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UPDATE ON DIAGNOSIS AND

MANAGEMENT OF
FETAL GROWTH RESTRICTION
Eduard Gratacos
Center for Maternal-Fetal Medicine and Neonatology
Hospital Clinic & Hospital Sant Joan de Deu - University de Barcelona
www.fetalmedicinebarcelona.org

www.fetalmedicinebarcelona.org/
Neonatal and Fetal GA-adjusted “normal”
weight in the same population

www.medicinafetalbarcelona.org/
Exclude primary fetal defect

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS


Perinatal and Long-term Outcomes

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD


(Doppler) Signs of adaptation NO signs of adaptation

IUGR SGA
Placental insufficiency Unknown (constitutional + others)

FGR vs. SGA: DIFFERENT MANAGEMENT

www.medicinafetalbarcelona.org/
Prognostic criteria of “poor outcome”-SGA
CS for distress and/or neonatal acidosis

UtA CPR
<p5 EFW CENTILE <3
>p95
(<p15)

50%
N=509 SGA + 509 controls 40%
40%

30%
%
20%

11%
10% 8%

0%
Controls All normal Any abnormal
www.medicinafetalbarcelona.org/ Figueras 2013
IUGR = abnormal CPR or UtA or EFW<p3
early vs late-onset IUGR

Savchev 2013
www.medicinafetalbarcelona.org/
RATIONALE FOR A STAGE-BASED APPROACH TO THE
MANAGEMENT OF FGR

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

Diagnostic/chronic markers Prognostic/Acute markers


Early and Late IUGR Early IUGR
Increment placental
impedance

cardiac
Diastoli
Centralization

cCTG: reduced STV

Systolic cardiac
Stage fetal
deterioration I II III IV failure

Risks of
prematurity LOW MODERATE HIGH

Red Line LATE IUGR Red Line EARLY IUGR

www.medicinafetalbarcelona.org/
1. Identify small fetus

2. FGR vs. SGA

3. Early vs. Late

4. Parameters for fetal follow-up

5. Stage-based management protocol

www.medicinafetalbarcelona.org/
1. Identify small fetus

2. FGR vs. SGA

3. Early vs. Late

4. Parameters for fetal follow-up

5. Stage-based management protocol

Return
www.medicinafetalbarcelona.org/
Neonatal and Fetal GA-adjusted “normal”
weight in the same population

www.medicinafetalbarcelona.org/
IMPROVING DETECTION: THE DEFINITION OF “RESTRICTION”
Birthweight inverse relation with perinatal outcome AND brain-cardiac remodelling

INTEGRATED 3T SCREENING FOR LATE-PREGNANCY COMPLICATIONS


Late-PE, Late-IUGR, Stillbirth !

www.medicinafetalbarcelona.org/ Mula 2013, Lobmaier 2013


1. Identify small fetus

2. FGR vs. SGA

3. Early vs. Late

4. Stage-based management protocol

Return
www.medicinafetalbarcelona.org/
Exclude primary fetal defect

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS


Perinatal and Long-term Outcomes

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD


(Doppler) Signs of adaptation NO signs of adaptation

IUGR SGA
Placental insufficiency Unknown (constitutional + others)

FGR vs. SGA: DIFFERENT MANAGEMENT

www.medicinafetalbarcelona.org/
The discovery of UA and hemodynamics of IUGR
Constitutionally small Placental insufficiency Extrinsic cause
Primary fetal
defect

SGA FGR

N  cases

UA Doppler +
(EARLY-ONSET)

UA Doppler N
(LATE-ONSET)
N  cases

Savchev  2013
20 25 30 35 40

FGR = abnormal UA Doppler

www.medicinafetalbarcelona.org/
SGA: proportion of perinatal adverse
outcomes in 376 consecutive cases

40

30

%
20

10

0
Neonatal acidosis CS for distress Abnormal NBAS Any

Figueras 2011
www.medicinafetalbarcelona.org/
50% 45%
40%
IMPACT OF NON-DETECTED IUGR ON
30%
LATE FETAL MORTALITY 30% 25%
Barcelona
20%
2005-2010
10%

0%
FGR Unknown Others

Classification of stillbirth by relevant condition at birth (ReCoDe):


population-based cohort study
Gardosi et al. BMJ 2005 and 2013

IUGR as relevant condition identified in 43-60%

Overall stillbirth rate (/ 1000 births) 4.2, but only 2.4 in non-SGA
pregnancies, increasing to
9.7 with antenatally detected IUGR and 19.8 in not detected IUGR.

www.medicinafetalbarcelona.org/
Prognostic criteria of “poor outcome”-SGA
CS for distress and/or neonatal acidosis

UtA CPR
<p5 EFW CENTILE <3
>p95

50%
N=509 SGA + 509 controls 40%
40%

30%
%
20%

11%
10% 8%

0%
Controls All normal Any abnormal
www.medicinafetalbarcelona.org/ Figueras 2012
Distribution of cases when IUGR = abnormal UA Doppler

Savchev 2013
www.medicinafetalbarcelona.org/
Distribution of cases when IUGR = abnormal CPR or UtA or EFW<p3

Savchev 2013
www.medicinafetalbarcelona.org/
1. Identify small fetus

2. FGR vs. SGA

3. Early vs. Late

4. Stage-based management protocol

Return
www.medicinafetalbarcelona.org/
IUGR= low CPR or high UtA or EFW<p3 or low PlGF

6 %

SGA?
3

IUGR
0

20 25 30 35 40

32w @diagnosis

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.

