Jane D. Carver

The role of nucleotides in human nutrition

Abstract Dietary NT are reported to have significant effects upon lymphoid, intestinal and hepatic tissues, and lipid metabolism (Table 3). The mechanism remains unknown, and the nutritional role of NT remains controversial. However, maintenance of the endogenous NT supply via de novo synthesis and salvage is metabolically costly. Preformed NT supplied by the diet may contribute to tissue NT pools and thus optimize the metabolic function of rapidly dividing tissues such as those of the gastrointestinal and immune systems. An exogenous source of NT may be particularly important for individuals whose dietary intake of NT is low and/or whose tissue needs are increased, for example, rapidly growing infants fed most cows milk-based formulas and individuals with disease related immunosuppression, intestinal, or liver injury. Under these conditions, dietary NTs may play a role as conditionally essential nutrients. In addition to serving as nucleic acid precursors, NTs and their related metabolic products are potent inter- and intracellular biological mediators. Certain effects of dietary NT may relate to one or more of these important functions. Area for future study include: 1. 1. The absorption and metabolism of nucleic acids, NTs, NSs, bases, and related metabolic products in humans, and the effects of age and disease upon these activities. 2. 2. Dietary NT effects upon gut-associated lymphoid tissues. 3. 3. The content of nucleic acid, NTs, NSs, bases, and their related metabolic products in human milk. 4. 4. The relative contribution of nucleic acid, NTs, NSs, and free bases to observed biologic effects, and the effects of individually administered purine and pyrimidine compounds.

The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects

The important role that neural tissue fatty acid composition plays in neurodevelopment and various pathological states is increasingly recognized. However, there are limited data regarding the fatty acid composition of normal human brain at various ages. The purpose of this study was to describe human cerebral cortex fatty acid composition from ages 2 to 88 years. The relationship between cerebral cortex and erythrocyte fatty acid composition was also investigated. Samples of frontal cerebral cortex and of erythrocytes were obtained from 58 human subjects on whom autopsies were performed. The mean age of subjects was 40 +/- 29 years, with a range of 2 to 88 years. The fatty acid composition of tissues was determined, and linear regression models were used to describe the relationship between age and the fatty acid composition of cerebral cortex and erythrocytes. The data were bilinear, with changes occurring after the approximate age of 18 years. Therefore, the cohort was divided into subjects with ages < or =18 and >18 years. In the younger group, the polyunsaturated fatty acids generally decreased with age, with the exception of 22:6n3, which demonstrated a significant increase. The level of mono-unsaturated fatty acids, in contrast, generally increased to the age of 18 years. Several of the polyunsaturated fatty acids also decreased with age in the older cohort, particularly 20:4n6. The levels of 18:2n6, however, increased significantly with age in the older cohort. Among subjects < or =18 years of age, there was no significant relationship between cerebral cortex and erythrocyte fatty acid levels. In the older cohort, there was a significant relationship between brain and erythrocyte levels for several fatty acids, particularly 16:0. These data demonstrate that levels of cerebral cortex fatty acids change from early childhood through late adulthood, and indicate that the levels of several erythrocyte fatty acids may be useful in predicting brain fatty acid levels in adults.

Dietary nucleotides: effects on the immune and gastrointestinal systems

Nucleotides (NT) and their related metabolic products play key roles in many biological processes. NT can be synthesized endogenously and thus are not considered essential nutrients. Studies have demonstrated, however, that dietary NT can have beneficial effects; the term “conditionally essential” has been used to describe their role in human nutrition. These nutrients may become essential when the endogenous supply is insufficient for normal function, even though their absence from the diet does not lead to a classic clinical deficiency syndrome. Most dietary NT are rapidly metabolized and excreted. However, some are incorporated into tissues, particularly at younger ages and with fasting. Under conditions of limited NT intake, rapid growth or certain disease states, dietary NT may spare the cost of de novo NT synthesis and optimize the function of rapidly dividing tissues such as those of the gastrointestinal and immune systems. Animals fed NT‐supplemented versus non‐NT supplemented diets have enhanced gastrointestinal growth and maturation, and improved recovery following small and large bowel injury. Indices of humoral and cellular immunity are enhanced, and survival rates are higher following infection with pathogens. Infants receive NT in human milk, where they are present as nucleic acids, nucleosides, nucleotides and related metabolic products. The NT content of human milk is significantly higher than most cows milk‐based infant formulae. Dietary NT are reported to enhance the gastrointestinal and immune systems of formula‐fed infants. Infants fed NT‐supplemented versus non‐supplemented formula have a lower incidence of diarrhea, higher antibody titers following Haemophilus influenzae type b vaccination and higher natural killer cell activity. These data suggest that human milk NT may contribute to the superior clinical performance of the breastfed infant.

Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation

Weanling mice fed chow or chow plus water supplemented with 3.5 mg of nucleotides per 100 ml of water for 6 weeks exhibited increased natural killer cell (NK) activity and lower macrophage activation compared to mice fed chow plus nonsupplemented water. In a dose-response study, NK activity, macrophage activation and spleen weight (as a percentage of body weight) were higher in mice fed up to 0.035% w/w nucleotides, however macrophage activation was decreased by feeding over 0.35% w/w compared to those receiving basal purified diet (BPD). Nucleotides in human milk may affect the immune response in breast-fed infants.

Effect of Docosahexaenoic Acid Content of Maternal Diet on Auditory Brainstem Conduction Times in Rat Pups

Previous studies of dietary docosahexaenoic acid (DHA; 22:6n–3) effects on neurodevelopment have focused mainly on effects on the visual system; these studies may be confounded by effects on the retina rather than on neural pathways. Auditory brainstem conduction times (ABCTs) provide an alternate measure of central neural development. We conducted a dose-response study in which ABCTs were measured in pups whose dams were fed diets containing one of three levels of DHA (2, 4 or 6% of total fatty acids) from a single cell oil. Diets were fed during pregnancy and lactation, and pups were randomly cross-fostered on postnatal day 3 to minimize litter effects. ABCTs showed a dose-response effect, with higher levels of dietary DHA being associated with longer conduction times on postnatal day 31 (p < 0.05). Higher dietary DHA was reflected in pup cerebrums collected on postnatal days 3 and 31, and levels of arachidonic acid (AA, 20:4n–6) were inversely related to levels of DHA. This study demonstrated that the auditory brainstem response is sensitive for identifying effects of diet on neurodevelopment, and that supplementing the maternal diet with high levels of DHA may negatively impact development of the central auditory system of offspring.

Maternal nativity as a risk factor for gastroschisis: A population‐based study

BACKGROUND The prevalence of gastroschisis is increasing in many parts of the world, although the etiology is largely unexplained. Young maternal age has been the only consistently identified, strong risk factor. The objective of this study was to examine the role of maternal nativity in relation to other suspected risk factors for gastroschisis in Florida. METHODS We conducted a retrospective cohort study of singleton infants born in Florida from 1998-2003. Gastroschisis cases were identified from the Florida Birth Defects Registry. Demographic and perinatal data were obtained from birth records. Multivariable Poisson regression was used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for each factor of interest. RESULTS The 6-year birth prevalence of gastroschisis was 3.26 per 10,000 live births, and the annual rate increased 41% during the study period. In addition to maternal age and marital status, maternal race/ethnicity and nativity were significantly associated with the risk of delivering an infant with gastroschisis. Compared with non-Hispanic white women, non-Hispanic black women had the lowest risk of delivering an infant with gastroschisis (PR, 0.19; 95% CI, 0.13-0.26), followed by Hispanic women (PR, 0.60; 95% CI, 0.43-0.83). Women born outside the United States were significantly less likely than U.S.-born women to deliver an infant with gastroschisis (PR, 0.59; 95% CI, 0.41-0.86). CONCLUSIONS Although young maternal age remains a strong significant risk factor for gastroschisis in Florida, other factors such as maternal race/ethnicity and nativity could be important in explaining the increasing prevalence of gastroschisis.

The use of quantitative ultrasound in assessing bone status in newborn preterm infants.

OBJECTIVE: Quantitative ultrasound is increasingly used to assess bone status in adults and children; however, few studies have been carried out in neonates. Our objective was to determine if tibial bone speed of sound (SOS) correlates with gestational age and birth anthropometrics, and if bone SOS is related to maternal factors.STUDY DESIGN: We prospectively studied 95 preterm infants to assess factors related to bone status as measured by quantitative ultrasound.RESULTS: We found significant (p≤0.001) positive correlations between SOS and gestational age, birth weight, length, head circumference and tibial length. There was no significant relationship between SOS and prenatal steroid use, gestational diabetes, pre-eclampsia, race or parity.CONCLUSIONS: Quantitative ultrasound is an easy to use and inexpensive tool for assessing bone status in preterm neonates. Tibial SOS correlated with gestational age and birth anthropometrics, and was not related by few maternal factors.

