key issues in (early and late) iugr k0hglflqd)hwdo%dufhorqd · key issues in (early and late) iugr...

www.fetalmedicinebarcelona.org/

Key issues in Key issues in (early and late) IUGR(early and late) IUGR

Eduard GratacósMaternal-Fetal Medicine Department, Hospital Clínic, University of Barcelona

www.fetalmedicinebarcelona.orgwww.fetalmedicinebarcelona.org

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Neonatal and Fetal GA-adjusted “normal”weight in the same population

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20 30 4025 35

0

N#cases

N#cases

GA@diagnosis

UA Doppler +(EARLY-ONSET)

UA Doppler N(LATE-ONSET)

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

PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS

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

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

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

High mortality and morbidity Low mortality but poor long outcome.

32w @diagnosis

Savchev#2013

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Early-onset IUGR(Doppler UA abnormal)

Late-onset IUGR(Doppler UA normal)

4

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FETAL DETERIORATION IN PLACENTAL INSUFFICIENCYFETAL DETERIORATION IN PLACENTAL INSUFFICIENCY

PLACENTAL DISEASE COMPENSATED HYPOXIA DECOMPENSATED HYPOXIA SERIOUS INJURYDEATH

cardiac ischemiaDiastolic failure

Systolic cardiacfailure

Centralization

Increment placentalimpedance

growth

MIDDLE CEREBRAL A.MIDDLE CEREBRAL A.

UMBILICAL A.UMBILICAL A.

DUCTUS VENOSUSDUCTUS VENOSUS

CTG ABNORMAL

UTERINE A.UTERINE A.

cCTG: reduced short-term variability

Ao ISTHMUSAo ISTHMUS

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umbilical arterynormal and anormalhemodynamics

DS

Cardiac pumpnormal function

Cardiac pumpabnormal function

Placental(status

<30%

placenta((+(cardiac(ischemia©

Medicin

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middle cerebral arterynormal and abnormalhrmodynamics

[marked vasodilation]

[normal waveform]

[mild vasodilation]

Normal oxygenation

hypoxia

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30 % venous return

REFLECTS DIASTOLICPRESSURE IN RIGHT (ANDLEFT) HEART

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ductus venosusnormal and abnormalhemodynamics

Venous vessel: pulsation due to retrogradepressure

S DA

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ductus venosusnormal and abnormalhemodynamics

compliance rightchambers: effect sobre

on venous return

DS A

P

P

P

P

Myocardialischemia

compliance

no

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Perinatal!!!!!!!!!!!!!!!!!!!>90%!!!!!!!!30'40%!!!!!!!!<10%Mortality


<26 26-28 >28

Baschat!2003Hecher!2003!Grivell!2009Cruz'Lemini!2012

Early-onset IUGRPROBLEM #1: MORTALITY

DVa!(rev)

YesNoYesYes

NoNo

0%20%40%60%80%100%0%

0%

20%

20%

40%

40%

60%

60%

80%

80%

100%

100%

cCTG'STV<3!ms

PathologicalCGT

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Perinatal!!!!!!!!!!!!!!!!!!!>90%!!!!!!!!30'40%!!!!!!!!<10%Mortality


<29 29-32 >32.0

Fouron!2004Del!Rio!2008Cruz'Martinez!2012

Early-onset IUGRPROBLEM #2: (NEUROLOGICAL) MORBIDITY

02040600

0

20

20

40

40

60

60

(%)

(%)

ControlsIUGR antegrade AoIIUGR retrograde AoIControls IUGR antegrade AoI IUGR retrograde AoI

0,010,020,030,040,050,060,00,0

0,0

10,0

10,0

20,0

20,0

30,0

30,0

40,0

40,0

50,0

50,0

60,0

60,0

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

**

Brain US anomalies in 30w IUGR

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Fetal I+D Protocol early-onset IUGR Sequence Doppler (and CTG) changes

CPRCPR<p5<p5

Ut A Ut A >p95>p95

MCAMCA<p5<p5

DV DV (a rev)(a rev)

CGT decelerations ofCGT decelerations ofreduced short-termreduced short-term

variabilityvariability

REDVREDVDV >p95DV >p95 UVpulsUVpuls

I Doppler normal but EFW<p3

II Increased resistance Initial redistribution

III Severely increased resistance and/or redistribution

IV Severe hemodynamic alteration

V High risk of death

AEDVAEDV AoI >p95AoI >p95

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FETAL DETERIORATION IN EARLY-ONSET IUGRFETAL DETERIORATION IN EARLY-ONSET IUGR




Centralization


cCTG: reduced STV

HIGHMODERATELOW

Risks of prematurity

VVIVIVIIIIIIIIII ©M

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Mort.!!!!!!!!!!!>90%!!!!!!!!50%!!!!!!!!<10%Morb.!!!!!!!!!!!!!!!!>90%!!!!!!!!!!!!!!!!50%


<26w 26-28 28-32 32-34 34-37

When DV(a-)cCTG!abn.CTG!dec.

