Keli M. Hawthorne

A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents

BACKGROUND Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans (prebiotics). Results have been inconsistent; however, and no studies have been conducted to determine whether this effect persists with long-term use. OBJECTIVE The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan. DESIGN Pubertal adolescents were randomly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product (fructan group) or maltodextrin placebo (control group). Bone mineral content and bone mineral density were measured before randomization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation. Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan. After 1 y, the fructan group had a greater increment in both whole-body bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group. CONCLUSION Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth. Effects of dietary factors on calcium absorption may be modulated by genetic factors, including specific vitamin D receptor gene polymorphisms.

High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support.

BackgroundOsteopenia and rickets are common among extremely low birth weight infants (ELBW, <1000 g birth weight) despite current practices of vitamin and mineral supplementation. Few data are available evaluating the usual course of markers of mineral status in this population. Our objectives in this study were to determine the relationship between birth weight (BW) and peak serum alkaline phosphatase activity (P-APA) in ELBW infants and evaluate our experience with the diagnosis of rickets in these infants.MethodsWe evaluated all ELBW infants admitted to Texas Childrens Hospital NICU in 2006 and 2007. Of 211 admissions, we excluded 98 patients who were admitted at >30 days of age or did not survive/stay for >6 weeks. Bone radiographs obtained in 32 infants were reviewed by a radiologist masked to laboratory values.ResultsIn this cohort of 113 infants, P-APA was found to have a significant inverse relationship with BW, gestational age and serum phosphorus. In paired comparisons, P-APA of infants <600 g (957 ± 346 IU/L, n = 20) and infants 600–800 g (808 ± 323 IU/L, n = 43) were both significantly higher than P-APA of infants 800–1000 g (615 ± 252 IU/L, n = 50), p < 0.01. Thirty-two patients had radiographic evaluation for evidence of rickets, based on P-APA greater than 800 IU/L, parenteral nutrition greater than 3 to 4 weeks, or clinical suspicion. Of these, 18 showed radiologic rickets and 14 showed osteopenia without rickets. Infants with BW <600 g were more likely to have radiologic rickets (10/20 infants) compared to those with BW 600–800 g (6/43 infants) and BW 800–1000 g (2/50 infants), p < 0.01 for each. P-APA was not significantly higher in infants with radiologic rickets (1078 ± 356 IU/L) compared to those without radiologic evidence of rickets (943 ± 346, p = 0.18).ConclusionElevation of P-APA >600 IU/L was very common in ELBW infants. BW was significantly inversely related to both P-APA and radiologic rickets. No single value of P-APA was related to radiological findings of rickets. Given the very high risk of osteopenia and rickets among ELBW infants, we recommend consideration of early screening and early mineral supplementation, especially among infants <600 g BW.

Effect of Beef and Soy Proteins on the Absorption of Non-Heme Iron and Inorganic Zinc in Children

Background: Iron and zinc deficiency remain substantial problems in small children in both developed and developing nations. Optimizing mineral absorption is an important strategy in minimizing this problem. Objectives: To assess the effects of beef and soy proteins on the bioavailability of non-heme iron and zinc in children. Methods: We measured iron (n = 26) and zinc (n = 36) absorption in 4–8 y old children from meals differing only in protein source (beef or a low-phytate soy protein concentrate). Iron and zinc absorption were measured using multi-tracer stable isotope techniques. Iron absorption was calculated from the red blood cell iron incorporation measured after 14 days and zinc absorption from the ratio of the oral and intravenous excretion of the zinc tracers 48 hours after dosing. Results: Iron absorption from the beef meal was significantly greater (geometric mean, 7.6%) than from the soy meal (3.5%, p = 0.0015). Zinc absorption from the beef meal was greater (mean ± SD, 13.7 ± 6.0%) than from the soy meal (10.1 ± 4.1%, p = 0.047). Conclusion: These findings indicate that beef protein increases both non-heme iron and zinc absorption compared to soy protein. The effect of protein source on non-heme iron and inorganic zinc absorption should be one of the factors taken into account when designing diets for children. The inhibitory effect of the soy based meal on iron and zinc absorption could be overcome by fortifying the soy protein with these minerals during the production process.

Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk–Based Diet

Abstract Objective: The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk–based diet (HUM). Materials and Methods: In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mothers own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2–3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). Results: A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group. Conclusions: Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

Fish Oil–Based Lipid Emulsions in the Treatment of Parenteral Nutrition-Associated Liver Disease: An Ongoing Positive Experience

We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Childrens Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1-26). The median time to resolution of cholestasis was 40 d (range 3-158). Compared with infants with mild cholestasis (CB of 2.1-5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates.

A Systematic Review of Controlled Trials of Lower-Protein or Energy-Containing Infant Formulas for Use by Healthy Full-Term Infants

Infant formulas have historically been developed based on providing macronutrients at intake concentrations approximately matching the composition of human milk. In most countries, targets of 1.4-1.5 g of protein/dL and 20 kcal/oz (67-68 kcal/dL) have been set as the protein and energy concentrations for formulas during the first year of life, although this may be an overestimation of these contents. Recent introduction of lower-protein and -energy formulas in full-term infants led us to systematically review the literature for its effects on growth. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, our inclusion criteria were studies that enrolled healthy full-term infants and evaluated lower-protein or lower-energy formula, reported anthropometric outcomes including weight and length, and followed infants for at least 6 mo. Six studies were eligible for inclusion. These studies varied in the content of nutrients provided in the intervention and control groups, by additional dietary components in the study groups, and the timing and length of the intervention, which limit their usefulness for interpreting newly introduced lower-protein and -energy formulas in the United States. These studies suggest adequate growth during infancy and early childhood with infant formulas with concentrations of protein and energy slightly below historical standards in the United States. Further long-term research is needed to assess the impact of the use of lower-protein and/or lower-energy products, especially for nutritionally at-risk populations such as preterm infants and infants who are born small for gestational age.