The Effects of Dietary Nucleotides on Intestinal Blood Flow in Preterm Infants

Nucleotides (NT) are reported to affect development of the immune and gastrointestinal systems, and they are currently added to most term infant formulas. In the present study, dietary NT effects on superior mesenteric artery blood flow were investigated. Formula-fed preterm infants were studied once with a 20 kcal/oz. term infant formula containing 80.6 mg/L of NT (NT+), and once with the same formula with no added NT (NT−) (n = 20, gestational age 28.0 ± 2.2 wk). A reference group of preterm infants fed human milk was also studied (n = 20, gestational age 29.0 ± 1.6 wk). Superior mesenteric artery blood flow velocities (BFV) were measured by Doppler ultrasound 15 min before and 30, 60, and 90 min after the start of the feed. BFV rose in all infants from baseline to 30 min after feed initiation, and progressively declined thereafter in infants fed NT− or human milk. However, NT+ feedings were associated with a minimal change in BFV between 60 and 90 min. As a result, the difference in blood flow velocities between baseline and 90 min was significantly greater with the NT+versus the NT− feedings for the mean, peak systolic, and end diastolic velocities (p = 0.03, 0.05, and 0.03, respectively). BFV after the NT− and human milk feedings were similar. These data suggest that orally administered NT are associated with effects on the intestinal vasculature.

Umbilical artery catheters do not affect intestinal blood flow responses to minimal enteral feedings

Objective:To investigate the effects of umbilical artery catheters (UACs) on superior mesenteric artery (SMA) blood flow velocity (BFV) following enteral feedings in very low birth weight preterm infants.Study design:Very low birth weight preterm infants who had UACs inserted as part of standard clinical care were enrolled in this prospective study. On the day the UAC was scheduled to be removed, pre- and postprandial SMA BFV (mean, peak systolic and end diastolic velocities) were measured in conjunction with a minimal enteral feeding given while the UAC was in place. The same measurements were made with the next feeding given after the UAC was removed. Preprandial measurements were made at least 3 h after the last enteral feeding, and postprandial measurements were made 30, 45 and 60 min after the feeding began. The same volume and type of feeding were used for both studies.Results:The birth weight and gestational age of the 19 infants who completed the study were 1014±221 g and 27.4±1.9 weeks, respectively. Infants were 4.6±1.7-days-old when the first SMA BFV measurement was made, the volume of enteral feedings was 1.3±0.6 ml, and the time between the two enteral feedings was 4.7±3.2 h. Preprandial SMA BFV did not differ with the UAC in place compared with the UAC removed. Peak postprandial velocities were at 45 min after feedings began. The percent increase from baseline was not significantly different with the UAC in place compared with the UAC removed.Conclusions:Preprandial SMA BFV and postprandial SMA BFV responses to minimal enteral feedings were not affected by the presence of a UAC.

Factors that influence mesenteric artery blood flow velocity in newborn preterm infants

Objectives:To identify demographic and clinical variables that relate to the postnatal increase in intestinal blood flow velocity in preterm infants.Study design:Fasting or preprandial peak systolic velocity (PSV) and time-averaged mean velocity (TAMV) in the superior mesenteric artery were measured once each day for the first 5 days of life. We investigated the relationship between blood flow velocity and the following variables: birth weight, gestational age, feeding volumes, number of days to reach full feeding volumes, type of feeding given, continuous positive airway pressure (CPAP) administration and hyperalimentation (HAL) administration.Results:Twenty-five infants with a mean birth weight of 1740 g and mean gestational age of 31.8 weeks were studied. There were significant increases in PSV (P<0.001) and TAMV (P=0.005) from postnatal day 1 to 5. The postnatal increase in TAMV and PSV was attenuated in infants administered CPAP or HAL for ⩾3 days; the results remained significant after controlling for birth weight and gestational age. There was a significant correlation (P<0.02) between volume of enteral feedings given on 2 of 5 days for TAMV, and on 1 of 5 days for PSV.Conclusions:These data support previous findings of significant increases in intestinal blood flow in preterm infants during the first week of life, and of inconsistent effects of enteral feeding volumes on fasting or preprandial intestinal blood flow. The reasons for, and the clinical implications of, attenuated increases in postnatal intestinal blood flow in infants on CPAP or HAL require further investigation.