Early Postnatal Changes of Bone Turnover Biomarkers in Very Low-Birth-Weight Neonates-The Effect of Two Parenteral Lipid Emulsions with Different Polyunsaturated Fatty Acid Content: A Randomized Double-Blind Study (original) (raw)
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It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with 3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n ϭ 10) or 1% (n3FA, n ϭ 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-B ligand, TNF-␣, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health.
Pediatric Research, 2005
Long-chain polyunsaturated fatty acids (LC PUFA) are associated with bone mass in animals and human adults, yet no data exist for human infants. Thus, the objective of this study was to establish that LC PUFA status is associated with bone mass in healthy infants. Thirty mother-infant pairs were studied for LC PUFA status by measuring maternal and cord blood red blood cells (RBC) for arachidonic acid (AA), eicosapentaenoic acid (EPA), and DHA. Infant anthropometry and lumbar spine 1-4, femur and whole-body bone mineral content (BMC) were measured within 15 d of delivery. Maternal and infant LC PUFA were tested for their relationship to BMC using Pearson correlation and backward step-wise regression analyses. At birth, the average gestational age was 39.3 Ϯ 1.1 wk and body weight was 3433 Ϯ 430 g. Cord RBC AA was positively correlated with whole-body BMC, AA:EPA positively correlated with lumbar spine 1-4 BMC and femur BMC. Maternal RBC AA was positively correlated with whole-body BMC. After accounting for infant weight using regression, whole-body BMC was positively predicted by cord RBC AA but none of the maternal LC PUFA; lumbar spine 1-4 BMC was positively predicted by cord RBCAA:EPA ratio but negatively by maternal DHA; and femur BMC was not predicted by cord LC PUFA but was negatively predicted by maternal DHA. Imbalances among the n-6 and n-3 LC PUFA by term gestation are associated with lower bone mass, suggesting that the maternal diet should be balanced in n-6 and n-3 LC PUFA.
British Journal of Nutrition, 2004
PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6þn-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0·4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6þ n-3 group than in the other groups. Cortical bone thickness in the n-6þn-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning. Diet: Bone mineral density: Fatty acids: Insulin-like growth factor-1 * Corresponding author: Dr Marina Korotkova, fax þ46 31 21 70 23, email Marina.Korotkova@cmm.ki.se
The Journal of …, 2005
In piglets, feeding arachidonic acid (AA) and docosahexaenoic acid (DHA) in a 5:1 ratio leads to elevated bone mass, but the optimal total quantity requires clarification. We studied bone mass and modeling of piglets that were randomized to receive 1 of 4 formulas for 15 d: control formula or the same formula with various levels of AA:DHA (0.5:0.1 g, 1.0:0.2 g or 2.0:0.4 g AA:DHA/100 g of fat). Measurements included: bone area (BA), mineral content (BMC), and density (BMD) of whole body, lumbar spine, and excised femurs; biomarkers of bone modeling were plasma osteocalcin and urinary cross-linked N-telopeptides of type 1 collagen (NTx), tibial ex vivo release of prostaglandin E 2 (PGE 2), plasma insulin-like growth factor-1 (IGF-1), and tissue fatty acids. Main effects were identified using ANOVA and post hoc Bonferroni t tests. In supplemented piglets, relations among liver fatty acid proportions and bone mass were assessed using Pearson correlations. Whole body (P ϭ 0.028) and lumbar spine (P ϭ 0.043) BMD were higher in the group supplemented with 0.5:0.1 g AA:DHA/100 g of fat than in controls. Tissue AA and DHA increased in proportion to diet levels. Liver eicosapentaenoic acid (EPA) correlated positively (r Ն 0.38, P Յ 0.05) with whole body and femur BMC and BMD and lumbar spine BMC. Liver AA:EPA ratio correlated negatively (r Ն Ϫ0.039, P Յ 0.05) with whole body, femur, and lumbar spine BMC plus whole body and femur BMD. Dietary 1.0:0.2 g AA:DHA/100 g reduced NTx relative to 2.0:0.4 g AA:DHA/100 g of fat (P ϭ 0.039). The diets did not affect the other biochemical variables measured. Low levels of dietary AA:DHA (0.5:0.1 g/100 g of fat) elevate bone mass, but higher amounts are not beneficial.
World review of nutrition and dietetics, 2013
Recent advances in neonatal care significantly increases survival rate in preterm and particularly in extremely low birth weight infants (ELBW infants) and nutrition is becoming one of the most challenging issue to improve short and long term health and developmental outcomes. Nutrition is also relevant for bone development and mineralization reducing the risk of osteopenia and metabolic bone disease (MBD). Osteopenia of prematurity is a multifactorial disease including predominantly nutritional but also biomechanical and environmental factors. At birth, the fetal active mineral transfer is interrupted and the preterm becomes related to the parenteral and enteral mineral supplies. On the other hand, physiological adaptation of bone to extra uterine life leads to an increase in bone resorption. This process occurring earlier in preterm than in term infants can be accompanied by an increased risk of bone fragility and fractures. Early provision of highly bioavailable mineral supplies,...
