Recent advances in management of PET

1. Recent
advances in
management of
PET
Aboubakr Elnashar
Benha university
Hospital, Egypt
ABOUBAKR ELNASHAR

2. Contents
1.Definition
2.Pathogenesis
3.Prevention
4.Prediction
5.Diagnosis
6.Treatment
Conclusion
ABOUBAKR ELNASHAR

3. 1. Definition
Syndrome of new onset of Hypertension
and either
Proteinuria or
End organ dysfunction
after 20 w in a previously normotensive woman
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4. 2. Pathogenesis
 Impaired vascular remodeling of the fetal maternal
interface
 Excessive immune response to paternal antigen
 Exaggerated systemic inflammatory response
 Placental & endothelial dysfunction
ABOUBAKR ELNASHAR

5. hemoconcentration
edema proteinuria
thrombocytopenia
oliguria
HTN
seizures abruption
liver
ischemia
Endothelial
activation
Vasoactive agents:
Prostaglandins nitric oxide
endothelins
Noxious agents:
Cytokines
Lipid peroxidases
Vasospasm
Capillary leak
Activation of
coagulation
Reduced uteroplacental perfusion
Maternal vascular
disease
Excessive
trophoblast
Faulty placentation
Genetic, immunologic,
inflammatory factors
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6. Pre - eclampsia is mostly
considered 2-stage disorder
Stage I
Impaired endothelization
of cytotrophoblast
Inadequate invasian of the spiral
arteries in to myometrium
Placental Ischemia
Placental hypoxia
↓Production of
Pro-angiogenic factors
PLGF, VEGF
Release of anti-angiogenic factors
such as SFLT-1, PGs & Cytokines into
the maternal circulation
Stage II (fate in pregnancy) Oxidatively stressed placenta
Systemic endothelial
dysfunction & Inflam. response
↑systemic vascular resistance
activation of coagulation cascade
clinical manifestation like hypertension & proteinuriaABOUBAKR ELNASHAR

7. 3. Prevention
Early administration of antiplatelet agents (aspirin)
prior to 16-w
reduce the risk of PET
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8. NICE, 2010
low dose (75 mg) aspirin for
 1 high risk factor for PE
1. chronic hypertension
2. kidney disease
3. diabetes
4. autoimmune disease
5. hypertension in previous pregnancy OR
2 moderate risk factors for PE
1. age ≥40 y
2. first pregnancy
3. multiple gestation
4. >10 y between pregnancies,
5. BMI≥35 kg/m2 at presentation
6. family history of PE
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9. ACOG, 2013
low dose aspirin
not recommended for women at low risk for PE.
Recommend in high risk women: women with
history of :
1. early onset PE
2. superimposed PE plus delivery at <34 w
3. PE in >1 pregnancy.
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10. US Preventive Services Task Force (USPSTF)
2014
≥1 high risk factors
Low dose aspirin:
81 mg/d
at 12 w
Discontinue
5 to 10 days before expected delivery
{diminish the risk of bleeding during delivery}
[Hirsh et al, 2008}
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11. 4. Prediction
1. Multiple risk factors
most are
not highly predictive of the disorder,
nor are they modifiable.
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12. 2. Clinically tests
Not distinguishing women who will develop PET
from those who will not.
not improve pregnancy outcome.
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13. 3. Measurement of angiogenic factors
E.g.:
VEGF
PlGF=placental growth factor
sFlt1
sEng
in blood or urine is the most promising approach
The ratio of sFlt1:VEGF (or sFlt1:PlGF), rather than
absolute levels of these factors: most useful.
investigational and are not available for clinical use
at present.
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14. 4. Uterine artery Doppler
second-trimester screening
The best predictor of PET is diastolic notch in the
uterine artery & RI>61.5 % after 22 w of gestation.
for women at high risk of developing PET
LR for the subsequent development of pre-eclampsia in
women with increased impedance to flow was about 6 but
that for those with normal Doppler results the LR was about
0.5.
{Papageorghiou et al, 2004]
First T screening:
far from perfect, even in combination.
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15. ACOG Guidelines, 2015
1. First-Trimester Risk Assessment for Early-Onset
Preeclampsia: low positive predictive value
2. Not recommend using laboratory or imaging tests
to screen for PET (Grade 1B).
3. Taking a detailed medical history to evaluate for
risk factors is currently the best and only
recommended screening approach for PET
4. All pregnant women should be assessed for and
educated about the signs and symptoms of the
disease.
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16. 5. Diagnosis
Measurement of proteinuria
1. Visual dipstick assessment:
2+ dipstick
1+ = 0.3 g/l
2+ = 1 g/l
3+ = 3 g/l.
Poor predictive value
False negative as well as false positive rates.
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17. 2. 24-h protein urine collection.
High false positive rates with dipsticks:
confirm significant proteinuria, unless the clinical
urgency dictates immediate delivery.
Inconvenient
Sometimes inaccurate
{improper collection}.
Excellent correlation with PCR in a random urine
sample
[Verdonk et al, 2014].
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18. 3. Spot protein creatinine ratio(PCR)
 ±valid alternative.
0.03 g/mmol equivalent to 0.3 g/24 h.
 serial PCR measurements in a 24-hour period
 correlated strongly with each other and with the
24-h protein excretion but did show variation
throughout the day
[Verdonk et al, 2014].
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19.  Creatinine excretion/d
 15-20mg/Kg= 1000-1500mg
 constant throughout the day regardless of changes in urine
flow rate.
 Protein excretion/d:
< 100 -150mg.
 Normal PCR:
100-150mg protein/ 1000-1500mg creatinine= < 0.1
 PCR in a random sample (in mg/mg):
 roughly equal to 24-h urine protein excretion in grams/day
 Reasonable “rule-out” test for detecting proteinuria of
0.3 g/day or more in hypertensive pregnancy.
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20. (Sibai, 2009)
I. Gestational hypertension plus 1 of the following:
1. Symptoms of PET
2. Haemolysis
3. Thrombocytopenia (<100,000/mm3)
4. Elevated liver enzymes
 (2 times the upper limit of the normal value for aspartate
aminotransferase or alanine aminotransferase)
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21. II. Gestational proteinuria plus 1 of the following:
1. Symptoms of preeclampsia
2. Haemolysis
3. Thrombocytopenia
4. Elevated liver enzymes
III. Early signs and symptoms of PET-E at < 20 w of
gestation.
IV. Late postpartum PET-E:
48 hs after delivery.
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22. Diagnosis of PET
(ACOG , 2015)
New-onset hypertension without proteinuria plus 1 of
the following:
1. Platelet count below 100,000/μL
2. Serum creatinine level above 1.1 mg/dL
3. Doubling of serum creatinine in the absence of
other renal disease
4. Liver transaminase levels at least twice the
normal concentrations
5. Pulmonary edema
6. Cerebral or visual symptoms
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23. Vascular disorder of pregnancy (VDP)
(Berhan, 2016)
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24. 6. Management
I. Antihypertensive
There is an increasing trend toward tighter blood
pressure control in PET in those with essential or
gestational hypertension.
keeping
SBP: below 150 mm Hg
DBP: below 80-100 mm Hg
Labetolol:
first-line treatment
[NICE, 2012]
ABOUBAKR ELNASHAR

