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Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth.. restriction F.[r]

(1)

Early screening for pre-eclampsia and growth-retardation

Katia Bilardo

(2)

SFD/ SGA

Foetal:

Chromos AberrationsGenetic Syndromes, Congen Anomlies

Maternaal:Idiopatisch

Chronic diseases

Abn placentation (PIH, PE,

HELLP) IUGR

Placental:

mosaicisme (CPM)

Uterus anomalies

Velamentous Insertion

External factors:

Smoke, Alcohol, DrugsInfections

Psycho/ Social

(3)(4)

Screening uterine artety at 22-24 wks

(5)

Failure of a fetus to reach its optimal growth potential

(6)

Blood Gases and

Metabolites in the IUGR fetus :

PO2 PC02 Glucose Triglycerids

 Essential Aminoacids

(7)

Early IUGR

Easy to identify, difficult to treat

Late IUGR

(8)(9)

Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth

(10)

Conclusions Angiogenic factors and uterine artery Doppler evaluation may be useful second-trimester screening tests for early-onset, but not late-onset,

(11)

The Fetal Medicine Foundation

Maternal history: a priori risk

Biophysical markers

Biochemical markers

+ +

Adjusted risk

(12)

The Fetal Medicine Foundation

Prospective screening study at 11-13 wks: 35,486 singletonsExclude miscarriage, termination, major defect, no FU n= 2,876

Included n=32,610; No-PE n=31,884 (97.8%)

Early-PE n=107 (0.3%), Middle-PE n=185 (0.6%), Late-PE

n=434 (1.3%)

Maternal history: a priori risk

0 10 20 30 40 50 60 70 80 90 100 Early-PE Late-PE Detection rate for FPR 10%

%

PE: Prediction at 11-13 wks 46% Middle-PE 38% 35% Assisted conception

0.1 10

BMI Black S Asian FH of PE Hypertension Previous PE Nulliparous No

(13)

The Fetal Medicine Foundation

Uterine artery Doppler at 11-13 wks

20,798 pregnancies; Early-PE n= 84 (0.4%), Middle-PE 144 (0.7%), Late-PE 342 (1.6%)Mean uterine PI, adjusted for CRL, BMI, age, race

(14)

The Fetal Medicine Foundation

MAP = Diastolic BP + (Systolic BP – Diastolic BP) /

Blood pressure at 11-13 wks

PE: Prediction at 11-13 wks

13,712 pregnancies; Early-PE n=69 (0.5%), Middle-PE n=112 (0.8%), Late-PE n=246 (1.8%)MAP, adjusted for CRL, BMI, age, race and smoking

(15)

The Fetal Medicine Foundation

PE: Prediction at 11-13 wks

History

History of

hypertension

Maternal history of PE

Previous PE No previous PE Parous

S Asian Black White Racial origin BMI (Kg/m2)

Ovulation drugs

Maternal history and biophysical testing

Early-PE Late-PE

Detection rate for FPR 10%

(16)

The Fetal Medicine Foundation

PE: Prediction at 11-13 wks

Maternal history and Papp-A, PlGF

Early-PE Late-PE

Detection rate for FPR 10%

0 10 20 30 40 50 60 70 80 90 100 % 46% Middle-PE 38% 35 % 81% Impaired trophoblastic invasion

of the maternal spiral arteries Placental hypoxia

Release of inflammatory cytokines

Platelet and endothelial cell activation and damage

Clinical symptoms of preeclampsia

64%

(17)

The Fetal Medicine Foundation

PE: Prediction at 11-13 wks

Combined testing

Early-PE Late-PE

Detection rate for FPR 10% (5%) 10 20 30 40 50 60 70 80 90 100 % 46% Middle-PE 38% 35% 95% (90%) 81% (70%) 63% (50%) History History of hypertension

Maternal history of PE

Previous PE No previous PE Parous

S Asian Black White Racial origin BMI (Kg/m2)

(18)

The Fetal Medicine Foundation

UOG 2010

Results:

Multivariate logistic regression analysis demonstrated that significant prediction for early PE was provided by maternal factors, MAP, uterine artery

L-PI and serum PlGF Significant prediction of late PE was provided by maternal factors, MAP, uterine artery L-PI, PlGF, activin-A and P-selectin.

The estimated detection rates, at a 5% false-positive rate, were 88.5%

(95% CI, 69.8–97.4%) for early PE and 46.7% (95% CI, 36.1–57.5%) for late PE .

Conclusion

Combined biophysical and biochemical testing at 11–13 weeks could effectively identify women at high risk for subsequent development of hypertensive disorders in pregnancy.

(19)

The Fetal Medicine Foundation

(20)(21)

The Fetal Medicine

(22)(23)

The Fetal Medicine Foundation

PE: Prediction at 11-13 wks

.2 1.21.41.61.82.0

< 16 wks

(n=222)

17-19 wks

(n=102)

> 20 wks

(n=993) 0.48 (0.33-0.68) 0.66 (0.17-1.76) 0.82 (0.62-1.09) Bujold 2009

Meta analysis on prophylactic aspirin 31 randomized studies, 32217 patients

• Preeclampsia 0.90 (95% CI 0.84-0.97)

Askie et al, Lancet 2007

(24)

RESULTS:

ONLY FIVE TRIALS ON A COMBINED TOTAL OF 556 WOMEN FULFILLED THE INCLUSION CRITERIA ASPIRIN INITIATED AT OR BEFORE 16 WEEKS OF GESTATION WAS ASSOCIATED WITH A MAJOR REDUCTION OF THE RISK OF PRETERM PREECLAMPSIA (RR 0.11, 95% CI 0.04–0.33)

CONCLUSION:

(25)

What happens in the western world

• Screening for PE is not yet performed in a standardized way

•Many obstetricians already prescribe Aspirin to pregnant women, as if it was … water

•Many pregnant women use Aspirin on their own initiative, without medical prescription or supervision

• No uniformity or information on use, dosage, compliance

(26)

The still unanswered questions

Is screening for PE equally effective in the “real world”?

Which is the most cost-effective algorithm?

Is Aspirin really effective ?

Is it safe?

Is it the best therapeutic strategy?

More evidence is necessary, a RCT is necessary to assess the real therapeutic

(27)

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