classification,pathophysiology, and screening of preeclampsia

1. PREGNANCY INDUCED
HYPERTENSION
CLASSIFICATION
PATHOPHYSIOLOGY
SCREENING TESTS
RAVALI.K
PG- 1ST year

2. INTRODUCTION
 PIH -Complicate 5- 10% of all pregnancies.
Eclampsia: 0.05 – 0.5% (1 – 2% of preeclampsia)
{ WHO international collaborative study of hypertensive disorders of pregnancy }
Estimated 50,000-60,000 preeclampsia related death / yr worldwide {WHO report 2005}
Major contributor to perinatal morbidity and mortality
Risk factor for future CVS and metabolic disease

3. BP MEASUREMENT
 Measure with patient comfortably seated, legs uncrossed and back & arm supported {Avoid
taking BP in left lateral position BP cuff above level of heart, falsely low BP}
 Middle of cuff is placed on upper arm at level of right atrium
 Appropriately sized cuff should be used-{length 1.5 times circumference of arm}
 Korotkoff: Phase V is usually used for DBP.
Phase IV: If heard till zero reading,

4. 1.Patient must be seated, with feet supported, for 2–3 minutes before B.P. is measured.
2. Left lateral recumbence is preferred than supine position in the bed-bound mother.
3. Blood pressure should be taken on both arms at the first antenatal visit.
4. The right arm should be used thereafter if there is no significant difference between the
arms.
5. First systolic blood pressure (SBP) should be taken at brachial artery by palpation method.
6. SBP is taken again with auscultatory method at Korotkoff phase I (KI).
7. Diastolic blood pressure (DBP) is recorded as Korotkoff phase V (K5) and if K5 is absent, it
can be recorded as Korotkoff phase IV (K4).
8. A standard cuff should be used for arms with a circumference of ≤33 cm while the large cuff
(15 × 33 cm bladder) when circumference is >33 cm with the lower end of the cuff 2.5 cm above
the antecubital fossa.
9. The mercury sphygmomanometer is the ‘gold standard’ for blood pressure measurement.
10. In absence of mercury manometer, calibrated and properly standardized aneroid / digital
equipments may be used

6. Classification
 Gestational hypertension:
(1) Transient HTN of pregnancy if no PE at time of delivery and BP returns to normal by 12 weeks
postpartum or
(2) chronic HTN if elevation persists.
 Preeclampsia-eclampsia (PE)
 Chronic hypertension
 Preeclampsia superimposed upon chronic HTN
 HELLP Syndrome : Severe form of preeclampsia characterized by hemolysis (abnormal PBS, bil >
1.2mg/dl), thrombocytopenia (platelets<1lakh/mm3) and elavated liver enzymes (SGOT,SPGT >70mg/dl)

7. GESTATIONAL HYPERTENSION
 BP> 140/90 mm Hg for the 1st time after 20 wks POG {2 recordings, 4-6hrs gap}
 No proteinuria
 BP returns to normal < 12 wks postpartum
 Final diagnosis made only postpartum
 Although transient, may be a sign of future chronic HTN
 Almost half of these women subsequently develop preeclampsia syndrome, which includes
findings such as headaches or epigastric pain, proteinuria, and thrombocytopenia

8. Chronic hypertension
 BP >140/90 mmHg (on 2 occasions measured 4 hrs apart) before pregnancy or 20 weeks
gestation not attributable to GTD
 Hypertension first diagnosed after 20 weeks gestation & persistent after 12 weeks
postpartum also considered chronic HTN
- ESSENTIAL HYPERTENSION- is diagnosed when there is no apparent underlying cause for
chronic hypertension
- SECONDARY HYPERTENSION- may be due to renal parenchymal disease or scarring,
renovascular disease, endocrine disorders or coarctation of aorta

9. PRE-ECLAMPSIA (ACOG 2013)
• pregnancy-specific syndrome that can affect virtually every organ system.
1.Blood pressure:
-SBP > 140 or DBP > 90 mm Hg ,after 20 wks POG, on 2 occasion > 4 hrs apart
-SBP > 160 or DBP > 110 mm Hg, confirm within minutes
2.Proteinuria
{OR}
in the absence of proteinuria,
new onset HTN with new
onset any of following

