Ethylglucuronide and ethylsulfate in meconium to assess gestational ethanol exposure: preliminary results in two Mediterranean cohorts.
BACKGROUND
In recent years, fatty acid ethyl esters (FAEEs) in meconium emerged as reliable, direct biological markers for establishing gestational ethanol exposure. Among the minor nonoxidative products of ethanol metabolism, there are ethyl glucuronide (EtG) and ethyl sulfate (EtS).


OBJECTIVE
The aim of the study was to analyse meconium specimens from two different Mediterranean cohorts to check for the presence of EtG and EtS, and to investigate the eventual correlation between meconium FAEEs and these two metabolites and their possible application as direct biomarkers of gestational ethanol exposure.


METHODS
FAEEs, EtG and EtS were quantified by liquid chromatography tandem mass spectrometry in meconium samples obtained from the Neonatal Intensive Care Unit of Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (N= 96) and from the Pediatric Service of the Hospital del Mar in Barcelona, Spain (N=81).


RESULTS
EtG was present in more than 80% meconium samples while EtS only in 50% specimens Although the samples from Spain and Italy originated from similar socio-demographic cohort, EtG values in the Barcelona samples (median value: 101.5 ng/g) were statistically higher than those from Reggio Emilia ones (median value: 15.6 ng/g). In the Barcelona cohort, EtG values could differentiate between samples with FAEEs below and those equal or above 2 nmol/g - the cut-off used to differentiate heavy maternal ethanol consumption during pregnancy from occasional or no use.


CONCLUSIONS
For the first time the presence of EtG and EtS in meconium has been proven, with EtG concentration likely to discriminate heavy maternal ethanol consumption during pregnancy disclosed by FAEEs concentration in this matrix. Further investigations are needed to verify the use of these two ethanol metabolites as alternative biomarkers of chronic in utero exposure to ethanol.
Pichini
Simona
S
1Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanitá, V.le Regina Elena 299, 00161 Roma, Italy. simona.pichini@iss.it
Morini
Luca
L
Marchei
Emilia
E
Palmi
Ilaria
I
Rotolo
Maria Concetta
MC
Vagnarelli
Federica
F
Garcia-Algar
Oscar
O
Vall
Oriol
O
Zuccaro
Piergiorgio
P
D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism; D015415:Biomarkers; D002853:Chromatography, Liquid / Q000379:methods; D015331:Cohort Studies; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005965:Glucuronates / Q000032:analysis*; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D008297:Male; D008470:Meconium / Q000737:chemistry*; D019083:Mediterranean Region; D011247:Pregnancy; D013030:Spain; D015813:Substance Abuse Detection / Q000379:methods; D013463:Sulfuric Acid Esters / Q000032:analysis*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
D015415:Biomarkers; D005965:Glucuronates; D013463:Sulfuric Acid Esters; C093924:ethyl glucuronide; D000431:Ethanol; C011612:diethyl sulfate