{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:47:59Z","timestamp":1792176479026,"version":"4.4.0"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Psychobiology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In recent years, there has been a sixfold increase in the number of pregnant people with opioid use disorder (OUD). Rates of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), have significantly increased in virtually every state and demographic group\u00a0(Healthcare\u00a0Cost\u00a0Utilization\u00a0Project,\u00a0HCUP,\u00a02010). NOWS is a condition resulting from chronic exposure to either therapeutic opioid use (e.g., medication for OUD, chronic pain conditions) or nonprescribed opioid use. To date, there is no known prenatal treatment to help decrease the risk of infants developing NOWS and subsequent neurodevelopmental outcomes. Given the increasing support for how placental signaling, or placental programming, may play a role in downstream pathology, prospective research investigating how the placenta is affected by chronic opioid exposure morphologically, histologically, and at the cellular level may open up potential treatment opportunities in this field. In this review, we discuss literature exploring the physiological roles of nitric oxide and dopamine not only in the vascular development of the placenta, but also in fetal cerebral blood flow, neurogenesis, neuronal differentiation, and neuronal activity. We also discuss histological preclinical studies that suggest chronic opioid exposure to induce some combination of placental dysfunction and hypoxia in a manner similar to other well\u2010known placental pathologies, as denoted by the compensatory neovascularization and increased utilization of the placenta's supply of trophoblast cells, which play an essential role in placental angiogenesis. Overall, we found that the current literature, while limited, suggests chronic opioid exposure negatively impacts placental function and fetal brain development on a cellular and histopathological level. We conclude that it is worthwhile to consider the placenta as a therapeutic target with the ultimate goal of decreasing the incidence of NOWS and the long\u2010term impacts of prenatal opioid exposure.<\/jats:p>","DOI":"10.1002\/dev.22378","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T15:10:30Z","timestamp":1677769830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A review of the literature: How does prenatal opioid exposure impact placental health and fetal brain development?"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-9432","authenticated-orcid":false,"given":"Audrey","family":"Humphries","sequence":"first","affiliation":[{"name":"Virginia Tech Carilion School of Medicine  Roanoke Virginia USA"},{"name":"Fralin Biomedical Research Institute at Virginia Tech Carilion  Roanoke Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Simcox","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Virginia Tech Carilion School of Medicine  Roanoke Virginia United\u00a0States"},{"name":"Department of Obstetrics and Gynecology Carilion Clinic  Roanoke Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Howell","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute at Virginia Tech Carilion  Roanoke Virginia USA"},{"name":"Department of Human Development and Family Science Virginia Tech  Roanoke Virginia USA"},{"name":"Pediatrics Virginia Tech Carilion School of Medicine  Roanoke Virginia United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/09687689309150256"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.04.043"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.6405"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u2010244X\u201014\u2010104"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3818"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.301.6746.259"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e31829cb9ca"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.07.063"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.01.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22022"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09972"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.247"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.2.8593833"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.235025"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002161"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019\u20100128"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2010.154864"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.10.011"},{"key":"e_1_2_9_20_1","first-page":"1163","article-title":"Impact of maternal drug dependency on birth weight and head circumference of offspring","volume":"141","author":"Doberczak T. 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