Rciu Gratacous Peru PDF

UPDATE ON DIAGNOSIS AND
MANAGEMENT OF
FETAL GROWTH RESTRICTION
Eduard Gratacs
BCNatal Barcelona Center of Maternal-Fetal and Neonatal Medicine

Hospital Clnic and Hospital Sant Joan de Du, Universitat de Barcelona
www.fetalmedicinebarcelona.org/
www.medicinafetalbarcelona.org/
Dichorionic twins. Doppler UA N. Born 34 w
Normal development so far
1950 g (p45) 1200 g (p1)
Dichorionic twins. Doppler UA N. Born 34 w
Normal development so far
1950 g (p45) 1200 g (p1)
Satchev, 2012
Lagercrantz H. Better born too soon than too small. Lancet 1997 Figueras 2006-2011
Baschat 2009, 2011
Vohr 2004
Geva 2002-2011
Marsal 00-06
Visser 01-11
Placental insufficiency = high risk of IUFD and fetal/neonatal acidosis
Fetal Smallness = higher risk of placental insufficiency
50
Fetal weight centile
10
50
10
0 100
Risk of placental insufficiency
50
10 Small
fetuses
0 100
50
10 Small
fetuses
Placental respiratory
smallness = risk distress + IUFD
0 100
50
10 Small
Non-respiratory smallness
= no distress/IUFD risk
fetuses
Placental respiratory
smallness = risk distress + IUFD
0 100
1. Identify small fetus
2. Identify placental insufficiency (FGR vs. SGA)
3. Determine timing of delivery
Neonatal and Fetal GA-adjusted normal
weight in the same population
Neonatal and Fetal GA-adjusted normal
weight in the same population
IMPROVING DETECTION: THE DEFINITION OF RESTRICTION
Birthweight inverse relation with perinatal outcome AND brain-cardiac remodelling
www.fetalmedicinebarcelona.org/ Mula 2013, Lobmaier 2013




C H
A R
S E
RE

decrease of fetal movements
5-15% during 3rd trimester
30% perinatal complications; 10-15% term stillbirth
4% preterm delivery
1% stillbirth
25% IUGR
70% Normal
www.medicinafetalbarcelona.org
4% preterm delivery
1% stillbirth
stillbirth
reduction
OR 0.36
25% IUGR increase IUGR
detection
(IUGR > 36 w not
diagnosed before)
70% Normal
4% preterm delivery
1% stillbirth
stillbirth
reduction
OR 0.36
25% IUGR increase IUGR
detection
(IUGR > 36 w not
diagnosed before)
70% Normal
Exclude primary fetal defect
Exclude extrinsic cause
ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Perinatal and Long-term Outcomes

Poor perinatal outcome + IUFD

(Doppler) Signs of adaptation

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD

(Doppler) Signs of adaptation NO signs of adaptation


FGR SGA
Placental insufficiency Unknown (constitutional + others)


FGR SGA


FGR SGA
FGR vs. SGA: DIFFERENT MANAGEMENT
The discovery of UA and hemodynamics of FGR
Constitutionally small Placental insufficiency Extrinsic cause
Primary fetal
defect
SGA FGR
Primary fetal
defect
SGA FGR
N cases
N cases
20 25 30 35 40
Primary fetal
defect
SGA FGR
N cases
UA Doppler +
(EARLY-ONSET)
N cases
20 25 30 35 40
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
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
FGR = abnormal UA Doppler?
r e
o
ym
FGR = abnormal
a UA Doppler?
n
o t
n
r e
o
ym
FGR = abnormal
a UA Doppler? n
o t
n
N cases
UA Doppler +
(EARLY-ONSET)
UA Doppler N
(LATE-ONSET)
N cases
Savchev 2013
20 25 30 35 40
Prognostic criteria for poor outcome among small fetuses
with normal UA Doppler
CPR Risk of CS for distress and/or

<p5 neonatal acidosis
N=509 SGA + 509 controls
UtA
>p95
EFW CENTILE <3
www.fetalmedicinebarcelona.org/ Figueras 2012


