Follow-up of a randomized trial on postdischarge nutrition in preterm-born children at age 8 y.

Background: Early nutritional interventions may modulate health risks in preterm-born infants. Previously, we showed that preterm-born infants fed an isocaloric protein- and mineral-enriched postdischarge formula (PDF) from term age to 6-mo corrected age (CA) gained more lean mass than did those fed term formula (TF). Long-term follow-up of randomized nutritional trials is important to test the hypothesis that short-term positive effects on health are sustainable.Objective: The aim of this follow-up study was to compare body size, body composition, and metabolic health at age 8 y in preterm-born children who were randomly assigned to receive either PDF or TF from term age until 6-mo CA.Design: A total of 79 of 152 children (52%) from the original randomized controlled trial were enrolled for follow-up at age 8 y. Weight, height, and head circumference were measured by using standard methods. Body composition, including fat mass, lean mass, bone mineral content, and bone mineral density, was determined by dual-energy X-ray absorptiometry. Blood pressure was measured in the supine position by using an automatic device. Metabolic variables, including glucose, insulin, insulin-like growth factor I, triglycerides, cholesterol, cortisol, and leptin, were measured after an overnight fast. Nutritional habits at age 8 y were assessed by using a 3-d nutritional diary.Results: At age 8 y, no differences were found in body size, body composition, bone variables, and metabolic health variables when comparing children fed PDF with those fed TF. Adjustment for known and possible confounders did not change these results.Conclusions: In this follow-up study in preterm-born children, we showed that the favorable effects of PDF at 6-mo CA either were not maintained or could not be confirmed because of attrition at the age of 8 y. We suggest that future research should focus on nutritional interventions in the pre- and postdischarge period as a continuum rather than as separate entities. This trial was registered at www.trialregister.nl as NTR 2972 (follow-up study [STEP-2 (Study Towards the Effects of Post-discharge Nutrition 2)]) and NTR 55 [original randomized controlled trial (STEP)].

Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term.

PURPOSE: An iron intake of >2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8-1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term. METHODS: At term age, 3 and 6 months post-term, ferritin (µg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated. RESULTS: Iron was supplemented to 71.7% of HM-fed and 83.7% of IFF-fed infants between term age and 3 months post-term and to 13% of HM-fed and 0% of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin <12 µg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8% and 26.3 vs. 9.5%, P < 0.02). CONCLUSION: This observational study demonstrates that ferritin <12 µg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8-1.0 mg iron/100 ml), as they achieve ferritin ≥12 µg/l without additional iron supplements between 3 and 6 months post-term.

Glutamine effects on brain growth in very preterm children in the first year of life.

BACKGROUND & AIMS: Glutamine supplementation in the neonatal period has been associated with increased brain structure volumes at school-age in very preterm children. The aim of this study was to clarify the emergence and specificity of differences in brain structure volumes, using growth trajectories of head circumference, weight, and length. METHODS: Sixty-five very preterm (<32 weeks gestation) children, who originally took part in a randomized controlled trial on glutamine supplementation, participated. Head circumference, weight, and length, were measured at the neonatal intensive care unit, and at routine follow-up assessments at the outpatient clinic and well baby clinics. Magnetic Resonance Imaging was used to determine brain structure volumes at school-age. Growth trajectories were investigated using multilevel modeling analyses. RESULTS: Head circumference in the first year of life was positively associated with white matter volume and grey matter volume (range r = 0.55-0.81, all p < 0.002) at school-age. Furthermore, neonatal glutamine supplementation was associated with increased head circumference growth (p = 0.008) in the first year of life, but not with increased growth in weight (p = 0.44) and length (p = 0.73). CONCLUSIONS: This study indicates a specific increase in head circumference growth in very preterm children that received neonatal glutamine supplementation, and suggests that group differences in brain structure volumes at school-age may have emerged during the first year of life.

Higher vitamin D intake in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula is associated with increased bone accretion.