(a)!28!wDV>p95!/!UV!puls!

(b)!30!wREDV

(a)!AEDV(b)!AoI>p95 CPR>p95

UtA>p95MCA<p5

EFW<p3

Stage V IV III II I

Delivery CS CS CS!or!LI LI

Early-onset IUGRManagement protocol according to severity stages

Follow5up Daily 1-2!d 2/w 1/w

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1 - <28 w : PROBLEM IS MORTALITY1 - <28 w : PROBLEM IS MORTALITYFirst determinant: GAFirst determinant: GA

Second (most useful) determinant 26-28w: DVSecond (most useful) determinant 26-28w: DV


4 - (IF PREECLAMPSIA NATURAL HISTORY ALTERED)4 - (IF PREECLAMPSIA NATURAL HISTORY ALTERED)

3 - NATURAL HISTORY: USE A PROTOCOL3 - NATURAL HISTORY: USE A PROTOCOL

2 - >28 PROBLEM IS NEUROLOGICAL MORBIDITY2 - >28 PROBLEM IS NEUROLOGICAL MORBIDITY

EARLY-ONSET IUGR Key points for clinical management

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Early-onset IUGR(Doppler UA abnormal)

Late-onset IUGR(Doppler UA normal)

20

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Neonatal acidosisCS for distressAbnormal NBASAnyNeonatal acidosis

Neonatal acidosis

CS for distress

CS for distress

Abnormal NBAS

Abnormal NBAS

Any

Any

0102030400

0

10

10

20

20

30

30

40

40

% %

Figueras 2011

SGA: proportion of perinatal adverseoutcomes in 376 consecutive cases

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5-7% newbornsdetection < 50%> 40% late pregnancy IUFDNeurological, cardiovascular and

metabolic impactdiagnosis SGA vs. Late-IUGR

••••

•

IUGR

SGA

20 30 4025 35

0

3

3%

CLINICAL PROBLEMS

PROBLEM 1: DIAGNOSISdetection <50%

PROBLEM 2: LATE-IUGR VS SGALate-IUGR = poor perinatal outcomelate-IUGR = 40% term IUFDs

PROBLEM 3: LONG TERM OUTCOMEFetal programming

••

poorer

perinataloutcome

normal

signsadaptation

yes

no

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FETAL DETERIORATION IN PLACENTAL INSUFFICIENCY FETAL DETERIORATION IN PLACENTAL INSUFFICIENCY EARLY VS LATE IUGR (>34s)EARLY VS LATE IUGR (>34s)




Centralization


growth

MIDDLE CEREBRAL A.MIDDLE CEREBRAL A.

UMBILICAL A.UMBILICAL A.

DUCTUS VENOSUSDUCTUS VENOSUS

CTG / BPP ABNORMAL

Placental injury <30%

mild hypoxiano cardiovascular adaptation

minimal tolerance to hypoxia

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UtAUtA>p95>p95

CPRCPR<p5<p5 EFW CENTILEEFW CENTILE

<3<3

ControlsAll normalAny abnormalControls

Controls

All normal

All normal

Any abnormal

Any abnormal

0%10%20%30%40%0%

0%

10%

10%

20%

20%

30%

30%

40%

40%

% %

Prognostic criteria of “poor outcome”-SGAPrognostic criteria of “poor outcome”-SGACS for distress and/or neonatal acidosis

N=447 SGA + 447 controls

Figueras 2012

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www.fetalmedicinebarcelona.org/Cruz et al, 2010

LATE-IUGR: SELECTION OF HIGHER RISK CASESMCA<p5 : CS AFTER INDUCTION >80 %

0"

10"

20"

30"

40"

50"

60"

70"

Cesarean"sec1on"for"distress"

Neonatal"acidosis"

AGA"

SGA"normal"MCA"

SGA"abnormal"MCA"

