Update on Prediction

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Update on Prediction prevention of Preeclampsia

• Prof. Aboubakr Elnashar
• Benha University Hospital, Egypt

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• Prediction
• Routine urine analysis
• Prevention
• Chocolate

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Outline

• Introduction
• Prediction
• Prevention

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Cochrane Systematic Review Gold Standard' for
high-quality systematic reviews
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• Preeclampsia
• Hypertension associated with proteinuria.

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• Pathogenesis
• unknown (Barton Sibai, 2008).
• Impaired trophoblast differentiation invasion
• Placental endothelial dysfunction
• Immune maladaptation to paternal Ags
• Exaggerated systemic inflam response.

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• Pathogenesis
• Differs with various risk factors
• PG Vs MG with previous PE
• preexisting vas dis
• preexisting DM or
• multifetal gestation.

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In PE Impaired trophoblast differentiation
invasion
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Placental and endothelial dysfunction
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PREDICTION OF PE

• Why prediction is important?
• The ideal screening test
• Methods
• I. Preconception factors
• II. Pregnancy-Related Factors
• 1. Risk factors
• 2. Markers

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• Why prediction is important
• The risk for recurrent PE can be as high as 65
  (Barton Sibai, 2008).
• PE is associated with substantial maternal
  perinatal complications

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The ideal Screening test Simple Noninvasive Rapi
d Inexpensive Easy to perform early in
pregnancy Highly sensitivity predictive.
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I. Preconception factors 1st step in the
management of a woman with a history of PE is to
conduct a detailed evaluation of potential risk
factors (Barton Sibai, 2008).
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Preconceptional Risk Factors Rates of
preeclampsia depend on severity of underlying
complications

combinations of risk factors.
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• II. Pregnancy-Related Factors
• Regular antenatal care is mandatory for the
  prevention early detection of PE.
• Risk factors Magnitude of risk depends on the
  number of factors
• Hydrops/hydropic degeneration of the placenta
• Multifetal gestation
• Unexplained FGR
• Gestational hypertension
• UTI
• Periodontal infection
• Markers
• Biophysical
• Biochemical

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• Markers
• Many
• Based on pathophysiological abnormalities

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• SCREENING TESTS FOR PE (WHO, 2004)
• I. Placental perfusion vascular resistance
  dysfunction
• Mean arterial blood pressure
• Roll over test
• Doppler ultrasound
• Isometric exercise test
• Intravenous infusion of angiotensin II
• Platelet angiotensin II binding
• Platelet calcium response to arginine vasopressin
  
• Renin
• 24-hour ambulatory blood pressure monitoring
• II. Fetoplacental unit dysfunction
• Human chorionic gonadotropin
• Alpha fetoprotein
• Estriol
• Inhibin A
• Pregnancy-associated plasma protein A
• Activin A
• Corticotropin release hormone

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III. Renal dysfunction Serum uric acid
Microalbuminuria Urinary calcium excretion
Urinary kallikrein Microtransferrinuria
N-acetyl- glucosarninidase
IV. Endothelial oxidant stress dysfunction
Platelet count Platelet activation and
endothelial cell adhesion molecules Prostacyclin C
ytokines Isoprostanes, Antiphospholipid
antibodies, Placenta growth factor Hematocrit Ant
ithrombin Ill Calcium Transferrin Atrial
natriuretic peptide
Fibronectin Endothelin Thromboxane
Homocysteine Serum lipids Insulin resistance
Plasminogen activator inhibitor Leptin Total
proteins Magnesium Ferritin Haptoglobin
microglobulin Genetic markers
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• I. Biophysical
• Mean arterial pressure
• (2D BPS BP)/3
• Better predictor of PE than S D BP (BMJ
  200817336111 Meta-analysis of 34 RCT)
• 2nd trimester MA BP 90 mm Hg had ve LR 3.5 and
  ve LR 0.46
• BP remains the cornerstone of early diagnosis
  although it has limitations
• measurement errors associated with
  sphygmomanometer
• effect of maternal posture on BP in pregnant
  women.

