PREGNANCY-RELATED

HYPERTENSION
FRANS O H PRASETYADI
SUBDEPT. OF OBSTETRICS & GYNECOLOGY
DR. RAMELAN INDONESIAN NAVAL HOSPITAL
SURABAYA
 INTRODUCTION

• One of the deadly triad  maternal morbidity &

mortality
• Incidence : ±5% 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 placentae ( 1-4% ) Preterm delivery (15-67%)

DIC / HELLP syndr ( 10-20%)
Fetal growth restriction (10-
Pulmonary oedema/aspiration (2-
5%)
25%)
ARF (1-5%) Hypoxia-neurologic injury

Eclampsia ( <1% ) (<1%)

Liver failure or haemorrhage (<1%)
Stroke ( rare )
Death ( rare )
Long-term cardiovascular morbidity
Perinatal death ( 1-2%)
Long-term cardiovascular
morbidity assiciated w/ LBW (
fetal origin of adult disease
hypothesis ) i.e. premature
atherosclerosis
 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
 • Tekanan darah ≥ 160/110
Kriteria • Proteinuria ≥ 2 gram/24 jam
minimum atau dipstick ≥+2
• Serum kreatinin > 1,2
mg/dL
• Trombosit < 100,000/mm3
Tensi ≥ 140/90
setelah 20 • Hemolisis mikroangiopatik
minggu (LDH meningkat)
kehamilan • ALT dan AST meningkat
• Sakit kepala
persisten/gangguan
Proteinuria ≥
visus/gangguan pada otak
Hipertensi 300mg/24 jam
atau dipstick ≥ • Nyeri epigastrium
Gestasional +1 persisten
Preeklampsia
Eklampsia
Superimposed
preeklamsia
Hipertensi kronis
 RISK FACTORS
-Limited sperm exposure
-Primipaternity
-Pregnancy after donor
insemination, oocyte donation,
embryo donation
-Protective effectof partner change in -Maternal infections
the case of previous PE pregnancy
-Maternal or pregnancy-related risk
factors
-Extremes of maternal age
-Multifetal gestation
-PE in a previous pregnancy
-Chronic HT or renal disease
-Rheumatic disease
-Maternal low birthweight
-Obesity & insulin resistance
-Pregestational DM
-Pre-existing thrombophilia
-Maternal susceptibility genes
-Family history of PE
-Smoking ( reduced risk )
-Hydropic degeneration of placenta
-PCOS, recurrent abortions
 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)
Karakteristik:

• Kerusakan endotel Vaskuler

dengan:
• vasospasme,
• transudasi plasma
• sequele iskemik dan trombotik

Dugaan Penyebab: (2003, Sibai)

• Invasi trofoblastik abnormal terhadap vasa

uterina
• Intoleransi imunologis antara jaringan ibu
dan janin
• Maladaptasi maternal terhadap perubahan
Kardiovaskuler dan proses radang
• Defisiensi diet
• Pengaruh genetik
Figure 4 Unifying hypothesis of pre-eclampsia pathophysiology

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

Nat Clin Pract Neprol 1: 98–114 doi:10.1038/ncpneph0035
Maternal Vasculer Excessive
Faulty Placentation
disease Trophoblasts

Genetic,
immunologic, or
inflamatory
factors

Reduced uteroplacental
perfusion
 Vasoactive agents: Noxious agents:
Prostaglandins, Cytokines, Lipid
nitric Oxide, Peroxidases
Endothelins

Endothelial
Activation

Vasospasm Activation of Coagulation

Capillary leak
Hypertension Trombocytopenia
Seizures
Oliguria
Reduced uteroplacental
Edema
Liver ischemia
perfusion
Hemoconcentratio
Abruption
n
Proteinuria
 Aktivasi, agregasi, konsumsi + ↑ Berhubungan dengan:
volume dan ↓ usia platelet • Tekanan afterload
thrombin  trombositopenia • Tekanan Preload
gkat
• Ekstravasasi cairan
nsi faktor
kuan karena
it penyerta
ectin
ung
gkat

Hemolisis  ↑ LDH,
perubahan bentuk eritrosit.
Akibat gangguan
endotelhemolisis
mikroangiopati
CO meningkat  CO
menurun + resitensi
• Hemokonsentrasi perifer 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
↓
 • Perdarahan akibat•ruptur
Hiperperfusi
arteri • Kehilangan
• Edema, iskemi, autoregulasi
hyperemia,trombosis,aliran darah
perdarahan serebral
• Klirens
• Infark arteri retina
plasenta
• Ablasio retina
menurun
• Laju aliran • Edema korteks dan
darah defek visual
plasenta
menurun
 Prediction of PE

• No known biomarkers

• No efective predictors

• Doppler velocimetry of uterine artery blood flow in

2nd trimester might be useful ( RI  or early diastolic
notch – uni- or 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
Mg or Zn supplementation (I)
Fish-oil supplementation & other
sources of fatty acids (I)
Calcium supplementation (I)
Low-dose aspirin (I)
Heparin or low-molecular-weight
heparin (III)
Antioxidant vitamins (C,E) (II)
Anti-HT medications in women w/
chronic HT
Levels of evidence (I – IV) as outlined by the US Preventive Task Force. *Insufficient evidence - small
Pregnancy outcome
No reduction in PE
No reduction in PE
No effect in low-risk or high-risk
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
16% reduction in fetal or neonatal
deaths
Reduced PEin women w/ renal dis. &
in women w/ thrombophilia
Reduced PE in one trial
Risk of women developing severe HT
reduced by half, but not risk of PE
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.
No evidence to recommend for
prevention
 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
 Management of pe
• Objectives :
1. termination of pregnancy with least
possible
trauma to mother and fetus
2. birth of an infant who subsequently
thrives
3. complete restoration of health to the
mother
Management of PE
Preeclampsia

Maternal & fetal

assessment

•Gestational age ≥38 weeks

•At ≥34 weeks’ gestation:
- Severe PE
- Labour or rupture of membranes YES
- Abnormal fetal testing Deliver

- Severe oligihydramnios or fetal growth

restriction

NO

Mild disease Severe disease < 23 weeks

• Hospital or office
22 – 32 weeks
management 33 – 34 weeks
• Maternal and
fetal assessment

• Worsening maternal • Steroids

• Steroids
or fetal condition
• Anti-HT
• Delivery after 48 h
• ≥38 weeks
• Daily assessment of
• Labour or rupture of maternal-fetal
membranes conditions
• Delivery at 34 weeks