Review
Determination of maternal-fetal biomarkers of prenatal exposure to ethanol: A review

https://doi.org/10.1016/j.jpba.2012.01.006Get rights and content

Abstract

The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioural and/or learning disabilities that are included in the term fetal alcohol spectrum disorder (FASD). Objective assessment of exposure to ethanol at both prenatal and postnatal stages is essential for early prevention and intervention. Since pregnant women tend to underreport alcohol drinking by questionnaires, a number of biological markers have been proposed and evaluated for their capability to highlight gestational drinking behaviour. These biomarkers include classical biomarkers (albeit indirect) of alcohol-induced pathology (mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) acetaldehyde-derived conjugates, and finally derivatives of non-oxidative ethanol metabolism (fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphaditylethanol (PEth)). Since ethanol itself and acetaldehyde are only measured few hours after ethanol intake in conventional matrices such as blood, urine and sweat, they are only useful to detect recent ethanol exposure. In the past few years, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and in some case wide time-window of detection in non-conventional matrices from the pregnant mother (oral fluid and hair) and fetus-newborn (neonatal hair, meconium, placenta and umbilical cord). This article reviews bioanalytical procedures for the determination of these markers of ethanol consumption during pregnancy and related prenatal exposure. In addition, clinical toxicological applications of these procedures are presented and discussed.

Highlights

► A complete review of assay methods to determine maternal-fetal biomarkers of prenatal exposure to ethanol is presented. ► Methods to determine derivatives of non-oxidative ethanol metabolism in maternal and neonatal biological matrices are reported. ► Assays for classical biomarkers of alcohol-induced are also included.

Introduction

Alcohol is the most popular legal drug used in our times, and its consumption by women of reproductive age remains a significant public health concern. The adverse effects of drinking in pregnancy have been well documented. Gestational alcohol use can result in a continuum of adverse fetal outcomes known as fetal alcohol spectrum disorder (FASD) [1], which encompasses distinctive craniofacial dysmorphology, growth retardation, and neurodevelopmental and cognitive deficits [2]. FASD may be as prevalent as 1% of live births and the affected person has increased risk for a wide range of mental disorders and social impairments over the entire lifespan [3]. Moreover, FASD is one of the most recurrent and at the same time easily preventable developmental disorder [4].

Another aspect to consider is the cost of caring for children and adults with FASD. In North Dakota, the mean annual cost of health care for a child with FAS from birth through 21 years of age was $2,342 more compared to a child without FAS [5]. Current cost includes health care, foster care, treatment for developmental disabilities, early intervention programs, special education, mental health, substance abuse treatment, for the most affected persons care for their entire adult life, and the cost of the corrections system including juvenile justice [6].

Currently, detection of prenatal alcohol exposure is based on maternal report, or suspicion of it based on history (lack of prenatal care, alcohol related life events, abuse, and alcohol impaired driving infractions). Until know, the only tools to obtain information about prenatal alcohol exposure have been questionnaires and interviews of the mother [7]. However, one of the major disadvantages of self-reports is that women tend to underreport the amount and frequency of their alcohol intake and they are reluctant to reveal gestational alcohol use, because the stigma and fear of punishment [8].

Thus, due to the difficulty in assessing alcohol-drinking behaviour from an objective point of view, in the last decades a number of biological markers considered far more reliable for documenting ethanol use have been introduced and validated. These biomarkers include direct measurements of ethanol and measurements of the products of oxidative and non-oxidative ethanol metabolism (Fig. 1).

We report on the “state of the art” of the methodology for testing maternal and fetal biomarkers of prenatal exposure to ethanol. The analytical procedures are summarized in Table 1.

Section snippets

Indirect maternal biomarkers

The clinical parameters used routinely for diagnosis of chronically high alcohol use are indirect markers, such as the liver enzymes gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), mean corpuscular erythrocyte volume (MCV), or carbohydrate-deficient transferrine (CDT). Moreover, there are also certain low-molecular-weight indirect markers, such as the plasma ratio of 5-hydroxytryptophol/5-hydroxyindolylacetic acid (5-HTOL/5-HIAA) which changes

Direct biomarkers

Direct alcohol markers are chemically derived from the ethanol molecule and contain still the two carbon atoms of ethanol. These are ethanol itself or metabolites of ethanol such as fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), or phosphaditylethanol (PEth). Concerning ethanol itself, it is usually measured in breath and blood, although to detect only very recent single drinking occasion and thus useless to eventually assess gestational use and consequent prenatal exposure to this

Conclusions and perspectives

The fetal, neonatal and maternal matrices are, to different extent, repositories of substances, among them ethanol and its biomarkers to which the fetus is exposed in utero.

Therefore the accurate assessment of fetal exposure to ethanol through the use of these objective biomarkers, could be of major importance since it provides the basis for appropriate treatment and adequate follow-up of exposed newborns. Whereas indirect maternal biomarkers are only indicative of chronic maternal alcohol use

Acknowledgement

This study was supported by a grant of the Plan Nacional Sobre Drogas (2008/085) from the Ministerio de Sanidad y Consumo (Spain).

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