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• Repeated routine urinalysis throughout pregnancy
  NOT useful for predicting PE
• (JAMA 2003 12289(10)1220)

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• Uterine artery Doppler ultrasound
• impaired trophoblastic invasion of the spiral
  arteries reduction in uteroplacental blood flow
• High pulsatility index and/or Notch in 1st 2nd
  trimesters poor predictor of PE(Papgeorghiou
  Leslie, 2007)
• Uterine artery Doppler plus biochemical markers
• Promising results
• Current data do not support this combination for
  routine screening for PE (Barton Sibai, 2008).

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• Diastolic Notch in uterine artery waveform

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The Roll over test Not of value in predicting
PE (Mahomed Lasiende,1990)
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II. Biochemical Markers Angiogenic factors
before after the onset of PE (Barton Sibai,
2008). Serum placental growth factor
reduced Soluble fms-like tyrosine kinase
elevated Endoglin elevated
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• Conclusion
• BP remains the cornerstone of early diagnosis
• Markers
• Reliability is inconsistent
• Many suffer from poor specificity predictive
  values.
• None provided a cutoff value that could be
  clinically useful for the prediction of PE
• (Widmer et al, 2007).

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• Currently
• There is no clinically useful screening test to
  predict PE (WHO, 2004)

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Prevention of PE

• Primary
• Secondary

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• Primary prevention
• Avoiding occurrence of the disease
• Obese
• achieve an ideal b wt before conception
  (Villamor Cnattingius, 2006)
• No RCT
• Ch hypertension
• Control BP before conception.
• No RCT

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• Pregestational DM
• -Complete her family as early as possible
  before vascular complications develop
• -Control DM before conception throughout
  pregnancy

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• Secondary
• Breaking off the disease process before emergence
  of obvious clinical disease
• Etiology of the disease is unknown
• To correct theoretical pathophysiology
• I. Non pharmacological
• II. Nutritional
• III. Pharmacological

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• I. Non pharmacological
• Daily Bed rest
• Rest for 4-6 h/d
• May reduce risk of
• PE for women with normal BP
• (level 2 evidence)
• (Cochrane Library 2006 Issue 2CD005939)

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• 2. Life-style changes
• High job stress greater risk of PE(Sharma
  Mittal, 2006)
• Reducing job stress may be beneficial in the
  prevention of PE
•  

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• 3. Regular prenatal exercise
• May prevent or oppose progression (Weissgerber
  et al, 2004)
• Stimulation of placental growth
• Reduction of oxidative stress
• Reversal of maternal endothelial dysfunction.
• Insufficient evidence
• Moderate intensity regular aerobic exercise
• (Cochrane Library 2006 Issue 2CD005942)
• Aerobic exercise cardiovascular exerciseany
  sustained rhythmic activity that involves large
  muscle groups makes the lungs work harder as the
  body's need for oxygen is increased.

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• Stretching exercises are more effective at
  reducing the risk of PE than walking
• (University of North Carolina,2008)

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• Smoking
• Reduced risk for PE (Sibai et al, 2005).
• Nicotine inhibition of interleukin-2 tumor
  necrosis factor
• Effects of nicotine on angiogenic proteins.
• Smoking
• abnormal fetal growth
• preterm birth
• Abruption
• Adverse effects on maternal health.

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• II. Nutritional
• 1. Higher total dietary fiber intake in early
  pregnancy may reduce risk for PE
• (level 2 evidence)
• Prospective cohort study
• Am J Hypertens 2008 Aug21(8)903

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2. Increasing dietary protein energy intake
RCT no benefit

• 5 or more servings of chocolate/w in 3rd
  trimester40 reduction
• (Triche, 2008 Epidemiology .19459-464), Yale
  University
• Chocolate, especially dark chocolate, is rich in
  theobromine stimulates the heart, relaxes smooth
  muscle dilates blood vessels, and has been used
  to treat chest pain, high blood pressure

