Effect of early nutritional intake on long-term growth and bone mineralization of former very low birth weight infants.

BACKGROUND: Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. OBJECTIVE: To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14days after birth was associated with improvement in length and bone development until 9-10years of age. DESIGN: Observational follow-up study of VLBW infants (birth weight<1500g or gestational age<32weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intake and clinical covariates on length and bone mineralization. RESULTS: Both cohorts achieved a catch-up in length to SDS within the normal range by 6months (length SDS: estimated mean (95% confidence interval (CI): 6months: Cohort 2004: -0.7 (-1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: ß 0.001; 95% CI (0.000, 0.003); p=0.03) There was no evidence of an association between early nutritional intake and bone mineralization. CONCLUSION: Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14days after birth was not associated with improvement in length and bone development.

Zinc protoporphyrin/heme ratio as parameter of iron status in moderately preterm infants: natural course and associations in the first 4 months.

OBJECTIVE: To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants. STUDY DESIGN: ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation. RESULTS: ZnPP/H levels decreased in the first 6 weeks and increased thereafter. At 4 months postnatal age, ZnPP/H was higher in the 11 (8.5%) infants with IDA (mean (s.d.): 260.8 (16.1)) but not in the 27 (21.3%) infants with ID (mean (s.d.): 177.0 (15.1)) compared with normal infants (mean (s.d.): 157.3 (12.5)). CONCLUSION: In moderately preterm infants, ZnPP/H can be of additional value to detect infants at risk for IDA due to iron-deficient erythropoiesis at 4 months of age.

Predictive factors of iron depletion in late preterm infants at the postnatal age of 6 weeks.

BACKGROUND/OBJECTIVES: Late preterm infants (born ⩾32 weeks of gestation) are at risk for developing iron deficiency and iron deficiency anaemia, and this may lead to impaired neurodevelopment. In the Netherlands, there is no guideline for standardised iron supplementation in these infants. Individualised iron supplementation has been suggested (that is, treating those infants with the highest risk), but risk factors for deprived iron stores in this specific group of infants are not well documented. SUBJECTS/METHODS: In this prospective multi-centre study, we analysed the iron status at the postnatal age of 6 weeks of 68 infants born between 32 and 35 weeks of gestation in the Netherlands. Serum ferritin (SF) <70 µg/l in the absence of infection (C-reactive protein <5 mg/l) was defined as iron depletion and whenever in combination with a haemoglobin level <110 mg/dl as iron-depleted anaemia. Medical charts were reviewed to identify risk factors. RESULTS: Iron depletion and iron-depleted anaemia were present in 38.2% and 30.9% of the infants, respectively. Infants with a birth weight <1830 g and a SF <155 µg/l in the first week of life had a 26.4 times higher risk to develop iron depletion (95% confidence interval 3.1-227.0, P=0.003). Multivariate regression analyses also showed that iron depletion was associated with a higher number of blood draws. CONCLUSIONS: Iron depletion is common in late preterm infants at the age of 6 weeks in a setting without standardised iron supplementation. One should consider early individualised iron supplementation for late preterm infants with a low birth weight (<1830 g), and a low SF in the first week of life (<155 µg/l), as they have a high risk to develop iron depletion.

Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age.

BACKGROUND/OBJECTIVES: Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life. SUBJECTS/METHODS: In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation. RESULTS: ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week. CONCLUSIONS: Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.

The enigma to achieve normal postnatal growth in preterm infants--using parenteral or enteral nutrition?

AIM: To evaluate whether increasing the amount of amino acids and energy in parenteral nutrition combined with rapid increment of enteral feeding improves postnatal growth in preterm infants. METHODS: Observational study; two consecutive year-cohorts of preterm infants; Cohort 2 received higher supplementation of parenteral amino acids and energy with more rapid enhancement of enteral feeding than Cohort 1. Nutritional intake, weight and head circumference (HC) were compared. RESULTS: Cohort 2 [N: 79, gestational age (GA): 29.8 ± 2.2 weeks, birth weight (BW): 1248 ± 371 g] achieved full enteral feeds earlier (p < 0.001) and had a higher protein/energy intake during the first week (p < 0.001) than Cohort 1 (N: 68, GA: 29.5 ± 2.3 weeks, BW: 1261 ± 339 g). Both cohorts developed cumulative protein/energy deficits, but less in Cohort 2 (p < 0.01). Appropriate for gestational age infants (AGA) of Cohort 2 improved weight gain until week 5 (p < 0.01) compared to AGA of Cohort 1, nevertheless all infants demonstrated a decline in mean standard deviation score (>1) for weight at term. Small for GA infants failed to improve HC. CONCLUSION: Improved parenteral intake may lead to improved short-term postnatal weight gain. Faster increase of enteral nutrition was well tolerated but failed to prevent nutritional deficits. Practising early enteral feeding with higher supplementation of nutrients may be needed and requires further study.

