Resonance Raman based skin carotenoid measurements in newborns and infants.

We describe Resonance Raman based skin carotenoid measurements in newborns and infants. Skin- and serum carotenoid levels correlate with high statistical significance in healthy newborns and infants, and with reduced accuracy also in prematurely born infants, who in general feature very low carotenoid levels and thin transparent skin giving rise to large background absorption effects. Skin carotenoid levels can be easily compared among subjects and/or tracked in longitudinal studies with the highly molecule-specific Raman method. It therefore holds promise as a rapid, non-invasive, carotenoid antioxidant assessment method for newborns and infants in the field of pediatrics.

Resonance Raman spectroscopy and the preterm infant carotenoid status.

OBJECTIVE: The aim of the study was to validate the noninvasive resonance Raman spectroscopy (RRS) method in infants in comparison with the high-performance liquid chromatography (HPLC) method, and to evaluate the carotenoid status in preterm infants fed with mother's milk or formula. METHODS: In the first phase of the study, resonance Raman measurements were made on male term infants' skin and correlated with tissue harvested at the time of circumcision. Each baby's foreskin was weighed, enzymatically digested, and the total carotenoids were extracted and quantitated by the HPLC. Next, to evaluate the carotenoid status of preterm infants (BW <1500 g), the skin and serum carotenoids in infants fed with either human milk or preterm formula were studied from the start of feedings and every 2 weeks until hospital discharge. Skin carotenoids were measured by RRS and the serum total carotenoids by HPLC. RESULTS: Foreskin carotenoid levels measured by RRS correlated with HPLC measurements of total serum carotenoids (R = 0.52, P < 0.01, n = 16). Forty preterm infants were studied for their carotenoid status. Thirty-two infants were fed mother's milk, whereas 8 were fed a preterm infant formula that was not enriched with carotenoids. The gestation and birth weight of the 2 feeding groups were similar. The infants fed human milk had a higher serum total carotenoid concentration and skin Raman counts than formula-fed infants. The skin Raman counts and total serum carotenoid correlated (R = 0.44, P = 0.01). The human milk-fed infants' serum total carotenoid concentrations and Raman values did not change during the study period; however, the formula-fed group's total serum and skin carotenoid decreased significantly during the study. CONCLUSIONS: RRS of infant's skin reliably assesses total carotenoid status noninvasively. Human milk-fed preterm infants have higher serum and skin carotenoids than formula-fed infants suggesting that formula-fed infants may benefit from carotenoid supplementation.

Observational study of caloric and nutrient intake, bone density, and body composition in infants and children with spinal muscular atrophy type I.

Clinical experience supports a critical role for nutrition in patients with spinal muscular atrophy (SMA). Three-day dietary intake records were analyzed for 156 visits in 47 SMA type I patients, 25 males and 22 females, ages 1month to 13years (median 9.8months) and compared to dietary reference intakes for gender and age along with anthropometric measures and dual-energy X-ray absorptiometry (DEXA) data. Using standardized growth curves, twelve patients met criteria for failure to thrive (FTT) with weight for age <3rd percentile; eight met criteria based on weight for height. Percentage of body fat mass was not correlated with weight for height and weight for age across percentile categories. DEXA analysis further demonstrated that SMA type I children have higher fat mass and lower fat free mass than healthy peers (p<0.001). DEXA and dietary analysis indicates a strong correlation with magnesium intake and bone mineral density (r=0.65, p<0.001). Average caloric intake for 1-3years old was 68.8±15.8kcal/kg - 67% of peers' recommended intake. Children with SMA type I may have lower caloric requirements than healthy age-matched peers, increasing risk for over and undernourished states and deficiencies of critical nutrients. Standardized growth charts may overestimate FTT status in SMA type I.

SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

BACKGROUND: Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. METHODS: This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. RESULTS: Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. CONCLUSIONS: This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.

SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

BACKGROUND: Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo. METHODS: Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures. RESULTS: At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007). CONCLUSIONS: This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials. TRIAL REGISTRY: Clinicaltrials.gov NCT00227266.

An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products.

OBJECTIVE: To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants. STUDY DESIGN: Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. RESULTS: The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention (P = .007). CONCLUSIONS: For extremely premature infants, an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk-based diet that also includes bovine milk-based products.

Phase II open label study of valproic acid in spinal muscular atrophy.

UNLABELLED: Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p

Nutritional therapy for burns in children and adults.

