Jeanette M. Peeples

Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin.

Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid(AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for ≥3 mo(n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.

Long-Term Feeding of Formulas High in Linolenic Acid and Marine Oil to Very Low Birth Weight Infants: Phospholipid Fatty Acids

ABSTRACT: Red blood cell (RBC) phospholipids of infants fed human milk compared with formula have more arachidonic acid (AA) and docosahexanoic acid (DHA). The addition of low levels of marine oil to infant formula with 0.6 to 2.0% α-linolenic acid (LLA, 18:3n-3) prevented declines in DHA in formula-fed infants; however, the feeding trials were short (4 to 6 wk), LLA concentrations were low compared with current formulas (3.0 to 5.0% LLA), and the formulas were unstable. Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and, in fact, if it was necessary with higher intakes of LLA. The results of acute (4 wk) and extended (to 79 wk postconception) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here. Control formulas were identical to commercially available formulas. Experimental formulas differed only in the addition of small amounts of marine oil. DHA in RBC and plasma phosphatidylethanolamine (PE) declined during four weeks of feeding but not if marine oil provided DHA (0.2% or 0.4%) and plasma phospholipid AA (g/100 g) decreased with time and marine oil feeding. Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium; however, RBC (g/100g) and plasma AA (g/100 g; mg/L plasma) decreased progressively until late infancy and were depressed further by marine oil. We conclude that 1) AA and DHA decline in RBC and plasma phospholipids of preterm infants when only their n-6 and n-3 fatty acid precursors are consumed; and 2) marine oil can maintain cord concentrations of RBC phosphatidylethanolamine DHA but further reduces AA.

High-DHA eggs: feasibility as a means to enhance circulating DHA in mother and infant.

Dietary DHA enhances infant attention and visual development. Because the DHA content of red blood cells and plasma lipids varies approximately threefold in pregnancy, maternal DHA status may influence subsequent infant function. It would be feasible to study the effects of higher maternal DHA intake on infant development if dietary intake of DHA could be increased by a reliable means. This study was designed to determine whether women provided with one dozen high-DHA hen eggs (135 mg DHA/egg) would consume the eggs and have higher blood DHA levels than women consuming ordinary eggs (18 mg DHA/egg). The study was a randomized, double-masked comparison of the effect of eggs with different concentrations of DHA on intake and blood lipid DHA content of women and their infants. A third nonrandomized group ate few eggs. In this study, DHA intake reported from eggs was eightfold higher in the high-DHA egg group compared to the ordinary egg group. Including all groups, DHA intake ranged from 0 to 284 mg/d. In this intake range, maternal blood lipid DHA content at enrollment best predicted DHA content at delivery, accounting for 36.5 and 51.7% of the variance in ordinary and high-DHA egg intake groups, respectively. The high-DHA vs. ordinary egg groups had similar maternal and cord blood lipid DHA, but there was a positive relationship between maternal plasma phospholipid DHA and daily DHA intake from eggs controlled for study duration (r=0.278, P=0.048). DHA intake and birth weight were also correlated (r=0.299, P=0.041). High-DHA eggs were well accepted and increased DHA intake. Other benefits of DHA intake during pregnancy were also suggested.

Effect of vegetable and marine oils in preterm infant formulas on blood arachidonic and docosahexaenoic acids

Adding docosahexaenoic acid (DHA) (22:6n-3) to formulas is more effective than increasing formula alpha-linolenic acid (18:3n-3) in maintaining blood phospholipid DHA levels similar to those in breast-fed infants. However, in long-term trials supplementary DHA given as marine oil reduces blood phospholipid arachidonic acid (AA) in preterm infants. This effect is not seen in short-term trials unless the total n-3 intake from marine oil exceeds 0.5% of the total fatty acids. In addition, there is considerable variability among individual preterm infants in blood phospholipid AA and DHA levels that is not dependent on diet. Within dietary treatments, a significant positive correlation between AA and DHA concentrations suggests that factor(s) other than marine oil supplementation affect both AA and DHA status. Docosahexaenoic acid and AA concentrations in plasma phospholipids are significantly correlated with DHA and AA concentrations in red blood cell phospholipids, suggesting that the observed individual differences in DHA and AA within groups represent true differences in fatty acid status. Preterm infants appear to be vulnerable to a poor status of both DHA and AA; further feeding trials are needed to identify the optimal balance of fatty acids for feeding these infants.