During the first half of infancy, bone accretion in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula (PDF) is higher compared with those fed term formula (TF) or human milk (HM). This may be related to higher protein, calcium, phosphorus, and vitamin D intakes. This study investigated serum calcium, phosphate, and 25-hydroxyvitamin D [25(OH)D] in relation to bone mineral content (BMC) in PDF-, TF-, and HM-fed preterm infants between term age (40 wk postmenstrual age) and 6 mo corrected age (CA). Between term age and 6 mo CA, 52 preterm infants were fed PDF (per 100 mL: 67 kcal, 1.7 g protein, 65 mg calcium, 38 mg phosphorus, 56 IU vitamin D), 41 were fed TF (per 100 mL: 67 kcal, 1.47 g protein, 50 mg calcium, 30 mg phosphorus, 48 IU vitamin D), and 46 were fed HM. Serum calcium, phosphorus, and 25(OH)D were measured at term age and at 3 and 6 mo CA. BMC (g) was measured by whole-body dual-energy X-ray absorptiometry at term age and at 6 mo CA. Between term age and 6 mo CA, intakes of calcium, phosphorus, and vitamin D were significantly higher in PDF- compared with TF-fed infants, and PDF-fed infants reached significantly higher serum 25(OH)D concentrations at 6 mo CA (103 ± 24.3 vs. 92.8 ± 15.5 nmol/L, P = 0.003). Between term age and 6 mo CA, increases in serum 25(OH)D were associated with an increase in BMC (ß = 0.001; 95% CI: 0.00, 0.003; P = 0.046). In conclusion, during the first 6 mo postterm, higher vitamin D intake and greater increase in serum 25(OH)D concentration in PDF-fed preterm infants were associated with increased bone accretion.

Neutral and acidic oligosaccharides supplementation does not increase the vaccine antibody response in preterm infants in a randomized clinical trial.

BACKGROUND: In preterm infants, a decreased immunological response and lower serological effectiveness are observed after immunizations due to ineffectiveness of both humoral and cellular immune mechanisms. OBJECTIVE: To determine the effect of 80% neutral oligosaccharides [small-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (scGOS/lcFOS)] in combination with 20% pectin-derived acidic oligosaccharides (pAOS) on antibody concentrations after DTaP-IPV-Hib immunization in preterm infants. DESIGN: In this randomized clinical trial, preterm infants with gestational age <32 weeks and/or birth weight <1500 g received enteral supplementation with scGOS/lcFOS/pAOS or placebo (maltodextrin) between days 3 and 30 of life. Blood samples were collected at 5 and 12 months of age. RESULTS: In total, 113 infants were included. Baseline and nutritional characteristics were not different in both groups. Geometric mean titers were not different after prebiotic supplementation at 5 months, Ptx (37/44 EU/ml), FHA (78/96 EU/ml), Prn (78/80 EU/ml), Diphtheria (0.40/0.57 IU/ml), Tetanus (0.74/0.99 IU/ml) and Hib (0.35/0.63 µg/ml), and at 12 months Ptx (55/66 EU/ml), FHA (122/119 EU/ml), Prn (116/106 Eu/ml), Diphtheria (0.88/1.11 IU/ml), Tetanus (1.64/1.79 IU/ml) and Hib (2.91/2.55 µg/ml). CONCLUSIONS: Enteral supplementation of neutral (scGOS/lcFOS) and acidic oligosaccharides (pAOS) does not improve the immunization response in preterm infants. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN16211826 ISRCTN16211826.

Increased gain in bone mineral content of preterm infants fed an isocaloric, protein-, and mineral-enriched postdischarge formula.

PURPOSE: Preterm infants are at risk for suboptimal bone mineralization. Postnatal bone formation requires optimal nutritional composition. This study evaluated the effect of isocaloric, protein-, and mineral-enriched postdischarge formula (PDF), standard term formula (TF), and human milk (HM) on gain in bone mineral content (BMC) of preterm infants between term age (40 weeks postmenstrual age) and 6 months corrected age (CA). METHODS: Between term age and 6 months CA, 93 preterm infants were randomized to be fed PDF (n = 52) or TF (n = 41) and 46 preterm infants were fed HM. Weight (g) and length (cm) were measured at birth, term age, and 6 months CA. BMC (g) was measured by whole-body dual-energy x-ray absorptiometry at term age and 6 months CA. RESULTS: Gain in BMC (expressed as median with interquartile range) between term age and 6 months CA was higher in PDF-fed infants (102.3 (32.4) g) compared to TF- and HM-fed infants (91.6 (24.5) and 84.5 (33.3) g, respectively), adjusted for gender, gestational age, birthweight, and gain in weight and length. CONCLUSION: Between term age and 6 months CA, isocaloric PDF enhances gain in BMC of preterm infants, independent of gain in weight and length. We speculate that higher gain in BMC during infancy may improve adult bone mass in preterm infants.