10. MEASUREMENT OF PROTIENUREA
 Pre eclampsia is much more than simply gestational hypertension with proteinuria, appearance of
proteinuria remains an important diagnostic criterion. Thus, proteinuria is an objective marker and
reflects the system-wide endothelial leak, which characterizes the preeclampsia syndrome.
 ≥ 3oo mg/24 urine collection
 Protein/creatinine ratio ≥ 0.3( each measured as mg/dl)
 Dipstick reading 1+( used only when other method not available)
 Dipstick measurments

11.  Term ‘mild preeclampsia’ has been removed
 Recommended term ‘preeclampsia without severe features’
 Severe features of preeclampsia
 SBP ≥160 or DBP ≥110 mm Hg, on 2 occasion ≥4 hr apart
 Platelet count < 100,000/µl
 Impaired liver function, elevated transaminase > 2 times
 Severe persistent RUQ or epigastric pain unresponsive to medication
 Progressive renal insufficiency(s. creatinine >1.1 ,doubling of creatinine in absence of other renal
disease)
 Pulmonary edema
 Cerebral or visual disturbance
 Early gestational age

12.  Headaches or visual disturbances such as scotomata can be premonitory symptoms
of eclampsia.
 Epigastric or right upper quadrant pain frequently accompanies hepatocellular
necrosis, ischemia, and edema that ostensibly stretches Glisson capsule.This
characteristic pain is frequently accompanied by elevated serum hepatic
transaminase levels.
 Finally, thrombocytopenia is also characteristic of worsening preeclampsia as it
signifies platelet activation and aggregation as well as microangiopathic hemolysis.
 Other factors indicative of severe preeclampsia include renal or cardiac involvement
and obvious fetal-growth restriction, which also attests to its duration

13. ECLAMPSIA
 New onset grand mal Seizures in woman with pre-eclampsia
 The seizures are generalized and may appear before, during,
or after labor
 Symptoms predicting impending eclampsia
Persistent frontal or occipital headache
Blurred vision
Photophobia
Epigastric or RUQ pain
Altered mental status

14. PRE-ECLAMPSIA SUPERIMPOSED ON CHRONIC HTN
 New onset proteinuria in hypertensive after 20 weeks
 Women with proteinuria before 20 wk with
 Exacerbation of HTN, need to escalate drug dose
 Increase in liver enzymes to abnormal level
 Platelet count < 100,000/µl
 Symptom such as RUQ pain, headache
 Pulmonary congestion or edema
 Develop renal insufficiency
 Substantial and sustained increase in protein excretion

15. Phenotypic Expression of
Preeclampsia Syndrome
There are at least two major subtypes differentiated by whether or not remodeling of uterine spiral arterioles
by endovascular trophoblastic invasion is defective.
This concept has given rise to the “two-stage disorder” theory of preeclampsia etiopathogenesis

16. Two-stage theory of the pathophysiology of preeclampsia.
Predisposing immunological, genetic, and preexisting maternal risk factors may affect abnormal
cytotrophoblast invasion of spiral arteries (abnormal placentation) (First stage).
The reduced uteroplacental perfusion induces placental release of antiangiogenic factors (soluble fms-like
tyrosine kinase 1 (sFlt1)) into the maternal circulation, which antagonizes proangiogenic factors, leading to
endothelial dysfunction and systemic vascular dysfunction (Second stage). Preexisting maternal conditions
such as chronic hypertension, systemic lupus erythematosus (SLE), and obesity is also associated with
endothelial dysfunction.

17.  It is consider that the two stage disorder includes “maternal and placental preeclampsia.”
 1. Preclinical (≤20 weeks): (placental)
– Inadequate invasion of maternal spiral arterioles by fetal cytotrophoblasts.
-Insufficient maternal vascular remodeling and angiogenesis
 2. Clinical (normally >20 weeks): (maternal)
– Oxidatively stressed/hypoxic placenta
- Generalized systemic inflammatory response with release of anti-angiogenic
Factors, inflammatory cytokines, and trophoblast debris.

