The Effect of Maternal Milk on Tolerance and Growth in Premature Infants: A Hypothesis-generating Study.

OBJECTIVE: Early growth rates and feeding advancement rates of preterm infants are thought to influence later health. Feeding advancement is often difficult because of feeding intolerance. Exclusive human milk feeding improves tolerance, but can result in a lower weight gain rate. The addition of human milk fortifier has advantages for growth, but there are concerns that it may nullify the beneficial effect of human milk on tolerance. Therefore, the objective of the present study was to evaluate the relation between the amount of fortified human milk or formula and feeding tolerance and growth in preterm infants. METHODS: Patients (n = 174) participating in the TOL trial and born with a gestational age 30 weeks or younger were divided into tertiles according to the amount of human milk received during feeding advancement. Data on feeding tolerance during the advancement phase of enteral nutrition and anthropometrics were analysed. RESULTS: The infants (n = 59) receiving the lowest percentage of their enteral intake as human milk (0%-57%) had the lowest amount of gastric residuals (P = 0.034) compared with the other 2 tertiles. Time to reach full enteral feeding and other tolerance parameters were not different among the groups. There was no dose response effect of the amount of human milk consumed on growth. CONCLUSIONS: In preterm infants, an association between type of feeding (human milk vs infant formula) and time to achieve full enteral feeding or short-term growth was not found. Future prospective trials are needed to verify our results and focus on means to improve tolerance further.

Intermittent Bolus or Semicontinuous Feeding for Preterm Infants?

OBJECTIVES: The aim of the present study was to assess the clinical benefits and risks of semicontinuous (CON) versus intermittent nasogastric tube feeding in low-birth-weight infants. METHODS: Infants with a birth weight <1750 g and gestational age <32 weeks were stratified according to birth weight and assigned to either CON or intermittent bolus (BOL) feeding. The primary endpoint was days to full enteral feeding (defined as 120 mL(-1) · kg(-1) · day(-1)). We also collected data on feeding tolerance, weight gain, respiratory support, and complications (sepsis, necrotising enterocolitis, and death). RESULTS: There was no difference between the 2 groups (CON n = 121, BOL n = 125) in days to reach full enteral feeding--7 (5-10) versus 6 (5-8) days, respectively, with a difference 1 (-0.05 to 2.1). Mean daily gastric residual volumes, however, were significantly lower in the BOL group (4.8 vs 3.9 mL/day, difference 0.9 mL/day [0.1-1.7]), as was the total number of patients with feeding interruptions (76 vs 59, difference 16% [3%-28%]). CONCLUSIONS: Bolus and continuous feeding are equally suitable feeding strategies for preterm neonates. BOL feeding, however, may be preferable.

Phenylalanine requirements of enterally fed term and preterm neonates.

BACKGROUND: Phenylalanine, which is an essential aromatic amino acid, is either used for protein synthesis or irreversibly hydroxylated to tyrosine. The provision of optimal amounts of dietary phenylalanine is not only important for growth and development but might also influence catecholamine synthesis and release rates. The current recommended aromatic amino acid requirement for infants aged 0-6 mo is based on the amino acid content of human milk. OBJECTIVE: We quantified the requirements for phenylalanine in the presence of excess tyrosine (166 or 177 mg/kg per day for term and preterm infants, respectively) for term and preterm neonates by using the indicator amino acid oxidation method with l-[1-(13)C]lysine 2HCl as an indicator. Hence, we determined the minimum obligatory phenylalanine requirement. DESIGN: Fully enterally fed term and preterm infants received randomly graded amounts of phenylalanine (5-177 mg/kg per day) as part of an elemental formula. Data are expressed as means ± SDs. RESULTS: Twenty term (birth weight: 3.19 ± 0.34 kg; gestational age: 38.9 ± 1 wk) and 16 preterm (birth weight: 1.75 ± 0.17 kg; gestational age: 32.5 ± 0.6 wk) Asian infants participated at a postnatal age of 17 ± 8 d. In total, 44 studies were performed. The minimum obligatory phenylalanine requirement was 58 mg/kg per day (95% CI: 38-78 mg/kg per day) and 80 mg/kg per day (95% CI: 40-119 mg/kg per day) for term and preterm infants, respectively. CONCLUSION: The determined mean phenylalanine-requirement estimates are lower than the contents of term and preterm formulas currently on the market. This trial was registered at www.trialregister.nl as NTR1610.