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Today: identification of SGA and of cases with poor perinatal outcomeEFW centile, UA, MCA, UV and UtA Dopplers (plus BPP)

All normal: control / 2 w

One abnormal: control /1 w and manage as IUGR with abnormal UA (delivery 37 w)

MCA abnormal: consider delivery at any time >34 w

Tomorrow: improve identification + prediction of long term outcome

EFW<p10

Exclusion of primarycauses

MANAGEMENT OF LATE-ONSET IUGR

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c

Spontaneous/Induction

Labor Induction

Induction/Elective CSLate

-La

te-

IUGR

IUGR

SGA

>p3

SGA

>p3

Late-onset IUGRProtocol for management of delivery

4/21

34-3

737

-38

37-4

1

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IUGR vs SGA: the era of UA Doppler

A new notion: “late-onset” IUGR

Clinical implications for today

Clinical implications for tomorrow

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5-7% newborns

detection < 50%

> 40% late pregnancy IUFD

Neurological, cardiovascular andmetabolic impact

diagnosis SGA vs. Late-IUGR

••••

•

IUGR

SGA

20 30 4025 35

0

5

10%

GOALS OF MANAGEMENT?

PROBLEM 1: DIAGNOSIS

PROBLEM 2: POOR OUTCOME

PROBLEM 3: LONG TERM OUTCOME

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control IUGR

Crispi 2012

Crispi 2010

Impact of prenatal severity onImpact of prenatal severity oncardiovascular programming in late-cardiovascular programming in late-

IUGRIUGRFetuses EFW<p10 evaluated at 5Fetuses EFW<p10 evaluated at 5yearsyears

Classified by CPR, p3 and UtA Doppler:All normal: SGAAll normal: SGAAny abnormal: late-IUGRAny abnormal: late-IUGR

••••

30

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Neurobehavior in SGA newbornsNeurobehavior in SGA newborns

* * * * *

* p <0.05Adjusted for GA, maternal age,socioeconomic status and smoking

Satchev, 2012Geva 2008

Figueras 2008Eixarch 2010

N=120 SGAvs

100 AGA

* * *

Bay

ley

Sco

re

20

40

60

80

100

120

cognitive language motor socio-emotional

adaptivebehavior

* * *

No differences in relation withprenatal prognostic factors

(EFW<p3, CPR or UtA Doppler)

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Findings Perinatal Outcome Long Term Outome

All normal(good reserve)

“Normal” Abnormal

One or more abnormal(no reserve)

Higher risk poor outcome Abnormal

MCA <p5(hypoxia)

Risk CS >80% Abnormal

EFW<p10

CPR (UA/MCA)Uterine ArteryEFW Centile

(HYPOTHESIS ON) DEGREES OF SEVERITYIN LATE-ONSET IUGR

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Today: identification of poor perinatal outcomeEFW centile, UA, MCA and UtA Dopplers

(Tomorrow: improve identification + prediction of long term outcome)

EFW<p10

Exclusion of primarycauses

MANAGEMENT OF LATE-ONSET IUGR

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LATE-IUGR: CLINICAL CONCLUSIONSSGA + (EFW<3th, abnormal CPR, UtA or UV flow)=IUGR:

manage as IUGR with abnormal UA

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20 30 4025 35

0

N#cases

N#cases

GA@diagnosis

UA Doppler +(EARLY-ONSET)

UA Doppler N(LATE-ONSET)

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

PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS

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

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

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

High mortality and morbidity Low mortality but poor long outcome.

32w @diagnosis

Savchev#2013

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Fetal Medicine Course on Placental Disease Intrauterine growth restriction and Preeclampsia Update in clinical management 18th -19th April 2013 | Barcelona

PROGRAMME ISUOG approved

Thursday, April 18th Panel 1: Feto-placental Doppler 09:00-09:30 Basis for the correct use of Doppler 09:30-10:15 Basic vessels: UA, UtA 10:15-11:00 Live demonstration 11:00-11:30 Coffee 11:30-12:15 Brain circulation: MCA, AoI. 12:15-13:00 Venous vessels: DV, UV 13:00-14:00 Lunch Panel 2: Early onset disease 14:00-14:45 Prediction and prevention 14:45-16:00 Management of early-onset IUGR 16:00-16:30 Coffee 16:00-18:00 Management of early-onset PE Friday, 19th April Panel 3: Late-onset disease 09:00-09:45

Prediction and the challenge of diagnosis.