Effects of glutamine on brain development in very preterm children at school age.

OBJECTIVES: The amino acid glutamine has been shown to reduce the number of serious neonatal infections in very preterm children, which may benefit long-term brain development. The aims of the current follow-up study were to (1) determine the long-term effects of glutamine-enriched feeding in the first month after birth in very preterm children on measures of brain development at school age, and (2) elucidate a potential mediating role of serious neonatal infections. METHODS: Fifty-two very preterm children who originally took part in a randomized controlled trial on enteral glutamine supplementation between day 3 and 30 after birth participated at a mean (SD) age of 8.6 (0.3) years. Measures of brain development included volumetric outcomes of major brain structures, as well as fractional anisotropy (FA) values of major white matter tracts. RESULTS: Glutamine supplementation in the first month was associated with medium-sized increases in white matter (d = 0.54, P = .03), hippocampus (d = 0.47, P = .02), and brain stem (d = 0.54, P = .04) volumes at school age. Exploratory analyses using an uncorrected P value indicated higher FA values of the bilateral cingulum hippocampal tract in the glutamine group. All differences were either strongly associated (hippocampus volume, brain stem volume, and FA values of cingulum hippocampal tract) or completely mediated (white matter volume) by the lower number of serious neonatal infections in the glutamine group. CONCLUSIONS: Short-term glutamine supplementation after birth increases white matter, hippocampus, and brain stem volumes in very preterm children at school age, mediated by a decrease in serious neonatal infections.

Effects of neonatal enteral glutamine supplementation on cognitive, motor and behavioural outcomes in very preterm and/or very low birth weight children at school age.

In very preterm ( < 32 weeks of gestation) and/or very low birth weight (VLBW, < 1500 g birth weight) children, serious neonatal infections are among the main causes of poor developmental outcomes later in childhood. The amino acid glutamine has been shown to reduce the incidence of serious neonatal infections in very preterm and/or VLBW children, while developmental effects beyond 24 months are unknown. We determined the cognitive, motor and behavioural outcomes at school age of a cohort of sixty-four very preterm and/or VLBW children (aged 7·5 (sd 0·4) years) who participated in a randomised placebo-controlled trial using enteral glutamine between day 3 and day 30 of life. Cognitive and motor outcomes were studied using the Wechsler Intelligence Scale for Children-III, the Movement Assessment Battery for Children (MABC), the Attention Network Test and a visual working memory task. Behavioural outcomes were evaluated using parent- and teacher-rated questionnaires. Intelligence quotient, processing speed, attentional functioning, working memory and parent- and teacher-rated behavioural outcomes were not different between children treated with glutamine or placebo; only visuomotor abilities as measured by the Ball Skills scale of the MABC (P = 0·002; d = 0·67) were poorer in the glutamine group. This effect persisted after taking into account the beneficial effects of lower serious neonatal infections rates in children treated with glutamine (P = 0·005). In conclusion, glutamine supplementation between day 3 and day 30 of life had neither beneficial nor detrimental effects on long-term cognitive, motor and behavioural outcomes of very preterm and/or VLBW children at school age, although visuomotor abilities were poorer in children that received glutamine.

Post term dietary-induced changes in DHA and AA status relate to gains in weight, length, and head circumference in preterm infants.