Threonine Requirement of the Enterally Fed Term Infant in the First Month of Life.

OBJECTIVE: Threonine is one of the essential amino acids. Its major fate is incorporation into intestinal mucosal proteins and synthesis of secretory glycoproteins. Therefore, it has an important function in the neonatal gut barrier integrity. The objective was to quantify the threonine requirement in fully enterally fed term neonates by means of the indicator amino acid oxidation (IAAO) method, using L-[1-C]phenylalanine as indicator. METHODS: After a 24-hour test diet adaptation, containing randomly assigned amounts of threonine (range 5-182 mg · kg · day), the participating neonates received a primed continuous infusion of [C]bicarbonate and L-[1-C]phenylalanine. At baseline and during the plateau phase of both infusions, breath samples were obtained for CO2. The fractional L-[1-C]phenylalanine oxidation (FCO2) was estimated and plotted against the threonine intakes. Biphasic linear regression crossover analysis was used to calculate the breakpoint of the FCO2, representing the mean threonine requirement. Data are presented as mean ±â€ŠSD. RESULTS: Thirty-two term neonates (gestational age 39 ±â€Š1 weeks, birth weight 3.3 ±â€Š0.3 kg, mean postnatal age 10 ±â€Š4 days) were studied. The mean threonine requirement was estimated to be 68 mg · kg · day with an upper and lower 95% confidence interval of 104 and 32 mg · kg · day, respectively (r = 0.37). CONCLUSIONS: The determined threonine requirement is extremely close to the existing requirement recommendations (∼90% of the present World Health Organization requirement guidelines). Infant formula preparations presently on the market, however, contain up to twice as much threonine as recommended. The threonine intake in formula-fed infants may therefore be reduced considerably.

Tryptophan requirement of the enterally fed term infant in the first month of life.

OBJECTIVES: Tryptophan not only is an amino acid essential to protein synthesis but also serves as a precursor in 2 important metabolic pathways: the serotonin and the kynurenine pathways. Tryptophan is related to sleeping patterns. The objective of the present study was to determine the tryptophan requirement of term infants using the indicator amino acid oxidation (IAAO) method with L-[1-C]phenylalanine as the indicator. METHODS: Enterally fed infants were randomly assigned to tryptophan intakes ranging from 0.5 to 73 mg ·â€Škg ·â€Šday as part of an elemental diet. After 1-day adaptation to the test diet, [C]bicarbonate and L-[1-C]phenylalanine tracers were given enterally. Breath samples were collected at baseline and during isotopic plateaus. The mean tryptophan requirement was determined by using the biphasic linear regression crossover analysis on the fraction of CO2 recovery from L-[1-C]phenylalanine oxidation (FCO2). Data are presented as mean ±â€Šstandard deviation. RESULTS: A total of 30 term neonates (gestational age 39 ±â€Š1 weeks) were studied at 9 ±â€Š4 days. FCO2 decreased until a tryptophan intake of 15 mg ·â€Škg ·â€Šday; additional increases in tryptophan intake did not affect FCO2. Mean requirement was determined to be 15 mg ·â€Škg ·â€Šday. CONCLUSIONS: The mean tryptophan requirement for elemental formula-fed term infants is 15 mg ·â€Škg ·â€Šday. This requirement is lower than the present recommended intake of 29 mg ·â€Škg ·â€Šday, which is based on the average intake of a breastfed infant.

Methionine requirement of the enterally fed term infant in the first month of life in the presence of cysteine.

