Recent

advances in

management of

PET

Aboubakr Elnashar

Benha university

Hospital, Egypt

ABOUBAKR ELNASHAR

Contents1.Definition

2.Pathogenesis

3.Prevention

4.Prediction

5.Diagnosis

6.Treatment

Conclusion

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1. DefinitionSyndrome of new onset of Hypertension

and either

Proteinuria or

End organ dysfunction

after 20 w in a previously normotensive woman

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2. Pathogenesis

Impaired vascular remodeling of the fetal maternal

interface

Excessive immune response to paternal antigen

Exaggerated systemic inflammatory response

Placental & endothelial dysfunction

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hemoconcentration

edema proteinuria

thrombocytopenia

oliguria

HTN

seizures abruption

liver ischemia

Endothelial activation

Vasoactive agents:Prostaglandins nitric oxide

endothelins

Noxious agents:Cytokines

Lipid peroxidases

VasospasmCapillary leak

Activation of coagulation

Reduced uteroplacental perfusion

Maternal vascular

diseaseExcessive trophoblast

Faulty placentation

Genetic, immunologic,

inflammatory factors

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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

3. PreventionEarly administration of antiplatelet agents (aspirin)

prior to 16-w

reduce the risk of PET

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NICE, 2010

low dose (75 mg) aspirin for

1 high risk factor for PE1. chronic hypertension

2. kidney disease

3. diabetes

4. autoimmune disease

5. hypertension in previous pregnancy OR

2 moderate risk factors for PE1. 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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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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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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4. Prediction1. Multiple risk factors

most are

not highly predictive of the disorder,

nor are they modifiable.

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2. Clinically tests

Not distinguishing women who will develop PET

from those who will not.

not improve pregnancy outcome.

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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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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.ABOUBAKR ELNASHAR

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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5. DiagnosisMeasurement 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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2. 24-h protein urine collection.

High false positive rates with dipsticks:

confirm significant proteinuria, unless the clinical

urgency dictates immediate delivery.InconvenientSometimes inaccurate

{improper collection}. Excellent correlation with PCR in a random urine sample[Verdonk et al, 2014].

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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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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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(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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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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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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Vascular disorder of pregnancy (VDP)(Berhan, 2016)

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6. ManagementI. 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]

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Indication of antihypertensive:

BP: more than 160/110 mm Hg(ACOG, 2013)

SBP: over 170 mm Hg.

(WHO)

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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.

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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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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.

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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)

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Conclusion1. 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. Preventionadministration of LDA prior to 16-w in high risk

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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. DiagnosisExcellent correlation with PCR in a random urine sample

6.ManagementTighter 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

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