PREGNANCYRELATED

HYPERTENSION
FRANS O H PRASETYADI

SUBDEPT. OF OBSTETRICS &

GYNECOLOGY
DR. RAMELAN INDONESIAN NAVAL
HOSPITAL
S U R A B A Y A

INTRODUCTION

One of the deadly triad maternal morbidity & mortality

US incidence in 2001 : 3.7% of pregnancies
16% pregnancy-related deaths ( US, 2003 )
Challenge the medical & obstetrical skills of the health care
team
understanding the patophysiology of the HT disorders disease
of theories
recognition of the pharmacokinetic changes occuring during
pregnancy & the possible fetal effects of therapeutic agents

Management & impact on the mother & fetus

depend on whether :
HT antedated the pregnancy, or
HT as the marker of pregnancy-specific
vasospastic syndrome
several systems of nomenclature and
classification

TERMINOLOGY AND
CLASSIFICATION
The

NIH working group on hypertension in

pregnancy ( 2000 ):
Gestational hypertension
Preeclampsia-eclampsia
Superimposed PE on chronic hypertension
Chronic hypertension

GESTATIONAL HYPERTENSION
BP

140/90
For the 1st time during pregnancy
No proteinuria
BP returns to normal < 12 weeks
postpartum
Final diagnosis made only postpartum
May have other signs or symptoms of PE,
i.e. :
epigastric discomfort or thrombocytopenia

PREECLAMPSIA

Minimum criteria
BP 140/90 after 20 weeks of gestation
Proteinuria 300 mg/24 hr or 1+ dipstick
Increased certainty of preeclampsia
BP 160/110
Proteinuria 2.0 g/24 hr or 2+ dipstick
Serum creatinine > 1.2 mg/dL unless known to be previously
elevated
Platelets < 100,000/mm3
Microangiopathic hemolysis ( LDH )
Elevated ALT or AST
Persistent headache or other cerebral or visual disturbance
Persistent epigastric pain

ECLAMPSIA
Seizures

that cannot be attributed to

other causes in a woman with
preeclampsia

SUPERIMPOSED PREECLAMPSIA
New

onset proteinuria 300 mg/24 hr in

hypertensive women but no proteinuria
before 20 weeks gestation
A sudden increase in proteinuria or blood
pressure or platelet count < 100,000/mm3
in women with hypertension and proteinuria
before 20 weeks gestation

CHRONIC HYPERTENSION
BP

140/90 before pregnancy or diagnosed

before 20 weeks gestation not
attributable to gestational trophoblastic
disease, or
Hypertension first diagnosed after 20
weeks gestation and persistent after 12
weeks postpartum

PREECLAMPSIA

Major cause of
- Maternal mortality ( 15-20% in developed
countries ) and morbidities ( acute and long-term)
- Perinatal deaths
- Preterm birth
- IUGR, oligohydramnios, abnormal oxygenation
Those morbidities & mortalities are in women
who :
-develop the disorder before 33 weeks gestation
-in those w/ pre-existing medical disorders
-in those from developing countries

Etiology and pathophysiology ?

Likely to develop in women who :
1. are exposed to chorionic villi for the first time
2. are exposed to a superabundance of
chprionic villi, as with twins or hydatidiform mole
3. have preexisting vascular disease
4. are genetically predisposed to
hypertension developing during pregnancy

PREECLAMPSIA

Is a multisystem disorder of unknown cause that

is unique to human pregnancy
Characterised by abnormal vascular response to
placentation that is associated with :
- systemic vascular resistance
- enhanced platelet aggregation
- activation of the coagulation system, and
- endothelial dysfunction
Clinical manifestations :
maternal syndrome
fetal syndrome

Maternal and fetal complications in

severe preeclampsia
Maternal complications

Neonatal complications

abruptio

Preterm

DIC

placentae ( 1-4% )

/ HELLP syndr ( 10-20%)

Pulmonary

oedema/aspiration

(2-5%)
ARF

(1-5%)

Eclampsia
Liver

( <1% )

failure or haemorrhage

(<1%)
Stroke
Death

( rare )

( rare )

Long-term

morbidity

cardiovascular

delivery (15-

67%)
Fetal

growth restriction
(10-25%)
Hypoxia-neurologic

injury

(<1%)
Perinatal

death ( 1-2%)

Long-term

cardiovascular
morbidity assiciated w/
LBW ( fetal origin of adult

DIAGNOSIS PE

HT + proteinuria, >20 weeks gestation, normotensive beforehand

BP measurements : 2 occasions, 4-6 h apart & <7 days

Accurate dx depends on precise BP measurements ( ie, cuff size, position

of arm at heart level, & calibration of equipment ) important in obese
women.

Definitive test 4 proteinuria : quantitative over 24 h

To be regarded serious / severe if ?

HT or proteinuria might be absent in 10-15% HELLP syndr & in 38% of

eclampsia

Hipertensi
Gestasional
Preeklampsia
Eklampsia
Superimposed
preeklamsia
Hipertensi kronis

RISK FACTORS
-Limited sperm exposure

-Chronic HT or renal disease

-Primipaternity

-Rheumatic disease

-Pregnancy after donor

insemination, oocyte donation,
embryo donation

-Maternal low birthweight

-Protective effectof partner

change in the case of previous
PE pregnancy

-Maternal infections

-Maternal or pregnancy-related
risk factors
-Extremes of maternal age
-Multifetal gestation
-PE in a previous pregnancy

-Obesity & insulin resistance

-Pregestational DM
-Pre-existing thrombophilia
-Maternal susceptibility genes
-Family history of PE
-Smoking ( reduced risk )
-Hydropic degeneration of
placenta

