Hypertensive disorders in pregnancy

Hypertensive disorders are the most common and yet serious conditions seen in obstetrics and The most frequent cause of iatrogenic prematurity.

1. Marwan AlhalabiMD PhD
Professor in Reproductive Medicine
Faculty of Medicine
Damascus University
And
Medical Director
Orient Hospital
Assisted Reproduction Center
Damascus –Syria

2. Hypertensive disorders are the most common
and yet serious conditions seen in obstetrics

3. •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.

4. •Decreasesduringthefirsttrimester,
•Reachingitslowestpointat20weeks,
•Returnstopre-pregnancylevelsduring
thethirdtrimester.

5. Classification
Pre-
eclampsia
Eclampsia
Preeclampsia
superimposed
on chronic
hypertension
Chronic
hypertension
with pregnancy
Gestational
hypertension

6. 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

7. GESTATIONAL HYPERTENSION
GESTATION ≥20 WEEKS
SUSTAINED HYPERTENSION ( ≥ 140/90)
No proteinuria

8. DEFINITION
SYMPTOMS
EXAMINATION
GESTATIONAL HYPERTENSION
Sustained B.P
No proteinuria
NONE
Unremarkable
GESTATIONAL HYPERTENSION

9. CRITERIAFOR MILD GESTATIONAL HYPERTENSION
BloodPressure >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

10. •Itisdefinedashypertensionofatleast140/90mmHg
recordedontwoseparateoccasionsatleast4hours
apartandinthepresenceofatleast300mgproteinina
24hourcollectionofurine,arisingafterthe20
th
weekof
gestationinapreviouslynormotensivewomanand
resolvingcompletelybythe6
th
postpartumweek.

11. Preeclamsia
Gestational
Hypertension
Proteinuria

12. RISK FACTORS for PREECLAMPSIA
DEMOGRAPHIC
OBSTETRICS
MEDICAL
NULLIPARA
(Age extremes <20yrs ,
>35yrs )
1.Multiple gestation
2.Molar pregnancy
3.Non-immune
hydrops
1.Diabetes mellitus
2.Chronic HTN
3.Renal disease
4.SLE

13. Genetic
Genetic
Predisposition
Family History
Race & Ethnicity
More Common in
black & Asians
Pregnancy by
ovum donation
Age &Parity
Teenage pregnancy
<18 yrs
Age>35 yrs
Long interval
between
pregnancy >10
years
Nulliparity
Partner Factors
Change of partner
Limited sperm
exposure
Pregnancy by
donor
insemination
Partner fathered
an eclamptic
pregnancy

14. Pregnancy Factors
Multiple pregnancy
Hydatiformmole
Hydropsfetalis
Fetal chromosomal
anomaly
(trisomy 13)
Underlying Medical
Diseae
Chronic hypertension
Diabetes mellitus
Renal Disease
Cardiovascular disease
Hyperthyroidism
Metabolic Syndrome
Others
Obesity BMI> 35
kg/m
2
Psychological stress
& strain
Smoking
Previous history of
preeclamsia
•Hyperhomocysteinemia ,
•Autoimmune disease
•Antiphospholipid antibodies,
•Thrombophilia

15. MILD PREECLAMPSIA
GESTATION ≥ 20 WEEKS
SUSTAINED HYPERTENSION (≥ 140/90)
Proteinuria (≥300mg /24 hr)

16. SYMPTOMS
EXAMINATION
PATHO -PYSIOLOGY
NONE
NONE
Diffuse Vasospasm
Capillary injury

17. LABORATORY
FINDINGS
MANAGEMENT
Proteinuria (1-2+)
Hemoconcentration
< 36 wks Conservative
>36 wks MgSO4 and
Delivery

18. GESTATIONAL HYPERTENSION
GESTATION ≥ 20 WEEKS
SUSTAINED HYPERTENSION (≥ 140/90)
NO PROTEINURIA
MILD PREECLAMPSIA
SUSTAINED HYPERTENSION (≥ 140/90)
Proteinuria (≥ 300mg /24 hr)
GESTATION ≥20 WEEKS

19. BLOOD PRESSURE
PROTEINURIA
SYMPTOMS
≥ 160/110
≥5grams
1.Headache
2.Epigastric pain
3.Visual changes

20. LABORATORY
FINDINGS
SIGNS
DIC
Elevated Liver
enzymes
1.Pulmonary edema
2.Oliguria
3.cyanosis

21. •newonsetofseizuresorunexplainedcoma
duringpregnancyinpatientswithpre-existing
preeclampsiaandwithoutpre-existing
neurologicaldisorder.

