Physiological response to fetal intravenous lipid emulsion in mid-gestation

Circulating lipid levels are typically low in fetuses, and exposure to high lipid levels at developmental stages prior to term birth is sometimes associated with pathology. Experimentally, near-term fetuses tolerate one week of high lipid concentrations; it is unknown whether this brief exposure to elevated circulating lipids is pathological at an earlier developmental age. We studied the physiological response to intravenous lipid emulsion during mid-gestation. Fetal sheep received intravenous Intralipid 20® (n = 9) or Lactated Ringer's Solution (n = 8) from 85.0 ± 0.7 to 97.0 ± 0.7 days of gestation (term = 147 days). Intralipid was administered according to manufacturer's recommendations, with an initial dose of 0.5-1 g/kg/d that increased daily to a maximum of 3 g/kg/d. Hemodynamic and arterial blood parameters were assessed throughout the study. Fetal growth, liver function, and lipid droplet accumulation were measured on the final day. Fetal hemodynamics and blood gases did not change as a result of the treatment. Compared with Controls, Intralipid fetuses had lower blood lactate concentrations (1.3 ± 0.2 vs. 1.0 ± 0.2 mmol/l, P=0.009) after eight days of treatment. Conjugated (0.4 ± 0.1 vs. 0.6±0.1 mg/dl, P<0.001) and unconjugated (0.3 ± 0.1 vs. 1.2 ± 0.5 mg/dl, P<0.001) bilirubin levels were higher in Intralipid-infused fetuses than in Controls. Fetal somatic growth was unchanged, but heart weight was lower in fetuses receiving Intralipid (6.9 ± 0.7 vs. 6.1±0.7 g, P=0.008). Compared with Controls, Oil Red O staining was elevated in the liver and heart of Intralipid-infused fetuses (liver score: 18.9 ± 17.2 vs. 371.7±44.2, P<0.0001; heart score: 1.8 ± 2.8 vs. 97.6 ± 60.1, P=0.0006). Our findings suggest that mid-gestation fetal sheep can tolerate intravenous lipid emulsion. Lipid accumulation in the liver and heart may precede pathologies associated with ectopic lipid storage, but further research is needed to understand the long-term consequences of Intralipid infusion at this developmental stage.