09:45-11:00 Management of late-onset IUGR 10:45-11:15 Coffee 11:15-12:00 Management of late-onset PE

12:00-13:00

Special conference: Long term consequences of early and late IUGR and implications for parental counseling

13:00-13:15 Conclusions and farewell

In spite of being among the most classical obstetrical complications, knowledge on PE and IUGR has been substantially renewed over recent years. Advances in management of these complications include prediction, integrating the notions of early and late onset disease, and counseling about long term impact in maternal and fetal health. Doppler fetal monitoring is still a mainstay in clinical management, but its correct use is still challenging for the average specialist. The main goal of the course is to improve clinical competence, by ensuring the use of Doppler according to best practice and the application of systematic clinical protocols based on most recent evidence. All clinical lectures are based on real clinical cases, which are used to consolidate learning of the essential concepts. There is continuous electronic self-evaluation during the lectures. Given the important relationship with Doppler, one third of the course is dedicated to the basis and correct use of Doppler in fetal medicine, including a live demonstration session of all relevant vessels.

• The correct use of Doppler in Fetal

Medicine.

• Early and late-onset IUGR and preeclampsia.

• Systematic approach to clinical

management based on evidence.

Course Directors | Eduard Gratacós and Francesc Figueras Venue | Facultat de Biologia. Aula Magna. Edifici Margalet. Avda Diagonal 645. Barcelona. Registration fee | EUR 220 Specialists | EUR 180 Residents and Fellows in training Language | English (simultaneous translation to Spanish will be available)

www.medicinafetalbarcelona.org

Click on the link for more information: http://www.medicinafetalbarcelona.org/docencia/cursos/cursos-presenciales/160-abr-2013-fetal-medicine-course-on-placental-disease-intrauterine-growth-restriction-and-preeclampsia-update-in-clinical-management.html

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KEY CURRENT ISSUES INKEY CURRENT ISSUES INIUGRIUGR

Eduard GratacósMaternal-Fetal Medicine Department

Hospital Clínic, Universidad de Barcelona

www.medicinafetalbarcelona.orgwww.medicinafetalbarcelona.org

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IMPACT OF NON-DETECTED IUGR ONLATE FETALMORTALITYHospital Clínic Barcelona2005-2010

FGRUnknownOthersFGR

FGR

Unknown

Unknown

Others

Others

0%10%20%30%40%50%0%

0%

10%

10%

20%

20%

30%

30%

40%

40%

50%

50%

Relevant Condition ReCoDe Relevant Condition ReCoDe

Classification of stillbirth by relevant condition at birth (ReCoDe): population-based cohort studyGardosi et al. BMJ 2005

N=2625 stillbirths

FGR as relevant condition identified in 43%

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1. Identification of IUGR

2. Pathophysiological insights

3. Goals of management

4. Suggestions according to evidence5. Conclusions ©

Medicin

a Fetal B

arcelo

na

Crispi et al. Circulation 2010

Cardiac remodelling

Cardiac shape

Systolic function

Diastolic function

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AttentionSocialOrganizationAttention

Attention

Social

Social

Organization

Organization

0,020,040,060,00,0

0,0

20,0

20,0

40,0

40,0

60,0

60,0

(%)

(%)

controlSGA with normal FMBVSGA with increased FMBVcontrol SGA with normal FMBV SGA with increased FMBV

*

*

*

* p<0.01

SocialAttentionOrganizationSocial

Social

Attention

Attention

Organization

Organization

0,04,08,012,016,020,00,0

0,0

4,0

4,0

8,0

8,0

12,0

12,0

16,0

16,0

20,0

20,0

OR

OR

SGA with normal FMBVSGA with increased FMBVSGA with normal FMBV SGA with increased FMBV

**

*

Risk of abnormal neurobehavior in SGA

*

*

*

*

* *

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Significant increase in the risk ofadverse perinatal outcome

Hershkovitz et al. Ultrasound Obstet Gynecol 2000

Severi et al. Ultrasound Obstet Gynecol 2002

Figueras et al . Eur J Obstet Gynecol Reprod Biol 2008

PI <p5

Early IUGR

e<p95

SGA

SGA = constitutionally small?

Significant increase in the risk ofadverse NEURODEVELOPMENT

outcomeEixarch et al. Ultrasound Obstet Gynecol 2008

Severi et al. Ultrasound Obstet Gynecol 2002

Figueras et al . Eur J Obstet Gynecol Reprod Biol 2008

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