18. GENISIS OF PREECLAMPSIA

19. ETIOLOGY
Culmination of factors likely involving number of maternal,
placental, and fetal factors:
 Abnormal trophoblastic invasion of uterine vessels
 Immunological maladaptive tolerance between maternal, paternal (placental), and fetal
tissues
 Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy
 Genetic: Inherited predisposing genes as well as epigenetic influences

20. TROPHOBLASTIC INVASION-
• Normal placental implantation shows proliferation of extravillous trophoblasts from an
anchoring villus. These trophoblasts invade the decidua and extend into the walls of the spiral arteriole to
replace the endothelium and muscular wall to create a dilated low-resistance vessel.
• In preeclampsia, there is defective implantation characterized by incomplete invasion of the spiral arteriolar
wall by extravillous trophoblasts. This results in a small-caliber vessel with high resistance to flow

21. Invasion defects in
preeclampsia.
• (A) In a normal placenta, extravillous
cytotrophoblast (ECTB) cells (green) move into the
decidua (endometrium) and myometrium via
interstitial invasion. Some ECTB cells enter maternal
spiral arteries and replace the endothelial cells of
the vessel walls, becoming endovascular ECTB
(eECTB) cells, increasing vessel compliance and
maximizing blood flow into placental blood spaces.
• (B) In the placenta of a preeclamptic
patient, interstitial invasion is
shallow and limited, with many
ECTB cells in the basal plate
remaining attached to anchoring villi
(AV). Endovascular invasion is
nearly absent, and spiral arterioles
remain ‘stiff’. FV, floating villi.

22.  Using electron microscopy, examination of arteries taken from the implantation site.Reported that
early preeclamptic changes included
- endothelial damage,
- insudation of plasma constituents into vessel walls,
-proliferation of myointimal cells, and
-medial necrosis.
Atherosis in a blood vessel from a placental bed.
A. Photomicrograph shows disruption of the endothelium that results in a narrowed lumen because of
subendothelial accumulation of plasma proteins and foamy macrophages. Some of the foamy macrophages
are shown by curved arrows, and straight arrows highlight areas of endothelial disruption.
B. Schematic diagram of the photomicrograph.

23.  Lipid accumulates first in myointimal cells and then within macrophages. These lipid-laden cell
changes were referred to as atherosis.
 vascular lesions including spiral arteriole narrowing, atherosis, and infarcts were more common in
placentas from women diagnosed with preeclampsia before 34 weeks.
 Diminished perfusion and a hypoxic environment eventually lead to release of placental debris or
microparticles that incite a systemic inflammatory response Defective placentation is posited to
further cause the susceptible (pregnant) woman to develop gestational hypertension, the
preeclampsia syndrome, preterm delivery, a growth-restricted fetus, and/or placental abruption
 acute atherosis identifies a group of women at increased risk for later atherosclerosis and
cardiovascular disease

24. IMMUNOLOGICAL FACTORS
 Loss of maternal immune tolerance to paternally derived placental and fetal antigens ,or perhaps
its dysregulation, is an theory cited to account for preeclampsia syndrome
 Certainly, the histological changes at the maternal-placental interface are suggestive of acute
graft rejection.
 Some of the factors possibly associated with dysregulation include “immunization” from a
previous pregnancy, some inherited human leukocyte antigen (HLA) and natural killer (NK)-cell
receptor haplotypes, and possibly shared susceptibility genes with diabetes and hypertension
 Beginning in the early second trimester in women who develop preeclampsia, Th1 action is
increased and the Th1/Th2 ratio changes.
 women with molar pregnancies have a high incidence of early-onset preeclampsia.
 Women with a trisomy 13 fetus also have a 30- to 40-percent incidence of preeclampsia. These
women have elevated serum levels of antiangiogenic factors, and the gene for one of these
factors, sFlt-1, is on chromosome 13.

25. Genetic factor
 From a hereditary viewpoint, preeclampsia is a multifactorial, polygenic disorder.
 Risk for preeclampsia
-20 to40 percent for daughters of preeclamptic mothers;
-11 to 37 percent for sisters of preeclamptic women;
-& 22 to 47 percent for twins
 The hereditary predisposition for preeclampsia likely is the result of interactions of literally
hundreds of inherited genes—both maternal and paternal—that control myriad enzymatic
and metabolic functions throughout every organ system.
 In this regard, phenotypic expression will differ among similar genotypes depending
on interactions with environmental factors.

26. GENES EFFECTED IN PRE ECLAMPSIA
Hundreds of genes have been studied for their
possible association with preeclampsia .
Several of those that may have positive significant
association with preeclampsia are listed in Table.
Because of the heterogeneity of the
preeclampsia syndrome and especially of the
other genetic and environmental factors that
interact with its complex phenotypic expression,
it is doubtful that any one candidate gene will
be found responsible

27. PATHOGENESIS
VASOSPASAM
ENDOTHELIAL CELL INJURY
ENDOTHELINS
ANTI ANGIOGENIC AND ANGIOGENIC FACTORS

28. Vasospasm-
 Endothelial activation causes vascular constriction with increased resistance and
subsequent hypertension.
 At the same time, endothelial cell damage causes interstitial leakage through which
blood constituents, including platelets and fibrinogen, are deposited
subendothelially.
 The much larger venous circuit is similarly involved, and with diminished blood flow
because of maldistribution, ischemia of the surrounding tissues can lead to necrosis,
hemorrhage, and other end-organ disturbances characteristic of the syndrome.
 One important clinical correlate is the markedly attenuated blood volume seen in
women with severe preeclampsia .

