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Alcohol consumption among
pregnant women in Barcelona
(Spain)
Oriol Vall
Paediatrics Unit, URIE, Neuropsychopharmacology Program
IMIM-Hospital del Mar
Barcelona
Alcohol and Pregnancy Conference
Brussels, 9 September 2009
Migrants
Ciutat Vella
Addicts
Barceloneta
Middle social class Gipsies
Vila Olimpica
H
La Mina
Our reality: Hospital del Mar
1.700 deliveries /yr
2.000 total paediatric admitions/yr
10.000 outpatients /yr
15.000 paediatric emergencies/yr
It is high the addiction among the
mothers of maternity ward
Analyzed substances
Tobacco
Opioids and opiates (heroin, methadone)
Cannabis
Cocaine
MDMA (Extasis)
Alcohol
Areca nut
Mate
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Plan Nacional de Drogas (2006) *
(Drugs Abuse National Plan)
General population between 15 and 64 years (by questionnaire):
35.1 %
tobacco
15.3 %
alcohol
6.5 %
cannabis
1.4 %
cocaine
0.6 %
amphetamines
Questionnaire and biomarkers
Drugs of abuse:
Biological matrices for
evaluation of prenatal exposure
to drugs of abuse
 Meconium
 Hair
 Teeth
 Placenta
 Cord blood
 Human milk
Ther Drug Monit 2007 Dec;29(6):711-34.
Advantages:
alternative bilogical matrices
 Non invasive collection
 Easy sample collection
 Wider time window for substance detection
 No degradation
Some results published in medical journals
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[Prenatal exposure to drugs of abuse using meconium analysis in a low
socioeconomic population in Barcelona]
[Article in Spanish]
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In 353 meconium samples analyzed for detection of FAEEs,
159 (45%) showed results  2 nmol/g meconium
2 nmol/g meconium:
reference value internationally considered for distinguishing
during the pergnancy an alcohol important maternal
consumption, from not consumption at all
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Prevalence of pregnant chronical consumers y
gestantes with meconio as biomarcaker:
Women Hawai:
16% (*)
Women Canadá:
22% (**)
Women Hosp. del Mar: 45%
(*)
Moore C,Jones J, Lewis D, Buchi K. Prevalence of fatty acid ethyl
esters in meconium specimens. Clin Chem. 2003;49:133-136.
(**) Chan D, Klein J, Karaskov T, Koren G. Fetal exposure to alcohol as
evidenced by fatty acid athyl esters in meconium in absence of
maternal drinking history in pregnancy. Ther Drug Monit 2004;
26:474-481.
Is the positive FAEEs more feasible on
polyconsumers pregnant women or addicted only to
alcohol?
- Positive Drug abuse and Positive FAAEs (45.7%)
- Negative Drug abuse and Positive FAAEs (44.7%)
Technicaly, ¿ How do we get the biomarkers ?
 FAEEs*: Liquid chromatography tandem mass spectrometry
(LC/MS/MS)
 Ethyl Glucoronide (EtG): Immuno assay or GC/MS or LC/MS
 Ethyl Sulphate (EtS): Immuno assay or GC/MS or LC/MS
 But!! FAEEs versus EtG/EtS: NO correlation
*FAEEs: Faty Acid Esters
ETHYLGLUCURONIDE AND ETHYLSULFATE IN MECONIUM:
NEW BIOMARKERS OF GESTATIONAL ETHANOL EXPOSURE?
Papaseit E*, Joya X*, Pichini S**, Garcí
García Algar O*, Morini L***, Vagnarelli F****,
Vall O* and de la Torre R*.
(*) Institut Municipal d’Investigació
Investigació Mèdicadica- Neuropsychopharmacology Programme,
Programme, Barcelona, Spain.
(**) Istituto Superiore di Sanità
Sanità, Rome, Italy.
(***) Department of Legal Medicine and Public Health,
Health, University of Pavia, Italy.
Italy.
[email protected]
(****) Arcispedale Santa Maria Nuova,
Nuova, Reggio Emilia, Italy.
Objectives: To investigate: (1) the presence and the
concentration of EtG and EtS in meconium from two
different European newborn cohorts and (2) the eventual
correlation between these two biomarkers and FAEEs
from the same meconium samples.
Material and methods: Liquid
chromatography tandem mass spectrometry
was applied to measure EtG, EtS and FAEE
in meconium samples obtained from Reggio
Emilia, Italy (n=60) and from Barcelona,
Spain (n=50).
Similar
sociodemographic
and
ethnic
characteristics
LOQ for EtS in meconium samples:
1 ng/g
LOQ for EtG in meconium samples:
5 ng/g
Results and Discussion
Prevalence of fetal alcohol exposure
MECONIUM ANALYSIS in 50 samples of Barcelona
Meconium analysis disclosed:
24 samples FAEE>2nmol/g sample and 26 FAEE<2nmol/g.