22. •additionofconvulsionsinawomanwithpreeclampsia
•occursin0.5-4%ofdeliveries
•25%haveeclampticseizuresbeforelabour,50%during
labour,and25%afterdelivery.
Eclampsia Preeclampsia
Seizure/
Convulsion/
Coma

23. rebra
SYMPTOMS
PATHO -
PYSIOLOGY
RISK FACTORS
Same as Preeclampsia
Cerebral vasospasm ,
ischemia and edema
Generalized tonic-clonic
SEIZURES
ECLAMPSIA

24. 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
ECLAMPSIA

25. MANAGEMENT
IV MgSO4 –To prevent convulsions
( continue 24 hrs post-partum )
LOWER B.P ( hydralazine or labetalol)
INDUCE LABOR (IV oxytocinand amniotomy)

26. •Blood pressure ≥
140/90 before 20
weeks of gestation.
OR
•persistence of
hypertension beyond
12 weeks after
delivery.

27. CHRONIC HYPERTENSION
GESTATION < 20 WEEKS OR Prepragnancy
SUSTAINED HYPERTENSION (≥140/90)
+/-PROTEINURIA

28. 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

29. MANAGEMENT OF CHRONIC HYPERTENSION
If antihypertensive meds needed
-Methyl dopais drug of choice (or labetalol)
Serial ultrasounds (increase risk of IUGR >30 weeks )
Induce labor at term
DC antihypertensive meds
(if B.P >100 mm Hg diastolic)
Serial B.P and urine protein
(watch for superimposed preeclampsia)

30. •New-onset proteinuria >300 mg/24 hrs in
hypertensive women but no proteinuria before 20
wksgestation.
•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.

31. CHRONIC HTN SUPERIMPOSED PIH
CHRONIC HYPERTENSION
Worsening BLOOD PRESSURE
Worsening proteinuria

32. 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 oxytocinand amniotomy)

33. •HTN patients with
hemolysis(H), elevated
liver enzymes (EL), low
plateletcount (LP)
•4-12%of pt. with severe
preeclampsia and
eclampsia develop HELLP
syndrome

34. •cardiovascular stabilization,
correction of coagulation
abnormalities, and delivery
•PLT transfusion before or after
delivery if PLT count is
<20,000/mm
3
(advised at
<50,000/mm
3
before cesarean)
•<32 weeks gestation; steroid therapy
may help stabilize maternal PLT count

35. •Complexdisease
•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)

36. Stage 0
3-8 weeks
Stage 1
8-18 weeks
Stage 2
20 weeks to
birth
Poor Immunoregulation
Inadequate tolerance to feto-
paternal antigens during conception
and implantation
Poor Placentation
Deficient trophoblast invasion and
spiral artery remodelling
Clinical manifestation
Over activation of maternal
endothelium and systemic
inflammatory network
Oxidative
Stress
Endoplasmic reticulum
Stress
Inflammatory
Stress

37. invasive
cytotrophoblastsof
fetal origin invade the
maternal spiral
arteries
transforms them from
small-caliberresistance
vessels to high-caliber
capacitance vessels
capable of providing
placental perfusion
adequate to sustain the
growing fetus
Normal
Pregnancy

38. cytotrophoblastsfail to adopt an
invasive endothelial phenotype
invasion of the spiral arteries is
shallow and they remain small caliber,
resistance vessels
placental ischemia
Preeclampsia

39. 39
Defective implantation, poor
Placentation
Successful implantation, but
failed Placentation
Complete implantation
failure
Infertility
Miscarriage
Pre-eclampsia

40. Stage 1:
reduced
placental
perfusion
Abnormal
implantation
Stage 2 :
maternal
syndrome
-hypertension
-proteinuria
-endothelial
dysfunction

41. NORMAL PREGNANCY
PREECLAMPSIA

43. Impair/ inadequate trophoblastinvasion 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

44. Stage 1: reduced
placental perfusion
Abnormal
implantation
Stage 2 :
maternal
syndrome
-hypertension
-proteinuria
-endothelial
dysfunction
WHAT GETS INTO MATERNAL CIRCULATION
???

45. ANTI-ANGIOGENIC
FACTORS
ANGIOGENIC
FACTORS
Vascular endothelial
growth (VEGF)
including placental
growth factor
Transforming growth
factor-beta (TGF-B)
Look after maternal
endothelium
Soluble endoglin(sEng)
Soluble FMS-like tyrosine
kinase-1 (sFlt-1)
Released from diseased
placenta

46. •1.vasodialator &vasoconstrictor.
•2. angiogenicand antiangiogenicfactors.

