Nasal continuous positive airway pressure affects pre- and postprandial intestinal blood flow velocity in preterm infants.

OBJECTIVE: To measure the effect of nasal continuous positive airway pressure (CPAP) on intestinal blood flow velocity responses to enteral feedings and left ventricular output (LVO). STUDY DESIGN: Eighteen infants completed the study (birth weight 1793+/-350 g, gestational age 32.1+/-1.1 weeks). On the day infants were weaned from CPAP to room air, pre- and postprandial (0, 30, 60 and 90 min after feeding) mean velocity (MV), peak systolic velocity (PSV) and end diastolic velocity (EDV) were measured for one feeding given when receiving CPAP ('on CPAP'), and for one feeding given after CPAP had been discontinued ('off CPAP'). Preprandial LVO was measured before and after CPAP discontinuation. RESULT: MV and PSV were significantly lower when infants were on CPAP (P<0.05). Maximum postprandial MV, PSV and EDV occurred at 30 min when on CPAP and at 60 min when off CPAP. Preprandial LVO was similar when infants were on and off CPAP. CONCLUSION: CPAP administration affects pre- and postprandial intestinal blood flow velocity, which may impact tolerance to enteral feedings.

Bone ultrasound velocity in small- versus appropriate-for-gestational age preterm infants.

OBJECTIVE: To compare bone status of small-for-gestational age (SGA) versus appropriate-for-gestational age (AGA) newborn preterm infants. STUDY DESIGN: Tibial speed of sound (SOS) was measured in 144 infants categorized as SGA or AGA using the reference tables of Lubchenco et al. and Alexander et al. RESULTS: By the Lubchenco tables, 22% of infants were SGA and 75% were AGA. The mean gestational ages of SGA and AGA were similar (33.3+/-2.6 and 32.5+/-2.4 weeks, respectively, P = 0.09); however, SGA infant birth weights were lower (1329+/-392 and 1829+/-481 g, respectively, P<0.001). SOS values were higher for SGA versus AGA infants (3098+/-135 and 3003+/-122 m/s, respectively. P<0.001). Use of the Alexander tables yielded a twofold increase in the percent of infants categorized as SGA; SOS values remained significantly greater for SGA infants (P<0.001). CONCLUSION: Higher tibial SOS values in SGA versus AGA infants indicate greater bone strength.

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 > or =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.

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.

Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.

OBJECTIVE: At hospital discharge, preterm infants may have low body stores of nutrients, deficient bone mineralization, and an accumulated energy deficit. This double-blind, randomized study evaluated the growth of premature infants with birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from hospital discharge to 12 months' corrected age (CA). METHODS: Infants were randomized to PDF or TF a few days before hospital discharge with stratification by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12 months' CA. Growth was evaluated using analysis of variance controlling for site, feeding, gender, and birth weight group. Interaction effects were also assessed. Secondary analyses included a repeated measures analysis and growth modeling. RESULTS: One hundred twenty-five infants were randomized; 74 completed to 6 months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2 months' CA, and were longer at 3 months' CA. There were significant interactions between feeding and birth weight group-among infants with birth weights <1250 g, those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in head circumference from study day 1 to term and to 1 month CA. The repeated measures and growth modeling analyses confirmed the analysis of variance results. The PDF formula seemed to be of particular benefit for the growth of male infants. Infants fed the PDF consumed less formula and had higher protein intakes at several time points. Energy intakes, however, were not different. CONCLUSIONS: Growth was improved in preterm infants fed a nutrient-enriched postdischarge formula after hospital discharge to 12 months' CA. Beneficial effects were most evident among infants with birth weights <1250 g, particularly for head circumference measurements.

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.

Transcutaneous absorption of vitamin A in newborn rats.

Very low birth weight neonates have low tissue concentrations of vitamin A, which may contribute to the development of lung disease. These infants, however, may not receive vitamin A supplementation for several days after birth. We determined if the relatively permeable skin of a newborn could be used to administer vitamin A. 25 control rat pups were killed and lungs and livers were collected. 20 microl (1,000 IU) of retinyl palmitate were applied to the skin surface of an additional 50 two-day-old pups. At 2.5 and 5 h after application, 25 pups were killed, and lungs and livers were collected. Concentrations of retinyl palmitate and retinol were significantly higher in the lungs of pups 5 h after administration of vitamin A compared with controls. There were no differences in concentrations of retinyl palmitate or retinol in livers. We conclude that transcutaneous administration may be an effective means of delivering vitamin A to the lungs of newborn rats.

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 cow's 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.

The fatty acid composition of maternal diet affects the response to excitotoxic neural injury in neonatal rat pups.

Fatty acids and their derivatives play a role in the response to neural injury. The effects of prenatal and postnatal dietary fatty acid composition on excitotoxic neural injury were investigated in neonatal rat pups. Dams were fed during gestation and lactation a diet whose fat source was either corn oil or menhaden fish oil. On postnatal day 3, litters were culled to 10 per dam. On postnatal day 4, excitotoxic neural injury was induced by infusion of the glutamate analog N-methyl-DL-aspartate (NMA) into the left cerebral hemisphere. Three days later, pups were killed and brains were removed for histological and volume assessments. Levels of arachidonic acid were 2.3-fold higher in cerebrums of pups in the corn oil group than in the fish oil group. Left cerebral hemispheres among all pups were atrophic. Right cerebral hemispheres of pups in the corn oil group showed more histological evidence of edema, and had significantly higher volumes than pups in the fish oil group (66 vs. 42 mm2, p=0.007). These data suggest that the fatty acid composition of prenatal and/or postnatal diet can affect the neonatal response to excitotoxic neural injury.

Maternal diet fatty acid composition affects neurodevelopment in rat pups.

The effect of pre- and postnatal maternal dietary fatty acid composition on neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning on d 2 of gestation and throughout lactation, either nonpurified diet (reference) or a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams of the same diet group and culled to 10 pups per dam. Milk was removed from stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups were assessed daily for the appearance of neurodevelopmental reflexes. Auditory brainstem conduction times were measured on postnatal d 23 and 29. Pups were killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The fatty acid composition of maternal milk and pup cerebrums reflected maternal diet with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil groups, respectively. The time of appearance of auditory startle was significantly delayed (P = 0.004), and auditory brainstem conduction times on postnatal d 23 and 29 were significantly longer in pups of the fish oil- than corn oil-fed dams (P

Postnatal inositol levels in preterm infants.

OBJECTIVE: To measure plasma inositol levels in preterm infants fed formula containing inositol at levels close to those in human milk. STUDY DESIGN: Plasma inositol levels were measured in 72 preterm infants fed formula containing 1110 mumol/L inositol and in cord blood of 12 healthy term infants. Preterm infant plasma levels were measured four times: (1) within the first 7 days of life, (2) intermediate enteral feeding, (3) at hospital discharge, and (4) 2 months after hospital discharge. RESULTS: Inositol concentrations in term cord blood samples were significantly lower than in preterm initial feeding, intermediate feeding, and discharge samples. Initial concentrations in blood of preterm infants were higher than in all other groups, and were significantly lower among infants with gestational ages of 31 to 33 weeks compared with those of 28 to 30 or 31 to 33 weeks. Days of parenteral nutrition were a significant predictor of inositol levels in the full feeding sample, with lower levels associated with prolonged parenteral nutrition. Clinical outcomes were not related to plasma inositol levels. CONCLUSIONS: Feeding preterm formula with inositol levels close to those reported for human milk may not prevent the postnatal decline in preterm infant plasma inositol levels.

The fatty acid composition of maternal diet affects lung prostaglandin E2 levels and survival from group B streptococcal sepsis in neonatal rat pups.

Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators. The effects of maternal dietary fatty acid composition upon lung prostaglandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups. Beginning on d 2 of gestation and throughout lactation, pregnant dams were fed a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered to dams of the same diet group to minimize litter effects; litters were then culled to 10 pups per dam. On postnatal d 7, pups were either injected with 1 x 10(7.5) GBS organisms or were killed for determination of lung tissue levels of PGE2 and lung and erythrocyte fatty acid composition. Arachidonic acid and PGE2 levels were significantly higher in the lungs of pups in the corn oil group compared with the fish oil group. Forty-nine percent of pups in the corn oil group survived the GBS challenge compared with 79% of pups in the fish oil group (P = 0.0005). These data suggest that the fatty acid composition of pre- and/or postnatal diet affects the neonatal response to immune challenge, which may be due in part to effects upon the synthesis of pro-inflammatory mediators.

Trophic factors for the gastrointestinal tract.

GI trophic factors that influence the coordinated pre- and postnatal growth and development of the GI tract have been identified. Studies in animals and humans demonstrate that GI trophic factors can initiate cellular growth and expression of differentiated function, and they are important in adaptation and repair following injury. Systemically as well as enterally administered growth factors can stimulate GI growth and maturation, suggesting that trophic factors in the serum of neonates may modulate GI growth via receptors on the serosal membranes of enterocytes. GI trophic factors may be synthesized endogenously or provided postnatally in milk. GI trophic factors in human milk play an important role in regulating the adaptive functional changes that accompany the transition to postnatal enteral feedings. Although human milk growth factors do not appear to be essential for infant survival, the elevated risk of gastrointestinal-related illnesses in formula-fed as compared with breast-fed infants (diarrhea, necrotizing enterocolitis, colitis, Crohn's disease) suggest that bioactive compounds in human milk contribute to the apparent protective effect of breast feeding. GI trophic factors have the potential to be used therapeutically to enhance GI maturation and repair following injury. These applications may be particularly useful in the premature or postsurgical infant. Several issues require further research, including (1) the mechanism of action, (2) the efficacy of oral versus systemic administration, (3) characterization of the complex interactions between the various growth factors, because some appear to act synergistically, (4) the effect of exogenously administered growth factors on endogenous production of that factor, its receptor, or other growth factors, (5) the effect of growth factors upon tissues not directly associated with the GI tract, and (6) the determination of safe and effective upper limits.

Diet affects hepatocyte membrane composition, fluidity, and taurocholate transport in suckling rats.

We postulated that age-related changes in hepatocyte basolateral membrane lipid composition might contribute to the diminished Na(+)-dependent taurocholate transport noted in suckling animals. Basolateral membrane vesicles (BLMVs) were prepared from suckling rats (day 11) whose dams were fed diets predominant in lard (LBLMV), corn oil (COBLMV), or fish oil (FOBLMV). Fatty acid compositions of milk and BLMV differed significantly among the groups. Membrane cholesterol was higher in FOBLMV compared with the COBLMV and LBLMV groups; lipid phosphorus and the relative distribution of phospholipid classes were similar. Fluorescence anisotropy (1,6-diphenyl-1,3,5-hexatriene) was higher in FOBLMV (0.230) than in LBLMV (0.222) or COBLMV (0.217). Excited state lifetimes were similar in all groups. Na(+)-dependent taurocholate transport was increased at 5 and 20 s in LBLMV and COBLMV compared with FOBLMV. In vitro alteration of membrane cholesterol-fluidity did not alter taurocholate transport. In conclusion, although affected by alterations in diet, simple changes in membrane fluidity-cholesterol content do not affect Na(+)-dependent taurocholate transport.

Dietary nucleotides affect hepatic growth and composition in the weanling mouse.

The effect of dietary nucleotides upon hepatic growth and composition was examined in weanling mice. For 5 weeks, mice were fed either Purina Rat Chow, a nucleotide-free diet (NT-), a nucleotide-free diet supplemented with a mixture of five nucleotides (0.21% w/w), (NT+) or a nucleotide-free diet supplemented with adenosine 5'-monophosphate (0.0425% w/w) (NTA). Hepatic cholesterol and lipid phosphorous were significantly higher, whereas liver weight (expressed as a percentage of body weight), and glycogen were lower in animals fed NT- vs all other groups. NTA-fed animals presented a greater contrast to the NT- group than did animals fed the mixture of nucleotides. Liver fatty acid composition and distribution of phospholipid subclasses were not affected by dietary nucleotide supplementation. Dietary nucleotide supplementation in weanling mice affects hepatic growth and composition; adenosine 5'-monophosphate may play a unique role in these effects.

