Preeclampsia is a disorder that is unique to human pregnancy, and the only known cure for this complication is delivery. Preeclampsia affects approximately 4% to 5% of pregnancies . The Preeclampsia Foundation states that: “Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. By conservative estimates, these disorders are responsible for 76,000 maternal and 500,000 infant deaths each year.” As is evident from the statement that, preeclampsia is a major contributor to maternal and fetal morbidity and mortality worldwide. In India, the incidence of preeclampsia is reported to be 8-10% among the pregnant women. According to a study, the prevalence of hypertensive disorders of pregnancy was 7.8% with preeclampsia in 5.4% of the study population in India

1. “Preeclampsia”
new concepts in an age-old
disease
Dr. Sujnanendra Mishra
MD (ObGyn)

2. DIC
CardioRenal
Syndrome
Elevated LFTs
Hypertension Proteinuria
HELLP Syndrome Abdominal pain
Seizure
Stroke
HUS Headaches
Thrombocytopenia
OliguriaScotomataFatty
LiverTTP PRES
Hemoconcentration
Hyperuricemia
Edema
Mirror Syndrome
Pulmonary edema
Hemolysis
IUGR

3. History
• 2200 BC Egypt: pregnant women with
fists
• 400 BC Hippocrates: pregnant women
with convulsions
• Eclampsia: Greek word: suddenly,
flash
• 1619: Varardus: first use of word
eclampsia
• 1843: Lever. Proteinuria. Swelling and
convulsions: Nephritic toxemia
• 1897: Vaquez. Hypertension
• 1899: Strogonov: treatment, sedation
• 1900s: prenatal care, preeclampsia
• New concept in the 20th century
• 1902: Ballantyne. Pro-maternity
clinic.
• 1910: USA. Nursing visits at
home.
• 1920: Prenatal visits: check for
hypertension, swelling,
proteinuria to detect :
Preeclampsia
• Maternal mortality reduced in
UK from 319/100,000 in 1936 to
15/100,000 in 1985
Eclampsia - Preeclampsia Prenatal Care
Lytic cocktail :- Artificial hibernation
Magnesium Sulfate
Treatment of eclampsia

4. 2200 BC – Egypt
400 BC -Greece MiddleAges
Third Papyrus
-Tongue biting at birth
_Olive oil treatment
Hippocrates
_Seizure in labor are fatal
_Eclampsia = brilliant light
Midwifery care
Fetus won’t survive fits
Toxic humors =>
phlebotomy, blistering,
starvation, purges
•Key observations
• 1797 – Edema
(Demanet)
• 1847 – Hypertension (Vaquez
and Nobelcourt)
• 1842 – Proteinuria
(Lever)

5. ICD 10 ( WHO )

7. Timely And Correctly Diagnosed
Preeclampsia brings Peace of mind
for physicians
• A disease where the clinical picture is not always clear.
• A disease where the onset is unpredictable.
• A disease where the assessment of the severity/ prognosis is difficult.
• A disease where timely decision can be critical both for mother and fetus.
Preeclampsia is a disease………………

8. Hypertensive Disorder in Pregnancy
Pregnancy induced hypertension
Gestational
hypertension w/o
proteinuria
Preeclampsia
(PIH + proteinuria)
Eclampsia
(PIH + convulsions)
HELLP
syndrome
Pre-existing
hypertension
(chronic
hypertension)
Preeclampsia syndrome
superimposed on
chronic hypertension
Unclassified
hypertension

11. RISK FACTORS with Odd Ratio.
Nulliparity (3:1) Immunologic factors :
Antiphospholipid syndrome
(10:1)
Previous pregnancy complicated by
Preeclampsia/Eclampsia/HELLP(2:1)
Family history of
Preeclampsia(5:1)
Obesity (3:1)
Multifetal gestation (unaffected by
zygosity) (4:1)

12. Primipaternity 4: 1 Black Race (2:1) Maternal infection12:1
Duration of relationship prior to
pregnancy & age at delivery of 1st
Pregnancy High body mass index (3:1) Smoking Reduces !! (1:3.5)
RISK FACTORS

13. Age >40 years (3:1) Chronic renal disease
(20:1)
Chronic hypertension
(10:1)
Diabetes mellitus
(2:1)
In vitro fertilization (2.5: 1) UA S/D ratio >2.6 (4:1)
RISK FACTORS
 Homozygosity for
angiotensinogen
gene T235 (20:1)
 Heterozygosity for
angiotensinogen
gene T235 (4:1)

14. PLACENTA,
Origin Of Life and the Disease Too ????

15. • POOR IMMUNOREGULATIONStage 0
3-8 weeks
• POOR
PLACENTATION
Stage 1
8-18 weeks
• CLINICAL
MANIFESTATION
Stage 2
20 weeks to
birth
Deficient trophoblast invasion and
spiral artery remodelling
Over activation of maternal endothelium and
systemic inflammatory network
Oxidative Stress
Endoplasmic reticulum Stress
Inflammatory Stress
Inadequate tolerance to feto-paternal
antigens during conception and implantation0- LAUNCHING PAD
1- IGNATION
2- TAKEUP
COURSE

16. Proposed Pathogenic Factors of the Maternal Syndrome of
Preeclampsia
Oxidative Stress Lipid Hydroperoxides
Placental trophoblast debris Inflammatory cytokines (TNF-a, IL-6)
Activated neutrophils monocytes and platelets
Inflammatory prostaglandins
(thromboxane)
Inhibitors of nitric oxide synthase
(ADMA)
Agonistic anti-angiotensin receptor
autoantibodies
Endothelin-1
Anti-angiogenic growth factors (sFlt-1, sEnd)

