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OBJECTIVE: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants. STUDY DESIGN: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data. RESULTS: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05). CONCLUSIONS: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

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The milk fat globule membrane (MFGM) in breast milk contains many bioactive components. Infant formulas traditionally have been devoid of the MFGM fraction, but dairy technology now has made the addition of bovine MFGM technically feasible. We identified 6 double-blinded randomized controlled trials exploring the effects of MFGM supplementation on the diets of infants or children. Results suggest that supplementation is safe and indicate positive effects on both neurodevelopment and defense against infections. MFGM supplementation of infant formula may narrow the gap in cognitive performance and infection rates between breastfed and formula-fed infants. Because of the small number of studies and the heterogeneity of interventions, more high-quality double-blinded randomized controlled trials are needed, with well characterized and clearly defined MFGM fractions, before firm conclusions on the effects of MFGM supplementation on the health and development of infants can be drawn.

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OBJECTIVES: To assess the prevalence of overweight/obese children and to explore body composition in a Swedish cohort of preschool children born with marginally low birth weight (MLBW, ie, 2000-2500 g). STUDY DESIGN: We included 285 Swedish children with MLBW (44% small for gestational age), and 95 control children with normal birth weights. At 3.5 years and 7 years of age, we assessed anthropometrics, including the prevalence of overweight/obese children. At 7 years, dual-energy X-ray was used for body composition. RESULTS: There were no significant differences between groups in the prevalence of overweight/obesity or in skinfold thickness; however, at 3.5 years, mean height, weight, and BMI in children with MLBW were 2.1 cm (95% CI 1.2-3.1), 1.2 kg (95% CI 0.7-1.6), and 0.47 kg/m(2) (95% CI 0.17-0.76) lower compared with controls. The corresponding mean differences also were lower in children with MLBW compared with control children at 7 years; 2.5 cm (95% CI 0.9-4.1), 1.6 kg (95% CI 0.6-2.8), and 0.48 kg/m(2) (95% CI 0.01-0.94). The differences were greater in those born small for gestational age. Dual-energy X-ray analyses showed lower fat-free mass index in MLBW infants and a similar trend in fat mass index. Within children with MLBW, BMI at 7 years correlated positively to growth velocity in infancy. CONCLUSION: Children with MLBW had lower BMI and did not show increased risk of overweight or obesity up to 7 years. Nevertheless, the BMI in MLBW children was positively correlated to growth-velocity in infancy. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00558454.

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Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data.

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AIM: To investigate whether iron supplements compromise copper status in infants. METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and 9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc-dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29 vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21 U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4-9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24 U/mg Hb, p=0.023) than those receiving placebo. CONCLUSION: There is a physiologic increase in p-Cu during the first 9 mo of life. Differences in copper status between Swedish and Honduran infants may be due to genetic or nutritional differences. Iron supplementation decreases CuZn-SOD activity, probably due to a negative effect on copper status. Possible clinical implications remain to be elucidated.

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BACKGROUND: Little is known about the regulation of iron, zinc, and copper in breast milk and the transport of these minerals across the mammary gland epithelium. OBJECTIVE: The objective was to study associations between breast-milk concentrations of iron, zinc, and copper and maternal mineral status. DESIGN: Milk samples from 191 Swedish and Honduran mothers were collected at 9 mo postpartum. Iron, zinc, and copper concentrations were measured by atomic absorption spectrometry. Blood samples from mothers were analyzed for plasma zinc and copper and 4 indexes of iron status: hemoglobin, plasma ferritin, soluble transferrin receptors, and zinc protoporphyrin. Complementary food energy (CFE) intake was used as an inverse proxy for breast-milk intake. RESULTS: Mean (+/-SD) breast-milk concentrations of iron were lower in the Honduran than in the Swedish mothers (0.21 +/- 0.25 compared with 0.29 +/- 0.21 mg/L; P < 0.001), and mean breast-milk concentrations of zinc and copper were higher in the Honduran than in the Swedish mothers [0.70 +/- 0.18 compared with 0.46 +/- 0.26 mg/L (P < 0.001) and 0.16 +/- 0.21 compared with 0.12 +/- 0.22 mg/L (P = 0.001), respectively]. Milk iron was positively correlated with CFE intake (r = 0.24, P = 0.001) but was not significantly correlated with any iron-status variable. Milk zinc was negatively correlated with CFE intake (r = -0.24, P = 0.001) but was not significantly correlated with maternal plasma zinc. Milk copper was not significantly correlated with CFE intake or maternal plasma copper. CONCLUSIONS: Milk iron, zinc, and copper concentrations at 9 mo postpartum are not associated with maternal mineral status, which suggests active transport mechanisms in the mammary gland for all 3 minerals. Milk iron concentrations increase and milk zinc concentrations decrease during weaning [corrected]

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Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.

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BACKGROUND: It is commonly assumed that there is no difference in iron status between male and female infants, despite a lack of studies addressing this question. OBJECTIVE: To study sex differences in different measures of iron status in infants. METHODS: At 4 months of age, 263 term, breastfed infants (121 Swedish and 142 Honduran) were randomized to receive iron supplements or placebo until 9 months of age. Blood samples at 4, 6, and 9 months of age were analyzed for hemoglobin (Hb), mean cell volume (MCV), zinc protoporphyrin (ZPP), plasma ferritin, and transferrin receptors (TfR). RESULTS: At 4, 6, and 9 months, boys had significantly lower Hb, MCV, and ferritin and higher ZPP and TfR than girls. At 9 months, boys had a 10-fold higher risk of being classified as having iron deficiency anemia. The differences at 9 months in MCV (71.6 vs 75.1 fL) and ZPP (59 vs 49 micro mol/mol heme) remained significant after controlling for iron supplementation, site, growth variables, and other possible confounders. For ferritin, there was a remaining sex difference at 9 months among Swedish (29 vs 53 micro g/L) but not Honduran infants. For Hb and TfR, sex differences at 9 months were larger in unsupplemented infants, especially in those with a birth weight of <3500 g. CONCLUSIONS: There are substantial sex differences in Hb and other indicators of iron status during infancy. Some of these may be genetically determined, whereas others seem to reflect an increased incidence of true iron deficiency in boys.

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