Download gestational hypertension

Marwan Alhalabi MD PhD
Professor in Reproductive Medicine
Faculty of Medicine
Damascus University
And
Medical Director
Orient Hospital
Assisted Reproduction Center
Damascus – Syria
Hypertensive disorders are the most common
and yet serious conditions seen in obstetrics
• Incidence is 5-10%.
• The most frequent cause of iatrogenic prematurity.
• Preterm delivery
• Intrauterine growth restriction (IUGR)
• Perinatal death
• Maternal cerebrovascular accidents ( CVA).
• Placental abruption.
• Decreases during the first trimester,
• Reaching its lowest point at 20 weeks,
• Returns to pre-pregnancy levels during
the third trimester.
Preeclampsia
Gestational
hypertension
Eclampsia
Classification
Chronic
hypertension
with pregnancy
Preeclampsia
superimposed
on chronic
hypertension
Blood Pressure ≥ 140/90mmHg on two
or more occasions
- in a previously normotensive patient
- after 20 weeks gestation
- without proteinuria
- returning to normal 12 weeks after
delivery
Almost half of these develop
preeclampsia syndrome
GESTATIONAL HYPERTENSION
GESTATION ≥ 20 WEEKS
SUSTAINED HYPERTENSION ( ≥ 140/90)
No proteinuria
GESTATIONAL HYPERTENSION
GESTATIONAL HYPERTENSION
DEFINITION
SYMPTOMS
EXAMINATION
Sustained B.P
No proteinuria
NONE
Unremarkable
CRITERIA FOR MILD GESTATIONAL HYPERTENSION
Blood Pressure
> 140 to < 160 mm Hg,
systolic
> 90 to < 110 mm Hg,
diastolic
Proteinuria
< 300 mg per 24-hr
collection
Platelet count
> 100,000/mm3
Liver enzymes
Normal
Maternal symptoms
Absent
IUGR / Oligohydramnios
Absent
• It is defined as hypertension of at least 140/90mm Hg
recorded on two separate occasions at least 4 hours
apart and in the presence of at least 300mg protein in a
24 hour collection of urine, arising after the 20th week of
gestation in a previously normotensive woman and
resolving completely by the 6th postpartum week.
Preeclamsia
Gestational
Hypertension
Proteinuria
RISK FACTORS for PREECLAMPSIA
DEMOGRAPHIC
OBSTETRICS
MEDICAL
NULLIPARA
(Age extremes <20yrs ,
>35yrs )
1. Multiple gestation
2. Molar pregnancy
3. Non-immune
hydrops
1.
2.
3.
4.
Diabetes mellitus
Chronic HTN
Renal disease
SLE
Genetic
Age &Parity
Partner Factors
Genetic
Predisposition
Teenage pregnancy
<18 yrs
Change of partner
Family History
Age>35 yrs
Limited sperm
exposure
Race & Ethnicity
Long interval
between
pregnancy >10
years
Pregnancy by
donor
insemination
Nulliparity
Partner fathered
an eclamptic
pregnancy
More Common in
black & Asians
Pregnancy by
ovum donation
Pregnancy Factors
Underlying Medical
Diseae
Others
Chronic hypertension
Multiple pregnancy
Diabetes mellitus
Obesity BMI> 35
kg/m2
Renal Disease
Hydatiform mole
Cardiovascular disease
Psychological stress
& strain
Smoking
Hyperthyroidism
Hydrops fetalis
Metabolic Syndrome
•
Hyperhomocysteinemia ,
•
Autoimmune disease
Fetal chromosomal
anomaly
•
Antiphospholipid antibodies,
(trisomy 13)
•
Thrombophilia
Previous history of
preeclamsia
MILD PREECLAMPSIA
GESTATION ≥ 20 WEEKS
SUSTAINED HYPERTENSION (≥ 140/90)
Proteinuria (≥300mg /24 hr)
PATHO -PYSIOLOGY
Diffuse Vasospasm
Capillary injury
SYMPTOMS
NONE
EXAMINATION
NONE
LABORATORY
FINDINGS
MANAGEMENT
Proteinuria (1-2+)
Hemoconcentration
< 36 wks Conservative
>36 wks MgSO4 and
Delivery
GESTATIONAL HYPERTENSION
GESTATION ≥ 20 WEEKS
SUSTAINED HYPERTENSION (≥ 140/90)
NO PROTEINURIA
MILD PREECLAMPSIA
GESTATION ≥ 20 WEEKS
SUSTAINED HYPERTENSION ( ≥ 140/90)
Proteinuria ( ≥ 300mg /24 hr)
BLOOD PRESSURE
PROTEINURIA
SYMPTOMS
≥ 160/110
≥ 5grams
1. Headache
2. Epigastric pain
3. Visual changes
LABORATORY
FINDINGS
SIGNS
DIC
Elevated Liver
enzymes
1. Pulmonary edema
2. Oliguria
3. cyanosis
• new onset of seizures or unexplained coma
during pregnancy in patients with pre-existing
preeclampsia
and
neurological disorder.
without
pre-existing
• addition of convulsions in a woman with preeclampsia
• occurs in 0.5-4% of deliveries
• 25% have eclamptic seizures before labour, 50% during
labour, and 25% after delivery.
