Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study.

BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (µg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Early Life Anti-Müllerian Hormone Trajectories in Infant Girls.

BACKGROUND: Minipuberty is a period of increased reproductive axis activity in infancy, but the importance of this period is not well understood, especially in girls. Previous studies reported a peak in hormone concentrations at 3 to 4 months old. Our objective is to describe anti-Müllerian hormone (AMH) trajectories in the context of other minipuberty factors among healthy infant girls using longitudinal measures of AMH. METHODS: The Infant Feeding and Early Development study is a longitudinal cohort study of healthy infants, recruited from hospitals in the Philadelphia area during 2010 to 2013. We measured AMH in 153 girls who contributed 1366 serum samples across 11 study visits over 36 weeks. We also measured follicle stimulating hormone (FSH), estradiol, and ovarian characteristics. We used latent class mixed effects models to cluster trajectories of AMH concentration with age. Using linear mixed models, we estimated FSH and ovarian characteristic trajectories separately by AMH cluster. RESULTS: We classified infants into four clusters that represent patterns of AMH that were high and decreasing (decreasing), had a peak around 12 weeks or 20 weeks (early peak and middle peak), or were consistently low (low). Infants in these clusters differed in their FSH trajectories, timing of estradiol production, and ovarian characteristics. CONCLUSIONS: The AMH clusters identified suggest variation in the timing and the magnitude of the minipuberty response in infant girls. The decreasing and low clusters have not been described previously and should be further evaluated to determine whether they represent an opportunity for the early identification of later reproductive conditions.

Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation.

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD. OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects. METHODS: Composite plasma [13C10]retinol response data collected from 22 subjects with SCD-HbSS for 28 d after isotope ingestion were analyzed using population-based compartmental modeling ("super-subject" approach); TBS and retinol kinetics were quantified for the group. TBS was also calculated for the same individuals using RID, as well as for healthy peers (n = 20) and for the subjects with SCD-HbSS after 8 wk of daily vitamin A supplements (3.15 or 6.29 µmol retinol/d [900 or 1800 µg retinol activity equivalents/d]). RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 µmol, equivalent to ∼11 mo of stored vitamin A; vitamin A disposal rate was 1.3 µmol/d. Model-predicted TBS was similar to that predicted by RID at 3 d postdosing (mean, 389 µmol; ∼0.3 µmol/g liver); TBS predictions at 3 compared with 28 d were not significantly different. Mean TBS in healthy peers was similar (406 µmol). RID-predicted TBS for subjects with SCD-HbSS was not significantly affected by vitamin A supplementation at either dose. CONCLUSIONS: Despite differences in plasma retinol concentrations, TBS was the same in subjects with SCD-HbSS compared with healthy peers. Because 56 d of vitamin A supplementation at levels 1.2 to 2.6 times the Recommended Dietary Allowance did not increase TBS in these subjects with SCD-HbSS, further work will be needed to understand the effects of SCD on retinol metabolism. This trial was registered as NCT03632876 at clinicaltrials.gov.

Glutamic acid intake by formula-fed infants: are acceptable daily intakes appropriate?

The 2017 European Food Safety Authority (EFSA) recommendation of an acceptable daily intake (ADI) of 30 mg glutamic acid/kg bw/day did not take into consideration the primary energy sources during infancy, including infant formulas. In the present study, we determined total daily intakes of glutamic acid in a contemporary cohort of healthy infants who were fed either cow milk formula (CMF) or extensive protein hydrolysate formula (EHF); the formulas differed substantially in glutamic acid content. The infants (n = 141) were randomized to be fed either CMF or EHF. Dietary intakes were determined from weighed bottle methods and/or prospective diet records, and body weights were measured on 14 occasions from 0.5 to 12.5 months. Secondary data analysis determined the glutamic acid content of the diet over time. The trial was registered at  http://www. CLINICALTRIALS: gov/ as NCT01700205, 3 October 2012. Glutamic acid intake from formula and other foods was significantly higher in infants fed EHF when compared to CMF. As glutamic acid intake from formula decreased, intake from other nutritional sources steadily increased from 5.5 months. Regardless of formula type, every infant exceeded the ADI of 30 mg/kg bw/day from 0.5 to 12.5 months.   Conclusion: Given that the ADI recommendation was not based on actual intake data of primary energy sources during infancy, the present findings on the growing child's ingestion of glutamic acid from infant formula and the complementary diet may be of interest when developing future guidelines and communications to parents, clinical care providers, and policy makers. WHAT IS KNOWN: • The 2017 re-evaluation of the safety of glutamic acid-glutamates and the recommended acceptable daily intake (ADI) of 30 mg/kg bw/d by the European Food Safety Authority (EFSA) did not include actual intake data of the primary energy sources during infancy. WHAT IS NEW: • During the first year, glutamic acid intake from infant formula and other food sources exceeded the ADI of 30 mg/kg bw/day.

