenesis < Anti-angiogenesis = preeclampsia. On
the other hand
 If Pro-angiogenesis > Anti-angiogenesis = Normal pregnancy
SEE PICTURE IN OLD TRANS (CAN’T SEEM TO PASTE IT HERE)
In vivo evidence

Sflt-1 neutralizes effect of VEGF and PIGF and the loss of
these GF damages the mother’s small blood vessels
Group01
Rizzy. Ner. Berna. Mon. Dan. Bry.
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HYPERTENSIVE DISEASE IN PREGNANCY
OBSTETRICS
Therefore, preeclampsia = high sFlt-1 and low PIGF
Angiogenic Markers and the Risk for Pre-eclampsia
Compairson of SFlt-1 among normotensive and hypertensive
pregnancies
PlGF clear difference
There should be a drop of PlGF after 48 hours
A.
Preeclampsia Physiology

Normal pregnancy: trophoblast invasion  loss of
tunica media elasticity  decreased resistance,
vasodilatation and increased perfusion

Vascular system in normal pregnancy: Prostacyclin
(endothelium-derived vasodilator)> Thromboxane
(platelet-derived vasoconstrictor)

Pre-eclampsia is the opposite of above

The normal functional balance between
vasoconstriction and vasodilation eicosanoids is
disturbed in preeclampsia

B.






V.
CLINICAL APPROACH
Leon Chesley: “Radical therapies: mastectomy,
oophorectomry, renal decapsulation, trephnation, alighment
of the patient with the earth’s magnetic fields” have been
employed as treatments for preeclampsia in the past
A.
Prediction
WHO Criteria for a Screening Test
a. Is there a significant burden?
b. Is there a preclinical (asymptomatic stage)?
c. Will detection improve outcomes?
d. Is the screening test cost-effective accurate
and acceptable to patients?
e. Is there an effective treatment available for
detected disease?



Group01

Patient Profile:
o Primigravida
o Poor
o Young
o Non-white
o Protein intake suboptional
o Prenatal checks: late or none
o Family history of hypertension
o Low SES
Risk Factors Associated with Pregnant Woman:
o High BMI is now a risk factor
Risk Factors Associated with Husband:
Rizzy. Ner. Berna. Mon. Dan. Bry.

o First time father
o Previously fathered a pre-eclamptic
Associated with Fetus:
o Multifetal pregnancy
o Hydrops/triploidy
o Hydatidiform mole
Physical Examination
Blood Pressure
Mean Arterial Pressure
o MAP = DBP + 1/3 (SBP-DBP)
o MAP-2 >90 mmhg OR MAP-3 >105 mmhg
associated with increased PIH and perinatal
deaths
o Absence of a mid trimester drop in blood
pressure may predict future PIH based on the
absence of arteriolar vasodilation
Roll Over Test (ROT)
o No longer used
Combined MAP-2 and ROT
o Performed singly the MAP-2 or the ROT
predicted >60% of those at risk of PIH
o Combining the MAP-2 and ROT predicted
>78% of those at risk of PIH
Uterine Artery Doppler
o Doppler ultrasound in high-risk pregnancy
(especially those with hypertension and IUGR)
were associated with reduction in perinatal
deaths (OR 0.71, 0.50 to 1.01)
Doppler Velocimetry
o Meta analysis of RCTs in high risk pregnancies
showed significant reduction in antennal
admission, labor induction, CS, fetal death and
distress
Placental volume
o 3D technology
o 1st trimester
o Identify future IUGR and preeclampsia
Quad test markers in Down Syndrome screening
o AFP, B-HCG, Ue3, Inhibin
o Pappa a and B-HCG
o VEGF, PIGF, SFLT1
o Endoglin
o Pp13: 90% detection rate
o Detection rate for combinations markers: 3444%: Uterine Doppler plus marker increase the
sensitivity
SUMMARY:

Assess Risk Factors: assess right away in the first
visit (1st visit)

Measure blood pressure (1st visit)

“Thin is in, stout is out” BMI/Obesity: counsel
against obesity

Use of diagnostic biochemical markers: available in
the market

PIGF, VEGF

SLFT1, endoglin

Pp13
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HYPERTENSIVE DISEASE IN PREGNANCY