Seizure/
Eclampsia
Preeclampsia
Convulsion/
Coma
ECLAMPSIA
RISK FACTORS
Same as Preeclampsia
rebra
PATHO PYSIOLOGY
Cerebral vasospasm ,
ischemia and edema
SYMPTOMS
Generalized tonic-clonic
SEIZURES
ECLAMPSIA
LABORATORY FINDINGS
MANAGEMENT
• Proteinuria
• Hemoconcentration
• DIC
• Elevated Liver enzymes
1. Stop convulsions with MgSO4
2. Prompt delivery at any gestational
age
3. Lower diastolic BP 90-100mm/Hg
MANAGEMENT
IV MgSO4 – To prevent convulsions
( continue 24 hrs post-partum )
LOWER B.P ( hydralazine or labetalol)
INDUCE LABOR (IV oxytocin and amniotomy )
•
Blood pressure ≥
140/90 before 20
weeks of gestation.
OR
• persistence of
hypertension beyond
12 weeks after
delivery.
CHRONIC HYPERTENSION
GESTATION < 20 WEEKS OR Prepragnancy
SUSTAINED HYPERTENSION (≥140/90)
+/- PROTEINURIA
GOOD PROGNOSIS
POOR PROGNOSIS
WORST
PROGNOSIS
B.P 140/90 to 179/109
No end organ damage
KIDNEYS: Renal disease
EYES : Retinopathy
HEART : Left Ventricular
Hypertrophy (B.P >180/110)
Uncontrolled HTN
Chronic HTN +Superimposed
PIH
MANAGEMENT OF CHRONIC HYPERTENSION
DC antihypertensive meds
(if B.P >100 mm Hg diastolic)
If antihypertensive meds needed
- Methyl dopa is drug of choice (or labetalol)
Serial ultrasounds (increase risk of IUGR >30 weeks )
Serial B.P and urine protein
(watch for superimposed preeclampsia)
Induce labor at term
• New-onset proteinuria > 300 mg/24 hrs in
hypertensive women but no proteinuria before 20
wks gestation.
• A sudden increase in proteinuria or blood pressure
or platelet count < 100,000/ cu mm in women with
hypertension and proteinuria before 20 wks
gestation.
CHRONIC HTN SUPERIMPOSED PIH
CHRONIC HYPERTENSION
Worsening BLOOD PRESSURE
Worsening proteinuria
MANAGEMENT of Chronic HTN and
superimposed PIH
MgSO4 – To prevent convulsions
( continue 24 hrs post-partum )
LOWER B.P - Diastolic 90-100 mm Hg
( hydralazine or labetalol)
INDUCE LABOR (IV oxytocin and amniotomy )
• HTN patients with
hemolysis (H), elevated
liver enzymes (EL), low
platelet count (LP)
• 4-12% of pt. with severe
preeclampsia and
eclampsia develop HELLP
syndrome
• cardiovascular stabilization,
correction of coagulation
abnormalities, and delivery
• PLT transfusion before or after
delivery if PLT count is
<20,000/mm3 (advised at
<50,000/mm3 before cesarean)
• <32 weeks gestation; steroid therapy
may help stabilize maternal PLT count
• Complex disease
• Appears to be
triggered by the
placenta
• Can occur in molar
pregnancies where fetus
absent
• Can also occur in
abdominal pregnancy
(pregnancy not in uterus)
Stage 0
3-8 weeks
Oxidative
Stress
Endoplasmic reticulum
Stress
Stage 1
8-18 weeks
Poor Immunoregulation
Inadequate tolerance to fetopaternal antigens during conception
and implantation
Poor Placentation
Deficient trophoblast invasion and
spiral artery remodelling
Inflammatory
Stress
Stage 2
20 weeks to
birth
Clinical manifestation
Over activation of maternal
endothelium and systemic
inflammatory network
invasive
cytotrophoblasts of
fetal origin invade the
maternal spiral
arteries
Normal
Pregnancy
transforms them from
small-caliber resistance
vessels to high-caliber
capacitance vessels
capable of providing
placental perfusion
adequate to sustain the
growing fetus
Preeclampsia
cytotrophoblasts fail to adopt an
invasive endothelial phenotype
invasion of the spiral arteries is
shallow and they remain small caliber,
resistance vessels
placental ischemia
39
Complete implantation
failure
Infertility
Successful implantation, but
failed Placentation
Miscarriage
Defective implantation, poor
Placentation
Pre-eclampsia
Stage 1:
reduced
placental
perfusion
Abnormal
implantation
Stage 2 :
maternal
syndrome
-hypertension
-proteinuria
-endothelial
dysfunction
NORMAL PREGNANCY
PREECLAMPSIA
Impair/ inadequate trophoblast invasion to the spiral arteries
Spiral arteries retain their charecteristic (narrow, tortuous, high resistance)
Reduce blood supply to placenta
Result in placental hypoperfusion
As a compensation
High BP in maternal
Stage 1: reduced
placental perfusion
Abnormal
implantation
Stage 2 :
maternal
syndrome
-hypertension
-proteinuria
-endothelial
dysfunction
WHAT GETS INTO MATERNAL CIRCULATION
???