Impact of Pancreatic Enzymes on Enteral Fat and Nitrogen Absorption in Short Bowel Syndrome.

OBJECTIVES: Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study. SUBJECTS/METHODS: This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively. RESULTS: There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy. CONCLUSIONS: There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response.

Endocrine-sensitive physical endpoints in newborns: ranges and predictors.

BACKGROUND: In neonates, endocrine-sensitive physical endpoints, including breast and reproductive tissues, may reflect effects of fetal environmental exposure. Studies using standardized measurement techniques that describe demographic and clinical variability in these endpoints are lacking. METHODS: Three hundred and eighty-eight healthy term newborns <3 days old were evaluated, 69% African American and 25% White. Measures included breast bud diameter, anogenital distance (AGD), stretched penile length (SPL), and testicular volume (TV). RESULTS: Breast buds were larger in females than males bilaterally (right: 13.0 ± 4.0 vs. 12.0 ± 4.0 mm, p = 0.008; left: 13.0 ± 4.0 vs. 11.0 ± 3.0 mm, p < 0.001). Breast bud size correlated positively with gestational age (regression coefficient = 0.46 ± 0.12 mm, p < 0.001) and weight Z-score (0.59 ± 0.24 mm, p = 0.02), and negatively with White race (-1.00 ± 0.30 mm, p = 0.001). AGD was longer in males (scrotum-to-anus) than females (fourchette-to-anus) (21.0 ± 4.0 vs. 13.0 ± 2.0 mm, p < 0.001) and did not differ by race. SPL was shorter in White infants (35.0 ± 5.0 vs. 36.0 ± 5.0 mm, p = 0.04). Median TV was 0.5 cm3, and larger in White males (odds ratio 1.71, 95% confidence interval: 1.02-2.88) CONCLUSIONS: This study provides a range of physical measurements of endocrine-sensitive tissues in healthy infants from the United States, and the associations with demographic and clinical characteristics. IMPACT: This study reports physical measurements for endocrine-sensitive endpoints in healthy US newborns, including breast buds, AGD, SPL, and TV. Associations of measurements to demographic and clinical factors (including race, gestational age, and newborn length and weight) are presented. Contemporary ranges and identification of predictive factors will support further study on effects of pre- and postnatal exposures to endocrine-sensitive tissues in the infant.

Characterization of ovarian development in girls from birth to 9 months.

BACKGROUND: The minipuberty of infancy is a period of increased reproductive axis activity. Changes in reproductive hormone concentrations and organ size occur during this period, but longitudinal changes have not been well described. OBJECTIVES: The objective of this study was to characterize ovarian growth trajectories and ovarian follicle development during the first 9 months of life in a large longitudinal cohort of healthy girls. METHODS: Data from the Infant Feeding and Early Development Study, a longitudinal cohort study of oestrogen-responsive outcomes in healthy infants, were used to estimate ovarian growth trajectories and describe the presence of ovarian antral follicles in girls 0-9 months old. Ovarian ultrasound evaluations were performed on the infants within 72 hours of birth (newborn visit) and at 4, 8, 16, 24, and 32 weeks of age. Mixed-effects regression splines were used to characterize changes in ovarian volume during infancy and assess the association between the presence of ovarian follicles at the newborn visit and ovarian growth. RESULTS: This analysis included 163 girls with two or more ovarian ultrasounds in the study. Results from the estimated overall ovarian growth trajectory show that ovarian volume increases more than sixfold during the first 16 weeks after birth and then remains relatively stable in the later weeks of infancy. Among girls with observable ovaries at the newborn visit (n = 133), girls with at least one visible ovarian follicle showed more rapid initial ovarian growth compared with girls without visible follicles. CONCLUSIONS: Infant ovarian volume increased to a peak at 16 weeks, which was influenced by the number and size of developing follicles. This research contributes to future development of reference ranges for postnatal ovarian growth in healthy, term infants.

Early Weight Gain Forecasts Accelerated Eruption of Deciduous Teeth and Later Overweight Status during the First Year.

