impact of (early and late) iugr on neurodevelopment impact of (early and late) iugr on...

www.fetalmedicinebarcelona.org/

Impact of (early and late) IUGR on neurodevelopment

Eduard GratacosMaternal-Fetal Medicine Department and Research Center

Hospitals Clinic and Sant Joan de Deu - University of Barcelonawww.fetalmedicinebarcelona.org

martes 18 de junio de 13

http://www.fetalmedicinebarcelona.org


http://www.medicinafetal

http://www.medicinafetal

1. IUGR vs. SGA - Early vs. Late

2. Early-onset IUGR and neurodevelopment

3. Late-onset IUGR and neurodevelopment


www.medicinafetalbarcelona.org/

Savchev 2013



The discovery of UA and hemodynamics of IUGR

Savchev 2013



Constitutionally small Placental insufficiency Extrinsic cause

Primary fetal defect


IUGR = abnormal UA Doppler

Savchev 2013





SGA IUGR



Savchev 2013





SGA IUGR



20 30 4025 35 Savchev 2013





SGA IUGR



20 30 4025 35

0

N cases

N cases

Savchev 2013





SGA IUGR



20 30 4025 35

0

N cases

N cases

UA Doppler +(EARLY-ONSET)

Savchev 2013





SGA IUGR



20 30 4025 35

0

N cases

N cases

UA Doppler +(EARLY-ONSET)

UA Doppler N(LATE-ONSET)

Savchev 2013



Distribution of cases when IUGR = abnormal UA Doppler

Savchev 2013



Distribution of cases when IUGR = abnormal CPR or UtA or EFW<p3

Savchev 2013



IUGR

SGA?

20 30 4025 35

0

3

6 %

IUGR= low CPR or high UtA or EFW<p3 or low PlGF





IUGR

SGA?

20 30 4025 35

0

3

6 %


32w @diagnosis





IUGR

SGA?

20 30 4025 35

0

3

6 %


EARLY IUGR (1%) LATE IUGR (5-7%)

32w @diagnosis





IUGR

SGA?

20 30 4025 35

0

3

6 %



PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS

32w @diagnosis





IUGR

SGA?

20 30 4025 35

0

3

6 %




Placental disease: high (UA+, PE high) Placental disease: low (UA-, PE low)

32w @diagnosis





IUGR

SGA?

20 30 4025 35

0

3

6 %





Hypoxia ++: systemic CV adaptation Hypoxia +/-: central CV adaptation

32w @diagnosis





IUGR

SGA?

20 30 4025 35

0

3

6 %






Tolerance to hypoxia. Natural history Low tolerance: no natural history

32w @diagnosis





IUGR

SGA?

20 30 4025 35

0

3

6 %






Tolerance to hypoxia. Natural history Low tolerance: no natural history

High mortality and morbidity Low mortality but poor long outcome.

32w @diagnosis





IUGR Controls p

n (fetuses) 90 90

GA at birth (wks) 31.2 (2.4) 31.1 (2.4) 0.73

Birthweight (g) 1078 1616 <0.001

0

7,5

15,0

22,5

30,0

(%)

BGL PVL IVH Brain abn.

***

* p<0.05

early-IUGR is associated with higher frequency of ultrasound brain lesions and abnormal neonatal neurobehaviour

0

7,5

15,0

22,5

30,0

%

Abnormal neurobehavior

Controls IUGR

Cruz et al. 2010

9

Controls IUGR





IUGR Controls p

n (fetuses) 90 90

GA at birth (wks) 31.2 (2.4) 31.1 (2.4) 0.73

Birthweight (g) 1078 1616 <0.001

0

7,5

15,0

22,5

30,0

(%)

BGL PVL IVH Brain abn.

*

***

* p<0.05

early-IUGR is associated with higher frequency of ultrasound brain lesions and abnormal neonatal neurobehaviour

0

7,5

15,0

22,5

30,0

%

Abnormal neurobehavior

Controls IUGR

*

Cruz et al. 2010

9

Controls IUGR




Perinatal >90% 30-‐40% <10%Mortality


<29 29-32 >32.0

Fouron 2004Del Rio 2008Cruz-‐Mar5nez 2012

Early-onset IUGRPREDICTION OF SERIOUS NEUROLOGICAL MORBIDITY




Perinatal >90% 30-‐40% <10%Mortality


<29 29-32 >32.0

Fouron 2004Del Rio 2008Cruz-‐Mar5nez 2012

Early-onset IUGRPREDICTION OF SERIOUS NEUROLOGICAL MORBIDITY

0

15

30

45

60

(%)

