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A Novel Biochemical Marker in Infants of Lower Birth Weight and Younger Gestational Age

Peter O. Kwiterovich, Jr, MD; Steven L. Cockrill, PhD; Donna G. Virgil, MS; Elizabeth S. Garrett, PhD; James Otvos, PhD; Carolyn Knight-Gibson, MS; Petar Alaupovic, PhD; Trudy Forte, PhD; Lin Zhang, MD, PhD; Zachlyn N. Farwig, PhD; Ronald D. Macfarlane, PhD

JAMA. 2005;293:1891-1899.

Context  Low birth weight is associated with increased cardiovascular disease in adulthood, and differences in the molecular weight, composition, and quantity of lipoprotein subclasses are associated with coronary artery disease.

Objective  To determine if there are novel patterns of lipoprotein heterogeneity in low-birth-weight infants.

Design, Setting, and Participants  Prospective study at a US medical center of a representative sample of infants (n = 163; 70 white and 93 black) born at 28 or more weeks of gestational age between January 3, 2000, and September 27, 2000. This sample constituted 20% of all infants born during the study period at this site.

Main Outcome Measures  Plasma levels and particle sizes of lipoprotein subclasses and plasma concentrations of lipids, lipoproteins (high-density lipoprotein [HDL] and low-density lipoprotein [LDL]), and apolipoproteins.

Results  An elevated lipoprotein peak of a particle with density between 1.062 and 1.072 g/mL was identified using physical-chemical methods. This subclass of large HDL was enriched in apolipoprotein C-I (apo C-I). Based on the amount of the apo C-I–enriched HDL peak, 156 infants were assigned to 1 of 4 groups: 0 (none detected), 17%; 1 (possibly present), 41%; 2 (probably present), 22%; 3 (elevated), 19%. Infants in group 3, compared with those in the other 3 groups, had significantly (P<.001) lower mean birth weight (2683.7 vs 3307.1 g) and younger mean gestational age (36.2 vs 39.3 wk). After correction for age, infants in group 3 had significantly higher levels of total and large HDL cholesterol and of total and large LDL cholesterol and LDL particle number. However, infants in group 3 had lower levels of small HDL, very low-density lipoproteins, and triglycerides than infants in the other 3 groups. This lipoprotein profile differed from that in infants born small for gestational age, who had significantly higher triglyceride (P<.001) and apo B (P = .04) levels, but lower levels of total and large HDL cholesterol (P<.001) and apo A-I (P<.001).

Conclusions  Because apo C-I–enriched HDL, and purified apo C-I alone, promotes apoptosis in vitro, increased amounts of this particle may have physiological significance and identify a novel group of low-birth-weight infants apparently distinct from traditionally classified small-for-gestational-age infants.

Author Affiliations: The Johns Hopkins Medical Institutions, Baltimore, Md (Drs Kwiterovich, Garrett, and Zhang and Ms Virgil); Laboratory for Cardiovascular Chemistry, Texas A & M University, College Station (Drs Cockrill, Farwig, and Macfarlane); LipoScience Inc, Raleigh, NC (Dr Otvos); Oklahoma Medical Research Foundation, Oklahoma City (Dr Alaupovic and Ms Knight-Gibson); and Donner Laboratory, University of California at Berkeley (Dr Forte).

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