MECONIUM ANALYSIS in 60 samples of Reggio Emilia
Meconium analysis revealed:
59 FAEE<2nmol/g of 60 total samples.
1.000,00
6,00
EtG
mean
45% ethanol consumption during pregnancy
in accordance with previous studies*.
studies*.
*Garcia-Algar O, Kulaga V, Gareri J, Koren G, Vall O, Zuccaro P, Pacifici R, Pichini S.
Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther Drug
Monit. 2008 Apr;30(2):249-54.
The preliminary results showed values of EtG
in meconium samples from Reggio Emilia
were statistically lower than those from
Barcelona specimens, similarly to what
happen with FAEEs.
EtS
mean
EtG ng/g
5,00
800,00
Barras 2
Barras 1
4,00
600,00
0
100
200
300
400
500
3,00
400,00
EtS ng/g
2,00
200,00
1,00
0,00
0,00
FAEE<2
FAEE MENOR 2
FAEE>2
FAEE<2
FAEE MAYOR 2
FAEE MENOR 2
FAEE>2
FAEE MAYOR 2
Fatty acid ethyl
esters (nmol/g)
0
0,5
1
1,5
2
2,5
3
3,5
4
Barcelona
Reggio Emilia
When considering only Barcelona samples with FAEEs
below 2 nmol/g, values of EtG that were still different in
the two cohorts. Conversely, EtS values were similar when
comparing the whole samples from the two city cohorts
and also RE samples with those from BCN with FAEEs
below 2 nmol/g.
EtG and EtS values did not correlate with total
amount of the seven FAEEs in both Reggio Emilia
and Barcelona meconium samples. This could be due
to the different mechanism of formation of these
metabolites.
The preliminary results of our study evidence for first time the presence of EtG and EtS in
meconium. Further investigations are ongoing to verify the use of these two ethanol metabolites
as alternative biomarkers of chronic in utero exposure to alcohol.
600
In summary
 FAEEs in meconium are the best markers in fetal ethanol
exposure diagnosis so far
 FAEEs in hair could be useful as well, but further studies are
needed
 EtG and EtS have been recently detected and quantified in
meconium. Evaluation of a possible cutoff is the next step
 The sensitivity and specificity of EtG in hair is well-known
and the determination of this metabolite in pregnant
women’s hair could be very useful in the diagnosis of
gestational ethanol exposure
Remember……
FASD* is 100% preventable
Neonatal screening for
prenatal alcohol exposure
Lead to
An alternative: Harm Reduction
approach to treat the mother, her
child, and her future pregnancies
* Fetal Alcohol Spectrum Disorder
Alcohol: newborns
 FASD*: FAS, Partial FAS (PFAS), Alcohol-Related birth defects (ARBD),
Alcohol-Related Neurodevelopment Disorder (ARND)
Facial dysmorphology
Growth retardation
CNS development abnormalities
 FASD is very infrequent as a diagnostic in our hospitals despite of the
high prenatal alcohol exposure
 Why? Maybe:
 Health care workers not trained.
 Adverse effects not identified or recognized (ADHD, school failure, etc.)
 Depend of differents habits of consumption?
* Fetal Alcohol Spectrum Disorders
Alcohol: newborns
• Ethanol is the main known teratogen
• Specially affects the neurodevelopment and has
negative cognitive effects
• Brain damage can not be repared...
• But an adequate follow up can achieve the best
possible neurodevelopment
Toronto (Canada): MOTHERISK
 Detection
 Follow up
 Intervention
Main objectives
To design and to implement a prenatal diagnosis and a neonatal
screening protocols of prenatal ethanol exposure
To design an intervention program:
- Consumption prevention (clinical guidelines)
- Diagnosis (biomarkers)
- Intervention (structured counseling)
- Follow up (clinical protocol): “Pregnancy Without Alcohol”
To check the effectiveness of the intervention
To follow up of children prenatally exposed to ethanol
Translational research and Integrate several areas
Health Education
Social problems
Addiction
Clinical Atenttion
Public Health
Resources
The Proposal
Is to work in conection with other clinicicians and
researchers groups in order to improve:
Coordination
Exchenge information and
Implementation
Towards decreased risks for
the fetus and the mother...
Also decreased the risks for the adolescents…
¡¡Botellones!!
And… by the time
a person reaches adult life
RR and 95% CI
associated with
alcohol intake
lower than
25g/day
Corrao G, Bagnardi V, Zambon A, la Vecchia C. A meta-analysis of alcohol consumption and
the risk of 15 diseases. Prev Med 2004,38:613-9.