ANGIOGENIC
FACTORS
ANTI-ANGIOGENIC
FACTORS
Vascular endothelial
growth (VEGF)
including placental
growth factor
Soluble FMS-like tyrosine
kinase-1 (sFlt-1)
Transforming growth
factor- beta (TGF-B)
Soluble endoglin (sEng)
Look after maternal
endothelium
Released from diseased
placenta
• 1.vasodialator & vasoconstrictor.
• 2. angiogenic and antiangiogenic factors.
47
Maternal
Syndrome
Fetal
Syndrome
Pre-eclampsia
Inadequate trophoblast invasion and defect
remodeling of spiral arteries
Placental ischemia and inflammation
Systemic
inflammation
Apoptosis
Oxidative
stress
Endothelial dysfunction
48
Relase of
placental
factor
vasoconstrictor
vasodialator
Syncytiotrophoblast
& endothelium
AngiotensinII
NO
Endothelin-I
PGI-2
Thromboxane A2
placenta
↓PGI2
↑TXA2
Vasoconstriction
Platelet aggregation
↑Vasopressor response
↑uterine activity
Activated endothelial cells promote coagulation
and increase vasopressor sensitivity
Widespread coagulation occur (DIC)
Fibrin deposition in kidney & placenta
HPT & placental insufficiency
Cardiovascular
• Generalized vasospasm
• Increased peripheral resistance
• Reduced central venous/
pulmonary pressure
Renal
• Proteinuria
• Decreased glomerular filtration rate
• Decreased urate excretion
Hepatic
Organ Specific Changes associated with Preeclampsia
Hematological
• Platelet activation and depletion
• Coagulopathy
• Decreased plasma volume
• Increased blood viscosity
• Periportal necrosis
• Subscapular hematoma
Central Nervous System
• Cerebral oedema
• Cerebral haemorrhages
Organ
Damage
utero-placenta
IUGR
Hematological
Epistaxis, DIC like features, hemoconcentration
CNS
Cerebral edema, cerebral hge seizures
Heart
Subendothelial hge , focal necrosis & hge,
cardiomyopathy, heart failure
Lungs
Pulmonary edema, hemorrhagic
brochopneumonia
Kidneys
glomerular endotheliosis, oliguria
liver
Subcapsular hge, ischaemiaperiportal
necrosis, HELLP
Antihypertensive drugs used in pregnancy are
• Methyldopa
• Hydralazine
• labetalol
• Routinely used in severe PE.
• Magnesium sulphate: most commonly used.
• Initiated with onset of labor till 24h postpsrtum.
• For caesarean, started 2hrs before the section
till 12hrs postpartum.
it can be given either IV or IM.
IV has good prognosis.
Loading dose for IV is 4g. i.e. 8 ml diluted in 12ml
normal saline. This 20 ml is given in 20 minutes.
Maintenance dose is 20 g i.e. 40ml diluted in 60ml
normal saline and given at rate of 1g/hr.
IM is also used.
Loading dose is as IV.
Maintenance dose is 5g every 4 hrs in
alternate buttocks for 24hrs.
Mgso4 acts on NM junction and inhibit entry of Ca++
ions thus inhibiting excitability of neurons.