47. Fetal
Syndrome
Maternal
Syndrome
47

48. Inadequate trophoblastinvasion and defect
remodeling of spiral arteries
Placental ischemia and inflammation
Systemic
inflammation
Apoptosis
Oxidative
stress
Relaseof
placental
factor
Endothelial dysfunction
Pre-eclampsia
48

49. vasodialator
NO
PGI-2
vasoconstrictor
Angiotensin-
II
Endothelin-I
Thromboxane A
2
placenta
Syncytiotrophoblast
& endothelium

51. ↓PGI2
↑TXA2
Vasoconstriction
Platelet aggregation
↑Vasopressor response
↑uterine activity

52. Activated endothelial cells promote coagulation
and increase vasopressor sensitivity
Widespread coagulation occur (DIC)
F
HPT & placental insufficiency

53. Cardiovascular
•Generalized vasospasm
•Increased peripheral resistance
•Reduced central venous/
pulmonary pressure
Hematological
•Platelet activation and depletion
•Coagulopathy
•Decreased plasma volume
•Increased blood viscosity
•Proteinuria
•Decreased glomerular filtration rate
•Decreased urate excretion
Renal
Hepatic
•Periportal necrosis
•Subscapular hematoma
•Cerebral oedema
•Cerebral haemorrhages
Central Nervous System
Organ Specific Changes associated with Pre-
eclampsia

54. Organ Damage
utero-placenta IUGR
HematologicalEpistaxis, DIC like features, hemoconcentration
CNS Cerebral edema, cerebral hgeàseizures
Heart Subendothelialhge , focal necrosis & hge,
cardiomyopathy, heart failure
Lungs Pulmonary edema, hemorrhagic
brochopneumonia
Kidneys glomerular endotheliosis, oliguria
liver Subcapsularhge, ischaemiaàperiportal
necrosis, HELLP

56. Antihypertensive drugs used in pregnancy are
•Methyldopa
•Hydralazine
•labetalol

57. •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.

58. 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.

59. 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.

60. •Maternal :
flushing
perspiration
headache,
muscle weakness
pulmonary oedema
•Neonatal:
lethargy
hypotonia
respiratory depression

61. Management of MgSO4
Toxicity

62. 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

63. 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

64. 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

65. •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

66. •Convulsions and coma (eclampsia).
•Cerebral haemorrhage.
•Renal failure.
•Heart failure.
•Liver failure.
•Disseminated intravascular coagulation.
•Abruptioplacentae.
•Residual chronic hypertension in about 1/3 of cases.
•Recurrent pre-eclampsiain next pregnancies.

67. a. Intrauterine growth retardation (IUGR).
b. Intrauterine foetaldeath.
c. Prematurity and its complications.

68. •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
•Calciumsupplementation: no effects unless women are
calcium deficient
•Antioxidants-Vitamin Cand E
•Nutritional supplementation: zinc, magnesium, fish oil,
low salt diet

69. vmeningitis
vencephalitis
vspace occupying lesion
velectrolyte disturbance
vvasculitis
vamniotic fluid embolism
vMedications
vorgan failure
vstroke

70. N.B: Grades of proteinuria(in g/L): Trace=0.1, 1+=0.3, 2+=1, 3+=3, 4+=10
Pregnancy
induced
Hypertension
Gestational
HTN
●BP ≥ 140/90mmHg
●No evidence of underlying
cause of HTN
●No associated symptoms
●Comes to normal within 6
wks of delivery
Pre-
eclampsia
Non Severe Severe
Eclampsia
PreEclamsia
+
Convulsion
±
Coma
N.B: Pre-eclampsiais 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.

71. •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…
Uterine Artery Doppler Velocimetry (abnormal
flow resistance/ diastolic notch in 2
nd
/ 3
rd
trimester)

72. In preeclamptic mother:
Showing early diastolic NOTCH
Decreased EDF
(due to high resistance)
In normal mother

75. ABNORMALITIES NONSEVERE SEVERE
Bloodpressure ≥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/mm
3)
HELLP syndrome Absent Maybe 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
Epigastricpain Absent Present
Fetal growth restriction Absent Obvious
Pulmonary oedema Absent present

76. •Pre-eclampsiais a pregnancy specific
disorder .
•It can occur in absence of the fetus.
•The disease is cured by the removal of
the placenta .
76

77. 77

78. Genetic Modulators
Pre-existing
Vascular
Pathology
Central players
Cytokines
Ros
78

79. qHemoglobin and hematocrit
platelet count : decreased, if < 1 lakh
coagulation profile
qLFTs : indicated in all patients
qRFTs : raised (S.urea creatinine is decreased in Normal
pregnancy)
qUrine Routine : proteinuria
OBSTETRIC MANAGEMENT
1. Maternal evaluation