Risk factors for sensorineural hearing loss in NICU infants compared to normal hearing NICU controls.

OBJECTIVES: To evaluate independent etiologic factors associated with sensorineural hearing loss in infants who have been admitted to the neonatal intensive care unit compared to normal hearing controls. METHOD: Between 2004 and 2009, 3366 infants were admitted to the neonatal intensive care unit of Sophia Children's Hospital, of which 3316 were screened with AABR. A total of 103 infants were referred for auditory brainstem response analysis after failure on neonatal hearing screening. We included all infants diagnosed with sensorineural hearing loss. Each patient was matched with two normal hearing controls from the neonatal intensive care unit of the same gender and postconceptional age. The following risk factors were studied: birth weight, dysmorphic features, APGAR scores (at 1, 5 and 10 min), respiratory distress (IRDS), CMV infection, sepsis, meningitis, cerebral bleeding, cerebral infarction, hyperbilirubinemia requiring phototherapy, peak total bilirubin level, furosemide, dexamethason, vancomycin, gentamycin and tobramycin administration. RESULTS: Fifty-eight infants were diagnosed with sensorineural hearing loss: 26 girls and 32 boys. The incidence of dysmorphic features (P=0.000), low APGAR score (1 min) (P=0.01), sepsis (P=0.003), meningitis (P=0.013), cerebral bleeding (P=0.016) and cerebral infarction (P=0.000) were significantly increased in infants with sensorineural hearing loss compared to normal hearing controls (n=116). CONCLUSION: Dysmorphic features, low APGAR scores at 1 min, sepsis, meningitis, cerebral bleeding and cerebral infarction are associated with sensorineural hearing loss independent of neonatal intensive care unit admittance.

Lysine kinetics in preterm infants: the importance of enteral feeding.

INTRODUCTION: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. PATIENTS AND METHODS: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) micromol/(kg x h); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) micromol/(kg x h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. RESULTS: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) micromol/(kg x h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) micromol/(kg x h); p<0.05). CONCLUSIONS: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.

Protein nutrition of the neonate.

The period of growth and development between birth and weaning is crucial for the long-term well-being of the organism. Protein deposition is very rapid, is achieved with a high nutritional efficiency, and is accompanied by marked differences in the growth rates of individual tissues and a series of maturational processes. These important aspects of development occur while the neonate is consuming a single and highly-specific food source, milk. Surprisingly, although there is a clear relationship between the nutrient density of milk and the growth rate of its recipient, this relationship does not apply to the overall amino acid composition of mixed milk proteins. Some amino acids, notably glycine and arginine, are supplied in milk in quantities that are much less than the needs of the neonate. The milk-fed neonate is therefore capable of carrying out a tightly-regulated transfer of N from amino acids in excess to those that are deficient. The rapid growth of the neonate is supported by a high rate of tissue protein synthesis. This process appears to be activated by the consumption of the first meals of colostrum. Recent research has identified that skeletal muscle and the brain are specifically responsive to an unidentified factor in colostrum. Following the initial anabolic response the rate of protein synthesis in some tissues, notably muscle, falls from birth to weaning. This decrease reflects a progressively smaller anabolic response to nutrient intake, which not only involves an overall fall in the capacity for protein synthesis, but also in responses to insulin and amino acids. The study of growth and protein metabolism, and their regulation in the neonate is not only important for pediatrics, but may provide important pointers to more general aspects of regulation that could be applied to the nutrition of the mature animal.

Immediate commencement of amino acid supplementation in preterm infants: effect on serum amino acid concentrations and protein kinetics on the first day of life.

