Hypertension in Pregnancy - Malang 23-9-201

Hypertension
in Pregnancy
Syakib Bakri
Makassar
Maternal mortality ratios for 2000 by medical cause
and world region
Ronsmans C, Graham WJ. Lancet 2006; 368:1189-1200.

Population-Level, Cause-Specific Proportionate Pregnancy-
Related Mortality
Creanga AA et al. Obstet Gynecol. 2017; 30:1-8

Circulatory Changes During Normal Pregnancy
Ouzounian J, Elkayam U. Cardiol Clin. 2012;30:317-329

Changes in Regional Blood Flow During Normal Pregnancy
Ouzounian J, Elkayam U. Cardiol Clin. 2012; 30:317-329

Classifica8on of Hypertension in Pregnancy
•  Chronic (pre-exis/ng) hypertension

•  Gestasional hypertension
•  Preeclampsia-Eclampsia
•  Super imposed preeclampsia in chronic
hypertension
Diagnosis of Hypertension in Pregnancy
•  Hypertension : Systolic Blood Pressure (SBP) ≥140
mmHg and/or Diastolic Blood Pressure (DBP) ≥90 mmHg
•  NICE Guidelines :
Mild: 140-149/90-99 mmHg
Moderate: 150-159/100-109 mmHg
Severe: ≥ 160/110 mmHg
•  American College of Obstetrician and Gynaecologists :
Mild: 140-150/90-109 mmHg
Severe : ≥ 160/110 mmHg
BP measurement
•  BP measurement in pregnancy should use non-
pregnancy standardized technique.
•  Non-severely elevated BP should be confirmed by
repeat measurement, at least 15 min apart at
that visit.
•  Up to 70% of women with non-severely elevated
BP an office measurement have a normal BP on
subsequent measurements on the same visit, or
by ambulatory blood pressure monitor or home
blood pressure measurement.
Chronic (pre-existing) Hypertension
•  Blood pressure ≥140/90 mmHg present before pregnancy,

before the 20th week of gestation, or persisting beyond the
6wk (12wk) postpartum.
•  1%-5% of pregnancies
•  90% essential or primary hypertension, 10% may have

underlying renal or endocrine disease
Vest AR, ChoL S. Cardiol. Clin. 2012;30:407-423

High risk chronic hypertension in pregnancy
•  Secondary hypertension
•  Target organ damage
•  Maternal age ≥40 years
•  Microvascular disease
•  Previous loss
•  BP ≥180/110 mmHg
Univariate logistic regression analysis demonstrating the
association of chronic hypertension with pregnancy
complications
Gestational Hypertension
•  Hypertension that (1) develops beyond 20 wk of gestation;

(2) can be with or without proteinuria, but is not associated
with other features of preeclampsia; and (3) usually
resolves within 6wk (12wk) postpartum

Preeclampsia/Eclampsia
•  Hypertension presenting beyond 20wk of gestation with

>300 mg protein in a 24-h urine collection or >30 mg/mmol
in a spot urine sample. Eclampsia is the occurrence of
seizures in a pregnant woman with preeclampsia

Diagnostic Criteria for Preeclampsia (1)
Robert JM et al. Am Coll Obstetric Gynecol. 2013:4.

Diagnostic Criteria for Preeclampsia (2)
Robert JM et al. Am. Coll. Obstet. Gynecol. 2013:4.

Superimposed preeclampsia in chronic hypertension
•  The onset of features diagnostic of preeclampsia in a

woman with chronic hypertension beyond 20 wk of
gestation
•  20%-25% of chronic hypertension pregnancies

Outcomes of pregnancy in women
chronic hypertension
Outcame No pre-eclampsia With superimposed pre-
eclampsia
Preterm birth 15% 51%
<37/40
Preterm birth 7% 23%
<34/40
Caesarean sec/on 44% 70%
SGA 21% 48%
BW <2.5kg 13% 44%
SGA : <10th cen/le using customised growth charts, BW, birthweight
Chappell LC et al,Hypertension 2008;51:1002-1009

Risk Factor for Preeclampsia
•  Advance maternal age

•  Nulliparity
•  Previous preeclampsia
•  Family history of preeclampsia
•  Multifetal gestation
•  Preexisting medical condition
ü Diabetes
ü Chronic hypertension
ü Renal disease
ü Systemic lupus erythematosus
ü Antiphospholipid antibody syndrome
•  Baseline proteinuria
•  Prolonged time between pregnancies
•  Increased body mass index
•  Baseline hypertension
Naderi S et al. Hypertensive disorder of pregnancy. Curr Atheroscler. Rep. 2017;19:15-21.