Dietary nucleotides: cellular immune, intestinal and hepatic system effects.

Investigations with animals demonstrate that dietary nucleotides influence immune function. Restriction of dietary nucleotides in mice decreases several indices of cell-mediated immunity as well as resistance to challenge with Staphylococcus aureus or Candida albicans. Spleen cells of mice maintained on nucleotide-free diet produce less interleukin-2 and have lower natural killer cell cytotoxicity and macrophage activation than those of animals fed nucleotide-supplemented diets. In vivo lymphoproliferative response, macrophage phagocytic activity and expression of interleukin-2 receptor and lyt1 surface marker are also lower in animals fed nucleotide-free diets. At 2 mo of age, infants fed breast milk or nucleotide-supplemented infant formula exhibit increased natural killer cell activity compared with infants fed unsupplemented formula. Dietary nucleotide restriction in animals may also result in hepatic lipid accumulation and decreased mucosal height and gut wall thickness. Adenosine monophosphate, a mediator of hepatic and small bowel blood flow, may play a unique role among the nucleotides studied. In conclusion, de novo synthesis and salvage of nucleotides is a metabolically costly process. An exogenous source of nucleotides from the diet may optimize the function of rapidly dividing tissues, particularly when growth is rapid and the diet is low in nucleotides.

Infant mortality statistics do not adequately reflect the impact of short gestation.

OBJECTIVE: To determine the accuracy of National Center for Health Statistics cause-specific infant mortality data. The National Center for Health Statistics compiles these data by applying World Health Organization (WHO) selection rules to death certificate data. The WHO rules arrange medical entities into a hierarchical order and select a single underlying cause of death (ULCD). DESIGN: A comparison was made between ULCD assigned to a cohort of 335 infant death certificates by (1) a neonatologist panel, and (2) application of WHO selection rules by the Florida State Office of Vital Statistics (OVS). RESULTS: Among the 146 infants with birth weights 1500 to 4649 g, agreement between neonatologists and OVS was 88%, while among the 189 infants with birth weights 0 to 1499 g (very low birth weight), agreement was just 41%. Neonatologists selected short gestation as the underlying cause of death for 82% of very low birth weight infant records, vs 25% by OVS. Due to the application of specific WHO selection rules, OVS frequently selected immediate causes of death, such as "cardiac arrest," as the ULCD, even when the medical certifier had indicated short gestation as the ULCD. In vital statistics reports, many of these immediate causes are reported as "other respiratory conditions of newborn," or "all other perinatal conditions." CONCLUSION: WHO ULCD selection rules should be modified to allow short gestation to have a higher priority over immediate causes of infant death.

Dietary nucleotide effects upon immune function in infants.

Nucleotide (NT) nitrogen, a component of nonprotein nitrogen, accounts for approximately 0.1% to 0.15% of the total nitrogen content of human milk. The results of studies in animals indicate that dietary NTs may be required for maintenance of normal immune function. Thirty-seven healthy term infants were either breast-fed (n = 9) or fed SMA formula supplemented with 33 mg of NTs per liter (n = 13, NT+) or standard SMA formula (n = 15; NT-). At 2 months of age, natural killer cell percent cytotoxicity was significantly higher in the breast-fed and NT+ groups compared with the NT- group (41.7 +/- 4.7, 32.2 +/- 3.4, 21.7 +/- 2.2%, respectively). Interleukin-2 production by stimulated mononuclear cells was higher in the NT+ compared with the NT- group at 2 months of age (0.90 +/- 0.28 U/mL, 0.27 +/- 0.11 U/mL, respectively); neither formula-fed group differed significantly from the breast-fed group. Rate of growth and incidence and severity of infections did not differ significantly among dietary groups. Nucleotides may be a component of human milk that contributes to the enhanced immunity of the breast-fed infant.