18. Pathophysiology of the Clinical
Manifestations of Preeclampsia
Pathogenesis
of
Preeclampsia
Genetic
factors
Abnormal
trophoblastic
invasion
Vasospasm
Endothelial cell
injury

20. PLACENTATION
Invasive cytotrophoblasts
of fetal origin invade the
maternal spiral arteries
Transforms them from
small-caliber resistance
vessels to high-caliber
capacitance vessels
Capable of providing
placental perfusion
adequate to sustain
the growing fetus
Normal
Pregnancy

21. Normal placentation
 Deep trophoblast invasion
 Remodeling of spiral artery
 Endovascular replacement
 Controlled, sequential perfusion
Pathological placentation
 Shallow trophoblast invasion
 Limited arterial remodeling
 Failed endovascular invasion
 Over, or under-perfusion of placenta
PLACENTATION

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

23. ANGIOGENESIS,
Key to Placental Development

24. SPIRAL ARTERY
REMODELING

25. Unmodeled decidual spiral artery
VSMC:- vascular smooth muscle cells
EC:- Endothelial cells
EVT:- Extra-villous trophoblast
SPIRAL ARTERY REMODELING (CELLULAR)

26. END RESULT SPIRAL ARTERY REMODELING DEFECT

27. NORMAL Endothelial Function
•Vasorelaxation
• Blood pressure
•Permeability
• Filtering
•Coagulation
• Thrombosis
•Adhesiveness
•Platelet and
•monocyte
•Proliferation
• Smooth muscle

28. Soluble Flt-1 (sFlt-1) causes endothelial
dysfunction by antagonizing vascular
endothelial growth factor (VEGF) and
placental growth factor (PlGF)
In normal pregnancy, the placenta
produces modest concentrations of VEGF,
PlGF, and soluble Flt-1
In preeclampsia, excess placental soluble
Flt-1 binds circulating VEGF and PlGF and
prevents their interaction with endothelial
cell-surface receptors
decreased prostacyclin
nitric oxide production
release of pro-coagulant
proteins
ENDOTHELIAL
DYSFUNCTION
ENDOTHELIAL DYSFUNCTION

29. Faulty placentation
Excessive trophoblastsMaternal vascular disease
Reduced Uteroplacental Perfusion
Genetic/Immunologic/Inflammatory factors
Activation of CoagulationCapillary Leak
Endothelial Activation
Vasospasm
Vasoactive Agents:
 Prostaglandin
 Nitric oxide
 Endothelins
Noxious Agents:
 Cytokines
 Lipid Peroxidases
 Multiple gestation
 Hydrops fetalis
SUMMARY

30. Activation of CoagulationCapillary LeakVasospasm
Abruption
Seizures
Hypertension
Liver Ischemia
Oliguria
Proteinuria
Edema
Hemoconcentration
Endothelial Activation
Thrombocytopenia
SUMMARY

32. Maternal Decidual Natural killer cells (dNK) are key
mediators of implantation
 Predominant lymphocyte in decidua
 Highly active
▪ Chemokines, angiogenic growth factors, proteinases
 Induce spiral arteriole remodeling
 Enhance trophoblast invasion and differentiation
 Suppress immune rejection
 dNK cells reduced (8-fold) in preeclampsia*
RobsonA, et al. FASEB J, 2012. *Lockwood C, et al. Am J Path, 2013

34. PREDICTION

35. “Preeclampsia is a
common
and potentially serious
condition
that presents a
continuing
challenge to clinicians
due to the
variable features and
lack
of diagnostic tests.”
“Our understanding of the
pathophysiology of
preeclampsia, including the
role of the placental factors
sFlt-1 and PlGF, has improved.
With this better
understanding comes the
opportunity to improve the
way we diagnose this common
and sometimes serious
condition.”

36. • sFlt-1/PlGF ratio < 38: Rule-out preeclampsia for 1 week.
• sFlt-1/PlGF ratio ≥ 38: Rule-in preeclampsia within 4 weeks.
Elecsys

37. Novel innovative sFlt-1/PlGF ratio test
Precise, consistent, reliable (Elecsys)
Positive And Negative Predictive Values (PPV And NPV Respectively

38. Endothelial Control Of Blood Pressure

39. ANGIOGENIC Blockade by sFlt-1 cause Hypertension

40. Recent Insights into the
Pathogenesis of Preeclampsia -
The Role of Nrf2 Activators and their Potential
Therapeutic Impact.
• It provides an overview
of the possible beneficial
effects of Nrf2 inducers
in PE.
• Potent Nrf2 activator
sulforaphane increase
Nrf2 protein levels and
led to the upregulation
of phase II antioxidant
enzymes.

41. • "Activation of the PAR1
receptor by MMP-1
causes changes in the
endothelial cells of
blood vessels that we
speculated could result
in contraction of blood
vessels. This new
information provides a
rationale for the use of
PAR1 inhibitors to treat
preeclampsia,"

42. Daily measurements
Mon Tue Wed Thu Fri Sat Sun
Blood pressure .
8am
4pm
12pm
Pulse
Weight
Urine protein
Fetal movements
Daily evaluation at home for non severe Preeclampsia cases

43. Complaints
Mon Tue Wed Thu Fri Sat Sun
Swelling (face, feet, hands)
Nausea-vomiting
Headache
Agitation
Visual disturbances (scotoma,
blurred vision)
Abdominal pain
Reduced urine output