Burns are a serious injury that requires optimal nutritional support. This review discusses the nutritional care for adults and children with major burns. A burned patient's metabolism is greatly accelerated with increased requirements for energy, carbohydrates, proteins, fats, vitamins, minerals, and antioxidants. Early nutrition by parenteral and enteral feedings is vital. Careful assessment of the nutritional state of the burn patient is also important to reduce infection, recovery time, and long-term sequelae.

Effects of a human milk-derived human milk fortifier on the antibacterial actions of human milk.

OBJECTIVES: To compare the effects of a human breastmilk-derived fortifier on the antibacterial activity of milk obtained from lactating mothers delivering prematurely with the effects of a powdered fortifier on the same milk. STUDY DESIGN: Human milk samples were obtained after the first week of postnatal life from 10 lactating mothers, who had delivered prematurely. A bovine milk-based powdered fortifier and a human breastmilk-based frozen fortifier were evaluated. All mothers were healthy and they were not on any medications, although they were taking prenatal vitamins during lactation. The effects of each fortifier on the antimicrobial activity of milk toward Enterobacter sakazaki (ES), Escherichia coli, Clostridium difficile (CD), and Shigella soneii (SS) were evaluated by both the filter paper method and the growth inhibition method. RESULTS: Human milk inhibited the growth of all of the test organisms. This antibacterial activity was almost totally inhibited by the addition of the bovine protein-based human milk fortifier, while it remained unaffected by the addition of the human breastmilk-based fortifier. CONCLUSIONS: Breastmilk from women who have delivered preterm has antibacterial activity that can be affected by the addition of bovine-based fortifier, but not by the addition of a human breastmilk-based fortifier.

Effects of dietary calcium intervention on adolescent mothers and newborns: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of dietary calcium (Ca) intervention on adolescent pregnant mothers and their newborns. METHODS: Seventy-two pregnant adolescent mothers were randomized into one of 3 groups: control, orange juice fortified with calcium, and dairy. The orange juice and dairy groups were required to take more than 1,200 mg Ca. Calcium tablets were added for those not able to meet required Ca. Maternal and infant weight, length, and blood pressure (BP) were recorded. Maternal dietary records were evaluated. Mother's blood was drawn for serum Ca, phosphate (P), magnesium (Mg), and vitamin 25-hydroxyvitamin D (D). Cord blood was collected for serum Ca and D. Newborn total body Ca was determined. RESULTS: All mothers were similar in weight, height, and BP. Mothers in the orange juice plus calcium and dairy groups had higher intakes of Ca (1,472 mg and 1,771 mg) than controls (862 mg). One half of the mothers in the orange juice plus calcium group required Ca tablets. Mothers in the dairy group had higher intakes of P, D, and Mg, higher serum folate and D, and higher cord D levels. Mothers in the orange juice plus calcium group had higher serum P but lower serum folate and D. Infants (3,517+/-273 g) in the dairy group were heavier than infants in the control (3,277+/-177 g) and orange juice plus calcium (3,292+/-165 g) groups. Infants in the dairy group had higher total body calcium than control infants. CONCLUSION: Calcium diet supplemented with dairy products during adolescent pregnancy resulted in higher maternal vitamin D and folate serum levels and higher newborn weight and bone mineralization compared with controls.

Calcium nutrition and metabolism during infancy.

Calcium is a vital mineral for the developing newborn infant. This review discusses perinatal and neonatal calcium metabolism, with an emphasis on enteral calcium absorption and the nutritional factors affecting calcium bioavailability including the three major endocrine hormones involved in calcium metabolism: parathyroid hormone, vitamin D, and calcitonin. The placenta transports calcium to the fetus throughout pregnancy, with the largest amount of fetal calcium accumulation occurring in the third trimester. At birth, the newborn transitions to intestinal absorption to meet the body's calcium needs. Most calcium is absorbed by paracellular passive diffusion in the small intestine. Calcium intestinal absorption is affected by the type and amount of calcium ingested. It is also affected by the amount of intestinal calcium that is bound to dietary fats and proteins. One major consequence of decreased calcium absorption is metabolic bone disease in which there is a failure of complete mineralization of the bone osteoid.

Effects of powdered human milk fortifiers on the antibacterial actions of human milk.

