ABSTRACT. Changes in high-density lipoprotein (HDL) subclass distribution were evaluated in a group of premature infants during the early postnatal period to ascertain whether enteral feeding brought about a rapid shift from neonatal to adult-like distributions. All infants were fed a combination of breast milk and formula. Cord blood of premature infants had a predominance of large, less dense (HDLlb),e and a paucity of intermediate-sized (HDL3a)gge particles. Lack of a peak in the (HDL3,),,, is a characteristic feature for cord blood, whereas a prominent (HDL,,), peak is characteristic of adult plasma. After the start of enteral feeding, blood was obtained at two timepoints: 6-14 days (sample A) and 17-32 days (sample B) postdelivery. With the onset of feeding, triglyceride increased significantly from an average of 34 mg/dl in cord blood to 120 mg/dl in sample B, and cholesterol increased from 86 to 112 mg/dl in the same period. Increases in plasma lipid concentrations were paralleled by a redistribution of subclasses such that three components of almost equal intensity were evident in sample B; these consisted of (HDLzb),,, (HDLz,,),,, and (HDbb)gge. A paucity of (HDL,,),, particles persisted even after onset of enteral feeding; thus, increases in plasma triglyceride and cholesterol per se are not sufficient to induce the adult-like distribution. It is suggested that development of the normal adult HDL subclass pattern is complex and is probably related to the development and interaction of several factors, including plasma enzymes involved in lipid hydrolysis and esterification, lipid exchange proteins, and hormonal status. (Pediatr Res 23:543-547, 1988 The HDL is the major lipoprotein component in human cord blood. As in adult plasma, cord blood HDL is not a single homogeneous population of particles but consists of several distinct subclasses. Using nondenaturing gge, we have previously shown that HDL subclass distribution based on particle size is different in cord blood as compared with adult HDL (1, 2). By the definition of Nichols et al. (3), adult HDL has five identifiable subclasses on gge, (HDL,,, HDL,,, HDL,,, HDL,,, and HDL3,),, and (HDL,,), is the predominant component. Unlike adult HDL, normal cord blood has a paucity of particles in the (HDL3,),, region, and two distinct components within the (HDL,,),, region. This normal cord blood HDL subclass distribution correlates with plasma cholesterol levels < 85 mg/dl and TG levels < 65 mg/dl(2). In addition to the normal (gge) pattern, two other (gge) patterns have been identified in newborn infants and, in both instances, were associated with abnormal plasma lipid levels (2). One pattern, termed the 2b(gge) pattern, is characterized by an increase in particles in the (HDL2b),e subclass and is found most commonly in cord blood with elevated TC and HDL-C. The other pattern, termed the 3b(gge) pattern, is characterized by a decrease of (HDL,,), and (HDL,,),, particles and by a predominance of particles in the (HDL3,Jgge and (HDL,,), subclasses. This pa...