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3. Garlic Insufficient evidence to recommend
for preventing PE Cochrane Library 2006
Issue3CD006065)
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• 4. Dietary sodium restriction
• No significant differences
• (Cochrane Library 2005 Issue 4CD005548)

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• 6. Fish Oil Supplementation
• Observational studies beneficial effects
• inhibition of platelet thromboxane A2 without
  affecting prostacyclin shifting the balance
  toward a reduced platelet aggregation and
  increased VD.
• RCT No benefit
• (Olsen et al, 2000)
• High doses increase the risk of PIH
• (Olafasdottir et al, 2006).
• Not recommended for the prevention of PE

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• 5. Weight Reduction
• Although obesity is a known risk factor, there is
  no evidence that limiting wt gain during
  pregnancy reduces its occurrence.
• Wt reduction is not recommended during pregnancy
  even in obese women (Kramer, 2004)

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III. Pharmacological

• 1. Low-dose Aspirin
• inhibits biosynthesis of platelet thromboxane A2
  with little effect on vascular prostacyclin
  production altering the balance in favor of
  prostacyclin.
• (50-150 mg/day)
• For women with a previous history of hypertension
  or PE (n6,107)
• Small to moderate benefits, safe.
• level 2 evidence
• (Cochrane Library 2007 Issue 2CD004659)

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• 2. Low-dose Aspirin/Heparin
• History of severe preterm PE LBW infants.
• (Sergio et al, 2006)
• Lower incidence of PE (3Vs 30)
• Greater gestational age at delivery
• Higher birth wt

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• 3. Calcium Supplementation
• Reduces the risk of PIH, particularly in
  populations that have diets deficient in calcium
• level 1 evidence (Cochrane Syt review , 2006)
• The relationship between cal risk of PIH is
  inconsistent inconclusive
• The relationship between cal the risk of PE is
  highly unlikely.
• Evidence-based review by FDA (2007)

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• 4. Antihypertensive Drugs
• Mild to moderate hypertension
• Halving in the risk of developing severe
  hypertension
• No difference in the risk of developing PE or
  proteinuria
• (Cochrane syst review, 2007)

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• 5. Diuretics
• No reduction in the incidence of PE or perinatal
  mortality
• May have deleterious effects
• reduced renal placental perfusion.
• (Cochrane Library 2007 Issue 1CD004451)

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6. Antioxidant supplementation may not affect
risk of PE or clinical outcomes level 2 evidence
(Cochrane Library 2008 Issue 1CD004227)
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• 7. Concomitant Vit C E supplementation
• PET imbalance of oxidant antioxidant
  activity multiorgan endothelial dysfunction.
• Vit C (1,000 mg/d) plus vit E (400 IU/ d)
• Did not prevent PE
• level 2 evidence (Obstet Gynecol 2007
  Dec110(6)1311)
• May increases rate of LBW infants might be
  associated with higher rate of SB
• level 2 evidence (Lancet 2006 Apr
  8367(9517)1145

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• 8. Magnesium
• Mg is beneficial for the prevention tt of
  severe PE E
• Decreased intracellular Mg in PE
• No effect
• (365 mg 500 mg).
• Cochrane syst review, 2004

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• 9. Folic acid other B-vits
• Deficiency of vit B2 may cause biochemical
  changes simulating abnormalities of PE
• No evidence that any of B vits can prevent PE
• (Shrama Mittal, 2006).

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• 10. Zinc supplementation
• Zinc concentrations are reduced in PE
• RCT No benefit
• (Jonsson et al, 1996)

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11. Nitric oxide Insufficient evidence for
preventing PE Cochrane Library 2007 Issue
2CD006490
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12. Progesterone Insufficient evidence for
preventing PE Cochrane review, 2006
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Conclusion Regular antenatal care is mandatory
for the prevention early detection of PE. For
prevention of PE Bed rest Reduction of job
stress High dietary fiber intake Low dose
aspirin Low dose aspirin/heparin Ca
supplementation
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Thank You
Aboubakr Elnashar