Physiological response to fetal intravenous lipid emulsion.

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.

How to build a healthy heart from scratch.

By any of several measures, the health of the American population has been worsening over the last two decades. Obesity, type 2 diabetes and heart failure have risen dramatically. All the while, the average birthweight at all gestational ages has declined. The relationship between robust growth in the womb and lifelong health is now well established. Likewise, babies born at the low end of the birthweight scale are known to have highly elevated risks for ischemic heart disease, hypertension, stroke and metabolic disease. The biological mechanisms by which developmental plasticity becomes a risk for cardiovascular disease are only now being understood. Translating from animal and human studies, low birthweight babies are likely to have endothelial dysfunction, fewer nephrons, fewer pancreatic beta cells, less vascular elastin, fewer cardiomyocytes, increased sympathetic tone and liver-derived dyslipidemias. Only in the past few years, however, has it become known that maternal and placenta phenotypes are associated with adult onset cardiovascular disease. Helsinki Birth Cohort studies have been especially important in the discovery of these relationships. Sudden cardiac death is associated with a thin placenta and heart failure is associated with a small placenta in short mothers. Coronary heart disease is associated with three combinations of maternal-placental phenotypes. Because the diet is important in providing nutrients for the development of the female body before pregnancy and for providing nutrients during pregnancy, there is increasing evidence that the western diet is an underlying cause for the increase in metabolic disease in the American population. A large segment of the American population suffers from high calorie malnutrition. Scientists in this field now have a responsibility to educate the public on the topic of nutrition and health. This chapter honors Lawrence Longo for decades of work in bringing health to pregnant women and their babies.