Diagnostic Criteria of Severe Preeclampsia
Townsend R, et al . Integr Blood Press Contr. 2016;9:79-94

Maternal and Fetal Complications in Severe Preeclampsia
Maternal Complications
Abruptio placentae (1% - 4%)
Disseminated coagulopathy / HELLP syndrome (10% - 20%)
Pulmonary edeme / aspiration (2% - 5%)
Acute renal failure (1% - 5%)
Eclampsia (<1%)
Liver failure of hemorrhage (<1%)
Stroke (rare)
Death (rare)
Long-term cardiovascular morbidity
Neonatal Complications
Preterm delivery (15% - 67%)
Fetal growth restriction (10% - 25%)
Hypoxia-neurologic injury (<1%)
Perinatal death (1% - 2%)
Long-term cardiovascular morbidity associated with low birth weight (fetal origin of adult
disease)
Pathogenesis of preeclampsia: two-stage
model
AT1-AA, autoan/bodies to angiotensin receptor 1; COMT, catechol-O-methyltransferase; HTN, hypertension; LFT, liver
func/on test; PlGF1, placental growth factor 1; PRES, posterior reversible encephalopathy syndrome; sEng, soluble endoglin;
sFlt-1, soluble fms–like tyrosine kinase 1; sVEGFR1, soluble vascular endothelial growth factor receptor 1; VEGF, vascular
endothelial growth factor
Clin J Am Soc Nephrol 11: 1102–1113,2016

The Two Stages of Preeclampsia
Stage 1
Poor
First half of No symptoms
placenta/on
pregnancy
Stage 2 Placental oxida/ve

Overt
Second half of stress and
pre-eclampsia
pregnancy inflamma/on
sFlt-1 and other

syncy/othropoblast derived
factors
Maternal systemic
inflammatory stress
Clinical sign of
pre-eclampsia
Aims of an8hypertensive treatment
•  Prevent and treat severe hypertension
•  Prolong pregnancy for as long as safety
possible
•  Maximizing the gesta/onal age of the
newborn
•  Minimize fetal exposure to medica/on that
may have adverse effects

Some facts related to ini/a/on an/-hypertensive
drugs in pregnant women with mild hypertension:

•  Lack of evidence that treatment of mild hypertension in pregnancy
leads to improved maternal outcomes
•  Assump/on that mild hypertension of 4–5 months dura/on does
not adversely affect immediate and long-term cardiovascular
disease (CVD)
•  Concern that decreased maternal BP may compromise
uteroplacental and fetal circula/on, thus, resul/ng in small-for-
gesta/onal–age (SGA) infant
•  Poten/al increase in risk for fetal adverse effects due to exposure
to poten/ally harmful medica/ons in utero.
Summary of society guidelines regarding blood
pressure treatment thresholds and targets
Abbrevia/ons: NHBPEP, the Na/onal High Blood Pressure Educa/on Program; ACOG, American College of
Obstetricians and Gynecologists; HTN, hypertension; NICE, Na/onal Ins/tute for Health and Clinical
Excellence
Vest AR, Cho LS. Cardiol Clin 30 (2012) 407–423
An8hypertensive Drugs in Pregnancy (1)

Methyldopa : firstline agent historically because it is
associated with stable uteroplacental blood flow &
fetal hemodynamic
Calcium channel blocker (Long-ac/ng formula/on):
firstline agent. Nifedipine, Dil/azem, Verapamil is
safe.
Beta-blockers : safety issue is controversial due to
reports of premature labor, fetal growth retarda/on,
neonatal apnea, bradycardia & hypoglycemia.
Should probably be avoided before third semester.
An8hypertensive Drugs in Pregnancy (2)
Diure8cs : the use of diure/c remains controversial.
Not contraindicated in pregnancy except in sekng in
uretoplacental perfusion is already reduced (i.e.
preeclampsia and/or fetal growth retarda/on
Drug ac8ng on Renin-Angiotensin System :
contraindicated, even in women are planning to
become pregnant (increased risk of malforma/ons,
fetal growth retarda/on, oligohydramnions, neonatal
renal failure, neonatal death)
Labetalol (alpha & beta-blockers) : firstline agent
according of many experts. Not available in Indonesia
Preven/on of preeclampsia
•  Low dose aspirin : use advised in women at
high risk
•  Fish oil supplementa/on : not recomended
•  Calcium supplementa/on : use advised in low
calcium intake popula6on
•  Vitamin C and E : not remcomended
•  Other an/-oxidant : not recomended
Brown CM, Garovic VD. Drugs. 2004;74:283-296

Patient Considered for Low-dose Apsirin
•  One of the following high-risk features:

ü History of preeclampsia
ü Multifetal gestation
ü Chronic hypertension
ü Diabetes (type I or type II)
ü Renal disease
ü Autoimmune disease
•  Multiple moderate risk factors:

ü Nulliparity
ü Obesity
ü Family history of preeclampsia
ü African American race
ü Age ≥35
ü Low socioeconomic status
ü Characteristics of previous pregnancy
Naderi S et al. Curr Atheroscler Rep. 2017;19:15-21.