50%
40%
UtA
>p95
30%
20%
EFW CENTILE <3 10%
0%
Controls All normal Any abnormal


50%
40%
UtA
>p95
30%
20%
EFW CENTILE <3 10% 8%
0%


50%
40%
UtA
>p95
30%
20%
11%
0%


50%
40%
40%
UtA
>p95 %
30%
20%
11%
0%

Cerebroplacental ratio is more
sensitive than UA or MCA alone
IPUA=p80 IPMCA=p20
CPR
+ = <p5
FGR = EFW <p10 + any of
CPR UtA
<p5 EFW CENTILE <3
>p95

Distribution of cases when FGR = abnormal UA Doppler
Savchev 2013
Distribution of cases when FGR = abnormal CPR or UtA or EFW<p3
Savchev 2013


FGR SGA
FGR vs. SGA: DIFFERENT MANAGEMENT
FGR = abnormal CPR or UtA or EFW<p3
Savchev 2013
Savchev 2013
Savchev 2013
Savchev 2013
Savchev 2013
Management = when should we deliver?
Savchev 2013
Late-mild
No IUFD <37w (risk at term)
PROBLEM: DETECTION
Q: Is it FGR or SGA?
Savchev 2013
Early-severe
High risk IUFD preterm
PROBLEM:TIMING DELIVERY
Q: Delivery? Next exam?
Late-mild
No IUFD <37w (risk at term)
PROBLEM: DETECTION
Q: Is it FGR or SGA?
Savchev 2013
RATIONALE FOR AN INTEGRATED STAGE-BASED
APPROACH TO THE MANAGEMENT OF FGR
PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH
Increment placental
impedance
Centralization
cardiac ischemia
Diastolic failure
Systolic cardiac
failure
Risks of
prematurity MINIMAL MILD HIGH
Increment placental
impedance
Centralization
cardiac ischemia
Diastolic failure
cCTG: reduced STV
BPP < 4
Systolic cardiac
failure
Risks of
Diagnostic/chronic markers
DIFFERENCE
FGR VS
Increment SGA
placental
impedance
Centralization
cardiac ischemia
Diastolic failure
cCTG: reduced STV
BPP < 4
Systolic cardiac
failure
Risks of
Diagnostic/chronic markers Prognostic/Acute markers

DIFFERENCE INDICATION ABOUT THE SHORT-TERM RISK
FGR VS
Increment SGA
placental OF IUFD/BRAIN INJURY
impedance
Centralization
cardiac ischemia
Diastolic failure
cCTG: reduced STV
BPP < 4
Systolic cardiac
failure
Risks of
Diagnostic/chronic markers Prognostic/Acute markers

DIFFERENCE INDICATION ABOUT THE SHORT-TERM RISK
FGR VS
Increment SGA
placental OF IUFD/BRAIN INJURY
impedance
Centralization
cardiac ischemia
Diastolic failure
cCTG: reduced STV
BPP < 4
Systolic cardiac
Stage fetal
deterioration I II III IV failure
deliver when risks are:

Risks of
Protocol FGR
First step: UtA + CPR + EFW = SGA or FGR
I low EFW (<p3) or mild placental

resistance / redistribution
II Severe placental resistance /

redistribution
III Severe hemodynamic adaptation

- Low suspicion acidosis
IV High suspicion of acidosis -

High risk of death
Protocol FGR

CPR Ut A EFW
resistance / redistribution <p5 >p95 <p3
II Severe placental resistance /

redistribution


High risk of death
Protocol FGR

CPR Ut A EFW
II Severe placental resistance / AEDV AoI >p95

redistribution


High risk of death
Protocol FGR

CPR Ut A EFW

redistribution
DV >p95 REDV

High risk of death
Protocol FGR

CPR Ut A EFW

redistribution
DV >p95 REDV
IV High suspicion of acidosis - DV CGT decelerations of