Calcified Tissue International, 2013
We aimed to compare the effect of 12-week feeding of commercially available infant formulas with different percentages of palmitic acid at sn-2 (beta-palmitate) on anthropometric measures and bone strength of term infants. It was hypothesized that feeding infants with high beta-palmitate (HBP) formula will enhance their bone speed of sound (SOS). Eighty-three infants appropriate for gestational age participated in the study; of these, 58 were formula-fed and 25 breast-fed infants, serving as a reference group. The formula-fed infants were randomly assigned to receive HBP formula (43 % of the palmitic acid is esterified to the middle position of the glycerol backbone, study group; n = 30) or regular formula with lowbeta palmitate (LBP, 14 % of the palmitic acid is esterified to the middle position of the glycerol backbone, n = 28). Sixtysix infants completed the 12-week study. Anthropometric and quantitative ultrasound measurements of bone SOS for assessment of bone strength were performed at randomization and at 6 and 12 weeks postnatal age. At randomization, gestational age, birth weight, and bone SOS were comparable between the three groups. At 12 weeks postnatal age, the mean bone SOS of the HBP group was significantly higher than that of the LBP group (2,896 ± 133 vs. 2,825 ± 79 m/s respectively, P = 0.049) and comparable with that of the breast-fed group (2,875 ± 85 m/s). We concluded that infants consuming HBP formula had changes in bone SOS that were comparable to those of infants consuming breast milk and favorable compared to infants consuming LBP formula.
Prostaglandins Leukotrienes and Essential Fatty Acids, 2002
This research investigates the effects of exogenous prostaglandin E 2 (PGE 2 ) treatment and arachidonic acid supplementation on the rate of growth in modelling bone of piglets.The piglet is a good model for the study of infant nutrition and bone growth.PGE 2 and long-chain polyunsaturated fattyacid (LC PUFA) supplementation, alone and in combination, are shown to have little or no effect on cortical bone thickness.Though exogenous PGE 2 supplementation and LC PUFA supplementation may both be effective in promoting bone growth and massin adults, they do not appear to have the same positive effect on bone growth ininfancyovera short term. A dynamic model for bone growthin pigletsisproposed here for the first time.This research addsto our knowledge of the relationship between the dynamic histology of bone, the rate of osteogenesis, and the link between nutrition and bone growth. &
Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2013
Long-chain n-3 PUFA (LCPUFA) and palmitate (16:0) positioning in the triacylglycerol (TAG) of infant formula may affect calcium-uptake which could affect bone health. We investigated if a human milk fat substitute (HMFS) with a modified TAG structure holding 16:0 predominantly in the sn-2-position compared with a control (CONT) and if increasing n-3LCPUFA intake giving fish oil (FO) compared with sunflower oil (SO) would affect bone parameters in piglets in two sets of controlled 14d-interventions (n ¼12/group). We assessed this by dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography and mechanical strength. Bone mineral content (BMC) was higher in the FO compared to the SO-group (p¼ 0.03). Despite similar weight gain in HMFS-and CONT-groups, body fat accumulation was higher with HMFS (po0.001), and BMC, bone area (BA) and cortical BA in femur were lower (p¼ 0.002, p¼ 0.005, and p¼0.02, respectively), indicating importance of both n-3LCPUFA and 16:0 TAG-positioning in infant formulas.
Background and Aim: Very premature newborns have an increased risk of low bone mass and metabolic bone disease. Most longitudinal studies report a significant decline in bone strength in the first weeks after birth. The aim of the study was to evaluate whether higher early calcium (Ca) and phosphorus (P) intake delivered by parenteral nutrition (PN) can prevent bone strength decline in preterm infants, within the first weeks after birth. Patients and Methods: This was a randomized controlled trial of consecutively admitted neonates born with 33 weeks of gestational age, assigned to receive either Ca 45 mg Á kg À1 Á day À1 (low dose [LD]) or Ca 75 mg Á kg À1 Á day À1 (high dose [HD]) by PN. P was added to the PN solutions at a fixed Ca:P ratio (mg) of 1.7:1. Bone strength was assessed by the speed of sound (SOS) using the quantitative ultrasound method. Measurements were performed weekly from birth until discharge. Low bone strength (SOS <10th centile of reference values) was the main outcome. Results: Eighty-six infants were enrolled, 40 assigned to LD group and 46 to HD group. Mean (standard error) gestational age was 29.6 weeks (2.1) and birth weight was 1262 g (0.356). In the HD group, the SOS values never fell below those recorded at birth and, up to the sixth week of life, low bone strength was significantly less frequent as compared with that in the LD group, in spite of progressive reduction in parenteral mineral intake and/or establishment of full enteral feeding. Conclusions: Early assigned parenteral intake of Ca 75 mg Á kg À1 Á day À1 and P 44 mg Á kg À1 Á day À1 significantly contributed to preventing short-term bone strength decline in preterm infants.
Journal of Parenteral and Enteral Nutrition, 2013
Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. (1) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk?