10 Ottobre 2014
11.00 - 13.30
Sessione Plenaria
PATOLOGIA
NEUROSENSORIALE
DEL LATE PRETERM
Auditorium
SARANNO FAMOSI
Michelangelo
Presidente: Costantino Romagnoli (Roma)
Moderatori: Fani Anatolitou (Athens-Greece) , Hercilia Guimaraes (Portugal)
Screening ecografico
11.00 - 13.30
Sala Tiziano 2
Simposio con il contributo non condizionato di MILTE
NUOVI APPROCCI IN TEMA DI NUTRIZIONE E DI PREVENZIONE NEI PRIMI ANNI DI VITA:
UN DIBATTITO
Conduce: Michele Mirabella (Roma)
Intervengono: Carlo
u Agostoni (Milano), Nicola D’Amario
T (er amo), L igi Memo (Belluno), Laura
Strohmenger (Milano)
14.30 - 16.30
Auditorium
Michelangelo
Sessione Parallela
PATOLOGIA NEUROSENSORIALE DEL LATE PRETERM
Presidente: Roberto Paludetto (Napoli)
Moderatori: Maurizio Finocchi (Roma), Onofrio Sergio Saia (Treviso)
Monica Fumagalli
Dismaturità cerebrale: rischio di IVH e LPV
Luca Ramenghi (Genova)
Ecografico
U.OScreening
di Neonatologia
e Terapia Intensiva Neonatale – Milano
Monica
Fumagalli
(Milano)
Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico Milano
Screening Clinico
Eugenio Mercuri (Roma)
Direttore: Prof Fabio Mosca
Vulnerabilità e disturbi neuropsichici "minori"
Cranial ultrasound screening in late preterm infants:
does it make sense?
1. Background
1. Background: impaired outcomes
Late-Preterm Birth and Its Association With Cognitive
and Socioemotional Outcomes at 6 Years of Age
Talge et al
Pediatrics 2010
WHAT’S KNOWNONTHIS SUBJECT: Late-preterm birth (34–36
weeks’ gestation) may be associated with cognitive and
socioemotional problems during childhood. It is unclear whether
these associations are independent of fetal growth and other
covariates such as neighborhood conditions and maternal IQ.
AUTHORS: Nicole M. Talge, PhD,a Claudia Holzman, DVM,
MPH, PhD,a Jianling Wang, MS,a Victoria Lucia, PhD,b
Joseph Gardiner, PhD,a and Naomi Breslau, PhDa
WHATTHIS STUDYADDS: Late-preterm birth, on average, is
associated with cognitive and socioemotional problems even
after adjusting for important covariates. Agreater proportion of
late-preterm births fall within the category of borderline/clinical
problems, but many are within the normal range.
KEY WORDS
preterm birth, intelligence, attention-deficit/hyperactivity
disorder, child development
abstract
a
Department of Epidemiology, Michigan State University, East
Lansing, Michigan; and bResearch Institute, William Beaumont
Hospitals, Royal Oak, Michigan
ABBREVIATIONS
LBW—low birth weight
NBW—normal birth weight
FSIQ—full-scale IQ
VIQ—verbal IQ
PIQ—performance IQ
CI—confidence interval
OR—odds ratio
aOR—adjusted odds ratio
INTRODUCTION: Late-preterm birth (34–36 weeks’ gestation) has
been associated witharisk for long-termcognitiveand socioemotional
problems. However, many studies have not incorporated measures of
important contributors to these outcomes, and it is unclear whether
effects attributed togestational ageareseparate from fetal growth or
its proxy, birth weight for gestational age.
www.pediatrics.org/cgi/doi/10.1542/peds.2010-1536
METHOD: Data came from a study of low- and normal-weight births
sampled from urban and suburban settings between 1983 and 1985
(low birth weight, n 473; normal birth weight; n 350). Random
sampling was used to pair singletons born late-preterm with a term
counterpart whosebirth weight zscore was within 0.1SDof his or her
PEDIATRICS (ISSNNumbers: Print, 0031-4005; Online, 1098-4275).
doi:10.1542/peds.2010-1536
Accepted for publication Aug 12, 2010
Address correspondence to Nicole M. Talge, PhD, Department of
Epidemiology, Michigan State University, B601 West Fee Hall, East
Lansing, MI 48824. E-mail: ntalge@epi.msu.edu.
Copyright © 2010 by the American Academy of Pediatrics
Chan E, et al. Arch Dis Child Fetal Neonatal Ed 2014
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
Funded by the National Institutes of Health (NIH).
1. Background: impaired outcomes
“...it is important to know whether the impaired outcomes seen
in this group represent a clear decrease in the means
of normally distributed scores…”
Neil Marlow Arch Dis Child Fetal Neonatal Ed 2014
1. Background: impaired outcomes
“...it is important to know whether the impaired outcomes seen
in this group represent a clear decrease in the means
of normally distributed scores…”
Neuordev
Academic
outcomes
Term
Neil Marlow Arch Dis Child Fetal Neonatal Ed 2014
Gestational age
1. Background: impaired outcomes
“…or whether it represents a small number
with OVERT BRAIN INJURIES among a group
with normal potential …”
Neil Marlow Arch Dis Child Fetal Neonatal Ed 2014
2. Background: the vulnerability of the late preterm BRAIN
• Although more mature than very preterm infants, their brain is still
immature, and can be damaged under adverse conditions.
• A five-fold increase in white matter volume occurs between 35 and 41
weeks of gestation.
• Structural maturation during late preterm gestations include,
increasing in neuronal connectivity, dendritic arborization and
connectivity; increasing in synaptic junctions; and maturation
neurochemical and enzymatic processes augmenting growth and
maturation of the brain.
Kinney H Seminars Perinatol 2006
2. Background: the vulnerability of the late preterm BRAIN
Sannia A, Fumagalli M, Ramenghi LA
J Matern Fetal Neonatal Med, 2013
Late preterm period
2. Background: the vulnerability of the late preterm BRAIN
2. Background: the vulnerability of the late preterm BRAIN
Lesions can be clinically subtle or silent
in the neonatal period
3. Background: the “burden of late preterm infants”
Distribution of preterm births by gestational age
…A universal
screening program in
the late preterm
population
represents a heavy
burden !
How to identify high-risk subgroups for impaired
neurodevelopmental outcome among the large population of
late preterm infants
in order to develop effective monitoring and
early intervention strategies
?
Study aim
Cranial ultrasound screening
to describe the pattern of cUS
abnormalities in the late preterm
population and to define the
potential need for cUS according to
perinatal risk factors
Study aim
Cranial ultrasound screening
To identify …
”…those babies who are more likely to develop
BRAIN ABNORMALITIES at cUS…”
MRI: not only pretty pictures !
Fig3 DEHSI grade 2
No significant corre
values and the DQ
threshold for the
identified.
Griffiths scale score at
36 months!
DQ3!
Locomotor!
Personal Social!
Hearing/language !
Eye/hand Coordination!
Performance!
Reasoning!
Mean
mm
The developing brain in VLBW infants…and cranial US
26 weeks
28 weeks CA
33 weeks CA
30 weeks CA
Term CA
Mastoid window
sett età corretta
Cranial ultrasound screening: does it make sense?
1st cUS
2nd cUS
0-7 days
28-35 days
Birth 34+0-36+6
Term age
Early neonatal morbidities
Fumagalli M Ramenghi L Bassi L De Carli A Sirgiovanni I Mosca F
Cranial ultrasound screening: does it make sense?