RELATIONSHIP OF ISOMERIC FATTY ACIDS IN HUMAN CORD BLOOD TO N3 AND N6 STATUS.† 1808

Trans isomers (t) and cis positional isomers (cp) of unsaturated fatty acids in the food supply are transferred from mother to fetus during pregnancy. Several European studies have found an inverse relationship between human fetal/preterm t and long chain n3 and n6 fatty acids derived from the essential fatty acids, which could have consequences for growth and neurodevelopment. We measured maternal (M) and cord blood (CB) plasma phospholipid (PL) and triglyceride (TG) fatty acids in 50 mother-term infant pairs. Plasma lipids were extracted, PL and TG separated, and fatty acid methyl esters (FAMES) prepared by standard procedures. FAMES were separated by capillary (SP-2560, 100 m × 0.25 mm) gas chromatography. M t intake(Harvard/Willett Food Frequency Questionnaire) correlated with MPL 18:1 t(n7-n11, g/100 g total fatty acids), which correlated with CBTG and CBPL 18:1 t (FASEB J 1996, in press). MPL 18:1 t and 18:1 cp (n5-n7) were also correlated (r=0.636, p<0.0001), and MPL 18:1 cp correlated with 18:1 cp in both CBTG (r=0.330, p<0.03) and CBPL (r=0.383, p<0.01). Having demonstrated relationships between M and CB 18:1 t and cp, we asked if these fatty acids in CB were related to CBPL docosahexaenoic acid (DHA, 22:6n3) and arachidonic acid (AA, 20:4n6). Both CBTG 18:1 t and cp were inversely related to CBPL DHA (r=-0.316, p<0.03 and r=-0.587, p<0.0001, respectively). CBTG 18:1 cp (but not t) was also inversely related to CBPL AA (r=-0.513, p<0.0001). Like CBTG 18:1 cp, CBPL 18:1 cp (but not t) was inversely correlated with CBPL AA (r=-0.498, p<0.0003) and CBPL DHA (r=-0.614, p<0.0001). Compared with t, cp may have been a more sensitive indicator of the inverse relationships between isomeric fatty acids and CBPL DHA and AA because cp was found in 3.6-fold (CBTG) and 6.3-fold (CBPL) higher amounts. On the basis of the relationships shown here, higher circulating M t and cp can be linked to poorer DHA and AA status at term birth, the consequences of which remain to be determined. Supported by Medical Student Research Fellowship Grant (USPHS GR DK07405).

Bioinformatic analysis of gene regulation in the metal-reducing bacterial family Geobacteraceae

Background Knowledge of how structural genome differences among microorganisms lead to variation in gene regulation is fundamentally important for our understanding of the functioning of gene regulatory pathways and their individual components. This knowledge is also necessary for our better understanding of the genomic changes leading to adaptation to diverse and changing environments. Our research focuses on Geobacteraceae, a metal-reducing family of delta-Proteobacteria, which are capable of harvesting electricity from organic matter and environmental bioremediation of organic and metal pollutants. We are investigating molecular mechanisms which allow these species to adapt and regulate their responses to environmental stimuli, which result in energy production and removal of environmental pollutants. Materials and methods In this presentation, we describe computational analysis of gene regulation in multiple species from this family. Our ongoing analyses include cataloguing and integrating information about gene regulation, in silico prediction of transcription factor binding sites, and investigation of functional effects of genome-scale and single nucleotide and amino acid level changes in transcription factors, operons, and regulatory sequence elements in Geobacteraceae. Specifically, we discuss our computational pipeline for comparative analyses of variation in regulatory organization among species and strains of Geobacteraceae, which allows us to investigate changes in operon organization and to track the effects of operon rearrangements and individual single nucleotide base pair level changes on regulatory sequence elements. We also describe our computational analyses of two systems of gene expression, one of gene regulation by the PilR enhancer binding protein and another by the TetR family of transcriptional regulators. Finally, we describe our ongoing efforts to catalog available information on gene regulation and operon organization of Geobacter sulfurreducens, a model representative of the Geobacteraceae family.

Bioinformatic analysis of gene regulation in Geobacter sulfurreducens

Address: 1Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA, 2Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA, 3Departamento de Ingenieria Celular y Biocatalisis, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Cuernavaca 62271, Mexico, 4Department of Molecular Microbiology, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Cuernavaca 62271, Mexico and 5Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA