Alcohol consumption among pregnant women in Barcelona

(Spain)

Alcohol and Pregnancy ConferenceBrussels, 9 September 2009

Oriol Vall

Paediatrics Unit, URIE, Neuropsychopharmacology ProgramIMIM-Hospital del Mar

Barcelona

Migrants Addicts Middle social class Gipsies

Ciutat Vella Barceloneta Vila Olimpica La Mina

H

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

Here comes your footer Page 4

Tobacco

Opioids and opiates (heroin, methadone)

Cannabis

Cocaine

MDMA (Extasis)

Alcohol

Areca nut

Mate

Analyzed substances

Plan Nacional de Drogas (2006) *(Drugs Abuse National Plan)

35.1 % tobacco

15.3 % alcohol

6.5 % cannabis

1.4 % cocaine

0.6 % amphetamines

General population between 15 and 64 years (by questionnaire):

Questionnaire and biomarkers

Drugs of abuse:

Meconium Hair Teeth Placenta Cord blood Human milk

Biological matrices for evaluation of prenatal exposure to drugs of abuse

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

Here comes your footer Page 10

Here comes your footer Page 11

[Prenatal exposure to drugs of abuse using meconium analysis in a low socioeconomic population in Barcelona]

[Article in Spanish]

Here comes your footer Page 12

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

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.

- Positive Drug abuse and Positive FAAEs (45.7%)

- Negative Drug abuse and Positive FAAEs (44.7%)

Is the positive FAEEs more feasible on polyconsumers pregnant women or addicted only to alcohol?

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

Technicaly, ¿ How do we get the biomarkers ?

*FAEEs: Faty Acid Esters

PapaseitPapaseit E* , E* , J oyaJ oya X* , Pichini S* * , X* , Pichini S* * , GarcGarcííaa AlgarAlgar O* , O* , MoriniMorini L* * * ,L* * * , VagnarelliVagnarelli F* * * * , F* * * * , Vall O* and Vall O* and de la Torre R* .de la Torre R* .(* ) (* ) I nstitutI nstitut Municipal Municipal dd’’I nvestigaciI nvestigacióó MMèèdicadica-- NeuropsychopharmacologyNeuropsychopharmacology ProgrammeProgramme, Barcelona, Spain., Barcelona, Spain.(* * ) (* * ) I stitutoI stituto SuperioreSuperiore didi SanitSanitàà, Rome, I taly., Rome, I taly.(* * * ) (* * * ) DepartmentDepartment of of LegalLegal Medicine and Public Medicine and Public HealthHealth, University of Pavia, , University of Pavia, I talyI taly..(* * * * ) (* * * * ) ArcispedaleArcispedale Santa Maria Santa Maria NuovaNuova, Reggio Emilia, I taly., Reggio Emilia, I taly.

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.

ETHYLGLUCURONIDE AND ETHYLSULFATE IN MECONIUM: ETHYLGLUCURONIDE AND ETHYLSULFATE IN MECONIUM: NEW BIOMARKERS OF GESTATIONAL ETHANOL EXPOSURE?NEW BIOMARKERS OF GESTATIONAL ETHANOL EXPOSURE?

Results and Discussion

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, I taly (n=60) and from Barcelona, Spain (n=50).

LOQ for EtS in meconium samples:1 ng/ g

LOQ for EtG in meconium samples:5 ng/ g

MECONI UM ANALYSI S in 60 samples of Reggio EmiliaMeconium analysis revealed:59 FAEE<2nmol/ g of 60 total samples.

MECONI UM ANALYSI S in 50 samples of BarcelonaMeconium analysis disclosed:24 samples FAEE>2nmol/ g sample and 26 FAEE<2nmol/ g.

simona.pichini@iss.itsimona.pichini@iss.it

FAEE MENOR 2 FAEE MAYOR 2

0,00

1,00

2,00

3,00

4,00

5,00

6,00

FAEE MENOR 2 FAEE MAYOR 2

0,00

200,00

400,00

600,00

800,00

1.000,00

FAEE>2

EtGmean

EtSmean

Fatty acid ethylesters (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 showed values of EtGin meconium samples from Reggio Emilia were statistically lower than those from Barcelona specimens, similarly to what

happen with FAEEs.

Prevalence of fetal alcohol exposure

45% 45% ethanolethanol consumptionconsumption duringduring pregnancypregnancy

in in accordanceaccordance withwith previousprevious studiesstudies* .* .*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 DrugMonit. 2008 Apr;30(2):249-54.

0 100 200 300 400 500 600

0 0,5 1 1,5 2 2,5 3 3,5 4

Barras 2Barras 1

EtG ng/ g

FAEE>2 FAEE<2FAEE<2

BarcelonaBarcelona

ReggioReggio EmiliaEmilia

Similar sociodemographic

and ethnic

characteristics

EtS ng/ g

When considering only Barcelona samples with FAEEsbelow 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.

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

An alternative: Harm Reduction approach to treat the mother, her child, and her future pregnancies

Neonatal screening for prenatal alcohol exposure

Remember……

FASD* is 100% preventable

Lead to

* 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

• 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

Alcohol: newborns

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

Social problemsAddiction

Clinical AtenttionHealth Education

Public HealthResources

Is to work in conection with other clinicicians and researchers groups in order to improve:

Coordination

Exchenge information and

Implementation

The Proposal

Towards decreased risks for

the fetus and the mother...

Also decreased the risks for the adolescents…

¡¡Botellones!!

And… by the timea person reaches adult life

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.

RR and 95% CI associated with alcohol intakelower than 25g/day