(a rev) reduced short-term
High risk of death variability
FGR
Management protocol according to severity stages
Stage IV III II I
DV(a-), cCTG, CTG dec DV>p95, REDV AEDV, AoI>95 EFW<p3, CPR <p5, UtA>95
Risk of IUFD/
VERY HIGH HIGH MODERATE LOW
brain injury
Deliver at Any 0me 30 34 37

Follow-up Hours/Daily 1-2 d 2/w 1/w
Mode CS CS CS or LI LI
<26w 26-28 28-30 30-34 34-37
Mort. >90% 50% <10%

Morb. >90% 50%
FGR
Stage IV III II I
Risk of IUFD/
brain injury

<26w 26-28 28-30 30-34 34-37
Mort. >90% 50% <10%

Morb. >90% 50%
FGR
Stage IV III II I
Risk of IUFD/
brain injury

<26w 26-28 28-30 30-34 34-37
Mort. >90% 50% <10%

Morb. >90% 50%
FGR
Stage IV III II I
Risk of IUFD/
brain injury

<26w 26-28 28-30 30-34 34-37
Mort. >90% 50% <10%

Morb. >90% 50%
FGR
Stage IV III II I
Risk of IUFD/
brain injury

<26w 26-28 28-30 30-34 34-37
Mort. >90% 50% <10%

Morb. >90% 50%
Stage 1
Delivery
First goal:
First goal:
Identify small fetus (EFW<p10)
First goal:
Second goal:
First goal:
Second goal:
Classify as FGR vs SGA using CPR, UtA and EFW<3.
First goal:
Second goal:
Third goal:
First goal:
Second goal:
Third goal:
Decide timing of delivery and follow-up scheme:
First goal:
Second goal:
Third goal:
Decide timing of delivery and follow-up scheme:
use a stage-based integrated protocol.
Early vs. Late onset FGR
Return
EARLY-ONSET LATE-ONSET
35 40
20 25 30
PREECLAMPSIA
35 40
20 25 30
PREECLAMPSIA
FGR
35 40
20 25 30
PREECLAMPSIA
PREECLAMPSIA + FGR
FGR
35 40
20 25 30
PREECLAMPSIA
1%
PREECLAMPSIA + FGR
1%
FGR
35 40
20 25 30
4-8 %
PREECLAMPSIA
1%
PREECLAMPSIA + FGR
1%
FGR
4-8 %
35 40
20 25 30
FGR= low CPR or high UtA or EFW<p3 or low PlGF
6 %
SGA?
3
FGR
0
20 25 30 35 40
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
EARLY FGR (1-2%) LATE FGR (5-6%)
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
Placental disease: high (UA+, PE high) Placental disease: low (UA-, PE low)
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
Hypoxia ++: systemic CV adaptation Hypoxia +/-: central CV adaptation
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
Tolerance to hypoxia. Natural history Low tolerance: no natural history
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
High mortality and morbidity Low mortality but poor long outcome.
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
cardiac ischemia
Diastolic failure
growth
CTG ABNORMAL
Systolic cardiac
failure

DEATH
Increment placental
impedance
UTERINE A. >p95
Centralization
cardiac ischemia
Diastolic failure
growth DUCTUS VENOSUS >p95 and a-
CTG ABNORMAL
Systolic cardiac
failure

DEATH
Increment placental
impedance
UTERINE A. >p95
Centralization
cardiac ischemia
Diastolic failure
cCTG: reduced short-term CTG ABNORMAL

variability
Systolic cardiac
failure

DEATH
Increment placental
impedance
UTERINE A. >p95
Centralization
MIDDLE CEREBRAL A. <p5 Ao ISTHMUS >p95
cardiac ischemia
Diastolic failure
cCTG: reduced short-term CTG ABNORMAL

variability
Systolic cardiac
failure
EARLY VS LATE FGR (>34s)

DEATH
Increment placental
impedance
UTERINE A. >p95
Centralization
cardiac ischemia
Diastolic failure
CTG / BPP ABNORMAL
Systolic cardiac
failure