OBJECTIVES: To determine whether early diet and weight gain velocity have independent or interactive effects on deciduous teeth emergence and overweight status during the first year. STUDY DESIGN: Monthly measures of anthropometry and teeth eruption were collected during a 1-year trial (0.5-12.5 months) on formula-fed infants in which the type of randomized infant formula (cow milk or extensively hydrolyzed protein) diet significantly affected early (0.5-4.5 months) weight gain velocity. Generalized linear mixed models determined whether early diet and weight gain velocity had independent or interactive effects on timing and pattern of teeth eruption. Data from a trial on breastfed infants were used to explore effects of breast milk vs infant formula diets on teeth eruption and overweight status at 10.5 months. RESULTS: Independent of infant formula diet, velocities of weight gain had direct effects on the age of first deciduous tooth (P < .04) and number of erupted teeth over time (P < .002). Greater velocity of weight gain from 0.5 to 4.5 months caused earlier and more frequent eruption of deciduous teeth from 4.5 to 12.5 months. Exploratory follow-up analyses on the breastfed and formula-fed diet groups found early weight gain velocity (P = .001), but not diet or its interaction, had significant effects. Infants in the upper quartile for weight gain velocity had more primary teeth (P = .002), and a greater proportion of them were overweight (P < .001) at 10.5 months. CONCLUSIONS: Faster weight gain accretion forecasted accelerated primary teeth eruption and increased percentage of children who were overweight-risk factors for dental caries and obesity. TRIAL REGISTRATION: ClinicalTrials.govNCT01700205 [2012-2015] and NCT01667549 [2012-2015].

Effect of High-dose Vitamin A Supplementation in Children With Sickle Cell Disease: A Randomized, Double-blind, Dose-finding Pilot Study.

Suboptimal vitamin A status (serum retinol <30 µg/dL) is associated with poor clinical outcomes in children with the hemoglobin-SS disease (HbSS), and supplementation with the recommended daily allowance of retinol is ineffective in improving vitamin A status. In a single-center randomized blinded dose-finding pilot study, we compared vitamin A and nutritional status in children with HbSS to healthy children and explored the impact of high-dose supplementation on the primary outcome serum vitamin A status. Exploratory outcomes included hematologic, nutritional, immunologic, and muscle function status in children with HbSS. A mixed-effects linear regression model evaluated associations between vitamin A dose, serum retinol, and exploratory outcomes. Twenty healthy children participated, and 22 subjects with HbSS were randomized to oral 3000 or 6000 IU/d retinol for 8 weeks; 21 subjects completed all evaluations. Serum retinol, growth, and nutritional status were all suboptimal in HbSS subjects at baseline, and supplementation did not change vitamin A status. Fetal hemoglobin (Δ=2.5, 95% confidence interval [CI], 0.5-4.3), mean corpuscular volume (Δ=2.7, 95% CI, 0.7-4.7), mean corpuscular hemoglobin (Δ=1.4, 95% CI, 0.5-2.3), and mean corpuscular hemoglobin concentration (Δ=0.5, 95% CI, 0.1-0.9) all improved with supplementation. Mild improvements in erythrocyte indices, growth status, and muscle function occurred independent of hydroxyurea use.

Growth and Nutrition in Cystic Fibrosis.

Optimal nutrition support has been integral in the management of cystic fibrosis (CF) since the disease was initially described. Nutritional status has a clear relationship with disease outcomes, and malnutrition in CF is typically a result of chronic negative energy balance secondary to malabsorption. As the mechanisms underlying the pathology of CF and its implications on nutrient absorption and energy expenditure have been elucidated, nutrition support has become increasingly sophisticated. Comprehensive nutrition monitoring and treatment guidelines from professional and advocacy organizations have unified the approach to nutrition optimization around the world. Newborn screening allows for early nutrition intervention and improvement in short- and long-term growth and other clinical outcomes. The nutrition support goal in CF care includes achieving optimal nutritional status to support growth and pubertal development in children, maintenance of optimal nutritional status in adult life, and optimizing fat soluble vitamin and essential fatty acid status. The mainstay of this approach is a high calorie, high-fat diet, exceeding age, and sex energy intake recommendations for healthy individuals. For patients with exocrine pancreatic insufficiency, enzyme replacement therapy is required to improve fat and calorie absorption. Enzyme dosing varies by age and dietary fat intake. Multiple potential impediments to absorption, including decreased motility, altered gut luminal bile salt and microbiota composition, and enteric inflammation must be considered. Fat soluble vitamin supplementation is required in patients with pancreatic insufficiency. In this report, nutrition support across the age and disease spectrum is discussed, with a focus on the relationships among nutritional status, growth, and disease outcomes.

Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations.

OBJECTIVE: To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. STUDY DESIGN: Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. RESULTS: There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P < .001) with increased (P < .05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P < .05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P < .01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P = .028) and ΔCFA% (r = 0.47; P = .032) and negatively with ΔREE% (r = -0.50; P = .017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R2 = 0.579; P = .0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. CONCLUSIONS: Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). TRIAL REGISTRATION: ClinicalTrials.gov: NCT02141464.

Muscle Strength, Power, and Torque Deficits in Children With Type SS Sickle Cell Disease.

In African-American children aged 5 to 17 years with and without type SS sickle cell disease (SCD-SS), dominant hand maximal handgrip strength, peak power, and plantar flexion isometric maximal voluntary contraction (MVC) torque were compared with adjustments for body size and composition. Children with SCD-SS (n=21; age, 11±1 y) compared with healthy control children (n=23; 10±1 y) did not differ by age, sex, or maturation stage, but had significantly lower Z scores for height, weight, body mass index, arm circumference, upper arm muscle area, and lean mass-for-height. Children with SCD-SS had significantly lower unadjusted handgrip strength (16±2 vs. 23±2 kg, P<0.01), peak power (1054±107 vs. 1488±169 W, P<0.04) and MVC torques at 2 angles (10 degrees: 27±3 vs. 42±5 Nm; 20 degrees: 21±3 vs. 34±4 Nm; all P<0.05). Performance decrements persisted when handgrip strength was adjusted for lean body mass and fat mass explaining 66% of the variance; peak power adjusted for age, lean body mass, fat mass, and height explaining 91% of the variance; and the highest MVC torque (10-degree angle) adjusted for left leg length, lean mass-for-height, and fat mass-for-height Z scores explaining 65% of the variance. This suggests additional factors contribute to the attenuated anaerobic performance.

Body composition estimation using skinfolds in children with and without health conditions affecting growth and body composition.

BACKGROUND: Body composition prediction equations using skinfolds are useful alternatives to advanced techniques, but their utility across diverse paediatric populations is unknown. AIM: To evaluate published and new prediction equations across diverse samples of children with health conditions affecting growth and body composition. SUBJECTS AND METHODS: Anthropometric and dual-energy X-ray absorptiometry (DXA) body composition measures were obtained in children with Down syndrome (n = 59), Crohn disease (n = 128), steroid-sensitive nephrotic syndrome (n = 67) and a healthy reference group (n = 835). Published body composition equations were evaluated. New equations were developed for ages 3-21 years using the healthy reference sample and validated in other groups and national survey data. RESULTS: Fat mass (FM), fat-free mass (FFM) and percentage body fat (%BF) from published equations were highly correlated with DXA-derived measures (r = 0.71-0.98), but with poor agreement (mean difference = 2.4 kg, -1.9 kg and 6.3% for FM, FFM and %BF). New equations produced similar correlations (r = 0.85-1.0) with improved agreement for the reference group (0.2 kg, 0.4 kg and 0.0% for FM, FFM and %BF, respectively) and in sub-groups. CONCLUSIONS: New body composition prediction equations show excellent agreement with DXA and improve body composition estimation in healthy children and those with selected conditions affecting growth.

The Association among Feeding Mode, Growth, and Developmental Outcomes in Infants with Complex Congenital Heart Disease at 6 and 12 Months of Age.

OBJECTIVE: To assess the association between early anthropometric measurements, device-assisted feeding, and early neurodevelopment in infants with complex congenital heart diseases (CHDs). STUDY DESIGN: Bayley Scales of Infant Development II were used to assess cognitive and motor skills in 72 infants with CHD at 6 and 12 months of age. Linear regression models were used to assess the association between mode of feeding and anthropometric measurements with neurodevelopment at 6 and 12 months of age. RESULTS: Of the 72 infants enrolled in the study, 34 (47%) had single-ventricle physiology. The mean Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores at 6 months of age were 92 ± 10 and 81 ± 14, respectively. At 12 months of age, the mean MDI and PDI scores were 94 ± 12 and 80 ± 16, respectively. Lower length-for-age z score (P < .01) and head circumference-for-age z score (P < .05) were independently associated with lower MDI at 6 months, and both increased hospital length of stay (P < .01) and lower length-for-age z score (P = .04) were associated independently with lower MDI at 12 months. Device-assisted feeding at 3 months (P = .04) and lower length-for-age z score (P < .05) were independently associated with lower PDI at 6 months. Both lower weight-for-age z score (P = .04) and lower length-for-age z score (P = .04) were associated independently with PDI at 12 months. CONCLUSION: Neonates with complex CHD who required device-assisted feeding and those with lower weight and length and head circumference z scores at 3 months were at risk for neurodevelopmental delay at 6 and 12 months of age.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Size of testes, ovaries, uterus and breast buds by ultrasound in healthy full-term neonates ages 0-3 days.