80. 2. Fetal evaluation:
qDaily fetal movement count
qUltrasound
qDoppler ultrasound for fetal blood flow

81. •Genetic factor
•Immunologic factor
•Endocrinologic factor
•Nutritional factor
•Infectious factor

82. Serious hypertension
üBP ≥160/110mmHg for at least 12h
üProtein in the urine is over 5g/24h or
+++~++++
üCreatinine level increases
üFunction of liver impaired obviously
üFunction of the placenta impaired
üFetus IUGR, asphyxia and even death

83. •Gestational HTN
•Transient HTN of
pregnancy
•Preeclampsia
•Mild
•Severe
•Eclampsia
•Chronic HTN
preceding pregnancy
•Chronic HTN with
superimposed
pregnancy-induced
hypertension
•Superimposed preeclampsia
•Superimposed eclampsia
Classification of the American College of
Obstetricians and Gynecologists

84. Endothelial
Dysfunction/Oxidant
Stress
Feto-Placental unit
Endocrine Dysfunction
Renal Dysfuntion Misc
Placental Perfusion/
Vascular Resistance
related Tests
Uterine Artery Doppler
Velocimetry
AT-III
ANPFree fetal DNA
Adapted from Conde-Agudeloand associates
(2009)

85. NO
YES
Neither forced nor
restricted

86. •Gestational HTN : only if
severe HTN
•Preeclampsia:
üIf diastolic pressure≥ 100mm
of Hg OR, there is proteinuriaOR,
there is fetal compromise.
ü37 completed weeks of
gestation.

87. HEMOLYSIS
(due to
passage of
RBCs
through
partially
obstructed
vessel)
s)
HEPATIC
DYSFUNCTION
(due to
intravascular
fibrin
deposition &
sinosoidal
obst.)
Decreased
Liver blood
flow
HELLP
Syndrome
THROMBO -
CYTOPENIA
(due to
platelet
aggregation
& diposition
in the sites of
endothhelial
damage)

88. Prompt delivery of fetus to achieve cure
Avoidance of diuretics & hyper osmotic agents
Limitation of I.V fluid
Intermittent antihypertensive to control BP
judiciously
Control of convulsion by MgSO4 (IM/IV route)
Protection & supporting care during convulsion
Protection in a railed
cot
Protection of airway &
prevention of tongue
bite
Correction of hypoxia &
acidosis
Managed in Eclampsia room.
88

89. “It is the most effective drug to
control even recurrent seizures
without any central nervous
system depression to mother &
fetus”
89
Magnesium
sulphate

90. 90
•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

91. Enviromental
Genetics
CVS and
inflammatory
changes
Maternal
immunological
intolerance
Abnormal
placental
implantaion

92. •Total protein in 24 hours urine > 300mg
•Protein : Creatinine ratio in random
sample > 0.1

93. •New onset of hypertension after 20
weeksof gestation without proteinuria,
followed by return of B.P. to normal
within 12 weeks post-partum.

94. •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

95. •Generalized tonic-clonic seizurein a patient
with Preeclampsia not attributed to any other
cause.
Eclampsia
Preeclampsi
a
Seizure/
Convulsion
/
Coma

96. •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

97. •New onsetproteinuria in hypertensive women
but no proteinuriabefore 20 weeks' gestation
•A sudden increasein proteinuria or blood
pressure or platelet count < 100,000/L in
women with hypertension and proteinuria
before 20 weeks' gestation

101. Primiparity Immunologic factors
Previous pregnancy complicated by
Preeclampsia/Eclampsia/HELLP
Family history of Preeclampsia BMI Pregnancy related conditions

102. Primipaternity Sexual co-habituation Maternal infection
Gestational age at delivery
of 1
st
Pregnancy
Socioeconomic status Smoking

103. Angiogenic
factor
•VEGF
•TFG-beta
•PlGF
Antiangiogenic
factor
•sFlt-1
•sEng

104. ØHistory of Preeclampsia in previous pregnancy
ØAdvanced maternal age
ØFamily history of Preeclampsia
ØHistory of placental abruption, IUGR, fetal death
ØObesity, BMI>35 doubles the risk
ØHypertension
ØDiabetes
ØThrombotic vascular diseases
ØMultiple gestation
ØMolar pregnancy
ØSmoking

105. ØLarge placenta
ØProlonged pregnancy
ØPlacental hydrops
ØChromosomal abnormality