Preterms need supplementation with docosahexaenoic (DHA) and arachidonic (AA) acids to prevent steep postnatal declines. Associations between growth and erythrocyte (RBC) DHA and AA were studied in 139 preterms (51% male, gestational age 30.3±1.5 weeks, birth weight 1341±288g) fed human milk with breast milk fortifier or preterm formula until term, followed by postdischarge formula (PDF; n=52, 0.4% DHA, 0.4% AA), term formula (TF; n=41, 0.2% DHA, 0.2% AA), or human milk (HM; n=46). At six months, PDF resulted in higher RBC-DHA than TF and HM, while RBC-AA was higher than TF, but similar to HM. There were no between-group differences in growth between term and six months. RHC-DHA related positively with gain in weight and length and negatively with gain in head circumference. RBC-AA related positively with gain in head circumference and negatively with gain in weight and length. In conclusion, PDF with higher DHA and AA than TF may promote postnatal growth of preterms.

Effect of neutral and acidic oligosaccharides on fecal IL-8 and fecal calprotectin in preterm infants.

The gastrointestinal inflammatory response may play a role in the susceptibility of preterm infants for infections. We previously reported a trend toward lower endogenous infection morbidity after enteral supplementation of neutral and acidic oligosaccharides (SC GOS/LC FOS/AOS). We hypothesize that enteral supplementation of prebiotics may decrease infectious morbidity by reducing intestinal inflammation. Therefore, we aimed to determine the effect of enteral supplementation of prebiotics on intestinal inflammation, as measured by fecal IL-8 (f-IL-8) and calprotectin (f-calprotectin), in preterm infants. In a randomized controlled trial, infants with a GA <32 wk and/or birth weight <1,500 g received enteral supplementation of prebiotics or placebo (maltodextrin) between d 3 and 30 of life. F-IL-8 and f-calprotectin was assessed at baseline, d 7, 14, and 30 of life. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different in the SC GOS/LC FOS/AOS (n = 55) and the placebo group (n = 58). Enteral supplementation of prebiotics had no effect on f-IL-8 and f-calprotectin. F-IL-8 and f-calprotectin were strongly correlated at all time points (p < 0.001). In conclusion, enteral supplementation of prebiotics (SC GOS/LC FOS/AOS) does not affect f-IL-8 and f-calprotectin levels in preterm infants.

The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants.

Preterm infants have an impaired gut barrier function. We aimed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides (short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides (LCFOS)) and acidic oligosaccharides (AOS) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life. Furthermore, we determined host- and treatment-related factors associated with intestinal permeability. In a randomised controlled trial, preterm infants with a gestational age < 32 weeks and/or birth weight (BW) < 1500 g received enteral supplementation of SCGOS/LCFOS/AOS or placebo (maltodextrin) between days 3 and 30 of life. Intestinal permeability, reflected by the urinary lactulose/mannitol (L/M) ratio after oral ingestion of lactulose and mannitol, was assessed at three time points: before the start of the study (t = 0), at day 4 (t = 1) and at day 7 (t = 2) of life. Data were analysed by generalised estimating equations. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS (n 55) and the placebo groups (n 58). SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2. In both the groups, the L/M ratio decreased from t = 0 to t = 2 (P < 0·001). Low BW increased the L/M ratio (P = 0·002). Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio (P < 0·001 and P < 0·05, respectively). In conclusion, enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life.

Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Serious infectious morbidity is high in preterm infants. Enteral supplementation of prebiotics may reduce the incidence of serious infections, especially infections related to the gastrointestinal tract. OBJECTIVE: The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic oligosaccharides (AOS) on serious infectious morbidity in preterm infants. DESIGN: In a randomized controlled trial, preterm infants (gestational age <32 wk and/or birth weight <1500 g) received enteral supplementation of 80% (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin) between days 3 and 30 of life. Serious infectious morbidity was defined as a culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The analysis was performed by intention-to-treat and per-protocol, defined as > or =50% supplementation dose during the study period. RESULTS: In total, 113 preterm infants were included. Baseline and nutritional characteristics were not different between groups. In the intention-to-treat analysis, the incidence of > or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups. In the per-protocol analysis, there was a trend toward a lower incidence of > or =1 serious endogenous infection and > or =2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants. However, there was a trend toward a lower incidence of serious infectious morbidity, especially for infections with endogenous bacteria. This finding suggests a possible beneficial effect that should be evaluated in a larger study. This trial was registered at isrctn.org as ISRCTN16211826.

Optimal growth and lower fat mass in preterm infants fed a protein-enriched postdischarge formula.