29. Endothelial cell injury
 Intact endothelium has anticoagulant properties, and endothelial cells blunt the response
of vascular smooth muscle to agonists by releasing nitric oxide.
 Damaged or activated endothelialcells may produce less nitric oxide and secrete
substances that promote coagulation and increase sensitivity to vasopressors.
 Increased Pressor Responses BY-
-Prostaglandins
- Nitric oxide

30.  PROSTAGLANDINS
 Several prostanoids are thought to be central to preeclampsia syndrome pathophysiology.
 Endothelial prostacyclin (PGI2) production is decreased in preeclampsia. This action appears to be
mediated by phospholipase A2 .
 Thromboxane A2 secretion by platelets is increased, and the prostacyclin:thromboxane A2 ratio
decreases. The net result favors increased sensitivity to infused angiotensin II and, ultimately,
vasoconstriction .
 These changes areapparent as early as 22 weeks in women who later develop preeclampsia

31.  NITRIC OXIDE
 This potent vasodilator is synthesized from l-arginine by endothelial cells.
 Inhibition of nitric oxide synthesis
-increases mean arterial pressure,
-decreases heart rate, and
-reverses the pregnancy induced refractoriness to vasopressors.
 nitric oxide likely is the compound that maintains the normal low-pressure vasodilated state
characteristic of fetoplacental perfusion
 It appears that the syndrome is associated with decreased endothelial nitric oxide synthase
expression, thus increasing nitric oxide inactivation.

32. Endothelins
 These 21-amino acid peptides are potent
vasoconstrictors, and endothelin-1 (ET-1) is the
primary isoform produced by human
endothelium
 Plasma ET-1 levels are increased in
normotensive pregnant women, but women with
preeclampsia have even higher levels.
 the placenta is not the source of increased ET-1
concentrations, and they likely arise from
systemic endothelial activation.
Placental ischemia induces endothelin-1 (ET-1) expression
through multiple pathways during preeclampsia. As a result of
placental ischemia, soluble fms-like tyrosine kinase-1 (sFlt-1)
is increased in the circulation, directly antagonizing vascular
endothelial growth factor (VEGF). Circulating levels of tumor
necrosis factor-α (TNF-α) and the agonistic angiotensin II type-
1 receptor auto-antibody (AT1-AA) are increased. Each of
these pathways in turn increase ET-1 production resulting in
maternal hypertension

33. Angiogenic and anti-angiogenic protiens
 Placental vasculogenesis is evident by 21 days after conception.
 There is an ever-expanding list of pro- and antiangiogenic substances involved in
placental vascular development.
 The families of vascular endothelial growth factor (VEGF) and angiopoietin (Ang) are
most extensively studied.
 Angiogenic imbalance is used to describe excessive amounts of antiangiogenic factors
that are hypothesized to be stimulated by worsening hypoxia at the uteroplacental
interface.
 Trophoblast of women destined to develop preeclampsia overproduces at least two
antiangiogenic peptides that enter the maternal circulation
- Soluble Fms-like tyrosine kinase 1 (sFlt-1)
-Soluble endoglin (sEng)

34. Soluble Fms-like tyrosine kinase 1 (sFlt-1)
 it is a variant of the Flt-1 receptor for placental growth
factor (PlGF) and for VEGF. Increased maternal sFlt-1
levels inactivate and decrease circulating free PlGF and
VEGF concentrations, leading to endothelial dysfunction .
 As sFlt-1 levels begin to increase in maternal serum
months before preeclampsia is evident.
 highlevels in the second trimester were associated with a
doubling of the risk for preeclampsia.
 This divergence from normal levels appears to occur
even sooner with early-onset preeclampsia

