High-dose parenteral amino acid intake in very low birthweight infants: what is the current evidence?

PURPOSE OF REVIEW: There is uncertainty regarding optimal dosing for parenteral amino acids in preterm infants and wide variability exists in clinical practice. There is new data from clinical trials trying to address these concerns. We review the recent evidence on parenteral high-dose amino acid intake in very low birth weight (VLBW) neonates with a focus on relevant clinical outcomes. RECENT FINDINGS: Preterm infants often receive less protein than intended in the first week of life. Parenteral amino acid administration in doses that exceed requirements, however, leads to increased oxidation and higher blood urea concentrations. Amino acid doses greater than 3.5 g/kg/day have not shown to improve mortality, neonatal morbidities including sepsis, necrotizing enterocolitis, chronic lung disease, growth parameters or neurodevelopmental outcomes at 2 years of age. SUMMARY: Parenteral amino acid administration in VLBW infants should be initiated soon after birth at a dose of at least 1.5 g/kg/day to maintain anabolism. The maximum dose for parenteral amino acid should be between 2.5 and 3.5 g/kg/day, with adequate nonprotein calories and micronutrients to ensure efficient protein utilization and growth.

Vitamin D deficiency and respiratory morbidity among African American very low birth weight infants.

BACKGROUND: Very low birth weight infants (VLBWI) have unexplained variation in respiratory morbidity, including respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). We examined a potential association to serum 25-hydroxyvitamin D (s-25OHD) on day one. STUDY DESIGN: Prospective, observational study on 89 VLBWI (≤1250 g). S-25OHD (day one and 21) and respiratory severity score (RSS) (day one) were examined. Other respiratory morbidities including BPD were compared between infants with s-25OHD ≤ 10 ng/ml (deficient) versus >10 ng/ml (adequate). RESULTS: Eighty one neonates (91%) were African Americans. The mean (SD) birthweight was 868 (229) g, gestational age 27 (2) weeks. On day one, mean (SD) s-25OHD was 15.48 (8.31) ng/ml, with 32 (37%) being vitamin D deficient. The deficiency and adequate VLBWI groups had similar birthweight; 860 (262) vs 873 (210) g, and gestational age; 27 (2) vs 27 (2) weeks. In 78 survivors, s-25OHD rose from 15.48 (8.31) ng/ml day one to 52.36 (22.49) ng/ml day 21 after supplementation, p < 0.001. On day one, increasing RSS was inversely related to s-25OHD, trend p = 0.054. Compared to the adequate group, the deficiency group had higher RSS (5.0 ±â€¯2.7 vs 3.6 ±â€¯1.9), required surfactant therapy more frequently (91% vs 72%), and needed home oxygen therapy more often (48% vs 26%), p ≤ 0.05 for all. Among infants with BPD, the severity of disease was inversely related to s-25OHD, trend p < 0.09. CONCLUSION: Lower levels of s-25OHD were associated with increased severity of RDS and BPD among a cohort of mostly African American VLBWI.

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.

Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants.

BACKGROUND: Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. OBJECTIVE: The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. METHODS: The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. RESULTS: Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04-2.47; p = 0.034) and umbilical artery resistance index (odds ratio, 7.72E-04; 95% confidence interval, 1.14E-06-0.523; p = 0.031). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. CONCLUSIONS: Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction.

Nutritional practices in very low birth weight infants: a national survey / ¿Cuál es la nutrición que administramos a nuestros recién nacidos de muy bajo peso en las unidades neonatales?: una encuesta nacional

Background: Significant efforts have been made to improve the nutritional support of very preterm infants. Large surveys may help to know the nutritional practices for preterm infants in neonatal units and identify if they are in line with the current guidelines. Methods: A multicentre nationwide web-based survey on clinical feeding practices in very low birth weight (VLBW) infants was conducted in tertiary neonatal hospitals that admit infants with a birth weight < 1,500 g and/or a gestational age of < 32 weeks. Results: The questionnaire was completed by 53 units (response rate, 59%). Over 90% of the units surveyed start amino-acid administration immediately after birth and more than half use novel intravenous fish oil-based lipid emulsions. Enteral nutrition is started within 24 hours of birth in 65% of units and 86% of these are medium-sized or large. Feeding volumes are increased at a rate of 10-30 ml/kg/day in > 90% of units. Monitoring of serum phosphorus was measured more frequently than albumin (p = 0.009) or triglycerides (p = 0.037), but only 28% of centres regularly measure pre-albumin as a nutritional biomarker. Human milk fortification and iron supplementation, starting at four weeks of age, are almost universal. However, only 30% of units administer 800 IU/day of vitamin D. Nearly 50% of the units discharge infants on preterm formula. Conclusion: Most Spanish neonatology units use early amino-acid supplementation and over half use novel fish oil-based lipid emulsions. Post-discharge nutrition practices and vitamin administration vary greatly (AU)