OBJECTIVES: To evaluate the effects of powdered fortifiers and the addition of iron and medium-chain triglycerides on preterm human milk antibacterial activity. STUDY DESIGN: Human milk samples were obtained from 42 preterm lactating mothers after the first week of postnatal life. Enfamil (EHMF) and Similac (SHMF) Human Milk Fortifiers were evaluated. All mothers were healthy and were on no medications except for vitamins during lactation. The effects of each fortifier against E. coli (E. coli), Staphylococcus (Staph), Enterobacter sakazakii (ES), and Group B Streptococcus (GBS) were measured by the filter paper method and growth of the bacteria with human milk alone as control. The addition of iron and medium-chain triglycerides (MCT) to human milk was also tested. RESULTS: Human milk inhibited the growth of E. coli, Staph, ES, and GBS. Only the SHMF and the addition of MCT had similar antibacterial action as human milk alone. EHMF and the addition of iron to human milk removed the milk's antibacterial action against these four organisms. CONCLUSIONS: Preterm human milk has antimicrobial activity against E. coli, Staph, ES, and GBS. This activity can be affected by the addition of iron and fortifiers that contain iron.

Sustained bone mineral density changes after burn injury.

BACKGROUND: Body-composition changes have been observed after burn injury. In particular, several studies have shown that bone mineral density (BMD) in burn patients is decreased when compared to the normal population. Little is known about the frequency, severity, or duration of these changes. The purpose of this study was to describe body-composition changes over time after burn injury. MATERIALS AND METHODS: Twenty-nine burn patients participated in this study. Portable dual-energy X-ray absorptiometry (pDEXA) measuring forearm BMD, fat, and lean mass was obtained as soon as possible after admission and repeated bi-weekly until discharge and, when possible, for 2 years post-injury. The scan showing the greatest change in BMD, fat, or lean mass was compared to the baseline scan for each individual. RESULTS: Although lean and fat mass did not change significantly after injury, BMD decreased significantly. The greatest change in BMD did not occur during the acute burn hospitalization, but rather 131 days after burn injury. Changes in post-burn BMD inversely correlated with % total body surface area (TBSA) and % 3rd-degree TBSA. The magnitude of change was similar between adults and children. CONCLUSIONS: These results confirm earlier studies, suggesting that BMD can be negatively altered post-injury, with the greatest changes occurring after patients are discharged from the hospital. Although the clinical significance of these changes is not known, this study supports the need for long-term musculoskeletal assessments in burn patients and for further research to elucidate the mechanisms of burn-induced body-composition changes.

Lecithin decreases human milk fat loss during enteral pumping.

BACKGROUND: The fat content of human milk provides the majority of calories for infants. However, large fat losses in human milk have been observed using enteral pump systems, causing poor growth in infants. The fat may adhere in the pump system. Lecithin, a phospholipid, has been used in the food industry as a lipophilic emulsifier of fats. OBJECTIVE: The purpose of this study was to evaluate the effects of lecithin on the delivery of human milk fat from an enteral pump. It is hypothesized that the addition of lecithin would decrease the fat loss during human milk delivery. METHODS: Six mothers at a mature stage of lactation (>4 weeks of lactation) donated human milk. The human milk samples were stored separately at -20 degrees C before analysis and evaluated individually. The fat content of the milk samples was estimated by the creamatocrit method, in which the samples were centrifuged in a standard hematocrit tube and the fat layer read with vernier calipers and expressed as a percentage of the length of the milk column to the nearest 0.5%. The accuracy of this method is 92%. The Kangaroo 324 Feeding Pump (Sherwood Medical, St. Louis, MO) was used as the continuous pump system. The human milk samples were divided into either control samples without lecithin or with lecithin (1 or 0.5 g soy lecithin dissolved in 50 mL milk). All samples were pumped at 10 to 50 mL/h for at least 4 hours. The pumped milk was collected in an iced container, and creamatocrits were determined in duplicate. RESULTS: There was significant fat loss in the control milk samples compared with the milk samples with added lecithin. The average fat loss was 58% +/- 13% for control samples and 55% +/- 26% for the milk with 0.5 g soy lecithin. Milk with 1 g soy lecithin averaged 2% +/- 2% fat loss. The pumping rate had no effect on fat loss. The greatest fat loss (70% +/- 6%)occurred during the first 4 hours of pumping. CONCLUSIONS: The addition of 1 g soy lecithin per 50 mL milk decreased the human milk fat loss during intermittent pumping and may help infants receive more calories from human milk administered by pump.