C.
o High dose calcium exerts a negative feedback
effect on parathyroid hormone  lowering
intracellular calcium ion levels  smooth
muscle
relaxation
and
diminished
responsiveness to pressor stimuli
o You cut the risk of developing preeclampsia by
50% with calcium intake.
 There is a theoretical risk of developing renal
calculi with high dose calcium but it has not been
proven
 Calcium will diminish by half the risk of
preeclampsia and reduce death or serious
morbidity
Use of Uterine Artery Doppler
o Observe diastolic notches, resistance and
pulsatility indices and placental volume
Combination: most important is to screen during
the middle of the pregnancy using Doppler and
biochemical marker measurement
At 17 weeks AOG, do biochemical tests
At 22 weeks AOG, do Doppler tests
Prevention
1. Bed Rest
2. Diuretics
3. Anti-platelets - low dose aspirin
 The normal functional balance between
vasoconstriction and vasodilation eicosanoids is
disturbed in preeclampsia
 Mechanism of action: the selective effect of ASA
on eicosanoids is mainly attributable to the cell
biologic differences between platelets and
endothelium. Platelets are anucleated, while
endothelium is nucleated and thus able to
regenerate.
 Mechanism of action: Deactelyated in peripheral
tissues
 make sure you use it only with high-risk patients.
 Aspirin may be given provided:
o Patients have been identified as high-risk
based on previous history of HPN, adverse
obstetric outcomes, MAP or roll-over tests,
abnormal Doppler waveforms or angiotensin
sensitivity tests.
o Patient has no history of aspirin allergy or
hypersensitivity (Acid peptic disease or
coagulopathy)
o Treatment is started during the second
trimester to prevent fetal malformations in the
first trimester
o Pediatric doses are kept at 60-80 mg/day
based on majority of reports
 Make sure you monitor platelet and coagulation
profile
 Monitor fetal ductus arteriosus and amniotic fluid
volume by ultrasound
 No deleterious effect on the fetus and neonate as
long as within pediatric dose of 60-80 mg/day.
 Antiplatelet trials have shown similar results.
4.
OBSTETRICS
High Dose Calcium
 Study of Guatemalan Indians: those who ate corn
with calcium did not develop preeclampsia while
those who ate only raw corn developed it.
 Prevention can be done by simply adding calcium
to the diet.
 There is a 30% drop of BP with calcium and a drop
in the incidence of preeclampsia
o Oral intake of 2 grams per day has been
proposed to prevent preeclampsia
Rizzy. Ner. Berna. Mon. Dan. Bry.
Nitric Oxide (NO) Donors
 AKA Endothelium-derived relaxing factor (EDRF)
 A byproduct of L-arginine metabolism and has a
vasodilatory and mitogenic effect
6.
Antioxidants
 Ex. Vitamins C and E
 Initial studies were done but current evidence
now shows that it is not beneficial.
7.
Anti-sFlt-1
 The Chinese have now developed these as
treatment through recombinant studies.
8.
Recombinant VEGF/PLGF
SUMMARY

Low-dose Aspirin

High-dose Calcium

Anti-SFLT1

Recombinant VEGF and PIGF
D.
Management of Eclampsia and Severe Preeclampsia
1. Anti-convulsants

Convulsion control with Magnesium Sulfate MgSO4

Halves the risk of pre-eclampsia and reduces
the risk of maternal death

Administered as follows
 A:
Loading dose: 4 gm IV bolus over 5 minutes +
Maintenance dose: 1 gm per hour IV drip
 B:
Loading dose: 4 gm IV bolus slowly over 5
minutes and 10gm IM (5 gm into each
buttock) followed by:
Maintenance dose: 5 gm IM every 6 hours

PRECAUTIONS:
1. The presence of deep tendon reflexes (DTRs)
2. Respiratory rate of >12 per minute
3. Urine output of at least 100 cc/4 hours
Note: continue anti-convulsion therapy even 24 hours
after the woman has delivered
Different Magnesium Sulfate levels in the body


Group01
5.
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HYPERTENSIVE DISEASE IN PREGNANCY
o
o
o
o
o
Group01
OBSTETRICS
2 meqs – normal, tolerable
7 – 10 meqs – lose patellar reflex
12 meqs - prolonged AV condutccion
15 meqs - respiratory failure
24 meqs – cardiac arrest
2.
Anti-Hypertensives
 Hydralazine – drug of choice
 Labetalol
 CA blockers (nifedipine, nicardipine)
 Alpha adrenergic blockers – Clonidine
 Low dose diazoxide
 Nitroprusside
 Do not give ACE inhibitors: can cause kidney
problems and bone lesions in the neonate
3.
Delivery
1) Age of gestation – once the 34 weeks of
pregnancy is achieved, delivery is
recommended for maternal safety
2) Severity of the disease

Severe preeclampsia patients are usually
delivered once 34 weeks of pregnancy is
achieved but conservative measures at
<34 weeks can be tried in high risk
centers. Properly informed patients with
mild preeclampsia can be managed from
home.
3) Maternal evaluation

Regular checks of the mother’s multipleorgan symptoms, vital signs, body weight,
input & output monitoring and regular
review of meaningful laboratory
examinations are mandatory
4) Fetal status

Fetus should be regularly monitored with
daily fetal counts, non-stress test,
contraction stress test, biophysical profile
growth monitoring, Doppler, steroids
have proven invaluable.
5) Nursery capability

Most Philippine nurseries report a high
survival rate at 34 weeks
Rizzy. Ner. Berna. Mon. Dan. Bry.
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HYPERTENSIVE DISEASE IN PREGNANCY
Group01
Rizzy. Ner. Berna. Mon. Dan. Bry.
OBSTETRICS
Page 6 of 6