Antecedentes: se han realizado esfuerzos significativos para mejorar la nutrición en los recién nacidos muy prematuros. Las grandes encuestas pueden ayudar a conocer cuál es la nutrición que reciben los recién nacidos prematuros en las unidades neonatales e identificar si están en línea con las directrices actuales. Métodos: se llevó a cabo una encuesta multicéntrica a nivel nacional sobre las prácticas clínicas empleadas en la alimentación en los recién nacidos de muy bajo peso en hospitales de nivel III que ingresan recién nacidos con un peso al nacer < 1.500 g y/o una edad gestacional < 32 semanas. Resultados: el cuestionario fue completado por 53 unidades neonatales (tasa de respuesta del 59%). Más del 90% de las unidades estudiadas inician la administración de aminoácidos inmediatamente después del nacimiento y más de la mitad utilizan nuevas emulsiones lipídicas intravenosas que contienen aceite de pescado. La nutrición enteral se inicia en las primeras 24 horas de nacimiento en el 65% de las unidades y el 86% de ellas son medianas o grandes. El volumen de alimentación aumenta a una velocidad de 10-30 ml/kg/día en > 90% de las unidades. El fósforo sérico se monitoriza con mayor frecuencia que la albúmina (p = 0,009) o los triglicéridos (p = 0,037), pero solo el 28% de los centros miden regularmente la prealbúmina como biomarcador nutricional. La fortificación de la leche humana y la suplementación con hierro, a partir de las cuatro semanas de edad, es casi universal. Sin embargo, solo el 30% de las unidades administran 800 UI/día de vitamina D. Casi el 50% de las unidades utilizan leche de fórmula del prematuro al alta de las unidades. Conclusión: la mayoría de las unidades neonatales españolas administran precozmente los suplementos de aminoácidos y más de la mitad emplean emulsiones de lípidos a base de aceite. Hay una importante variación en las prácticas nutricionales posteriores al alta y en la administración de vitaminas (AU)

Changes in Biochemical Parameters of the Calcium-Phosphorus Homeostasis in Relation to Nutritional Intake in Very-Low-Birth-Weight Infants.

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP); and urinary ratios for Ca/creatinin (creat) and P/creatinin in Very-Low-Birth-Weight infants on Postnatal Days 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High (n = 30) and Low (n = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; and gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP (p = 0.04) and decreased ALP (p = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP (p ≤ 0.02) and caused decrease in TrP (p = 0.00). Protein intake decreased sP (p = 0.000), while low gestational age and male gender increased renal excretion of P (p < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender.

Breast milk supplementation and preterm infant development after hospital discharge: a randomized clinical trial / Suplementação do leite materno e desenvolvimento de lactentes pré-termo após alta hospitalar: ensaio clínico randomizado

Abstract Objectives: To assess the effect of maternal breast milk supplementation on the development of exclusively breast-fed very low birth weight preterm infants at 12 months of corrected age. Methods: A randomized clinical trial with 53 infants followed-up after discharge from the neonatal unit until a corrected gestational age of 12 months. Newborns in the intervention group were breastfed exclusively with maternal milk and received 2 g of a multinutrient supplement (Pré-Nan®, Nestlé, Vevey, Switzerland) added to expressed breast milk twice a day until a corrected age of 4–6 months. The control group was exclusively breastfed without supplementation. After monthly follow-up, developmental assessment was performed using the Bayley III Scale. Results: There was no statistically significant difference on the Bayley III Scale between the intervention and control groups in any of the assessed domains: motor, cognitive, and communication. However, scores in the three domains were always higher in the group that received the supplement. There were a similar number of cases of developmental delay in both groups: seven (28%) in the group that received the supplement and nine (33.3%) in the group that was exclusively breastfed. Conclusions: The results failed to show an association between post-discharge multinutrient supplementation and development in the assessed infants.