Docosahexaenoic acid (DHA) supplementation of orange juice increases plasma phospholipid DHA content of children.

The major dietary source of docosahexaenoic acid (DHA) is fish, which is not widely consumed by children. There is concern, therefore, that children may not receive adequate DHA and so might benefit from dietary supplementation. The aim of the present study was to evaluate the effects of providing a supplement of microencapsulated algal DHA in juice. We assessed the effects of two levels of DHA supplementation on the plasma phospholipid DHA content of healthy 4- to 6-year-old and 7- to 12-year-old children who were randomly assigned to consume 180 mL juice containing either 50 mg (lower dose) or 100 mg (higher dose) DHA daily for 6 weeks. Plasma phospholipid DHA content (mole % of total fatty acids) was measured before and after 6 weeks of daily juice consumption. Because there are no data for plasma phospholipid DHA content in healthy children, data were compared to that of breastfed infants. At baseline, plasma phospholipid DHA content was lower in both age groups and dose groups than observed in breastfed infants. It increased significantly in both dose groups, but more so in the higher dose group of both age groups (P<0.05, overall mean+/-standard deviation: 3.72+/-0.66 vs 4.64+/-0.77); reaching levels similar to or greater than content of breastfed infants. Thus, DHA supplementation of juice at either 50 mg/day or 100 mg/day for 6 weeks was effective in increasing plasma phospholipid DHA contents of children.

Zinc homeostasis in 1-4 year olds consuming diets typical of US children.

Few data have evaluated Zn balance in young children after the first year of life. The objective of the present study was to study the relationships among Zn intake, absorption, endogenous faecal excretion, and retention in a group of healthy children. Thirty children, aged 15-48 months, were studied on a diet representative of their usual daily mineral intake. Zn absorption was assessed using a dual-tracer stable-isotope technique. Endogenous Zn faecal excretion and Cu absorption were determined in a subset of children. We found that Zn intake from the in-patient weighed dietary record (5.0 (SD 2.1) mg/d) was significantly greater than the current estimated average requirement (EAR; 2.5 mg/d; P 0.4, for all). Absolute Zn absorption was significantly related to Zn intake (r2 0.696; P < 0.0001), as was Zn retention (r2 0.506; P < 0.0001). Cu absorption was relatively high (75.1 (sd 10.8) %) despite the high Zn intake. The EAR for Zn based on this dataset would appear to be between 4.2 and 4.7 mg/d to allow for a net average retention of 120 microg/d consistent with growth needs. We concluded that at relatively high Zn intakes there was little evidence of down regulation of absorption or up regulation of urinary or endogenous faecal Zn excretion across the intake range studied. Zn retention was positively correlated with intake. A Zn intake between 4.2 and 4.7 mg/d should meet the requirement for normal growth for this age group.

Fortifier and Cream Improve Fat Delivery in Continuous Enteral Infant Feeding of Breast Milk

Premature and high-risk infants require accurate delivery of nutrients to promote appropriate growth. Continuous enteral feeding methods may result in significant fat and micronutrient loss. This study evaluated fat loss in enteral nutrition using current strategies for providing high-risk infants fortified human milk (HM). The fat content of HM was measured by IR analyzer in a simulated feeding system using the Kangaroo ePump™ and the MedFusion™ 2010 pump. Comparisons in fat loss were made between HM, HM supplemented with donor HM-derived fortifier Prolacta + H2MF™ (H2MF), and HM supplemented with H2MF and donor HM-derived cream ProlactCR™ (cream). When using the Kangaroo ePump™, the addition of H2MF and cream to HM increased fat delivery efficiency from 75.0% ± 1.2% to 83.7% ± 1.0% (p < 0.0001). When using the MedFusion™ 2010 pump, the addition of H2MF to HM increased fat delivery efficiency from 83.2% ± 2.8% to 88.8% ± 0.8% (p < 0.05), and the addition of H2MF and cream increased fat delivery efficiency to 92.0% ± 0.3% (p < 0.01). The addition of H2MF and cream to HM provides both the benefits of bioactive elements from mother’s milk and increased fat delivery, making the addition of H2MF and cream an appropriate method to improve infant weight gain.

A Novel Approach to Improving Fat Delivery in Neonatal Enteral Feeding

Continuous infusion systems used for enteral nutrition support in the neonatal intensive care unit deliver as little as 60% of the fat in human milk to the neonate. This study determined the effect of mixing common feedings for preterm infants in the feeding bag and tubing on fat losses during enteral feeding. Laboratory models were developed to assess the contribution of various mixing techniques to delivered fat content. Fat content was measured periodically during feeding and compared to baseline measurements. A multistage approach incorporating a feeding bag inverter and a tubing circulation loop delivered >90% of milk fat when used in conjunction with a commercial continuous infusion system. With unfortified human milk, this approach delivered 91.9% ± 1.5% of fat content over a one hour feed, significantly greater (p < 0.01) than 77.5% ± 2.2% delivered by continuous infusion controls (Mean ± SEM). With fortified human milk, this approach delivered 92.1% ± 2.4% of fat content, significantly greater (p < 0.01) than 79.4% ± 1.0% delivered by a non-adapted infusion system (Mean ± SEM). Mixing human milk during continuous infusion improves fat delivery, which may improve nutrition and growth outcomes in low birth weight neonates.