DEATH
Increment placental
impedance
UTERINE A. >p95 Placental injury <30%
Centralization
cardiac ischemia
Diastolic failure
CTG / BPP ABNORMAL
Systolic cardiac
failure

DEATH
Increment placental
impedance
Centralization
cardiac ischemia
Diastolic failure
CTG / BPP ABNORMAL
Systolic cardiac
failure

DEATH
Increment placental
impedance
Centralization
cardiac ischemia
Diastolic failure
CTG / BPP ABNORMAL
mild hypoxia
no cardiovascular adaptation Systolic cardiac
failure

DEATH
Increment placental
impedance
Centralization
growth
CTG / BPP ABNORMAL
mild hypoxia
no cardiovascular adaptation

DEATH
Increment placental minimal tolerance to hypoxia
impedance
Centralization
growth
CTG / BPP ABNORMAL
mild hypoxia
PLACENTAL DISEASE DECOMPENSATED HYPOXIA SERIOUS INJURY

DEATH
impedance
Centralization
growth
CTG / BPP ABNORMAL
mild hypoxia
PLACENTAL DISEASE DECOMPENSATED HYPOXIA SERIOUS INJURY

DEATH
impedance
Centralization
MIDDLE CEREBRAL A. <p5 Ao ISTHMUS >p95
growth
CTG / BPP ABNORMAL
mild hypoxia
6 %
SGA?
3
FGR
0
20 25 30 35 40
32w @diagnosis
High mortality and morbidity Low mortality but poor long outcome.
Parameters for fetal follow up in FGR
Return
S D
umbilical artery
normal and anormal
hemodynamics
Cardiac pump
normal function
S D
umbilical artery
normal and anormal
hemodynamics
<30%
Cardiac pump
normal function
S D
umbilical artery
normal and anormal
hemodynamics
<30%
Cardiac pump
normal function
S D
umbilical artery
normal and anormal
hemodynamics
<30%
Cardiac pump
normal function
Cardiac pump
abnormal function
S D
umbilical artery
normal and anormal
hemodynamics
Placental status
<30%
Cardiac pump
normal function
Cardiac pump
abnormal function
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
hypoxia
normal and abnormal
hemodynamics
Normal oxygenation
[normal waveform]
hypoxia
normal and abnormal
hemodynamics
Normal oxygenation
[normal waveform]
[mild vasodilation]
hypoxia
normal and abnormal
hemodynamics
Normal oxygenation
[normal waveform]
[mild vasodilation]
[marked vasodilation]
hypoxia
Cerebroplacental ratio is more
sensitive than UA or MCA alone
IPUA=p80 IPMCA=p20
CPR
+ = <p5
30 % venous return
REFLECTS DIASTOLIC PRESSURE IN
RIGHT (AND LEFT) HEART
ductus venosus
normal and abnormal
hemodynamics
ductus venosus
normal and abnormal
hemodynamics
Venous vessel: pulsation due to retrograde

pressure
ductus venosus
normal and abnormal
hemodynamics

pressure
ductus venosus
normal and abnormal
hemodynamics
S D

pressure
ductus venosus
normal and abnormal
hemodynamics
S D
A

pressure
ductus venosus
normal and abnormal
hemodynamics
S D
A

pressure
ductus venosus
normal and abnormal
hemodynamics
compliance right
chambers: effect sobre P
on venous return
no
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
no
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
S D A
ductus venosus
normal and abnormal
hemodynamics
compliance right
on venous return
Myocardial
ischemia
P
compliance
P
When and how to deliver
Return
Early-severe
High risk IUFD preterm
Late-mild
Low risk IUFD (high at term)
Stage II to IV Stage I
PROTOCOL >37w
Savchev 2013
Early-onset FGR
PROBLEM #1: MORTALITY
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
60%
DVa (rev)
19%
Yes No
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
cCTG-STV<3 ms
Pathological
CGT
60%
DVa (rev)
19%
Yes No
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
cCTG-STV<3 ms
Pathological
CGT
60%
DVa (rev)
19%
Yes No
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
cCTG-STV<3 ms
Pathological
CGT
60%
DVa (rev)
19%
Yes No
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
cCTG-STV<3 ms
Pathological
CGT
60%
DVa (rev)
19%
Yes No
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Stage IV Stage III Stage II
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
BPP
cCTG-STV<3 ms IUFD 23% in BPP=6 and 11% in BPP=8
Poor correlation with DVa(rev)
Pathological Cochrane: poor contribution to prediction
CGT Baschat 2007, Kafur 2008, Lalor 2010,
60%
DVa (rev)
19%
Yes No
<26 26-28 29-30 31-34
Perinatal >90% 30-40% <10%