Characteristics of the study population
Early neonatal morbidities
Early neonatal morbidities
N (%)
Transient Tachypnea
25 (2.1)
nCPAP
102 (8.7)
INSURE
19 (1.6)
Mechanical Ventilation
45 (3.8)
Hypoglycaemia
22 (1.8)
HIE
3 (0.2)
Congenital malformation
34 (3)
NEC
3 (0.2)
Sepsis
0
cUS abnormalities
Normal
Mild abnormalities
Germinolytic cysts, mild ventricular dilatation
(<95° pct) cyst of chorioid plexus,
lenticulostriate vasculopathy
Periventricular hyperechogenicity (PHE)
when isoechogenic/
hyperechogenic
to the choroid plexus
Severe abnormalities
germinal matrix-intraventricular haemorrhage
(GHM-IVH), cystic periventricular leukomalacia,
cPVL, venous or arterial stroke and
malformations.
Changes in the incidence of cUS findings between 1st and 2nd cUS
N babies
1st cUS
2nd cUS
Periventricular
Hyperechogenicity
Periventricular hyperechogenicity (PHE)…flaring…echodensities…
• It is a common finding in preterm infants
in the first week of life and it is more
pronounced with declining GA
• It can be either pathological (pre-cystic
phase of PVL) or transient (related to
increased water content) and not
resulting in a definite lesion
• Pathological prolonged flaring is defined by a duration of 14 days or more
according to Dammann and Leviton
DevMed Child Neurol. 1997
Univariate logistic regression for variables
PHE + severe cUS abnormalities at 2° scan
Univariate logistic regression for variables
PHE + severe cUS abnormalities at 2° scan
Fumagalli M Ramenghi L Bassi L De Carli A Mosca F (manuscript in preparation)
Univariate logistic regression for variables
PHE + severe cUS abnormalities at 2° scan
Fumagalli M Ramenghi L Bassi L De Carli A Mosca F (manuscript in preparation)
Univariate logistic regression for variables
PHE + severe cUS abnormalities at 2° scan
Fumagalli M Ramenghi L Bassi L De Carli A Mosca F (manuscript in preparation)
Rate of severe abnormalities /PHE at 5 weeks through GA and comorbidities
OR
babies
6%
GA 34 weeks
1
GA 35 weeks
0.54
GA 36 weeks
0.25
5%
4%
comorbidity
3%
without
comorbidity
2%
1%
0%
34 wks
35 wks
36 wks
0.60
0.40
0.20
Reference line
GA, Apgar<=5 at 5', comorbidity
0.00
Sensitivity
0.80
1.00
Prediction of unfavorable cranial US at term corrected-age
plus cUS at birth
0.00
0.20
0.40
0.60
1 - Specificity
0.80
1.00
Model with GA, Apgar<=5 at 5', comorbidity: AUC=74.6%
Model with GA, Apgar<=5 at 5', comorbidity, cUS at birth: AUC=89.4%
…to identify high-risk subgroups for abnomal cUS among the
late preterm population…according to perinatal risk factors…
38
…to identify high-risk subgroups for abnomal cUS among the
late preterm population…
Indication to cUS
• Gestational age at birth and the occurrence of early neonatal
comorbitidies are the most important risk factors to develop brain
abnormalities detected by cUS
• The combination of being born at 34 weeks gestation and the
occurrence of RDS represents the strongest indication to perform a cUS
scan
40
Optimizing timing of cUS
1° cranial ultrasound (within the first week of life) can detect
severe cUS abnormalities with 72% Sensitivity and 82% Specificity
Periventricular hyperechogenicity at 1st cUS resolve in 91.3% of
cases at term age.
The indication to perform a cUS in a LP infant should be
modulated according to GA and the severity of the
postnatal course
Thanks to…
The Neuroradiologists
Luca Ramenghi
IGG Genova
Laura Bassi
Alessandra Ometto
Ida Sirgiovanni
Agnese De Carli
Francesca Dessimone
Michela Groppo
Silvia Pisoni
Sofia Passera
Dr Fabio Triulzi
Dr Claudia Cinnante
Dr Sabrina Avignone
Dr Elisa Scola