Metabolic and genetic factors contributing to alcohol induced effects and fetal alcohol syndrome

Gemma, Simonetta; Vichi, Susanna; Testai, Emanuela

doi:10.1016/j.neubiorev.2006.06.018

Cited by 53 publications

(60 citation statements)

References 44 publications

(54 reference statements)

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“…The enzyme alcohol dehydrogenase (ADH) metabolizes ethanol to acetaldehyde and accounts for 90-95% of the metabolism by the liver. 12,13 In a controlled field drinking trial mothers of children with FAS were found to drink faster, get drunk quicker, obtain higher BACs and to have an increased prevalence of an ADH polymorphism. The mothers also weighed less and had more children.…”

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

“…The studies suggest that the ADH2*2 allele in either the mother or the fetus may have a protective effect. 13 The remaining 5-10% of liver oxidation is catalyzed by Cytochrome P450 enzymes, most notably by CYP2E1, in a microsomal system. 12,13 When the ADH enzymes are saturated ethanol exposure increases CYP2E1 metabolism by four to 10-fold.…”

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

“…18 In the presence of chronic exposure CYP2E1 is likely related to the development of tolerance observed in people with chronic alcohol abuse. 13,15 Placental CYPE2E1 is inducible by ethanol exposure and has a higher affinity for ethanol than placental ADH. Although induction by PAE is variable, CYP2E1 may have important roles in placental pathways influencing fetal susceptibility to PAE.…”

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

“…Although induction by PAE is variable, CYP2E1 may have important roles in placental pathways influencing fetal susceptibility to PAE. 13,16 …”

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

“…Cutaneous elimination is usually small (0.1%) and can be impacted by hydration status and activity level. 13,17 The percent of ethanol eliminated through pulmonary excretions in an adult ranges from 0.7 to 3% at low ethanol concentrations and 6 to 8% at higher concentrations; elimination by renal excretion is between 0.3 to 10%. 13,17 Transfer of ethanol across the placenta The dispersion of alcohol through the placenta into the fetal compartment is the initial pathway of PAE.…”

Section: Bac and Aer For Mother Fetus And Newborn L Burd Et Almentioning

confidence: 99%

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Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

2012

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Fetal alcohol spectrum disorders (FASDs) are a common cause of intellectual impairment and birth defects. More recently, prenatal alcohol exposure (PAE) has been found to be a risk factor for fetal mortality, stillbirth and infant and child mortality. This has led to increased concern about detection and management of PAE. One to 2 h after maternal ingestion, fetal blood alcohol concentrations (BACs) reach levels nearly equivalent to maternal levels. Ethanol elimination by the fetus is impaired because of reduced metabolic capacity. Fetal exposure time is prolonged owing to the reuptake of amniotic-fluid containing ethanol by the fetus. Alcohol elimination from the fetus relies on the mother's metabolic capacity. Metabolic capacity among pregnant women varies eightfold (from 0.0025 to 0.02 g dl À1 h À1 ), which may help explain how similar amounts of ethanol consumption during pregnancy results in widely varying phenotypic presentations of FASD. At birth physiological changes alter the neonate's metabolic capacity and it rapidly rises to a mean value of 83.5% of the mother's capacity. FASDs are highly recurrent and younger siblings have increased risk. Detection of prenatal alcohol use offers an important opportunity for office-based interventions to decrease exposure for the remainder of pregnancy and identification of women who need substance abuse treatment. Mothers of children with FAS have been found to drink faster, get drunk quicker and to have higher BACs. A modest increase in the prevalence of a polymorphism of alcohol dehydrogenase, which increases susceptibility to adverse outcomes from PAE has been reported. Lastly, detection of alcohol use and appropriate management would decrease risk from PAE for subsequent pregnancies.

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Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

“…Although induction by PAE is variable, CYP2E1 may have important roles in placental pathways influencing fetal susceptibility to PAE. 13,16 …”

Section: Maternal Metabolism Of Ethanolmentioning

confidence: 99%

Section: Bac and Aer For Mother Fetus And Newborn L Burd Et Almentioning

confidence: 99%

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Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

2012

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Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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This review covers molecular mechanisms involving oxidative stress and DNA damage that may contribute to morphological and functional developmental disorders in animal models resulting from exposure to alcohol (ethanol, EtOH) in utero or in embryo culture. Components covered include: (a) a brief overview of EtOH metabolism and embryopathic mechanisms other than oxidative stress; (b) mechanisms within the embryo and fetal brain by which EtOH increases the formation of reactive oxygen species (ROS); (c) critical embryonic/fetal antioxidative enzymes and substrates that detoxify ROS; (d) mechanisms by which ROS can alter development, including ROS-mediated signal transduction and oxidative DNA damage, the latter of which leads to pathogenic genetic (mutations) and epigenetic changes; (e) pathways of DNA repair that mitigate the pathogenic effects of DNA damage; (f) related indirect mechanisms by which EtOH enhances risk, for example by enhancing the degradation of some DNA repair proteins; and, (g) embryonic/fetal pathways like NRF2 that regulate the levels of many of the above components. Particular attention is paid to studies in which chemical and/or genetic manipulation of the above mechanisms has been shown to alter the ability of EtOH to adversely affect development. Alterations in the above components are also discussed in terms of: (a) individual embryonic and fetal determinants of risk and (b) potential risk biomarkers and mitigating strategies. FASD risk is likely increased in progeny which/who are biochemically predisposed via genetic and/or environmental mechanisms, including enhanced pathways for ROS formation and/or deficient pathways for ROS detoxification or DNA repair.

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Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

Richardson

Browne

Rasmussen

et al. 2011

Birth Defects Research Part A: Clinical and Molecular Teratolog

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Metabolic and genetic factors contributing to alcohol induced effects and fetal alcohol syndrome

Cited by 53 publications

References 44 publications

Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn

Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

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