Epidemiology & risk factors

2% - 7% in healthy nulliparous women

Generally regarded as a disease of first pregnancy

Importance of paternal factors : dangerous father

Primipaternity concept ? >< women w/ no previous PE ~ risk of

PE with increasing time interval between births
Concept : healthy pregnancy is a state of systemic
inflammation, at least in the 3rd trimester PE is the
extreme end of a range of maternal systemic inflammatory
responses engendered by the pregnancy itself

In pregnancy, the spiral arteries are remodeled by extravillous trophoblast cells and NK cells. The left panel
shows the nonpregnant endometrium in the secretory phase of the menstrual cycle just before menstruation. The
right panel shows the endometrium in the second half of normal pregnancy when the spiral arteries are remodeled
to a depth that penetrates the myometrium. The middle panel shows the situation in preeclampsia where the
extent and depth of remodeling is less than in normal pregnancy. These vascular changes are effected by
extravillous trophoblast cells (EVT) with the help of activated NK cells. In the process, the enlarged vessels
become lined with endovascular trophoblast cells (ENVT)

Figure 4Unifying hypothesis of pre-eclampsia

pathophysiology

Noris M et al. (2005) Mechanisms of Disease: pre-eclampsia

Nat Clin Pract Neprol 1: 98114 doi:10.1038/ncpneph0035

Maternal
Vasculer
disease

Faulty
Placentation

Genetic,
immunologic,
or inflamatory
factors

Reduced
uteroplacental
perfusion

Excessive
Trophoblasts

Noxious
agents:
Cytokines,
Lipid
Peroxidases

Vasoactive
agents:
Prostaglandin
s, nitric Oxide,
Endothelins

Endothelial
Activation
Activation of
Coagulation

Vasospasm
Capillary leak
Hypertension
Seizures
Oliguria
Liver ischemia
Abruption

Trombocytopenia
Reduced

Edema
uteroplacental
Hemoconcentrati
perfusion
on
Proteinuria

Aktivasi, agregasi,
konsumsi + volume
dan usia platelet
trombositopenia
Waktu thrombin
meningkat
Defisiensi faktor
pembekuan
karena penyakit
penyerta
Fibronectin
cenderung
meningkat

Hemolisis LDH,
perubahan bentuk
eritrosit.
Akibat gangguan
endotelhemolisis
mikroangiopati

Berhubungan
dengan:
Tekanan
afterload
Tekanan Preload
Ekstravasasi
cairan

CO meningkat
CO menurun +
Hemokonsentra
resitensi perifer
si
meningkat
Hati-hati pada
perdarahan
waktu
persalinan

 RAA system
menurun akibat
retensi air + Na
Vasopressin
tetap
Atrial
natriuretik
peptide
menurun

Kerusakan
endotel retensi
cairan edema
generalisata
Elektrolit
cenderung tetap
normal
Pada kejang
eklamsia pH
dan bicarbonat

 Hiperperfusi
Perdarahan akibat
ruptur arteri Kehilangan
Edema, iskemi, autoregulasi
aliran darah
hyperemia,trombosis
, perdarahan serebral
Klirens
plasenta
menurun
Laju aliran
darah
plasenta
menurun

Infark arteri
retina
Ablasio retina
Edema korteks
dan defek visual

Prediction of PE

No known biomarkers

No efective predictors

Doppler velocimetry of uterine artery blood flow in 2 nd

trimester might be useful ( RI or early diastolic notch unior bilateral ) for those at very high risk

Fetal Velocity Waveforms

Medical Physiology Lippincott Williams & Wilkins, 2nd edition 2004

Prevention of PE

Diet

and exercise (I)

Protein

or salt (II)restriction

Pregnancy
outcome

Mg or Zn supplementation (I)

No reduction in PE

Fish-oil supplementation & other

sources of fatty acids (I)

No reduction in PE

Calcium

supplementation (I)

Low-dose

aspirin (I)

No effect in low-risk or highrisk populations

Reduced PE in those at high-risk
& with low baseline dietary
calcium intake
No effect on perinatal outcome
19% reduction in risk of PE

Heparin

16% reduction in fetal or

neonatal deaths

Antioxidant

Reduced PEin women w/ renal

dis. & in women w/ thrombophilia

or low-molecularweight heparin (III)

Anti-HT

vitamins (C,E) (II)

medications in women
w/ chronic HT

Reduced PE in one trial

Recommendation
Insuff. evidence to recommend
Not recommended*
Insufficient evidence to
recomm.*
Recommended for women at high
risk of gestational HT, & in
communities w/ low dietary
calcium intake
Consider in high-risk populations

Lack of randomised trials, not

recommended
Insufficient evidence to
recomm.

Risk of women developing severe

No evidence to recommend for
HT reduced by half, but not risk
Levels of evidence (I IV) as outlined by the US Preventive Task Force. *Insufficient evidence - prevention
small
of PE

Management of PE

Adequate & proper prenatal care is most important

( identification of women at high risk, early detection by the recognition of clinical
signs & symptoms, progression of the condition to severe state )

The main objective : safety of the mother

Delivery or expectant?

~ fetal gestational age, fetal status, severity of

maternal condition at time of assessment

Management of PE
Preeclampsia
Maternal & fetal
assessment
Gestational age 38 weeks
At 34 weeks gestation:
- Severe PE
- Labour or rupture of membranes
- Abnormal fetal testing

YES

Deliver

- Severe oligihydramnios or fetal growth

restriction

NO
Mild disease

Hospital or office
management

Severe disease

22 32 weeks

< 23 weeks

33 34 weeks

Maternal and
fetal assessment

Worsening maternal
or fetal condition
38 weeks
Labour or rupture of
membranes

Steroids
Anti-HT
Daily assessment of
maternal-fetal
conditions
Delivery at 34 weeks

Steroids
Delivery after 48 h