BACKGROUND AND OBJECTIVES: Postdischarge formulas with extra energy and protein improve short-term growth but may also influence long-term body composition in an unwanted manner. Energy- and protein-enriched formulas with an increased protein-to-energy ratio improves gain of lean mass. The objective of the study was to investigate whether feeding a nutrient-enriched formula without extra energy after term, usually 3 to 4 weeks after discharge, would influence growth and body composition in infancy. METHODS: In this randomized controlled trial preterm infants were fed fortified human milk or preterm formula until term. At term, 102 infants were randomized to a nutrient-enriched formula without extra energy or standard formula until 6 months corrected age. Twenty-six infants received unfortified human milk after term. At term and 6 months corrected age, anthropometry and a dual-energy x-ray absorptiometry (DEXA) scan were performed. Lean and fat mass (FM) were corrected for height. RESULTS: There were no differences in growth or body size between the feeding groups. Infants fed the enriched formula gained less FM and had lower FM corrected for body size at 6 months corrected age than infants fed standard formula. Infants fed human milk had lower lean mass and higher FM corrected for body size at 6 months corrected age than formula-fed infants. CONCLUSIONS: Feeding nutrient-enriched formula without extra energy after term does not change quantity of growth but does influence type of weight gain and body composition of preterm infants. Infants fed the nutrient-enriched formula had lower FM corrected for body size at 6 months corrected age than infants fed standard formula or human milk.

Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study.

BACKGROUND: Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut. METHODS/DESIGN: In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated. DISCUSSION: Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16211826.

A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations.

OBJECTIVE: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short-term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants. METHODS: In a double-blind placebo-controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. RESULTS: Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non-essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30). CONCLUSIONS: Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.

Whole body protein turnover and urea production of preterm small for gestational age infants fed fortified human milk or preterm formula.

OBJECTIVES: To investigate protein metabolism and urea production in preterm small for gestational age neonates fed a preterm formula or fortified human milk. METHODS: Ten preterm small for gestational age neonates were fed either their own mother's milk fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1-13C]valine. Urea production was determined from steady-state [13C]urea kinetics. RESULTS: Mean protein intake was 24% higher in the preterm formula group than in the fortified human milk group. No differences in protein turnover, synthesis and breakdown were observed between the two groups, but protein accretion was 71% to 79% higher in the preterm formula group than the fortified human milk group. Urea production rates were not different in the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics. CONCLUSIONS: Preterm formula and fortified human milk appear equally well tolerated by preterm small for gestational age neonates, but protein accretion was higher in the preterm formula group. In preterm small for gestational age infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.

Arginine and mixed amino acids increase protein accretion in the growth-restricted and normal ovine fetus by different mechanisms.

Protein metabolism may be perturbed in intrauterine growth restriction (IUGR). Arginine is indispensable for growth and nitrogen balance in young mammals. Fetuses with IUGR therefore may benefit from arginine supplementation. The purpose of this study was to determine 1) the effects of IUGR on protein metabolism in the ovine fetus and 2) the effects of arginine or mixed amino acid (AA) infusion on protein metabolism in these fetuses. Pregnant ewes and their fetuses were catheterized at 110 d gestation and randomly assigned to control or IUGR groups. IUGR was induced by repetitive placental embolization. Parameters of fetal protein metabolism were determined from [ring-(2)H(5)]phenylalanine kinetics at baseline and in response to a 4-h infusion of either arginine or an isonitrogenous AA mixture. There were no differences in protein metabolism between control and IUGR groups either at baseline or in response to arginine or AA treatment. Both arginine and AA infusion increased fetal protein accretion in both groups. Arginine did this by decreasing protein turnover, synthesis, and breakdown. AAs increased protein turnover and synthesis while decreasing protein breakdown. AA infusion resulted in a significantly higher increase in protein accretion than arginine infusion. Thus, in the ovine fetus, placental embolization has no clear effect on protein metabolism. Arginine and AAs both stimulate protein accretion but do so in distinctly different ways. Mixed AA infusion has a greater effect on protein accretion than arginine alone and therefore may be a better strategy for stimulating fetal growth.