Resumo Objetivos: Avaliar o efeito da suplementação do aleitamento materno exclusivo com aditivo multicomponente no desenvolvimento de lactentes nascidos pré-termo de muito baixo peso aos 12 meses de idade gestacional corrigida. Método: Ensaio clínico randomizado com 53 lactentes, acompanhados da alta hospitalar na Unidade Neonatal até o 12° mês de idade gestacional corrigida. Aqueles alocados no grupo intervenção permaneciam em aleitamento materno exclusivo e recebiam dois gramas de suplemento multicomponente em pó (Pré-Nan®, Nestlé, Vevey, Suíça), adicionados ao leite ordenhado duas vezes ao dia, por quatro a seis meses de idade gestacional corrigida. O grupo controle permanecia em aleitamento materno exclusivo sem suplementação. Após acompanhamento mensal, foi feita avaliação do desenvolvimento por meio da Escala de Bayley III. Resultados: Na comparação do desenvolvimento pela Escala de Bayley III entre os grupos intervenção e controle, não houve diferença estatística significativa nos domínios estudados: motor, cognitivo e linguagem. Porém, os valores dos escores foram sempre maiores no grupo intervenção do que no grupo controle nos três domínios. O atraso de desenvolvimento se distribuiu de forma similar nos grupos: sete casos (28%) no grupo intervenção e nove (33,3%) no grupo controle. Conclusões: Os resultados não mostraram associação entre suplementação multicomponente pós-alta e desenvolvimento dos lactentes analisados pela Escala de Bayley III.

Breast milk supplementation and preterm infant development after hospital discharge: a randomized clinical trial.

OBJECTIVES: To assess the effect of maternal breast milk supplementation on the development of exclusively breast-fed very low birth weight preterm infants at 12 months of corrected age. METHODS: A randomized clinical trial with 53 infants followed-up after discharge from the neonatal unit until a corrected gestational age of 12 months. Newborns in the intervention group were breastfed exclusively with maternal milk and received 2g of a multinutrient supplement (Pré-Nan(®), Nestlé, Vevey, Switzerland) added to expressed breast milk twice a day until a corrected age of 4-6 months. The control group was exclusively breastfed without supplementation. After monthly follow-up, developmental assessment was performed using the Bayley III Scale. RESULTS: There was no statistically significant difference on the Bayley III Scale between the intervention and control groups in any of the assessed domains: motor, cognitive, and communication. However, scores in the three domains were always higher in the group that received the supplement. There were a similar number of cases of developmental delay in both groups: seven (28%) in the group that received the supplement and nine (33.3%) in the group that was exclusively breastfed. CONCLUSIONS: The results failed to show an association between post-discharge multinutrient supplementation and development in the assessed infants.

Understanding the Biologic Therapies of Probiotics, Prebiotics, and Synbiotics: Exploring Current Evidence for Use in Premature Infants for the Prevention of Necrotizing Enterocolitis.

Necrotizing enterocolitis remains a significant cause of morbidity and mortality in very low-birth-weight infants (<1500 g), with current preventive strategies unclear. Scientific evidence has recently emerged, suggesting that probiotics, prebiotics, and synbiotics may effectively and safely alter the premature intestinal microbiota, enhancing a deficient innate immune response and maturing the intestinal barrier to prevent necrotizing enterocolitis development. Currently, formal recommendations do not support routine use of these dietary supplementations for premature infants. Here, we examine how probiotic, prebiotic, and synbiotic preparations physiologically alter the underdeveloped intestinal microbial environment to potentially reduce necrotizing enterocolitis incidence and discuss current evidence that has examined safety and efficacy factors potentially supporting routine use among the premature infant population.

Supplemented vs. unsupplemented human milk on bone mineralization in very low birth weight preterm infants: a randomized clinical trial.

