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The contribution of post-conceptional level of maturation to pathology that some neonates experience is difficult to untangle from the global pathophysiology of premature birth. In the present study, we determined fetal physiological responses to intravenous lipid emulsion. Fetal sheep were given intravenous Intralipid 20\u00ae (n = 4 females, 7 males) or Lactated Ringer\u2019s Solution (n = 7 females, 4 males) between 125 \u00b1 1 and 133 \u00b1 1 d of gestation (term = 147 d). Manufacturer\u2019s recommendation for premature human infants was followed: 0.5\u20131 g\/kg\/d initial rate, increased by 0.5\u20131 to 3 g\/kg\/d. Hemodynamic parameters and arterial blood chemistry were measured, and organs were studied postmortem. Red blood cell lipidomics were analyzed by LC-MS. Intravenous Intralipid did not alter hemodynamic or most blood parameters. Compared with controls, Intralipid infusion increased final day plasma protein (P=0.004; 3.5 \u00b1 0.3 vs. 3.9 \u00b1 0.2 g\/dL), albumin (P = 0.031; 2.2 \u00b1 0.1 vs. 2.4 \u00b1 0.2 g\/dL), and bilirubin (P&amp;lt;0.001; conjugated: 0.2 \u00b1 0.1 vs. 0.6 \u00b1 0.2 mg\/dL; unconjugated: 0.2 \u00b1 0.1 vs. 1.1 \u00b1 0.4 mg\/dL). Circulating IGF-1 decreased following Intralipid infusion (P&amp;lt;0.001; 66 \u00b1 24 vs. 46 \u00b1 24 ng\/mL). Compared with control Oil Red O liver stains (median score 0), Intralipid-infused fetuses scored 108 (P=0.0009). Lipidomic analysis revealed uptake and processing of infused lipids into red blood cells, increasing abundance of saturated fatty acids. The near-term fetal sheep tolerates intravenous lipid emulsion well, although lipid accumulates in the liver. Increased levels of unconjugated bilirubin may reflect increased red blood cell turnover or impaired placental clearance. Whether Intralipid is less well tolerated earlier in gestation remains to be determined.<\/jats:p>","DOI":"10.1042\/cs20231419","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T12:41:56Z","timestamp":1706013716000},"page":"117-134","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Physiological response to fetal intravenous lipid emulsion"],"prefix":"10.1042","volume":"138","author":[{"given":"Brian\u00a0D.","family":"Piccolo","sequence":"first","affiliation":[{"name":"1USDA\/ARS-Arkansas Children\u2019s Nutrition Center, Little Rock, AR, U.S.A."},{"name":"2Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athena","family":"Chen","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Oregon Health and Science University, Portland, OR, U.S.A."},{"name":"4Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Louey","sequence":"additional","affiliation":[{"name":"4Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kent\u00a0L.R.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"4Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-2562","authenticated-orcid":false,"given":"Sonnet\u00a0S.","family":"Jonker","sequence":"additional","affiliation":[{"name":"4Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"2024020211521448500_B1","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S0022-3476(84)81111-7","article-title":"Triglycerides, free fatty acids, free fatty acids\/albumin molar ratio, and cholesterol levels in serum of neonates receiving long-term lipid infusions: controlled trial of continuous and intermittent regimens","volume":"104","author":"Kao","year":"1984","journal-title":"J. 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