www.fetalmedicinebarcelona.org/
FETAL DETERIORATION IN PLACENTAL INSUFFICIENCY

PLACENTAL DISEASE COMPENSATED HYPOXIA DECOMPENSATED HYPOXIA SERIOUS INJURY


DEATH

Increment placental
impedance

UTERINE A. >p95

CPR <p5 UMBILICAL A. >p95

Centralization

MIDDLE CEREBRAL A. <p5 Ao ISTHMUS >p95

cardiac ischemia
Diastolic failure

growth DUCTUS VENOSUS >p95 and a-

cCTG: reduced short-term CTG ABNORMAL


variability

Systolic cardiac
failure

www.medicinafetalbarcelona.org/
FETAL DETERIORATION IN PLACENTAL INSUFFICIENCY
EARLY VS LATE IUGR (>34s)

PLACENTAL DISEASE COMPENSATED HYPOXIA DECOMPENSATED HYPOXIA SERIOUS INJURY


DEATH
Increment placental minimal tolerance to hypoxia
impedance

UTERINE A. >p95 Placental injury <30%

CPR <p5 UMBILICAL A. >p95

Centralization

MIDDLE CEREBRAL A. <p5 Ao ISTHMUS >p95

cardiac ischemia
Diastolic failure

growth DUCTUS VENOSUS >p95 and a-

CTG / BPP ABNORMAL

mild hypoxia
no cardiovascular adaptation Systolic cardiac
failure

www.medicinafetalbarcelona.org/
IUGR= low CPR or high UtA or EFW<p3 or low PlGF

6 %

SGA?
3

IUGR
0

20 25 30 35 40

32w @diagnosis

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.

www.fetalmedicinebarcelona.org/
1. Identify small fetus

2. FGR vs. SGA

3. Early vs. Late

4. Parameters for fetal follow up

4. Stage-based management protocol

Return
www.medicinafetalbarcelona.org/
S D
umbilical artery
normal and anormal
hemodynamics

Placental  status

<30%
Cardiac pump
normal function

placenta    +  cardiac  ischemia

Cardiac pump
abnormal function
middle cerebral artery
normal and abnormal
hemodynamics

Normal oxygenation

[normal waveform]

[mild vasodilation]

[marked vasodilation]

hypoxia
30 % venous return
REFLECTS DIASTOLIC PRESSURE IN
RIGHT (AND LEFT) HEART
www.medicinafetalbarcelona.org/
ductus venosus
normal and abnormal
hemodynamics

S D
A

Venous vessel: pulsation due to retrograde


pressure
S D A
ductus venosus
normal and abnormal
hemodynamics

compliance right
chambers: effect sobre P
on venous return

no
Myocardial
ischemia
P
compliance

P
Early-onset IUGR
PROBLEM #1: MORTALITY

cCTG-­‐STV<3  ms

Pathological  
CGT

60%

DVa  (rev)
19%

Yes No

<26 26-28 >28

Perinatal           >90%   30-­‐40%   <10%


Mortality

Baschat  2003
Hecher  2003  
Grivell  2009
www.medicinafetalbarcelona.org/ Cruz-­‐Lemini  2012
Early-onset IUGR
PROBLEM #2: (NEUROLOGICAL) MORBIDITY
Brain US anomalies in 30w IUGR
Controls Controls
IUGR antegrade AoI IUGR DV<5 z-score
IUGR retrograde AoI IUGR DV>5 z-score

60
*
*
45
(%)

30

15

<29 29-32 >32.0

Perinatal           >90%   30-­‐40%   <10%


Mortality
Fouron  2004
Del  Rio  2008
Cruz-­‐MarOnez  2012
www.medicinafetalbarcelona.org/
1. Identify small fetus

2. FGR vs. SGA

3. Early vs. Late

4. Parameters for fetal follow up

5. Stage-based management protocol

Return
www.medicinafetalbarcelona.org/
IUGR = abnormal CPR or UtA or EFW<p3

Savchev 2013
www.medicinafetalbarcelona.org/
RATIONALE FOR A STAGE-BASED APPROACH TO THE
MANAGEMENT OF FGR

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

Diagnostic/chronic markers Prognostic/Acute markers


Early and Late IUGR Early IUGR
Increment placental
impedance

cardiac
Diastoli
Centralization

cCTG: reduced STV

Systolic cardiac
Stage fetal
deterioration I II III IV failure

Risks of
prematurity LOW MODERATE HIGH

Red Line LATE IUGR Red Line EARLY IUGR

www.medicinafetalbarcelona.org/
Protocol IUGR
First step: UtA + CPR + EFW = SGA or IUGR

CPR Ut A MCA
I low EFW (<p3) or mild placental
resistance / redistribution <p5 >p95 <p5

III Severe placental resistance / AEDV AoI >p95


redistribution

DV >p95 REDV
III Severe hemodynamic adaptation
- Low suspicion acidosis

IV High suspicion of acidosis - DV CGT decelerations of


(a rev) reduced short-term
High risk of death variability

www.medicinafetalbarcelona.org/
IUGR
Management protocol according to severity stages

Stage IV III II I

DV>p95 EFW<p3
DV(a-­‐) (a)  AEDV
Criteria UV  puls   (b)  AoI>95 CPR>p95
cCTG  abn.
REDV UtA>p95
CTG  dec.
MCA<p5
Delivery Any  Ome 30 34 37

Follow-­‐up Hours/Daily 1-­‐2  d 2/w 1/w

Mode CS CS CS  or  LI LI

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

Mort.         >90%   50%   <10%


Morb.     >90%     50%

www.medicinafetalbarcelona.org/
The main goal in FGR is identification

Small fetus (EFW<p10) must be divided in:


FGR (placenta, poor perinatal and long-term outcome)
SGA (we don’t know, perinatal outcome N, poor long term)

Early and late-onset FGR (GA 32s) represent two


distinct phenotypes of the same disease

Clinically, a single stage-based protocol allows


optimizing decisions in all cases

www.medicinafetalbarcelona.org/