ELEVATION OF PLASMA LATHOSTEROL, AS AN INDICATOR OF INCREASED CHOLESTEROL-SYNTHESIS, IN PRETERM (23-32 WEEKS GESTATION) INFANTS GIVEN INTRALIPID

Hypercholesterolemia is common in preterm infants administered 10% Intralipid perhaps because of excess phospholipid in plasma causing efflux of cholesterol from tissues. The purpose of this study was to determine if cholesterol synthesis (as measured by plasma lathosterol) is increased in preterm infants (23-32 wk gestation) during infusion of up to 4 g 10% Intralipid/kg body wt/d. Two groups of infants were studied. Intralipid intake was compared to: 1) plasma cholesterol in blood sampled over the first 100 d of life (preliminary study, n = 22) and 2) plasma cholesterol, lathosterol, and apo AI and B in blood taken at birth (cord), d 3-4 of life, and at least three additional times over the next 25 d (lathosterol study, n = 22). Lathosterol was quantitated by gas liquid chromatography and apo AI and B by immunoprecipitation. In the preliminary study, plasma cholesterol levels rose (to 4.06-10.70 mM) with Intralipid administration. Infants who received < 2 g Intralipid/kg body wt/d were not hypercholesterolemic. In the lathosterol study, plasma cholesterol increased (1.86-2.24 mM, p = 0.06) and apo AI and B did not change, but lathosterol and the cholesterol:lathosterol ratio decreased (5.24-2.88-mu-M, p = 0.01, and 284-124 10(2) x mmol lathosterol:mol cholesterol, p = 0.007, respectively) from birth to d 3-4 (n = 11 paired samples). Infants followed longitudinally had increased cholesterol and lathosterol (4- to 7-fold) with increasing Intralipid administration, which decreased after discontinuation of infusion. Apo AI and B decreased upon Intralipid infusion. The results of this study show that 10% Intralipid administration to preterm infants (23-32 wk gestation) results in increased plasma lathosterol. The coincident fall in plasma apo AI and B suggests that the elevated cholesterol synthesis may be extrahepatic.