35. Soluble endoglin (sEng)
 It is a placenta-derived 65-kDa molecule that blocks endoglin, which is a surface
coreceptor for the TGFβ family. {TGF β1 and β3.}
 Serum levels of sEng also begin to increase months before clinical preeclampsia
develops
 Highly expressed on cell membranes of vascular endothelium and
syncytiotrophoblasts.
 Placental endoglin is up-regulated in preeclampsia, releasing soluble endoglin in
maternal circulation.
 Soluble endoglin is an antiangiogenic protein that inhibit TGF-β1 isoforms from
binding to endothelial receptors and results in decreased endothelial nitric oxide-
dependent vasodilatation

36.  Soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) causes endothelial dysfunction by
antagonizing vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β1 signaling.
 VEGF and TGF-β1 are required to maintain endothelial health in several tissues, including the kidney and
other vascular beds.
 During normal pregnancy, vascular homeostasis is maintained by physiological levels of VEGF and TGF-β1
signaling in the vasculature.
 In preeclampsia, excess placental secretion of sFlt1 and sEng (2 endogenous circulating antiangiogenic
proteins) inhibits VEGF and TGF-β1 signaling, respectively, in the vasculature. This results in endothelial
cell dysfunction, including decreased prostacyclin, nitric oxide production, and release of procoagulant
proteins.

37. Endothelial nitric oxide
synthase {eNOS}

38.  The cause of placental overproduction of antiangiogenic proteins remains an enigma.
 Concentrations of the soluble forms are not increased in the fetal circulation or amnionic fluid,
and their levels in maternal blood dissipate after delivery

39. PATHOGENISIS

40. Maternal vascular
disorders
Faulty placentation Excessive trophoblast
Genetic, inflammatory,
immunological factors
Reduced uteroplacental
perfusion
Vasoactive agents PGs,
NO, Endothelin
Noxious agents-
cytokines,
Lipid peroxidases
Endothelin activation
Activation of coagulation
Capillary leak
vasospasm
edema
hemoconcentration
thrombocytopenia
protienuria
Liver ischemia
abruption
seizures
HTN
oliguria

41. PATHOPHYSIOLOGY
 Cardiovascular:
 Hemoconcentration With inc hematocrit values
 Normally expected hypervolemia is severely curtailed.
 Coagulation disturbance:
 Thrombocytopenia, dec in fibrinogen, anti thrombin III
 ↑fibronectin , d-dimer, thrombin
 Volume homeostasis
 ↓Angiotensin, renin, ↑ANP excretion
 Net effect-intravascular dehydration and extravascular overhydration.
 Normal electrolytes

42. Kidney:
 GFR and Renal blood flow-
decreased { so Inc. S.Uric Acid.}
 Decreased excretion of Ca. due to
tubular reabsorption.
 Acute renal failure induced by
hypotension and hypovolemia and
associated with obst. Hemorrhage.

43.  Liver:
 infarction, subcapsular haematoma
 Periportal hemorragic necrosis due to thrombosis of arterioles.
 Brain:
 Vasogenic edema due to loss of autoregulatory cerebral vasoconstriction
 leading to hyperperfusion.
 Supratentorial herniation is fatal.
 PRES (posteror reversible encephalopathy syndrome )
 Neurologic manifestations:
• Headache and scotomatas
• Convulsions
• Confusion- coma

45. SCREENING
 No reliable and accurate screening method in low risk population
 Women with risk factors for pre-eclampsia : observed more carefully
 Screening to predict PE beyond obtaining appropriate medical history for
risk factors: not recommended ACOG 2012-13
 Effective screening for
 Early onset PE can be achieved in first-trimester
 Late onset PE remains a significant challenge

46. Prediction of Preeclampsia:
 ✓ Universal screening is recommended but there is no single effective screening
test.
 ✓ None of the tests proposed till date to predict the at-risk population for
preeclampsia
 qualify to be recommended for the general population screening
 ✓ Thus, assessment of clinical risk factors helps us to be more vigilant.
 ✓ A careful history taken early in first trimester can warrant attention for effective
 prediction and prevention towards mothers ‘at risk’ very early.
 ✓ This can be done by any health care worker by using HDP-Gestosis Score.

47.  Primary clinical assessment for screening and prediction of preeclampsia can be
objectively performed by ‘easy to use’ HDP-Gestosis score.
 Process of risk scoring:
 ✓ This score involves all the existing and emerging risk factors in the pregnant
woman.
 ✓ Score 1, 2 and 3 is allotted to each clinical risk factor as per its severity in
development of preeclampsia.
 ✓ With careful history and assessment of woman a total score is obtained time to
time.
 ✓ When total score is =/> 3; pregnant woman should be marked as ‘At risk for
Preeclampsia’.

