{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:25:03Z","timestamp":1791120303249,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES030743"],"award-info":[{"award-number":["R01ES030743"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Cincinnati Children\u2019s Hospital Medical Center Trustee Grant","award":["R01ES030743"],"award-info":[{"award-number":["R01ES030743"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by \u22120.02 (95% CI \u22120.03, \u22120.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes.<\/jats:p>","DOI":"10.3390\/toxics11100855","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T01:03:12Z","timestamp":1697158992000},"page":"855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neonatal AVPR1a Methylation and In-Utero Exposure to Maternal Smoking"],"prefix":"10.3390","volume":"11","author":[{"given":"Nichole","family":"Nidey","sequence":"first","affiliation":[{"name":"Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Bowers","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-0620","authenticated-orcid":false,"given":"Hong","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6905-5024","authenticated-orcid":false,"given":"Robert T.","family":"Ammerman","sequence":"additional","affiliation":[{"name":"Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Yolton","sequence":"additional","affiliation":[{"name":"Division of General and Community Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3893-885X","authenticated-orcid":false,"given":"E. Melinda","family":"Mahabee-Gittens","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alonzo T.","family":"Folger","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.15585\/mmwr.mm6744a2","article-title":"Tobacco Product Use Among Adults\u2014United States, 2017","volume":"67","author":"Wang","year":"2018","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12978-019-0807-5","article-title":"Prevalence and patterns of cigarette smoking before and during early and late pregnancy according to maternal characteristics: The first national data based on the 2003 birth certificate revision, United States, 2016","volume":"16","author":"Kondracki","year":"2019","journal-title":"Reprod. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6701a1","article-title":"Disparities in Preconception Health Indicators\u2014Behavioral Risk Factor Surveillance System, 2013\u20132015, and Pregnancy Risk Assessment Monitoring System, 2013\u20132014","volume":"67","author":"Robbins","year":"2018","journal-title":"MMWR Surveill. Summ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.15585\/mmwr.mm7111a1","article-title":"Tobacco Product Use Among Adults\u2014United States, 2020","volume":"71","author":"Cornelius","year":"2022","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_5","unstructured":"(2022, September 01). America\u2019s Health Rankings. Available online: https:\/\/assets.americashealthrankings.org\/app\/uploads\/americashealthrankings-2021annualreport.pdf."},{"key":"ref_6","unstructured":"Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, and Office on Smoking and Health (2010). Publications and Reports of the Surgeon General, How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e20191346","DOI":"10.1542\/peds.2019-1346","article-title":"The Effects of Nicotine on Development","volume":"145","author":"Gorzkowski","year":"2020","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S125","DOI":"10.1080\/14622200410001669187","article-title":"The epidemiology of smoking during pregnancy: Smoking prevalence, maternal characteristics, and pregnancy outcomes","volume":"6","author":"Cnattingius","year":"2004","journal-title":"Nicotine Tob. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2188\/jea.JE20140040","article-title":"Maternal smoking during pregnancy and growth in infancy: A covariance structure analysis","volume":"25","author":"Zheng","year":"2015","journal-title":"J. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Abraham, M., Alramadhan, S., Iniguez, C., Duijts, L., Jaddoe, V.W., Den Dekker, H.T., Crozier, S., Godfrey, K.M., Hindmarsh, P., and Vik, T. (2017). A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170946"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/pubmed\/fdw050","article-title":"Impact of maternal and paternal smoking on birth outcomes","volume":"39","author":"Inoue","year":"2017","journal-title":"J. Public Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/jp.2017.172","article-title":"Effect of maternal smoking on stress physiology in healthy neonates","volume":"38","author":"Haslinger","year":"2018","journal-title":"J. Perinatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e20172465","DOI":"10.1542\/peds.2017-2465","article-title":"Maternal Smoking and Attention-Deficit\/Hyperactivity Disorder in Offspring: A Meta-analysis","volume":"141","author":"Huang","year":"2018","journal-title":"Pediatrics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105997","DOI":"10.1016\/j.ypmed.2020.105997","article-title":"Development of a prediction model to target screening for high blood pressure in children","volume":"132","author":"Hamoen","year":"2020","journal-title":"Prev. Med."},{"key":"ref_15","first-page":"751","article-title":"Correlation between childhood hypertension and passive smoking before and after birth","volume":"48","author":"Hu","year":"2019","journal-title":"Wei Sheng Yan Jiu"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/ntr\/ntx117","article-title":"Maternal Smoking: A Life Course Blood Pressure Determinant?","volume":"20","author":"Cabral","year":"2018","journal-title":"Nicotine Tob. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s12967-015-0690-y","article-title":"Short and long term health effects of parental tobacco smoking during pregnancy and lactation: A descriptive review","volume":"13","author":"Banderali","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.ajhg.2016.02.019","article-title":"DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis","volume":"98","author":"Joubert","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/j.1471-4159.2011.07633.x","article-title":"Nicotine stimulates secretion of corticosterone via both CRH and AVP receptors","volume":"120","author":"Lutfy","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fmed.2015.00019","article-title":"A review of the nonpressor and nonantidiuretic actions of the hormone vasopressin","volume":"2","author":"Mavani","year":"2015","journal-title":"Front. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.neuron.2010.02.020","article-title":"Genetics of human social behavior","volume":"65","author":"Ebstein","year":"2010","journal-title":"Neuron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/geno.1996.0055","article-title":"Structure, sequence, expression, and chromosomal localization of the human V1a vasopressin receptor gene","volume":"31","author":"Thibonnier","year":"1996","journal-title":"Genomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0146-0005(96)80079-6","article-title":"The maternal and fetal physiologic effects of nicotine","volume":"20","author":"Lambers","year":"1996","journal-title":"Semin. Perinatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/34413","article-title":"Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine","volume":"391","author":"Picciotto","year":"1998","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0165-3806(98)00046-7","article-title":"Regional distribution of nicotinic receptors during prenatal development of human brain and spinal cord","volume":"108","author":"Gorbounova","year":"1998","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1152\/physrev.00035.2011","article-title":"Vasopressin V1a and V1b receptors: From molecules to physiological systems","volume":"92","author":"Koshimizu","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/sj.npp.1301466","article-title":"Chronic nicotine self-administration augments hypothalamic-pituitary-adrenal responses to mild acute stress","volume":"33","author":"Chen","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0091-3057(90)90153-9","article-title":"Cortisol response to a psychological stressor and\/or nicotine","volume":"36","author":"Pomerleau","year":"1990","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.psyneuen.2014.05.017","article-title":"Maternal smoking during pregnancy and infant stress response: Test of a prenatal programming hypothesis","volume":"48","author":"Stroud","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/j.1471-0528.2006.01089.x","article-title":"The effect of tobacco exposure on the fetal hypothalamic-pituitary-adrenal axis","volume":"113","author":"McDonald","year":"2006","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/dmcn.14149","article-title":"Environmental influences on health and development: Nutrition, substance exposure, and adverse childhood experiences","volume":"61","author":"Gentner","year":"2019","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/molehr\/gas050","article-title":"Maternal smoking as a model for environmental epigenetic changes affecting birthweight and fetal programming","volume":"19","author":"Suter","year":"2013","journal-title":"Mol. Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2217\/epi-2019-0066","article-title":"Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking","volume":"11","author":"Sikdar","year":"2019","journal-title":"Epigenomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1093\/aje\/kwz184","article-title":"Mediation by Placental DNA Methylation of the Association of Prenatal Maternal Smoking and Birth Weight","volume":"188","author":"Cardenas","year":"2019","journal-title":"Am. J. Epidemiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev-publhealth-040617-014629","article-title":"Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations","volume":"39","author":"Martin","year":"2018","journal-title":"Annu. Rev. Public Health"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/bdr2.1550","article-title":"Smoking and pregnancy: Epigenetics and developmental origins of the metabolic syndrome","volume":"111","author":"Rogers","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1017\/S0954579412000776","article-title":"The epigenetics of maternal cigarette smoking during pregnancy and effects on child development","volume":"24","author":"Knopik","year":"2012","journal-title":"Dev. Psychopathol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, G., Wang, H., Wang, K., Wang, W., Dong, F., Qian, Y., Gong, H., Hui, C., Xu, G., and Li, Y. (2017). The association between smoking and blood pressure in men: A cross-sectional study. BMC Public Health, 17.","DOI":"10.1186\/s12889-017-4802-x"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1164\/rccm.200901-0135OC","article-title":"Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation","volume":"180","author":"Breton","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnbeh.2019.00014","article-title":"Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age","volume":"13","author":"Folger","year":"2019","journal-title":"Front. Behav. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/bioinformatics\/btw691","article-title":"Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi","volume":"33","author":"Fortin","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1093\/nar\/gkt090","article-title":"Low-level processing of Illumina Infinium DNA Methylation BeadArrays","volume":"41","author":"Triche","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1093\/bioinformatics\/btw285","article-title":"RCP: A novel probe design bias correction method for Illumina Methylation BeadChip","volume":"32","author":"Niu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Du, P., Zhang, X., Huang, C.-C., Jafari, N., Kibbe, W.A., Hou, L., and Lin, S.M. (2010). Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-587"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/15592294.2017.1325065","article-title":"Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife","volume":"13","author":"Tehranifar","year":"2018","journal-title":"Epigenetics"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rzehak, P., Saffery, R., Reischl, E., Covic, M., Wahl, S., Grote, V., Xhonneux, A., Langhendries, J.P., Ferre, N., and Closa-Monasterolo, R. (2016). Maternal Smoking during Pregnancy and DNA-Methylation in Children at Age 5.5 Years: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155554"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1253\/circj.CJ-14-0368","article-title":"Low cardiac output stimulates vasopressin release in patients with stage d heart failure","volume":"78","author":"Imamura","year":"2014","journal-title":"Circ. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1046\/j.1523-1755.2003.00172.x","article-title":"Prenatal exposure to nicotine modifies kidney weight and blood pressure in genetically susceptible rats: A case of gene-environment interaction","volume":"64","author":"Pausova","year":"2003","journal-title":"Kidney Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1093\/hmg\/ddu739","article-title":"Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)","volume":"24","author":"Richmond","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/15592294.2021.1903376","article-title":"Prenatal medication exposure and epigenetic outcomes: A systematic literature review and recommendations for prenatal pharmacoepigenetic studies","volume":"17","author":"Olstad","year":"2022","journal-title":"Epigenetics"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/11\/10\/855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:06:00Z","timestamp":1760130360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/11\/10\/855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":52,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["toxics11100855"],"URL":"https:\/\/doi.org\/10.3390\/toxics11100855","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,13]]}}}