25. Indication of antihypertensive:
BP: more than 160/110 mm Hg
(ACOG, 2013)
SBP: over 170 mm Hg.
(WHO)
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26. Labetalol:
Acute and severe:
IV: 20 mg;
subsequent doses of 40, 80, 80 mg IV at 20-min
intervals.
Maintenance: 40 mg/h
Chronic, moderate
100 mg bid
should be avoided in asthma.
ABOUBAKR ELNASHAR

27. II. Magnesium sulphate
Indication:
1. Severe PET to prevent eclamptic seizures in
the mother
[Altman et al, 2002].
2. Mild to moderate PET
for fetal neuroprotection in PTL(<37 w):
preventing cerebral palsy
(relative risk 0.68, 95% CI 0.54-0.87)
(Cochrane SR, 2009)
NNT: 63
(95% CI 43-155)
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28. III. Delivery
conservative management below 34 w’ and urge
that elective delivery before 34 w not be
considered.
(NICE, 2014)
For women with mild gestational hypertension or
PET without severe features, delivery at 37 w
{ACOG, 2013]
little evidence regarding the benefits of elective
delivery between 34 and 37w for those with mild or
moderate hypertension
 It remains unclear whether the risks of late
preterm elective delivery for the baby outweigh the
risks of severe disease and associated morbidity
with conservative management.
ABOUBAKR ELNASHAR

29. IV. Anaesthesia
In the absence of contraindications, all of the following
are acceptable for women undergoing CS:
 epidural,
 spinal,
 combined spinal-epidural, and
 general anaesthesia. (A)
Regional anaesthesia is a choice for women on
LMWH:
 12 hours after a prophylactic dose or
 24 hours after a therapeutic dose. (B)
ABOUBAKR ELNASHAR

30. Conclusion
1. Definition
Syndrome of new onset of Hypertension
and either Proteinuria or End organ dysfunction
after 20 w in a previously normotensive woman
2. Pathogenesis
3. Prevention
administration of LDA prior to 16-w in high risk
ABOUBAKR ELNASHAR

31. 4. Prediction:
Angiogenic markers, particularly PlGF, have considerable
potential in the prediction and diagnosis
Taking a detailed medical history to evaluate for risk factors is
currently the best and only recommended screening approach
for PET
5. Diagnosis
Excellent correlation with PCR in a random urine sample
6.Management
Tighter control of blood pressure may impact on stroke risk
Threshold for delivery has come down in recent years, and
risk/benefit of earlier elective delivery is being investigated.
Mg S: protects the preterm baby from neurological insults
ABOUBAKR ELNASHAR

32. ABOUBAKR ELNASHAR
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