• Maternal :
flushing
perspiration
headache,
muscle weakness
pulmonary oedema
• Neonatal:
lethargy
hypotonia
respiratory depression
Management of MgSO4
Toxicity
The only definitive treatment
Preeclamptic patients divided into 3 categories
A- Preeclampsia features fully subside
B- partial control, but BP maintains a steady high level
C- persistently increasing BP to severe level or addition
of other features
A: can wait till spontaneous onset of labor
don’t exceed Expected Date of Delivery
B: >37wk terminate without delay
<37wk, expectant management at least
till 34wks
C: terminate irrespective of POG
start seizure prophylaxis and steroids if<34wks
Unless contraindicated: Eclamptic women
should undergo normal vaginal delivery
Indications for caesarean section Fetal distress
Placental abruption
Unfavourable cervix
Failed induction of labour
Recurrent seizures
• Urine: 24 hour urine, Proteinuria.
• Kidney functions: serum creatinine, urea, creatinine
clearance and uric acid.
• Liver functions: bilirubin, Enzymes
• Blood: CBC, HCt , Hemolysis and Platelet count
(Thrombocytopenia).
• Coagulation Profile: Bleeding and clotting time
•
•
•
•
•
•
•
•
•
Convulsions and coma (eclampsia).
Cerebral haemorrhage.
Renal failure.
Heart failure.
Liver failure.
Disseminated intravascular coagulation.
Abruptio placentae.
Residual chronic hypertension in about 1/3 of cases.
Recurrent pre-eclampsia in next pregnancies.
a. Intrauterine growth retardation (IUGR).
b. Intrauterine foetal death.
c. Prematurity and its complications.
• Regular Antenatal checkup:
rapid gain in weight
rising blood pressure
edema
proteinuria/deranged liver or renal profile
• Low dose Aspirin in High risk group: ↑PGs and↓TXA2
• Calcium supplementation: no effects unless women are
calcium deficient
• Antioxidants- Vitamin C and E
• Nutritional supplementation: zinc, magnesium, fish oil,
low salt diet









meningitis
encephalitis
space occupying lesion
electrolyte disturbance
vasculitis
amniotic fluid embolism
Medications
organ failure
stroke
Pregnancy
induced
Hypertension
Gestational
HTN
● BP ≥ 140/90mmHg
●No evidence of underlying
cause of HTN
Preeclampsia
Non Severe
Eclampsia
Severe
PreEclamsia
●No associated symptoms
+
●Comes to normal within 6
wks of delivery
Convulsion
N.B: Pre-eclampsia is principally a syndrome
of signs and when symptoms appear it is
usually late.
Assessment of the severity of pre-eclampsia
is given in the next slide.
N.B: Grades of proteinuria (in g/L): Trace=0.1,
1+=0.3,
2+=1,
±
Coma
3+=3,
4+=10
Uterine Artery Doppler Velocimetry (abnormal
flow resistance/ diastolic notch in 2nd/ 3rd
trimester)
• is most promising, but currently, none of them is completely
suitable for clinical use. (Conde-Agudelo, 2014;
Kleinrouweler, 2012; Myatt, 2012a).
• These have value for fetal-growth restriction but not
preeclampsia (ACOG, 2013a).
• As a result of these trials, some methods to prevent
Preeclampsia have been theorized…
In normal mother
In preeclamptic mother:
Showing early diastolic NOTCH
Decreased EDF
(due to high resistance)
ABNORMALITIES
NONSEVERE
SEVERE
Blood pressure
≥140/90mmHg but
<160/110mmHg
≥160/110mmHg
Proteinuria
≤2+
≥3+
Oliguria
Absent
<400ml/day
Headache
Absent
Present
Visual disturbances
Absent
Present
Platelet count
Normal
Thrombocytopenia
(<100,000/mm3)
HELLP syndrome
Absent
May be present
ALT,AST >70 IU/L
LDH>600 IU/L
Bilirubin >1.2g/L
Serum
transaminases(AST,ALT)
Normal (<40 IU/L)
Elevated
Serum Creatinine
Normal
Elevated
Epigastric pain
Absent
Present
Fetal growth restriction
Absent
Obvious
• Pre-eclampsia is a pregnancy specific
disorder .
• It can occur in absence of the fetus.
• The disease is cured by the removal of
the placenta .