BACKGROUND: The essential amino acid methionine can be used for protein synthesis but also serves as a precursor for homocysteine and cysteine. OBJECTIVE: The objective of this study was to determine the minimal obligatory methionine requirement of infants in the presence of excess cysteine (91 mg ⋅ kg(-1) ⋅ d(-1)) by using the indicator amino acid oxidation (IAAO) method with l-[1-(13)C]phenylalanine as the indicator. DESIGN: Fully enterally fed term infants <1 mo of age were randomly assigned to methionine intakes that ranged from 3 to 59 mg ⋅ kg(-1) ⋅ d(-1) as part of an elemental formula. After 1 d of adaptation to the test diet, [(13)C]bicarbonate and l-[1-(13)C]phenylalanine tracers were given enterally. Breath samples were collected at baseline and during isotopic plateaus. The mean methionine requirement was determined by using biphasic linear regression crossover analysis on the fraction of (13)CO(2) recovery from l-[1-(13)C]phenylalanine oxidation (F(13)CO(2)). Data are presented as means ± SDs. RESULTS: Thirty-three neonates (gestational age: 39 ± 1 wk) were studied at 13 ± 6 d. With increasing methionine intakes, F(13)CO(2) decreased until a methionine intake of 38 mg ⋅ kg(-1) ⋅ d(-1); additional increases in methionine intake did not affect F(13)CO(2). The mean methionine requirement was determined at 38 mg ⋅ kg(-1) ⋅ d(-1), and the upper and lower CIs were 48 and 27 mg ⋅ kg(-1) ⋅ d(-11), respectively (P < 0.0001, r(2) = 0.59). CONCLUSIONS: Although the current recommended methionine intake of 28 mg ⋅ kg(-1) ⋅ d(-1) is within the CIs of our study, the estimated mean requirement is substantially higher. However, most of the infant formulas provide a methionine intake of 49-80 mg ⋅ kg(-1) ⋅ d(-1), which is above the upper CI of our study. This trial was registered at www.trialregister.nl as NTR1610.

Lysine requirement of the enterally fed term infant in the first month of life.

BACKGROUND: Infant nutrition has a major impact on child growth and functional development. Low and high intakes of protein or amino acids could have a detrimental effect. OBJECTIVE: The objective of the study was to determine the lysine requirement of enterally fed term neonates by using the indicator amino acid oxidation (IAAO) method. L-[1-(13)C]phenylalanine was used as an indicator amino acid. DESIGN: Twenty-one neonates were randomly assigned to lysine intakes that ranged from 15 to 240 mg · kg(-1) · d(-1). Breath, urine, and blood samples were collected at baseline and during the plateau. The mean lysine requirement was determined by using biphasic linear regression crossover analysis on the fraction of (13)CO(2) recovery from L-[1-(13)C]phenylalanine oxidation (F(13)CO(2)) and phenylalanine oxidation rates calculated from the L-[1-(13)C]phenylalanine enrichment of urine and plasma. RESULTS: The mean (±SD) phenylalanine flux calculated from urine and plasma L-[1-(13)C]phenylalanine enrichment data were 88.3 ± 6.9 and 84.5 ± 7.4 µmol · kg(-1) · h(-1), respectively. Graded intakes of lysine had no effect on phenylalanine fluxes. The mean lysine requirement determined by F(13)CO(2) was 130 mg · kg(-1) · d(-1) (upper and lower CIs: 183.7 and 76.3 mg · kg(-1) · d(-1), respectively). The mean requirement was identical to the requirement determined by using phenylalanine oxidation rates in urine and plasma. CONCLUSIONS: The mean lysine requirement of enterally fed term neonates was determined by using F(13)CO(2) and phenylalanine oxidation rates calculated from the L-[1-(13)C]phenylalanine enrichment of urine and plasma. These methods yielded a similar result of 130 mg lysine · kg(-1) · d(-1). This study demonstrates that sampling of (13)CO(2) in expired air is sufficient to estimate the lysine requirement by using the IAAO method in infants. This trial was registered at www.trialregister.nl as NTR1610.