Physiological response to fetal intravenous lipid emulsion

Authors: PICCOLO, BRIAN - University Arkansas For Medical Sciences (UAMS); CHEN, ATHENA - Oregon Health & Science University; LOUEY, SAMANTHA - Oregon Health & Science University; THORNBURG, KENT - Oregon Health & Science University; JONKER, SONNET - Oregon Health & Science University

Submitted to: Clinical Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2024
Publication Date: 2/2/2024
Citation: Piccolo, B.D., Chen, A., Louey, S., Thornburg, K.L., Jonker, S.S. 2024. Physiological response to fetal intravenous lipid emulsion. Clinical Science. 138(3):117-134. https://doi.org/10.1042/CS20231419.
DOI: https://doi.org/10.1042/CS20231419

Interpretive Summary: Premature babies can require extra fats and lipids, given through tube feeing, to support brain development. However, tube feeding these lipids can lead to fat accumulation in other organs, like the lung and liver, which can cause additional health problems to the premature infant. Understanding response and distribution of fat and lipid feeding to premature infants is important to optimize this intervention. In this study, a near-term fetal sheep model was used to measure blood chemistry, fetal growth, and lipid transfer into red blood cells in response to eight days of an intravenous lipid emulsion mixture infusion (Intralipid 20®). Preterm fetal sheep receiving the lipid infusion did not have any differences in blood chemistry measurements when compared to preterm fetal sheep receiving a fluid replacement solution control. The lipid infusion increased blood protein levels, including albumin, made by the liver and blood bilirubin levels, a marker of red blood cell turnover. Lipid staining of fetal livers showed >9-fold increase in liver lipid deposition in those who received the lipid infusion. Lipid profiling also showed a distinct pattern of infused lipids in red blood cells, with an increasing abundance of saturated fatty acids. Overall, fetal sheep that were near term tolerated a lipid infusion mixture well. Although the lipid infusion increased lipid deposition in the liver and altered the lipid profiling of red blood cells, the lack of differences in the blood chemistry measurements suggested that the liver was functioning properly. More work is needed to understand whether this specific lipid mixture can be tolerated at earlier premature windows.

Technical Abstract: In preterm neonates unable to obtain sufficient oral nutrition, intravenous lipid emulsion is life-saving. 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® (n = 4 females, 7 males) or Lactated Ringer’s Solution (n = 7 females, 4 males) between 125±1 and 133±1 d of gestation (term = 147 d). Manufacturer’s recommendation for premature human infants was followed: 0.5–1 g/kg/d initial rate, increased by 0.5–1 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±0.3 vs. 3.9±0.2 g/dL), albumin (P = 0.031; 2.2±0.1 vs. 2.4±0.2 g/dL), and bilirubin (P<0.001; conjugated: 0.2±0.1 vs. 0.6±0.2 mg/dL; unconjugated: 0.2±0.1 vs. 1.1±0.4 mg/dL). Circulating IGF-1 decreased following Intralipid infusion (P<0.001; 66±24 vs. 46±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.