76
77
Genetic Modulators
Pre-existing
Vascular
Pathology
Cytokines
Ros
Central players
78
OBSTETRIC MANAGEMENT
1. Maternal evaluation
 Hemoglobin and hematocrit
platelet count : decreased, if < 1 lakh
coagulation profile
 LFTs : indicated in all patients
 RFTs : raised (S.urea creatinine is decreased in Normal
pregnancy)
 Urine Routine : proteinuria
2. Fetal evaluation:
 Daily fetal movement count
 Ultrasound
 Doppler ultrasound for fetal blood flow
• Genetic factor
• Immunologic factor
• Endocrinologic factor
• Nutritional factor
• Infectious factor
Serious hypertension
BP ≥ 160/110mmHg for at least 12h
Protein in the urine is over 5g/24h or
+++~++++
Creatinine level increases
Function of liver impaired obviously
Function of the placenta impaired
Fetus IUGR, asphyxia and even death
• Gestational HTN
• Transient HTN of
pregnancy
• Preeclampsia
Classification of the American College of
Obstetricians and Gynecologists
•
Mild
•
Severe
• Eclampsia
• Chronic HTN
preceding pregnancy
• Chronic HTN with
superimposed
pregnancy-induced
hypertension
•
Superimposed preeclampsia
•
Superimposed eclampsia
Endothelial
Feto-Placental unit
Dysfunction/Oxidant
Endocrine Dysfunction
Stress
Placental Perfusion/
Vascular Resistance
related Tests
Uterine Artery Doppler
Velocimetry
AT- III
Renal Dysfuntion
Misc
Free fetal DNA
Adapted from Conde-Agudelo and associates
(2009)
ANP
YES
Neither forced nor
restricted
NO
• Gestational HTN : only if
severe HTN
• Preeclampsia :
 If diastolic pressure≥ 100mm
of Hg OR, there is proteinuria OR,
there is fetal compromise.
37 completed weeks of
gestation.
HEMOLYSIS
(due to
passage of
RBCs
through
partially
obstructed
vessel)
HEPATIC
DYSFUNCTION
(due to
intravascular
fibrin
deposition &
sinosoidal
obst.)
Decreased
Liver blood
flow
s)
HELLP
Syndrome
THROMBOCYTOPENIA
(due to
platelet
aggregation
& diposition
in the sites of
endothhelial
damage)
Managed in Eclampsia room.
Protection & supporting
convulsion
Protection ofcare
airway during
&
Protection in a railed
cot
prevention of tongue
bite
Correction of hypoxia &
acidosis
Control of convulsion by MgSO4 (IM/IV route)
Intermittent antihypertensive to control BP
judiciously
Limitation of I.V fluid
Avoidance of diuretics & hyper osmotic agents
88
Prompt delivery of fetus to achieve cure
Magnesium
sulphate
“It is the most effective drug to
control even recurrent seizures
without any central nervous
system depression to mother &
fetus”
89
• Not used to lower bp
• Produce intravascular volume
depletion
• Worsen maternal
hemoconcentration
• Use is limited to presence of
pulmonary edema (FUROSEMIDE)
• May be used in persistent severe
postpartum hypertension
90
Enviromental
Abnormal
placental
implantaion
Maternal
immunological
intolerance
Genetics
CVS and
inflammatory
changes
• Total protein in 24 hours urine > 300mg
• Protein : Creatinine ratio in random
sample > 0.1
• New onset of hypertension after 20
weeks of gestation without proteinuria,
followed by return of B.P. to normal
within 12 weeks post-partum.
• New onset of hypertension after 20 weeks
of gestation along with properly
documented proteinuria, followed by
return of B.P. to normal within 12 weeks
post-partum.
Preeclamsia
Gestational
Hypertensio
n
Proteinuria
• Generalized tonic-clonic seizure in a patient
with Preeclampsia not attributed to any other
cause.
Seizure/
Eclampsia
Preeclampsi
a
Convulsion
/
Coma
• Hypertension before pregnancy / Diagnosed
before 20 weeks of pregnancy not due to
gestational trophoblastic disease.
• Hypertension diagnosed after 20 weeks but
persistent after 12 weeks postpartum
• New onset proteinuria in hypertensive women
but no proteinuria before 20 weeks' gestation
• A sudden increase in proteinuria or blood
pressure or platelet count < 100,000/L in
women with hypertension and proteinuria
before 20 weeks' gestation
Primiparity
Immunologic factors
Previous pregnancy complicated by
Preeclampsia/Eclampsia/HELLP
Family history of Preeclampsia
BMI
Pregnancy related conditions
Primipaternity
Sexual co-habituation
Maternal infection
Gestational age at delivery
of 1st Pregnancy
Socioeconomic status
Smoking
Angiogenic
factor
• VEGF
• TFG-beta
• PlGF
Antiangiogenic
factor
• sFlt-1
• sEng











History of Preeclampsia in previous pregnancy
Advanced maternal age
Family history of Preeclampsia
History of placental abruption, IUGR, fetal death
Obesity, BMI>35 doubles the risk
Hypertension
Diabetes
Thrombotic vascular diseases
Multiple gestation
Molar pregnancy
Smoking

Large placenta

Prolonged pregnancy

Placental hydrops

Chromosomal abnormality