ControlsIUGR antegrade AoIIUGR retrograde AoI

ControlsIUGR DV<5 z-scoreIUGR DV>5 z-score

**

Brain US anomalies in 30w IUGR





Early-onset IUGR: TARGETED NEUROSONOGRAPHYAbnormal findings = 16% (n=108)

Eixarch 2013



SEVERE IUGR: TARGETED NEUROSONOGRAPHY


Early-onset IUGR has a strong association with poor short-term and long-term adverse neurological

outcome

Early-onset IUGR: Indication for neurosonography

If NSG normal: strongest predictor is GA<30wBest predictor aside of GA: aortic isthmus (32-37w)


exposure


Fetal programming

Brain reorganiza5on(+/-‐ injury)

exposure


Batalle 2012Eixarch 2012


Dichorionic Twins. Born 34 weeksTwin 1: 1950 g (p45)Twin 2: 1200 g (p1). Normal Doppler



Satchev, 2012Figueras 2006-2011Baschat 2009, 2011

Vohr 2004Geva 2002-2011

Marsal 00-06Visser 01-11

* * *

Bayl

ey S

core

20

40

60

80

100

120

cognitive language motor socio-emot adaptivebehavior



Satchev, 2012Figueras 2006-2011Baschat 2009, 2011

Vohr 2004Geva 2002-2011

Marsal 00-06Visser 01-11

* * *

Bayl

ey S

core

20

40

60

80

100

120

cognitive language motor socio-emot adaptivebehavior

Lagercrantz H. Better born too soon than too small.

Lancet 1997


Clinical implications:

Does delivery at 37 weeks improve outcomes?

Does SGA vs IUGR affect prognosis?

Prediction with biomarkers


www.medicinafetalbarcelona.org/docencia

292 24-‐months SGA >37 weeks

Effects on (neuro)developmental and behavioral outcome at 2 years of age Induced labor vs. expectant management in late SGA (EFW<10th cen5le)

(DIGITAT trial) AJOG 2012

13/21


Bayley’s scores at 2 years

Neurobehavioral performance of term SGA vs IUGR

* * *

Bay

ley

Sco

re

2

4

6

8

10

12

cognitive language motor socio-emotional adaptive

behavior




* * *

Bay

ley

Sco

re

2

4

6

8

10

12


behavior

No differences in relation with IUGR or SGA status (EFW<p3, CPR or UtA Doppler)




* * *

Bay

ley

Sco

re

2

4

6

8

10

12


behavior

No differences in relation with IUGR or SGA status (EFW<p3, CPR or UtA Doppler)

Egaña 2013

Cortical measures


Brain cortical development in patients with high risk of abnormal neurodevelopment (IUGR)

Egaña 2013

Abnormal! ! NormalA A


Brain cortical development in patients with high risk of abnormal neurodevelopment (IUGR)

Egaña 2013

Integrated algorithm with several brain CD measures

Composite score= e-(Y)/ (1 + e-(Y)), where Y= 6.259 + [(LID/BPD * RID/BPD * -41.264) +

(LPOD/BPD * -16.247)].

Abnormal! ! NormalA A


Fetus Young OldChild Mature

IMPACT OF ENVIRONMENT

BIOLOGIC PROGRAMMING AND AGEEarly and Late-Onset IUGR


Fetus Young OldChild Mature

IMPACT OF ENVIRONMENT

BIOLOGIC PROGRAMMING AND AGEEarly and Late-Onset IUGR

OPPORTUNITY FOR CORRECTION


Fetus Child

Problem evident

WINDOW OF OPPORTUNITY

Brain organiza5on

BIRT

H


Fetus Child

Problem evident


Brain organiza5on

BIRT

H

IDENTIFICATION OF RISK

INDIVIDUALBIOMARKERS

INTERVENTION


Fetus Child

Problem evident


Brain organiza5on

BIRT

H

IDENTIFICATION OF RISK

INDIVIDUALBIOMARKERS

INTERVENTION

Intelligence

Fetal(Early)

postnatal

Genes


Being small for gestational age has a strong association with poor long-term adverse neurological outcome

regardless of the cause

Detection of smallness is an opportunity to improve long-term health outcomes and ageing

Individualized prediction of risk will likely be possibly but not applicable as public health


impact of (early and late) iugr on neurodevelopment impact of (early and late) iugr on...

Documents