To determine whether the general reluctance to begin amino acid administration to preterm infants from birth onward might lead to loss of lean body mass and impairment of growth, we measured amino acid levels and protein kinetics in 18 preterm infants. Nine infants received amino acids (1.15 +/- 0.06 gm.kg-1.day-1) and glucose (6.05 +/- 1.58 gm.kg-1.day-1), whereas the other nine infants received only glucose (6.48 +/- 1.30 gm.kg-1.day-1) from birth onward. Protein kinetics on the first postnatal day were measured with a stable isotope dilution technique with [1-13C]leucine as a tracer. No statistically significant differences were noted in blood pH, base excess, urea concentration, or glucose levels. Both total amino acid concentration and total essential amino acid concentration were significantly lower and were below the reference range in the nonsupplemented group. Plasma amino acid levels of five essential amino acids (methionine, cystine, isoleucine, leucine, arginine) were below the reference range in the nonsupplemented group, whereas only cystine was below the reference range in the supplemented group. Nitrogen retention was improved significantly by the administration of amino acids (-110 +/- 44 mg nitrogen per kilogram per day in the glucose-only group vs +10 +/- 127 mg nitrogen per kilogram per day in the group given glucose and amino acids; p = 0.001); leucine oxidation was not significantly increased in the supplemented group (41 +/- 13 mumol.kg-1.hr-1 vs 46 +/- 16 mumol.kg-1.hr-1). Leucine balance also improved significantly (-41 +/- 13 mumol.kg-1.hr-1 vs -8 +/- 16 mumol.kg-1.hr-1; p = 0.01) because of a combination of an increased amount of leucine being used for protein synthesis and a lower amount of leucine coming from protein breakdown. Plasma cystine concentration, the only amino acid below the reference range in the supplemented group, was highly predictive for protein synthesis in that group. We conclude that the administration of amino acids to preterm infants from birth onward seems safe and prevents the loss of protein mass.

Feeding premature newborn infants palmitic acid in amounts and stereoisomeric position similar to that of human milk: effects on fat and mineral balance.

The effect of the structure of human milk triglycerides on intestinal fat absorption remains controversial. Twelve infants were each fed, for 1 wk in a crossover design, two formulas that differed only in triglyceride configuration. The "beta" formula contained triglycerides similar to those in human milk (26% palmitic acid, esterified predominantly to the sn-2 position) whereas in the "alpha" formula, which contained triglycerides similar to those in formulas currently marketed, palmitate was mainly at the sn-1,3 positions. Fatty acid, fat, and mineral balances were measured at the end of each 1-wk period. Myristic, palmitic, and stearic acids were absorbed better from the beta formula, but total fat excretion was not reduced. During the feeding of beta formula fecal calcium excretion was lower, urinary calcium higher, and urinary phosphate lower. A formula containing triglycerides similar to those in human milk has significant effects on fatty acid intestinal absorption and improves mineral balance in comparison with a conventional formula.

Effects of early amino acid administration during total parenteral nutrition on protein metabolism in pre-term infants.

1. We investigated the effects of starting amino acid administration on post-natal day 2 on protein turnover and nitrogen balance in appropriate-for-gestational-age, very-low-birth-weight infants. Eighteen infants were divided into two groups. Group A received from day 2 onwards an amino acid solution, whereas group B started on this solution after day 4. Both groups were exclusively parenterally fed, 200 kJ day-1 kg-1 on post-natal days 3 and 4. Group A (birth weight 1.5 +/- 0.3 kg) received 4.6 g of glucose, 1.9 g of fat and 2.3 g of amino acids day-1 kg-1 body weight. Group B (birth weight 1.4 +/- 0.2 kg) received 7.0 g of glucose and 1.9 g of fat day-1 kg-1 body weight. 2. At post-natal day 3, a primed constant infusion of 3 mg of [15N]glycine day-1 kg-1 was given. Protein flux, protein synthesis and protein breakdown were calculated from the 15N enrichment in urinary ammonia. In five out of nine infants in group B no plateau of 15N enrichment in urinary urea could be detected, whereas in group A two out of nine infants did not reach a plateau. For this reason we did not use the end product urea for our calculations. 3. The administration of the amino acids resulted in a higher protein flux (6.9 +/- 1.5 g day-1 kg-1 versus 5.2 +/- 0.9 g day-1 kg-1) and a higher protein synthesis rate (6.0 +/- 1.4 g day-1 kg-1 versus 4.6 +/- 0.8 g day-1 kg-1) in group A.(ABSTRACT TRUNCATED AT 250 WORDS)