Ethyl Linoleate in Meconium: A Biomarker for Prenatal Ethanol Exposure

Bearer, Cynthia F.; Lee, Siemay; Salvator, Ann; Minnes, Sonia; Swick, Alan R.; Yamashita, Toyoko S.; Singer, Lynn T.

doi:10.1111/j.1530-0277.1999.tb04142.x

Cited by 79 publications

(73 citation statements)

References 28 publications

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“…Prior research on a broad range of xenobiotics indicates that metabolites of compounds to which the fetus has been exposed can be detected in meconium. These include metabolites of illicit drugs (25)(26)(27)(28)(29)(30)(31)(32) , nicotine (33), alcohol (34), analgesics, antihistamines, anesthetics, the food additive butylated hydroxytoluene (BHT), and heavy metals (26). One study has also measured pesticide levels in meconium (26).…”

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confidence: 99%

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Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

Whyatt

Barr

2001

Environ Health Perspect

144

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Experimental data have linked exposure to prenatal organophosphates to adverse neurocognitive sequalae. However, epidemiologic research has been hampered by lack of reliable dosimeters. Existing biomarkers reflect short-term exposure only. Measurements of pesticides in postpartum meconium may yield a longer-term dosimeter of prenatal exposure. As the initial step in biomarker validation, this research determined background levels, detection limits, and stabilities of six organophosphate metabolites in meconium: diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), dimethylphosphate (DMP), dimethylthiophosphate (DMTP), and dimethyldithiophosphate (DMDTP). Calibration curves were also constructed. The meconium was collected from 20 newborns at New York Presbyterian Hospital; analyses were undertaken at the Centers for Disease Control and Prevention (CDC). DEP was detected in 19/20 samples (range 0.8-3.2 microg/g) and DETP was detected in 20/20 (range 2.0-5.6 microg/g). DMP and DEDTP were each detected in 1/20 (at 16 and 1.8 microg/g, respectively). DMTP and DMDTP were not detected. Detection limits were comparable to or lower than those in urine; levels were similar to those seen in adult urine in population-based research. Metabolites were stable at room temperature over 12 hr. Calibration curves were linear over the range tested (0.5-400 microg/g); recoveries ranged from 18% to 66%. Using isotope dilution, recoveries of each analyte in individual samples can be corrected automatically based on the recovery of the respective stable isotope-labeled analogue, making this method fully quantitative. Results indicate that measurements of organophosphate metabolites in meconium have promise as biomarkers of prenatal exposure. Further research is needed to determine the time frame of exposure represented by pesticide levels in meconium and to evaluate the dose-response relationship.

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confidence: 99%

“…The authors reasoned that the drugs reached the fetal circulation by absorption across the umbilical cord or diffusion across the placental surface. Evidence suggests that the half-life of xenobiotics in meconium can be protracted and that measured levels may reflect exposures from the second trimester of pregnancy through delivery (26,28,34,35,37).…”

mentioning

confidence: 99%

Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

Whyatt

Barr

2001

Environ Health Perspect

144

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“…Fatty acid ethyl esters (FAEE) are non-oxidative metabolites formed via the breakdown of ethanol. These metabolites have been established as biomarkers of chronic excessive alcohol use in adults (Auwarter et al 2001;Pragst et al 2001) and in-utero exposure to alcohol (Bearer et al 1992(Bearer et al , 1999Hungund and Gokhale 1994;Klein et al 1999;Caprara et al 2005). FAEE have also been established as mediators of toxicity, because they have been demonstrated to reduce cell proliferation, uncouple oxidative phosphorylation, increase the fragility of lysosomes, decrease protein synthesis, increase the formation of lipid droplets, and incorporate into organic bilayers leading to their disordering Best and Laposata 2003).…”

Section: Other Mechanisms Of Alcohol Teratogenesismentioning

confidence: 99%

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

Kapur

Baber

2018

Biochem. Cell Biol.