Mortality
Stage IV Stage III Stage II
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
Early-onset FGR
PROBLEM #2: (NEUROLOGICAL) MORBIDITY
<29 29-32 >32.0
Neurological >90% 30-40% <10%

Morbidity
Fouron 2004
Del Rio 2008
Cruz-MarJnez 2012
Early-onset FGR
Neonatal brain US anomalies in 30-34w FGR
Controls IUGR ant AoI IUGR REV AoI
60
45
(%)
30
15
<29 29-32 >32.0

Morbidity
Fouron 2004
Del Rio 2008
Cruz-MarJnez 2012
Late-onset FGR
PROBLEM #1: WHEN AND HOW TO DELIVER
37-38 w (+/- check lung maturity)
Do not use prostaglandins (Foley/Balloon)
Select high risk cases (MCA Doppler)
Cesarean section for fetal distress after labor
induction in term SGA according to MCA Doppler
(N=202)
70"
60"
50"
40" AGA"
30"
SGA"normal"MCA"
20"
SGA"abnormal"
10" MCA"
0"
Cesarean"sec1on"for" Neonatal"acidosis"
distress"
(OVERALL RISK OF CS AFTER INDUCTION 80 %)

Cruz et al, 2010
RISK RESPIRATORY MORBIDITY
JAMA Pediatrics 2013
Bonet, UOG 2014
N=144
Singleton
pregnancies
29.0 - 38.6 w
Axial thoracic
section
Bonet, UOG 2014
N=144
Singleton
pregnancies
29.0 - 38.6 w
Axial thoracic
section
Non Invasive Assessment of the
risk of Neonatal Respiratory morbidity
www.quantusFLM.com
Neonatal Respiratory
Morbidity (*):
Patient & Provider Information
PATIENT NAME: CLINIC NAME:
Name Surname Complete Center Name
PATIENT ID: REFERRING/ORDERING CLINICIAN:
Sabino Arana 38 1 1 NHC12345678 Clinician Name Surname

08028 Barcelona, Spain QUANTUSFLM ID: REPORT DATE:
CIF: B 65084675 btech 123 (dd/mm/yyyy) 01/01/2000
Respiratory Distress
Sample Information Test Result NEONATAL RESPIRATORY MORBIDITY
QUANTUSFLM ID:
btech 123
RESULT:
Syndrome
LOW RISK
Theoretical risk for ## weeks of gestation:
##.# %
quantusFLM risk:
##.# %
Transient tachypnea of
RECOMMENDATION:
(dd/mm/yyyy)
Review results with patient
GESTATIONAL AGE:
## weeks # days AUTHORIZED SIGNER/S:
newborn
US ACQUISITION DATE:
(dd/mm/yyyy) 01/01/2000 Imatge Firma
REQUEST DATE: Technical Responsible:
(dd/mm/yyyy hh:mm) 01/01/2000 00:00 Elisenda Bonet i Carn, MSc
Graphic Test Result NEONATAL RESPIRATORY MORBIDITY RISK
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
HIGH LOW
RISK Theoretical Risk* RISK
(*) RDS: Respiratory symptoms (eg,

quantusFLM Risk
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
TEST DESCRIPTION CLINICAL DATA SPECIFICATIONS