Schausberger CE et al. Geburtsh Frauenheilk 2013;73: 7–52
Pregnancy Hypertension 2012;2:350–357

The risk of future disease following hypertensive pregnancy/
preeclampsia
Green A et al. Royal Coll. Obstet. Gynaecol. 2012;14:99-105.

Mechanism Common to Hypertensive
Disorders of Pregnancy and CVD
1.  Endothelial dysfunc/on

2.  Metabolic abnormality
3.  Oxida/ve stress
4.  Inflammatory response
5.  Hypercoagulability
Garovic VD, Hayman SR. Nat Clin. Pract. Nephrol. 2007;3(11):613-622

Summary
•  Hypertensive disorder represent major causes of pregnancy-relared morbidity and
mortality worldwide.
•  Hypertension in pregnancy consist of chronic (preexis/ng) hypertension,

gestasional hypertension, preeclampsia-Eclampsia and super imposed
preeclampsia in chronic hypertension.
•  The op/mal /ming and choice of therapy for hypertensive pregnancy disorders
involves carefully weighing the risk-versus-benefit ra/o for each individual pa/ent,
with an overall goal of improving maternal and fetal outcomes.
•  Methyldopa and calcium channel blocker can be used as a firstline drugs. Diure/cs
and betablockers can be used as a secondline drugs by taking into account risk-
benefit ra/o. Drugs ac/ng on renin-angiotensin system are contraindicated in
pregnancy.
•  Increasing evidence indicates that hypertension in pregnancy is an

underrecognized risk factor for cardiovascular disease

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Hypertension

Ronsmans C, Graham WJ. Lancet 2006; 368:1189-1200.

Creanga AA et al. Obstet Gynecol. 2017; 30:1-8

Ouzounian J, Elkayam U. Cardiol Clin. 2012;30:317-329

Ouzounian J, Elkayam U. Cardiol Clin. 2012; 30:317-329

• Chronic (pre-exis/ng) hypertension

• Blood pressure ≥140/90 mmHg present before pregnancy,

• 90% essential or primary hypertension, 10% may have

Vest AR, ChoL S. Cardiol. Clin. 2012;30:407-423

• Hypertension that (1) develops beyond 20 wk of gestation;

Vest AR, ChoL S. Cardiol. Clin. 2012;30:407-423

• Hypertension presenting beyond 20wk of gestation with

Vest AR, ChoL S. Cardiol. Clin. 2012;30:407-423

Robert JM et al. Am Coll Obstetric Gynecol. 2013:4.

Robert JM et al. Am. Coll. Obstet. Gynecol. 2013:4.

• The onset of features diagnostic of preeclampsia in a

• 20%-25% of chronic hypertension pregnancies

Vest AR, ChoL S. Cardiol. Clin. 2012;30:407-423

SGA : <10th cen/le using customised growth charts, BW, birthweight

Chappell LC et al,Hypertension 2008;51:1002-1009

• Advance maternal age

Naderi S et al. Hypertensive disorder of pregnancy. Curr Atheroscler. Rep. 2017;19:15-21.

Townsend R, et al . Integr Blood Press Contr. 2016;9:79-94

Clin J Am Soc Nephrol 11: 1102–1113,2016

Stage 2 Placental oxida/ve

sFlt-1 and other

Brown CM, Garovic VD. Drugs. 2004;74:283-296

• One of the following high-risk features:

• Multiple moderate risk factors:

Naderi S et al. Curr Atheroscler Rep. 2017;19:15-21.

Pregnancy Hypertension 2012;2:350–357

Green A et al. Royal Coll. Obstet. Gynaecol. 2012;14:99-105.

1. Endothelial dysfunc/on

Garovic VD, Hayman SR. Nat Clin. Pract. Nephrol. 2007;3(11):613-622

• Hypertension in pregnancy consist of chronic (preexis/ng) hypertension,

• Increasing evidence indicates that hypertension in pregnancy is an

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•  Chronic (pre-exis/ng) hypertension

•  Blood pressure ≥140/90 mmHg present before pregnancy,

•  90% essential or primary hypertension, 10% may have

•  Hypertension that (1) develops beyond 20 wk of gestation;

•  Hypertension presenting beyond 20wk of gestation with

•  The onset of features diagnostic of preeclampsia in a

•  20%-25% of chronic hypertension pregnancies

•  Advance maternal age

•  One of the following high-risk features:

•  Multiple moderate risk factors:

1.  Endothelial dysfunc/on

•  Hypertension in pregnancy consist of chronic (preexis/ng) hypertension,

•  Increasing evidence indicates that hypertension in pregnancy is an