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Alcohol consumption during pregnancy remains a significant cause of preventable birth defects and developmental disabilities; however, the mechanism of toxicity remains unclear. Methanol is present as a congener in many alcoholic beverages and is formed endogenously. Because ethanol is preferentially metabolized over methanol, it has been found in the sera and cerebro-spinal fluid of alcoholics. Toxicity resulting from methanol has been attributed to formic acid. Formic acid is present in significantly higher quantities in the biofluids of alcoholics. These higher levels can be cytotoxic and cause neuronal cell death. However, the adverse effects can be mitigated by adequate levels of hepatic folic acid, because formic acid elimination depends on folic acid. During pregnancy, folate concentrations are at least 2-fold higher in cord blood then in maternal blood, owing to increased folate requirements. The reverse has been demonstrated in pregnancies with alcohol abuse, suggesting downregulation of folate transporters and low fetal folate levels. Moreover, formic acid can cross the placenta and its adverse effects can be mitigated by folic acid. Thus, the combination of low fetal folate levels and presence of formic acid form a potent cytotoxic combination that may play a significant role in the etiology of fetal alcohol spectrum disorder.Key words: formic acid, methanol, folic acid, FASD, neurotoxicity.Résumé : La consommation d'alcool pendant la grossesse demeure une cause significative de déficiences congénitales et développementales évitables, mais le mécanisme responsable de sa toxicité est encore flou. Le méthanol est présent comme congénère dans plusieurs boissons alcooliques et il est formé de manière endogène. Puisque l'éthanol est préférentiellement métabolisé par rapport au méthanol, ce dernier a été trouvé dans le sérum et le liquide céphalorachidien des personnes alcooliques. La toxicité résultant du méthanol a été attribuée à l'acide formique. L'acide formique est présent en quantité significativement plus élevée dans les liquides biologiques des patients alcooliques. Ces niveaux plus élevés peuvent être cytotoxiques et causer la mort neuronale. Cependant, ces effets nocifs peuvent être atténués par des niveaux appropriés d'acide folique hépatique, car l'élimination d'acide formique dépend de l'acide folique. Durant la grossesse, les concentrations de folate sont au moins deux fois plus élevées dans le cordon ombilical que dans le sang maternel à cause des besoins accrus en folate. L'inverse a été démontré chez les femmes enceintes qui abusent d'alcool, suggérant une régulation à la baisse des transporteurs du folate et de faibles niveaux foetaux de folate. En outre, l'acide formique peut traverser le placenta et ses effets nocifs peuvent être atténués par l'acide folique. Ainsi, de faibles niveaux foetaux de folate et la présence d'acide formique forment une combinaison cytotoxique puissante qui peut jouer un rôle significatif dans l'étiologie de troubles du spectre de l'alcoolisation foet...

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“…Products of the nonoxidative metabolism of ethanol, FAEEs can be detected in the alcoholexposed infant's meconium, blood, cord blood, hair, and placenta. The sensitivity of FAEEs extracted from meconium has been found to vary widely [44][45][46][47][48], partly because of differences in study populations. Ostrea et al [49] analyzed FAEEs in the meconium of 124 singleton infants and concluded that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for exposure to alcohol prenatally.…”

Section: Biomarkers Of Fasdmentioning

confidence: 99%

Identification of Children With Prenatal Alcohol Exposure

Coriale¹,

Fiorentino²,

Kodituwakku

et al. 2014

Curr Dev Disord Rep

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The term "fetal alcohol spectrum disorders" (FASD) denotes the broad spectrum of morphological changes and functional deficits seen in children exposed to alcohol prenatally. While some children on the spectrum show the characteristic pattern of malformations called "fetal alcohol syndrome" (FAS), a significant proportion of alcohol-exposed children do not evidence clinically identifiable morphological alterations. The term "alcohol-related neurodevelopmental disorder" (ARND) is used to label the latter group. The identification of children with ARND has proven to be challenging because of the lack of clinically discernable physical signs. Therefore, some investigators have used the strategy of assessing maternal drinking during pregnancy and then tracking developmental outcomes in offspring longitudinally. Other methods that investigators have utilized to identify children with prenatal alcohol exposure in population-based studies include multi-source surveillance and active case ascertainment. In the current review, we discuss the merits and demerits of these methodologies and then present novel methods of identifying prenatal alcohol exposure (e.g., biomarkers) and subtle effects of morphological alterations and neural effects (e.g., neuroimaging).

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Ethyl Linoleate in Meconium: A Biomarker for Prenatal Ethanol Exposure

Cited by 79 publications

References 28 publications

Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

Identification of Children With Prenatal Alcohol Exposure

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