UNLABELLED: Very low birth weight preterm newborns weighing less than 1500 g were randomized to receive human milk supplemented with FM 85® or not. They have similar bone mineral content (BMC) at baseline, but, at the end of study, BMC was increasingly higher in the FM 85® group. INTRODUCTION: The purpose of this study is to evaluate the effectiveness of a human milk supplement (FM 85®; Nestlé, Vevey, Switzerland) developed for the purpose of improving nutrition, including bone mineralization, in very low birth weight preterm newborns. METHODS: Preterm infants weighing less than 1500 g at birth admitted to the neonatal intensive care unit of a university hospital were studied. During hospitalization, they were fed at least 50 % of human milk. Newborns with ≥20 days of age were randomly assigned to the intervention group (n = 19) to receive human milk supplemented with FM 85® or to a control group (n = 19) to receive human milk only. Anthropometric measurements, whole-body bone densitometry (DXA), and biochemical tests were performed at study entry and at the end of the study (shortly before discharge when the infant had reached 2000 g). RESULTS: There were no start- or end-of-study differences between the two groups, except for daily increase in length (p = 0.010). At baseline, both groups had similar BMC: 5.49 ± 3.65 vs. 4.34 ± 2.98 g (p = 0.39) for the intervention and control group, respectively. However, at the end of the study, BMC was higher in the intervention group: 10.3 ± 4.71 vs. 6.19 ± 3.23 g (p = 0.003). The mean increase in BMC during the observation period was 4.90 ± 4.46 g for the intervention group and 1.86 ± 3.17 g for the control group (p = 0.020). Serum alkaline phosphatase levels were higher in the control group (720 ± 465 vs. 391 ± 177 IU/L; p = 0.007). CONCLUSIONS: Our data suggest that supplementation of human milk with FM 85® leads to improved bone mineralization in very low birth weight preterm newborns.

Fecal short-chain fatty acids of very-low-birth-weight preterm infants fed expressed breast milk or formula.

OBJECTIVES: In preterm infants, the metabolic responses of gastrointestinal (GI) bacteria to different diets are poorly understood despite the possible effects on GI health. Therefore, we tested the hypothesis that diet influences bacterial metabolism by measuring short-chain fatty acids (SCFAs) in stool samples from very-low-birth-weight (VLBW) preterm infants without GI disorder as surrogate biomarkers of bacterial metabolism. METHODS: Ion chromatography was used to measure fecal SCFAs (acetate, formate, propionate, butyrate, and isobutyrate), lactate, and chloride in fresh stool samples collected from 32 preterm infants (without major congenital anomalies, GI disorders, or a recent history of antibiotic administration and on full feed of either expressed maternal breast milk [EBM; n = 13] or a formula for preterm infants [Similac Special Care Formula; preterm formula, PTF; n = 19]). RESULTS: The mean birth weight was 972 g, the mean gestational age was 27 weeks, and the mean postnatal age at first stool sample was 36 days. When adjusted for gestational age, the stools of EBM infants had higher concentrations (micromoles per gram of stool) of total SCFA (128 vs 68; P = 0.002), acetate (41 vs 13; P = 0.005), propionate (15.1 vs 4.4; P = 0.003), and chloride (21,814 vs 10,652; P = 0.02). Interactions between postnatal age and diet were detected for lactate (P = 0.05), propionate (P = 0.03), and butyrate (P = 0.03). CONCLUSIONS: Diets fed to VLBW preterm infants influence fecal SCFA profiles, and hence the metabolism of the GI bacteria, and potentially the health of preterm infants. The responses of bacterial metabolism to diet are influenced with postnatal age and gestational age at birth.

Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants.

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

Early exposure to maternal voice: effects on preterm infants development.

BACKGROUND: Preterm infants complete their development in Neonatal Intensive Care Unit being exposed to environmental stimuli that lead to the early maturation of the sensory systems. It is known that the fetus perceives sounds and reacts to them with movements since the 26th-28th week of gestational age. Maternal voice represents a source of sensory stimulation for the fetus. AIMS: To investigate the effect of the exposure to maternal voice, administered by bone conduction, on preterm infants autonomic and neurobehavioral development. STUDY DESIGN: Longitudinal, explorative, case control study. SUBJECTS: 71 preterm infants with birth weight <1500g, born adequate for gestational age OUTCOME MEASURES: vital and neurobehavioral parameters at term, neurofunctional assessment at 3 and 6months of corrected age. RESULTS: Infants in the treatment group had lower heart rate values and a higher proportion of stable skin color at each study point as compared to the control group. The scores in the visual attention performance and in the quality of the general movements at term were better in the treatment group than in the control one. Neurofunctional assessment score at 3months of corrected age was higher in the treatment group whereas no difference between the two groups was detected at 6months of corrected age. CONCLUSIONS: Early exposure to maternal voice exerts a beneficial effect on preterm infants autonomic and neurobehavioral development.