quantusFLM offers an automatic assessment of neonatal respiratory morbidity risk using an ultrasound
image of the lateral axial transverse section of the fetal thorax at the level of the 4 chamber section of the Accuracy 87% (95% CI:82 90%)
g r u n J n g , a r i n g , t a c h y p n e a ,
fetal heart. quantusFLM is based on quantitative ultrasound texture analysis to extract information from
ultrasound images and a classifier which uses the extracted information to assess the risk. Test result Sensitivity 91% (95% CI:77 98%)
depends on the delineation of the fetal lung and incorporated the gestational age. Neonatal respiratory
morbidity is defined as respiratory distress syndrome or transient tachypnea of the newborn. Specificity 86% (95% CI:82 90%)
Test has been validated in singleton pregnancies from 28.0 to 39.0 weeks of gestation. Test are neither
Positive Predictive Value 47% (95% CI:35 59%)
intended nor validated for use in pregnancies with fetal structural abnormalities, chromosomal
abnormalities, multiple pregnancies or maternal BMI>35. This result should not be considered as a final Negative Predictive Value 98% (95% CI:96 99%)
retracJons), O2 requirement + chest

indication but as additional information to be considered in evaluation of the patient.
REFERENCE: Quantitative ultrasound texture analysis of fetal lung to predict neonatal respiratory morbidity. UOG (2014)
quantusFLM Test is intended for clinical use and should not be regarded as investigational or for research. Present result has been obtained using quantusFLM X.X.
Under the previous of Law 15/1999 normative, we inform you that your data will be included in a data base owned by TransmuralBiotech, S.L. for its clinical treatment. You may exercise the rights of access,
rectification, cancellation and opposition contacting us at info@transmuralbiotech.com.
Rx + NICU admission
Bonet, UOG 2014 TT: chest Rx impression + clinical
diagnosis by clinician in charge.
JAMA 2010
Performance of Quantus FLM and comparison with currently used lab
8quantusFLM ha sido validado mediante 144 muestras ciegas.
Late FGR with MCA<p5
Planned delivery at 37.0 weeks
BASELINE GA-ADJUSTED = 4%
PERSONALIZED: FETAL LUNG MATURITY
LOW RISK
=1.5%
Deliver
LOW RISK HIGH RISK

=1.5% =25%
Deliver Wait and follow-up until

37.6-38.0
Early and late-onset determines different
severity, fetal response and natural history
Doppler is the main tool for follow-up and

timing of delivery in stage II to IV
Stage I: challenge is to determine best timing

and mode of delivery
Return
BEING SMALL EARLY IN PREGNANCY IS A PROBLEM
<26 26-28 >28
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
60%
DVa (rev)
19%
Yes No
<26 26-28 >28
Perinatal >90% 30-40% <10%

Mortality
Baschat 2003
Hecher 2003
Grivell 2009
Cruz-Lemini 2012
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
Cruz-Lemini 2012
Early-onset FGR
<29 29-32 >32.0

Morbidity
Fouron 2004
Del Rio 2008
Cruz-MarJnez 2012
Early-onset FGR
Neonatal brain US anomalies in 30-34w FGR
Controls IUGR ant AoI IUGR REV AoI
60
45
(%)
30
15
<29 29-32 >32.0

Morbidity
Fouron 2004
Del Rio 2008
Cruz-MarJnez 2012
BEING SMALL LATE IS ALSO A PROBLEM
SGA
<p95
e
SGA = constitutionally small?