BACKGROUND: Hormonally sensitive organs in the neonate can change size within days of birth as circulating maternal estrogen wanes. Although several reports document the size of these organs through infancy, few focus attention on the near-birth period. Clinical and research evaluation of hormonal and genitourinary disorders would benefit from reference size standards. OBJECTIVE: We describe the size of the uterus, ovaries, testes and breast buds in healthy term neonates. MATERIALS AND METHODS: As part of the Infant Feeding and Early Development (IFED) study, we sonographically measured the largest diameter of these organs in sagittal, transverse and anterior-posterior planes for 194 female and 204 male newborns up to 3 days old. We calculated mean, median and percentiles for longest axis length and for volume calculated from measured diameters. We evaluated size differences by laterality, gender and race and compared our observations against published values. RESULTS: Mean length and mean volume were as follows: uterus, 4.2 cm and 10.0 cm3; ovary, 1.0 cm and 0.2 cm3; testis, 1.1 cm and 0.3 cm3 (0.4 cm3 Lambert volume); female breast bud, 1.2 cm and 0.7 cm3; male breast bud, 1.1 cm and 0.6 cm3. Breast buds were larger in females than males. Laterality differences were typically below the precision of clinical measurement. No significant race differences were detected. CONCLUSION: Using data from our large cohort together with published values, we provide guidelines for evaluating the size of reproductive organs within the first 3 days of age. Discrepancies between our results and published values are likely attributable to technique.

Antibiotic Exposure During the First 6 Months of Life and Weight Gain During Childhood.

IMPORTANCE: Early-life antibiotic exposure has been associated with increased adiposity in animal models, mediated through the gut microbiome. Infant antibiotic exposure is common and often inappropriate. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results. OBJECTIVE: To assess the association between early-life antibiotic exposure and childhood weight gain. DESIGN AND SETTING: Retrospective, longitudinal study of singleton births and matched longitudinal study of twin pairs conducted in a network of 30 pediatric primary care practices serving more than 200,000 children of diverse racial and socioeconomic backgrounds across Pennsylvania, New Jersey, and Delaware. PARTICIPANTS: Children born between November 1, 2001, and December 31, 2011, at 35 weeks' gestational age or older, with birth weight of 2000 g or more and in the fifth percentile or higher for gestational age, and who had a preventive health visit within 14 days of life and at least 2 additional visits in the first year of life. Children with complex chronic conditions and those who received long-term antibiotics or multiple systemic corticosteroid prescriptions were excluded. We included 38,522 singleton children and 92 twins (46 matched pairs) discordant in antibiotic exposure. Final date of follow-up was December 31, 2012. EXPOSURE: Systemic antibiotic use in the first 6 months of life. MAIN OUTCOMES AND MEASURES: Weight, measured at preventive health visits from age 6 months through 7 years. RESULTS: Of 38,522 singleton children (50% female; mean birth weight, 3.4 kg), 5287 (14%) were exposed to antibiotics during the first 6 months of life (at a mean age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7%; 95% CI, -0.1% to 1.5%; P = .07, equivalent to approximately 0.05 kg; 95% CI, -0.004 to 0.11 kg of added weight gain between age 2 years and 5 years). Among 92 twins (38% female; mean birth weight, 2.8 kg), the 46 twins who were exposed to antibiotics during the first 6 months of life received them at a mean age of 4.5 months. Antibiotic exposure was not significantly associated with a weight difference (-0.09 kg; 95% CI, -0.26 to 0.08 kg; P = .30). CONCLUSIONS AND RELEVANCE: Exposure to antibiotics within the first 6 months of life compared with no exposure was not associated with a statistically significant difference in weight gain through age 7 years. There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them.

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

Vitamin B(12) status in children with cystic fibrosis and pancreatic insufficiency.

OBJECTIVES: Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI. STUDY DESIGN: Serum B12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B12 above reference range for age and sex [Hi-B12]) or within reference range (serum B12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed. RESULTS: A total of 106 subjects, mean age 10.4 ±â€Š3.0 years, participated in the study. Median serum B12 was 1083 pg/mL, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B12 group had significantly greater supplement-based B12 intake than the serum B12 within reference range for age and sex group (1000% vs 583% RDA, P < 0.001). Multiple logistic regression analysis showed that high supplement-based B12 intake and age >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R = 0.18, P < 0.001). CONCLUSIONS: Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and forced expiratory volume at 1 second.