49. FEW SCREENING TESTS
 Provocative Pressor Tests.
 Three tests have been extensively evaluated to assess the blood pressure rise in response
to a stimulus.
-The roll-over test measures the hypertensive response in women at 28 to 32 weeks
who are resting in the left lateral decubitus position and then roll over to the supine position.
Increased blood pressure of 20mmg or more signifies a positive test.
-The isometric exercise test employs the same principle by squeezing a handball.
- The angiotensin II infusion test is performed by giving incrementally increasing doses
intravenously, and the hypertensive response is quantified.
 In their updated metaanalysis, sensitivities of all three tests to range from 55 to70 percent,
and specificities approximated 85 percent.

50. Uterine artery doppler velocimetry for prediction of pre-eclampsia
 At 22-24 weeks is useful to identify women destined to devlop preeclampsia.
 Increased resisstance to blood flow within uterine arteries results in
abnormal waveform pattern
 Increased resistance or pulsality index {PI} or pesistance of U/L or B/L
diastolic notch
 Better predictor of early than term PE
 Major pitfalls:
 Wide variablity, operator dependent
 Poor predictive accuracy
 No improved maternal or fetal outcome who underwent this screening

51.  Trans abdominal.
 Trans vaginal.

52.  Pulse Wave Analysis.
- Like the uterine artery, finger arterial pulse “stiffness” is an indicator of
cardiovascular risk.
-Investigators have preliminarily evaluated its usefulness in preeclampsia prediction.
 Fetal-Placental Unit Endocrine Function
-Several serum analytes that have been proposed to help predict preeclampsia.
-Newer ones are continuously added & also found to be associated with other
pregnancy abnormalities such as neural-tube defects and aneuploidy .
-Although touted for hypertension prediction, in general, none of these tests has been
shown to be clinically beneficial for that purpose.

53. Tests of Renal Function
 Serum Uric Acid.
-One of the earliest laboratory manifestations of preeclampsia is hyperuricemia.
- It likely results from reduced uric acid clearance from diminished glomerular filtration, increased
tubular reabsorption, and decreased secretion. It is used by some to define preeclampsia,
-reported that its sensitivity ranged from 0 to 55 percent, and specificity was 77 to 95 percent.
 Microalbuminuria.
-As a predictive test for preeclampsia, microalbuminuria has sensitivities ranging from 7 to 90 percent
and specificities between 29 and 97 percent) likewise found unacceptable sensitivity and specificity for
urine albumin:creatinine ratios.
-however, concluded that neither cellular nor total fibronectin levels were clinically useful to predict
preeclampsia.
 Coagulation Activation.
- -Although markers of coagulation activation are increased, the substantive overlap with levels in
normotensive pregnant women stultifies their predictive value

54.  Angiogenic Factors.
-evidence has accrued that an imbalance between proangiogenic and antiangiogenic factors is related
to preeclampsia pathogenesis.
-Serum levels of some proangiogenic factors—vascular endothelial growth factor (VEGF) and placental
growth factor (PlGF)—begin to decrease before clinical preeclampsia develops
-Sensitivities for all cases of preeclampsia ranged from 30 to 50 percent, and specificity was about 90
percent.
-Their predictive accuracy was higher for early-onset preeclampsia.
 Cell-Free Fetal DNA
- cell-free fetal DNA can be detected in maternal plasma. It has been reported that fetalmaternal cell
trafficking is increased in pregnancies complicated by preeclampsia.
-cell-free fetal DNA quantification is not yet useful for prediction purposes

55.  Oxidative Stress.
 Increased levels of lipid peroxides coupled with decreased antioxidant activity have raised
the possibility that markers of oxidative stress might predict preeclampsia.
 Other markers-iron, transferrin, and ferritin; blood lipids, including triglycerides, free fatty
acids, and lipoproteins; and antioxidants such as ascorbic acid and vitamin E
 Hyperhomocysteinemia causes oxidative stress and endothelial cell dysfunction and is
characteristic of preeclampsia. Although women with elevated serum homocysteine levels
at midpregnancy had a three- to fourfold risk of preeclampsia, these tests have not been
shown to be clinically useful predictors

57. REFFERANCES
 WILLIAMS 25TH ED
 ARIAS 5TH ED
 GESTOSIS SCORE- https://www.fogsi.org/wp-content/uploads/gcpr/hdp-fogsi-
gestosis-icog-gcpr-2019.pdf