Significant increase in the risk of

SGA adverse 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
<p95
e


SGA adverse perinatal outcome
Hershkovitz et al. Ultrasound Obstet Gynecol 2000

<p95 adverse neurodevelopment
e
Eixarch et al. Ultrasound Obstet Gynecol 2008

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
50% 45%
40%
IMPACT OF NON-DETECTED FGR ON
30%
LATE FETAL MORTALITY 30% 25%
Barcelona
20%
2005-2010
10%
0%
FGR Unknown Others
50% 45%
40%
IMPACT OF NON-DETECTED FGR 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
FGR 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 FGR and 19.8 in not detected FGR.
Neurobehavioral performance of term
SGA newborns
* * * N=120
* * SGA vs
100 AGA
* p <0.05
Adjusted for GA, maternal age,
socioeconomic status and smoking
Neurobehavioral performance of term
SGA newborns
* * * N=120
* * SGA vs
100 AGA
* p <0.05
Adjusted for GA, maternal age,
socioeconomic status and smoking
*
120
100
* ** **
80
Bayley Score
60
40
Satchev, 2012
20 Geva 2008
Figueras 2008
Eixarch 2010
cognitive language motor socio-emotional adaptive
behavior
Cardiovascular programming in
SGA / late-FGR
control IUGR
Crispi 2010
SGA / late-FGR
control IUGR Fetuses EFW<p10 evaluated at 5 years
Classified by CPR, p3 and UtA Doppler:

All normal: SGA
Any abnormal: late-FGR
Crispi 2010
SGA / late-FGR
control IUGR Fetuses EFW<p10 evaluated at 5 years
Classified by CPR, p3 and UtA Doppler:

All normal: SGA
Any abnormal: late-FGR
Crispi 2010
www.fetalmedicinebarcelona.org/ Crispi 2012

n=3450 (spontaneous deliveries)
US DaJng
<14.0 w: CRL (Robinson)
14-24 w: BPD (Mul)
>24 w: HCLFL (Snijders)
GA at delivery
1.Robinson HP. Br J OBtstet Gynaecol 1975;82:702-710.

2.Mul T. Ultrasound Obstet Gynecol 1996; 8: 397402.
3. Hadlock FP. Radiology. 1984 Feb;150(2):535-40.
US DaJng

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UPDATE ON DIAGNOSIS AND

BCNatal Barcelona Center of Maternal-Fetal and Neonatal Medicine

1950 g (p45) 1200 g (p1)

1950 g (p45) 1200 g (p1)

2. Identify placental insufficiency (FGR vs. SGA)

3. Determine timing of delivery

www.fetalmedicinebarcelona.org/ Mula 2013, Lobmaier 2013

www.fetalmedicinebarcelona.org/ Mula 2013, Lobmaier 2013

www.fetalmedicinebarcelona.org/ Mula 2013, Lobmaier 2013

www.fetalmedicinebarcelona.org/ Mula 2013, Lobmaier 2013

www.fetalmedicinebarcelona.org/ Mula 2013, Lobmaier 2013

2. Identify placental insufficiency (FGR vs. SGA)

3. Determine timing of delivery

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Poor perinatal outcome + IUFD

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD

FGR vs. SGA: DIFFERENT MANAGEMENT

FGR = abnormal UA Doppler

CPR Risk of CS for distress and/or

EFW CENTILE <3

www.fetalmedicinebarcelona.org/ Figueras 2012

CPR Risk of CS for distress and/or

EFW CENTILE <3 10%

www.fetalmedicinebarcelona.org/ Figueras 2012

CPR Risk of CS for distress and/or

EFW CENTILE <3 10% 8%

www.fetalmedicinebarcelona.org/ Figueras 2012

CPR Risk of CS for distress and/or

www.fetalmedicinebarcelona.org/ Figueras 2012

CPR Risk of CS for distress and/or

www.fetalmedicinebarcelona.org/ Figueras 2012

www.fetalmedicinebarcelona.org/ Figueras 2012

Exclude extrinsic cause

ISOLATED FETAL SMALLNESS = POORER PROGNOSIS

Poor perinatal outcome + IUFD Perinatal outcome normal - No IUFD

FGR vs. SGA: DIFFERENT MANAGEMENT

2. Identify placental insufficiency (FGR vs. SGA)

3. Determine timing of delivery

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

cCTG: reduced STV

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

cCTG: reduced STV

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

Diagnostic/chronic markers Prognostic/Acute markers

cCTG: reduced STV

PLACENTAL DISEASE HYPOXIA ACIDOSIS SERIOUS INJURY DEATH

Diagnostic/chronic markers Prognostic/Acute markers

cCTG: reduced STV