{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:16:30Z","timestamp":1789038990146,"version":"build-2803163510"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005648","name":"American Association of Orthodontists Foundation","doi-asserted-by":"publisher","award":["Biomedical Research Award"],"award-info":[{"award-number":["Biomedical Research Award"]}],"id":[{"id":"10.13039\/100005648","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Preterm human infants often show periodic breathing (PB) or apnea of prematurity (AOP), breathing patterns which are accompanied by intermittent hypoxia (IH). We examined cause-effect relationships between transient IH and reduced facial bone growth using a rat model. Neonatal pups from 14 timed pregnant Sprague-Dawley rats were randomly assigned to an IH condition, with oxygen altering between 10% and 21% every 4 min for 1 h immediately after birth, or to a litter-matched control group. The IH pups were compared with their age- and sex-matched control groups in body weight (WT), size of facial bones and nor-epinephrine (NE) levels in blood at 3, 4, and 5-weeks. Markedly increased activity of osteoclasts in sub-condylar regions of 3-week-old IH-treated animals appeared, as well as increased numbers of sympathetic nerve endings in the same region of tissue sections. Male IH-pups showed significantly higher levels of NE levels in sera at 3, 4 as well as 5-week-old time points. NE levels in 4- and-5-week-old female pups did not differ significantly. Intercondylar Width, Mandible Length and Intermolar Width measures consistently declined after IH insults in 3- and 4-week-old male as well as female animals. Three-week-old male IH-pups only showed a significantly reduced (p &lt; 0.05) body weight compared to those of 3-week controls. However, female IH-pups were heavier than age-matched controls at all 3 time-points. Trabecular bone configuration, size of facial bones, and metabolism are disturbed after an IH challenge 1 h immediately after birth. The findings raise the possibility that IH, introduced by breathing patterns such as PB or AOP, induce significantly impaired bone development and metabolic changes in human newborns. The enhanced NE outflow from IH exposure may serve a major role in deficient bone growth, and may affect bone and other tissue influenced by that elevation.<\/jats:p>","DOI":"10.1371\/journal.pone.0282937","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T17:32:06Z","timestamp":1697045526000},"page":"e0282937","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intermittent hypoxia in neonatal rodents affects facial bone growth"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-8767","authenticated-orcid":true,"given":"Eung-Kwon","family":"Pae","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"pone.0282937.ref001","first-page":"15","article-title":"Transient Intermittent Hypoxia Exposure Disrupts Neonatal Bone Strength.","volume":"4","author":"G Kim","year":"2016","journal-title":"Front Pediatr"},{"issue":"9","key":"pone.0282937.ref002","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/s41372-021-01010-z","article-title":"Immature control of breathing and apnea of prematurity: the known and unknown.","volume":"41","author":"G Erickson","year":"2021","journal-title":"J Perinatol"},{"issue":"11","key":"pone.0282937.ref003","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/ppul.24451","article-title":"Physiological instability after respiratory pauses in preterm infants.","volume":"54","author":"AP Marshall","year":"2019","journal-title":"Pediatr Pulmonol"},{"issue":"9","key":"pone.0282937.ref004","first-page":"1","article-title":"Births: final data for 2012.","volume":"62","author":"JA Martin","year":"2013","journal-title":"Natl Vital Stat Rep"},{"issue":"2","key":"pone.0282937.ref005","first-page":"1","article-title":"Births: Final Data for 2019.","volume":"70","author":"JA Martin","year":"2021","journal-title":"Natl Vital Stat Rep."},{"issue":"442","key":"pone.0282937.ref006","first-page":"1","article-title":"Births in the United States, 2021.","author":"JA Martin","year":"2022","journal-title":"NCHS Data Brief."},{"issue":"3","key":"pone.0282937.ref007","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s10286-021-00793-7","article-title":"Cerebral cortical autonomic connectivity in low-risk term newborns.","volume":"31","author":"SB Mulkey","year":"2021","journal-title":"Clin Auton Res"},{"issue":"6","key":"pone.0282937.ref008","doi-asserted-by":"crossref","first-page":"e13620","DOI":"10.14814\/phy2.13620","article-title":"Impaired autonomic function in adolescents born preterm.","volume":"6","author":"K Haraldsdottir","year":"2018","journal-title":"Physiol Rep"},{"issue":"4","key":"pone.0282937.ref009","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s00421-019-04075-z","article-title":"Heart rate recovery after maximal exercise is impaired in healthy young adults born preterm. 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