Review of macronutrients in parenteral nutrition for neonatal intensive care population.

Parenteral nutrition (PN) has become essential in the management of sick and growing newborn populations in the NICU. In the past few decades, PN has become fundamental in the nutritional management of the very low birth weight infant (<1,500 g).1 Although the components in PN are commonly determined and ordered by the physician or neonatal nurse practitioner provider, the NICU nurse is responsible for confirming the components in the daily PN prior to infusion and is responsible for maintaining the infusion of PN. Nurses should understand the nutritional components of PN as well as the indications, side effects, and infusion limitations of each component. The purpose of this article is to review the macronutrients in PN, including carbohydrates, protein, and fat. A subsequent article will review the micronutrients in PN, including electrolytes, minerals, and vitamins.

VitaminA, E, and D deficiencies in tunisian very low birth weight neonates: prevalence and risk factors.

BACKGROUND: Preterm neonates are at high risk of vitamin deficiencies, which may expose them to increased morbidity and mortality. This study aimed to determine the prevalence and risk factors for vitamin A, E, and D deficiencies in Tunisian very low birth weight (VLBW) neonates. METHODS: A total of 607 VLBW and 300 term neonates were included in the study. Plasma vitamins A and E were assessed by high performance liquid chromatography and vitamin D was assessed by radioimmunoassay. RESULTS: Prevalence of vitamin A, E, and D deficiencies were dramatically elevated in VLBW neonates and were significantly higher than term neonates (75.9% vs. 63.3%; 71.3% vs. 55.5%; and 65.2% vs. 40.4%, respectively). In VLBW neonates, the prevalence of vitamin deficiencies was significantly higher in lower classes of gestational age and birth weight. Vitamin E deficiency was associated with pre-eclampsia [odds ratio (OR) (95% confidence interval, 95% CI), 1.56 (1.01-2.44); p < 0.01] and gestational diabetes [4.01 (1.05-17.0); p < 0.01]. Vitamin D deficiency was associated with twin pregnancy [OR (95% CI), 2.66 (1.33-5.35); p < 0.01] and pre-eclampsia [2.89 (1.36-6.40); p < 0.01]. CONCLUSION: Vitamin A, E, and D deficiencies are very common in Tunisian VLBW neonates and are associated with pre-eclampsia. Improved nutritional and health support for pregnant women and high dose vitamins A, E, and D supplementation in VLBW neonates are strongly required in Tunisia.

Safety and efficacy of early parenteral lipid and high-dose amino acid administration to very low birth weight infants.

OBJECTIVE: To assess the efficacy and safety of early parenteral lipid and high-dose amino acid (AA) administration from birth onwards in very low birth weight (VLBW, birth weight <1500 g) infants. STUDY DESIGN: VLBW infants (n = 144; birth weight 862 ± 218 g; gestational age 27.4 ± 2.2 weeks) were randomized to receive 2.4 g of AA kg(-1) · d(-1) (control group), or 2.4 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (AA + lipid group), or 3.6 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (high AA + lipid group) from birth onwards. The primary outcome was nitrogen balance. The secondary outcomes were biochemical variables, urea rate of appearance, growth rates, and clinical outcome. RESULTS: The nitrogen balance on day 2 was significantly greater in both intervention groups compared with the control group. Greater amounts of AA administration did not further improve nitrogen balance compared with standard AA dose plus lipids and was associated with high plasma urea concentrations and high rates of urea appearance. No differences in other biochemical variables, growth, or clinical outcomes were observed. CONCLUSIONS: In VLBW infants, the administration of parenteral AA combined with lipids from birth onwards improved conditions for anabolism and growth, as shown by improved nitrogen balance. Greater levels of AA administration did not further improve the nitrogen balance but led to increased AA oxidation. Early lipid initiation and high-dose AA were well tolerated.

Vitamin D, vitamin A, maternal-perinatal considerations: old concepts, new insights, new questions.

Vitamins A and D are essential nutrients that play important roles in growth and development. Preterm and low birth weight infants have low levels of these nutrients and are at risk for developing detrimental health consequences associated with vitamin A and vitamin D deficiencies. Preliminary data suggest that vitamin A and D supplementation is needed to prevent deficiency. More work is needed to define optimal doses, timing, and modes of administration to ensure that an adequate supply of these vitamins is available to meet the critical needs during pregnancy and in high-risk neonates.

