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Prenatal choline supplements attenuate PAE-induced behavioral and growth deficits; however, the underlying mechanisms are unknown. Alcohol alters nutrient metabolism and potentially increases nutrient needs. Here, we investigate how alcohol affects choline metabolism in the maternal\u2013fetal dyad and the role of supplemental choline. Methods: Pregnant C57BL\/6J mice were assigned to one of four groups: alcohol-exposed (3 g\/kg alcohol\/day) or control +\/\u2212 100 mg\/kg choline daily from embryonic day (E)8.5\u201317.5. We performed an exploratory hypothesis-generating analysis of targeted metabolomics on choline-related metabolites in the maternal liver, plasma, placenta, and fetal brain at E17.5 and Spearman correlation analyses to determine their association with gestational and fetal growth outcomes. Results: Although choline levels were largely unaffected by alcohol or choline, alcohol increased many lipid products in the CDP\u2013choline pathway; this was not normalized by choline. Alcohol increased placental CDP\u2013ethanolamine and reduced the maternal hepatic SAM\/SAH ratio as well as dimethylglycine and the serine\/glycine ratio across the dyad, suggesting a functional insufficiency in methyl donor pools. These outcomes were rescued by supplemental choline. Correlation analyses among choline metabolites and fetal growth outcomes suggest that maternal plasma methionine, serine, and the serine\/glycine ratio may be predictive of maternal\u2013fetal choline status. Conclusions: The increased hepatic lipid synthesis that characterizes chronic alcohol exposure may draw choline into phospholipid biosynthesis at the expense of its use as a methyl donor. We propose that PAE increases choline needs, and that its supplementation is necessary to fulfill these competing demands for lipid and methyl use.<\/jats:p>","DOI":"10.3390\/metabo15050289","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:18:02Z","timestamp":1745475482000},"page":"289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Alcohol Exposure May Increase Prenatal Choline Needs Through Redirection of Choline into Lipid Synthesis Rather than Methyl Donation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5187-7792","authenticated-orcid":false,"given":"Hannah G.","family":"Petry","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6775-3486","authenticated-orcid":false,"given":"Nipun","family":"Saini","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"UNC Nutrition Research Institute, Kannapolis, NC 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4782-6857","authenticated-orcid":false,"given":"Susan M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"UNC Nutrition Research Institute, Kannapolis, NC 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-2518","authenticated-orcid":false,"given":"Sandra M.","family":"Mooney","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"UNC Nutrition Research Institute, Kannapolis, NC 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/uog.11112","article-title":"Neurodevelopmental Delay in Small Babies at Term: A Systematic Review","volume":"40","author":"Arcangeli","year":"2012","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1111\/acer.14656","article-title":"Gestational Age and Birth Growth Parameters as Early Predictors of Fetal Alcohol Spectrum Disorders","volume":"45","author":"Hasken","year":"2021","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e20154256","DOI":"10.1542\/peds.2015-4256","article-title":"Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders","volume":"138","author":"Hoyme","year":"2016","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Weider, S., L\u00e6rum, A.M.W., Evensen, K.A.I., Reitan, S.K., Lydersen, S., Brubakk, A.M., Skranes, J., and Indredavik, M.S. (2023). Neurocognitive Function and Associations with Mental Health in Adults Born Preterm with Very Low Birthweight or Small for Gestational Age at Term. Front. Psychol., 13.","DOI":"10.3389\/fpsyg.2022.1078232"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1001\/jama.2017.21896","article-title":"Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities","volume":"319","author":"May","year":"2018","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.15585\/mmwr.mm7101a2","article-title":"Alcohol Consumption and Binge Drinking During Pregnancy Among Adults Aged 18\u201349 Years\u2014United States, 2018\u20132020","volume":"71","author":"Gosdin","year":"2022","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ntt.2009.07.002","article-title":"Prenatal Choline Supplementation Mitigates the Adverse Effects of Prenatal Alcohol Exposure on Development in Rats","volume":"31","author":"Thomas","year":"2009","journal-title":"Neurotoxicol Teratol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Waddell, J., and Mooney, S.M. (2017). Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol. Nutrients, 9.","DOI":"10.3390\/nu9101080"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1111\/acer.13817","article-title":"Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies","volume":"42","author":"Akison","year":"2018","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.alcohol.2015.08.005","article-title":"The Impact of Micronutrient Supplementation in Alcohol-Exposed Pregnancies on Information Processing Skills in Ukrainian Infants","volume":"49","author":"Kable","year":"2015","journal-title":"Alcohol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1111\/acer.14672","article-title":"Maternal Choline Supplementation Mitigates Alcohol Exposure Effects on Neonatal Brain Volumes","volume":"45","author":"Warton","year":"2021","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1111\/acer.13769","article-title":"Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"42","author":"Jacobson","year":"2018","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3945\/ajcn.114.099168","article-title":"Choline Supplementation in Children with Fetal Alcohol Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"102","author":"Wozniak","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s11689-020-09312-7","article-title":"Four-Year Follow-up of a Randomized Controlled Trial of Choline for Neurodevelopment in Fetal Alcohol Spectrum Disorder","volume":"12","author":"Wozniak","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s11689-022-09470-w","article-title":"Long-Term Follow-up of a Randomized Controlled Trial of Choline for Neurodevelopment in Fetal Alcohol Spectrum Disorder: Corpus Callosum White Matter Microstructure and Neurocognitive Outcomes","volume":"14","author":"Gimbel","year":"2022","journal-title":"J. Neurodev. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xu, F., Thomas, J.D., Goldowitz, D., and Hamre, K.M. (2023). The Ameliorative Effects of Choline on Ethanol-Induced Cell Death in the Neural Tube of Susceptible BXD Strains of Mice. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1203597"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1111\/acer.12554","article-title":"Choline partially prevents the impact of ethanol on the lipid raft dependent functions of L1 cell adhesion molecule","volume":"38","author":"Tang","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.alcohol.2016.12.006","article-title":"Postnatal Choline Supplementation Selectively Attenuates Hippocampal microRNA Alterations Associated with Developmental Alcohol Exposure","volume":"60","author":"Balaraman","year":"2017","journal-title":"Alcohol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1111\/j.1530-0277.2012.01784.x","article-title":"Choline supplementation and DNA methylation in the hippocampus and prefrontal cortex of rats exposed to alcohol during development","volume":"36","author":"Otero","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/acer.12082","article-title":"Gestational Choline Supplementation Normalized Fetal Alcohol-Induced Alterations in Histone Modifications, DNA Methylation and POMC Gene Expression in \u03b2-Endorphin-Producing POMC Neurons of the Hypothalamus","volume":"37","author":"Bekdash","year":"2013","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"107990","DOI":"10.1016\/j.neuropharm.2020.107990","article-title":"Rescue of Ethanol-Induced FASD-like Phenotypes via Prenatal Co-Administration of Choline","volume":"168","author":"Bottom","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"RP92135","DOI":"10.7554\/eLife.92135.3","article-title":"Early Moderate Prenatal Alcohol Exposure and Maternal Diet Impact Offspring DNA Methylation Across Species","volume":"12","author":"Bestry","year":"2024","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/19390211.2019.1639875","article-title":"Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists","volume":"17","author":"Wallace","year":"2020","journal-title":"J. Diet. Suppl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1093\/advances\/nmac082","article-title":"Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies","volume":"13","author":"Obeid","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.nutr.26.061505.111156","article-title":"Choline: Critical Role During Fetal Development and Dietary Requirements in Adults","volume":"26","author":"Zeisel","year":"2006","journal-title":"Annu. Rev. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Derbyshire, E., and Obeid, R. (2020). Choline, Neurological Development and Brain Function: A Systematic Review Focusing on the First 1000 Days. Nutrients, 12.","DOI":"10.3390\/nu12061731"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Obeid, R., Sch\u00f6n, C., Derbyshire, E., Jiang, X., Mellott, T.J., Blusztajn, J.K., and Zeisel, S.H. (2024). A Narrative Review on Maternal Choline Intake and Liver Function of the Fetus and the Infant; Implications for Research, Policy, and Practice. Nutrients, 16.","DOI":"10.3390\/nu16020260"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wallace, T.C., and Fulgoni, V.L. (2017). Usual Choline Intakes Are Associated with Egg and Protein Food Consumption in the United States. Nutrients, 9.","DOI":"10.3390\/nu9080839"},{"key":"ref_29","unstructured":"Institute of Medicine (US), Food and Nutrition Board, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes NAD Its Panel on Folate, Other B Vitamins, and Choline, and Subcommittee on Upper Reference Levels of Nutrients Choline (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, National Academies Press."},{"key":"ref_30","first-page":"754","article-title":"Phosphatidylcholine Biosynthesis and Lipoprotein Metabolism","volume":"1821","author":"Cole","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1093\/jn\/125.12.3049","article-title":"Pregnancy and Lactation Are Associated with Diminished Concentrations of Choline and Its Metabolites in Rat Liver","volume":"125","author":"Zeisel","year":"1995","journal-title":"J. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dymek, A., Oleksy, \u0141., Stolarczyk, A., and Bartosiewicz, A. (2024). Choline\u2014An Underappreciated Component of a Mother-to-Be\u2019s Diet. Nutrients, 16.","DOI":"10.3390\/nu16111767"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.placenta.2017.03.019","article-title":"Maternal Choline Supplementation during Murine Pregnancy Modulates Placental Markers of Inflammation, Apoptosis and Vascularization in a Fetal Sex-Dependent Manner","volume":"53","author":"Kwan","year":"2017","journal-title":"Placenta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1093\/jn\/125.11.2851","article-title":"Choline Distribution and Metabolism in Pregnant Rats and Fetuses Are Influenced by the Choline Content of the Maternal Diet","volume":"125","author":"Garner","year":"1995","journal-title":"J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.3945\/ajcn.113.066092","article-title":"Pregnancy Alters Choline Dynamics: Results of a Randomized Trial Using Stable Isotope Methodology in Pregnant and Nonpregnant Women","volume":"98","author":"Yan","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e22063","DOI":"10.1096\/fj.202101401RR","article-title":"Choline Metabolome Response to Prenatal Choline Supplementation across Pregnancy: A Randomized Controlled Trial","volume":"35","author":"Taesuwan","year":"2021","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1111\/acer.14730","article-title":"Prenatal Choline Supplementation during Mouse Pregnancy Has Differential Effects in Alcohol-Exposed Fetal Organs","volume":"45","author":"Kwan","year":"2021","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Smith, S.M., Pjetri, E., Friday, W.B., Presswood, B.H., Ricketts, D.K., Walter, K.R., and Mooney, S.M. (2022). Aging-Related Behavioral, Adiposity, and Glucose Impairments and Their Association Following Prenatal Alcohol Exposure in the C57BL\/6J Mouse. Nutrients, 14.","DOI":"10.3390\/nu14071438"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Virdee, M.S., Saini, N., Kay, C.D., Neilson, A.P., Kwan, S.T.C., Helfrich, K.K., Mooney, S.M., and Smith, S.M. (2021). An Enriched Biosignature of Gut Microbiota-Dependent Metabolites Characterizes Maternal Plasma in a Mouse Model of Fetal Alcohol Spectrum Disorder. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80093-8"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zeisel, S.H., and Corbin, K.D. (2012). Choline. Present Knowledge in Nutrition, John Wiley & Sons, Ltd.","DOI":"10.1002\/9781119946045.ch26"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4300\/JGME-D-12-00156.1","article-title":"Using Effect Size\u2014Or Why the P Value Is Not Enough","volume":"4","author":"Sullivan","year":"2012","journal-title":"J. Grad. Med. Educ."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Bernhard, W., B\u00f6ckmann, K.A., Minarski, M., Wiechers, C., Busch, A., Bach, D., Poets, C.F., and Franz, A.R. (2024). Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition\u2014A Narrative Review. Nutrients, 16.","DOI":"10.3390\/nu16121873"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rucker, R.B., Zempleni, J., Suttie, J.W., and McCormick, D.B. (2012). Choline. Handbook of Vitamins, CRC Press.","DOI":"10.1201\/b15413"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18335","DOI":"10.1074\/jbc.M510623200","article-title":"Regulation of Folate-Mediated One-Carbon Metabolism by 10-Formyltetrahydrofolate Dehydrogenase","volume":"281","author":"Anguera","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.cmet.2016.09.011","article-title":"Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway","volume":"24","author":"Ducker","year":"2016","journal-title":"Cell Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.3945\/jn.115.227983","article-title":"Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123","volume":"146","author":"Huebner","year":"2016","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/ajcn\/nqab165","article-title":"Prenatal Alcohol-Related Alterations in Maternal, Placental, Neonatal, and Infant Iron Homeostasis","volume":"114","author":"Carter","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Seitz, H.K., Moreira, B., and Neuman, M.G. (2023). Pathogenesis of Alcoholic Fatty Liver a Narrative Review. Life, 13.","DOI":"10.20944\/preprints202305.0606.v1"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ferdouse, A., and Clugston, R.D. (2022). Pathogenesis of Alcohol-Associated Fatty Liver: Lessons from Transgenic Mice. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.940974"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/0026-0495(90)90007-Y","article-title":"Serum Lipids and Lipoproteins in Alcoholic Women during Pregnancy","volume":"39","author":"Keso","year":"1990","journal-title":"Metabolism"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Naik, V.D., and Ramadoss, J. (2023). Untargeted and Targeted Blood Lipidomic Signature Profile of Gestational Alcohol Exposure. Nutrients, 15.","DOI":"10.3390\/nu15061411"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Arumugam, M.K., Paal, M.C., Donohue, T.M., Ganesan, M., Osna, N.A., and Kharbanda, K.K. (2021). Beneficial Effects of Betaine: A Comprehensive Review. Biology, 10.","DOI":"10.3390\/biology10060456"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s10020-024-00950-4","article-title":"Oral Supplementation of Choline Attenuates the Development of Alcohol-Related Liver Disease (ALD)","volume":"30","author":"Baumann","year":"2024","journal-title":"Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1111\/j.1530-0277.2007.00407.x","article-title":"S-Adenosylmethionine Attenuates Hepatic Lipid Synthesis in Micropigs Fed Ethanol with a Folate-Deficient Diet","volume":"31","author":"Esfandiari","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lacal, J.C., Zimmerman, T., and Campos, J.M. (2021). Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060788"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e23172","DOI":"10.1096\/fj.202300788R","article-title":"Alcohol Blunts Pregnancy-Mediated Insulin Resistance and Reduces Fetal Brain Glucose despite Elevated Fetal Gluconeogenesis, and These Changes Associate with Fetal Weight Outcomes","volume":"37","author":"Saini","year":"2023","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hasken, J.M., de Vries, M.M., Marais, A.-S., May, P.A., Parry, C.D.H., Seedat, S., Mooney, S.M., and Smith, S.M. (2022). Untargeted Metabolome Analysis of Alcohol-Exposed Pregnancies Reveals Metabolite Differences That Are Associated with Infant Birth Outcomes. Nutrients, 14.","DOI":"10.3390\/nu14245367"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Saini, N., Virdee, M., Helfrich, K., Kwan, S.T.C., Mooney, S., and Smith, M.S. (2022). Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders. Nutrients, 14.","DOI":"10.3390\/nu14051096"},{"key":"ref_61","unstructured":"(1995). National Research Council (US) Subcommittee on Laboratory Animal Nutrition Nutrient Requirements of Laboratory Animals: Fourth Revised Edition, 1995, National Academies Press (US)."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Flentke, G.R., Wilkie, T.E., Baulch, J., Huang, Y., and Smith, S.M. (2024). Alcohol Exposure Suppresses Ribosome Biogenesis and Causes Nucleolar Stress in Cranial Neural Crest Cells. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0304557"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1111\/j.1471-4159.2005.03461.x","article-title":"Ethanol Disrupts Cell Cycle Regulation in Developing Rat Cortex Interaction with Transforming Growth Factor \u03921","volume":"95","author":"Siegenthaler","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/s41380-022-01862-7","article-title":"Impact of Alcohol Exposure on Neural Development and Network Formation in Human Cortical Organoids","volume":"28","author":"Adams","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1053\/gast.2002.33613","article-title":"Alcohol and Mitochondria: A Dysfunctional Relationship","volume":"122","author":"Hoek","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/acer.14052","article-title":"Global DNA Methylation and Histone Posttranslational Modifications in Human and Nonhuman Primate Brain in Association with Prenatal Alcohol Exposure","volume":"43","author":"Jarmasz","year":"2019","journal-title":"Alcohol. Clin. Exp. 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