Lactation is a physiologic state in which the nutritional status of the mother can have a profound impact on the growth and development of the child. A large body of literature suggests that adequate neonatal intake of docosahexaenoic acid (DHA) is critical for optimal brain maturation. However, the neonate has a limited capacity to convert dietary essential fatty acid precursors into DHA; thus, the infant may be critically dependent upon mother's milk for an adequate supply of DHA. However, the lactating breast cannot synthesize DHA; thus it must derive from dietary sources. Post-prandial chylomicrons play a central role in the transport of dietary DHA to the lactating breast. Therefore, maternal genetic polymorphisms that alter chylomicron metabolism could also affect the efficiency of DHA transport into breast milk, and could ultimately be a major determinant as to whether an infant receives an adequate DHA intake. We therefore propose the following hypotheses: 1) In the post prandial state the magnitude and duration of post prandial chylomicronemia will directly correlate with the transport efficiency of dietary DHA into breast milk; 2) Genetic polymorphisms that modulate chylomicron assembly, intravascular metabolism, or hepatic clearance will have a direct impact on the transport efficiency of dietary DHA into breast milk. To examine these hypotheses we propose two specific aims: 1) Examine postprandial chylomicron metabolism in an unselected cohort of lactating women and correlate chylomicron DHA transport with the transport of DHA into breast milk; 2) Examine the specific impact of the apo A-IV-2 allele, which is known to delay chylomicron clearance, on postprandial chylomicron metabolism and the transport of DHA into breast milk in matched cohorts of allele carriers and controls. We anticipate that data forthcoming from this pilot study could establish the foundation for future studies of other genetic polymorphisms that regulate the nutritional content of breast milk. This knowledge could eventually enable the identification of women who require specific fatty acid or vitamin supplementation to assure optimal infant nutrition.

R03DK062226

2002-07-01

2004-10-31