Effect of low versus high early parenteral nutrition on plasma amino acid profiles in very low birth-weight infants.

OBJECTIVE: To study the efficacy of early high doses parenteral nutrition (PN) versus early low dose with progressive increments PN regimens, we performed a prospective randomized study in very low birth-weight infants. STUDY DESIGN: Forty-one appropriate gestational age preterm infants with birth weights ranging from 750-1500 g were randomly assigned into two groups. In Group 1, infants started on 3.0 g/kg/day amino acids (AA) and 3 g/kg/day of 20% lipid; in Group 2, AA and lipid were started on 1 g/kg/day, and advanced over 3 days to a maximum 3 g/kg/day. Blood samples were obtained for AA concentrations before starting of the PN, and at the 7th and 14th days. RESULTS: The mean (±SD) birth weight was 1335 g (240), gestational age was 29.7 weeks (1.7) of the study group. The mean body weight and head circumference was similar in the Group 1 and Group 2 at the 14th postnatal days. There was no difference in the blood levels of triglyceride, blood urea nitrogen, creatinine, ammonia, lactat and bicarbonate in the two groups. There was no significant difference in the concentrations of AA except for arginine and asparagine. On day 14, the mean arginine concentrations were significantly higher and asparagine concentrations were lower in Group 2. CONCLUSION: Although earlier more aggressive administration of AA and fat is not associated with any significant metabolic abnormalities, growth rates and plasma AA concentrations of the infants were similar to infants who AA and lipid given lower in the first day of life.

Attention among very low birth weight infants following early supplementation with docosahexaenoic and arachidonic acid.

AIM: To investigate the effect of supplementation with docosahexaenoic acid (DHA) and arachidonic acid (AA) in early neonatal life on cognitive functions among human milk fed very low birth weight infants (<1500 g) at 20 months chronological age. METHODS: Randomized, double-blinded, placebo-controlled intervention supplementing human milk with 0.5 mL oil (containing 32 mg DHA and 31 mg AA or placebo) per 100 mL milk from 1 week after birth until discharge from hospital (9 weeks on average). The intervention and control group included 44 and 48 children, respectively. Attention capacity was evaluated by two 'free-play' sessions. General cognitive functions were evaluated by the Bayley Mental Development Index (MDI) and an Ages and Stages Questionnaire. RESULTS: The results from the free-play sessions suggested positive effects from supplementation on functions related to attention. Neither the Bayley MDI nor the Ages and Stages Questionnaire showed significant difference between the intervention and control group. Plasma DHA concentration at discharge was positively correlated with both 'Sustained Attention' and the Bayley MDI according to chronological age. CONCLUSION: A positive effect of early supplementation with DHA and AA on 20 months attention capacity was indicated. These findings need further investigation.

Enhanced lumbar spine bone mineral content in piglets fed arachidonic acid and docosahexaenoic acid is modulated by severity of growth restriction.

The infant born small size for gestational age (SGA) has low bone mass. Since dietary arachidonic acid (AA) and DHA enhance bone mass in normal-birth-weight piglets the objective of the present study was to test for such benefits in the SGA piglet. In the present 15 d study, two levels of dietary AA and DHA (6:1 ratio of AA:DHA diets, 0.6:0.1 or 1.2:0.2 g/100 g dietary fat) v. a control diet were tested for effects on growth, fatty acid status, whole-body and regional bone mineral content (BMC) and metabolism in SGA piglets categorised as either very low birth weight (VLBW; < or = 1.0 kg; n 12) or low birth weight (LBW; 1.1 to 1.2 kg; n 18). Differences in outcomes for each body weight category were detected using ANOVA with post hoc Bonferroni tests. Growth was not influenced by diet, yet the LBW piglets fed 0.6:0.1 AA and DHA as g/100 g fat had elevated BMC in the spine, whereas the VLBW piglets had higher BMC of the spine if fed the higher intake of AA and DHA. In both weight categories, the higher intake of AA and DHA lowered bone resorption relative to controls, whereas bone formation was unchanged. Tissue fatty acid concentrations reflected dietary AA and DHA, especially trabecular bone of VLBW piglets. Whether the enhanced lumbar spine BMC is due to enhanced Ca absorption and thus suppression of bone resorption remains to be established.