Early-Life Nutrition and Cognitive Development: Imaging Approaches.

Brain development in the first years of life is the most dynamic and perhaps the most important phase of brain maturation. While it is widely recognized that nutrition plays a key role in early brain development, particular nutrients will most likely differentially affect distinct aspects of brain development. The critical dosage windows and time frames for various nutrients at different stages of brain development are likely dissimilar. Therefore, efforts have been devoted to identifying potential associations between nutrients and early brain development. However, behavioral assessments are typically employed as the outcome measures, which are known to suffer from low sensitivity and the inability to provide neural substrates underlying brain functional maturation. In contrast, magnetic resonance imaging is capable of providing detailed anatomical and functional information - an ideal tool to characterize brain functional development and nutrition. Our team has developed strategies that enable imaging of typically developing children from birth to teens without sedation. Quantitative assessments of brain structural and functional development during the first years of life have been accomplished, which reveal important features of early brain development. These developed tools will most likely substantially enhance our ability to rigorously characterize the interplay between nutrients and early brain development.

Infant Feeding Regimens and Gastrointestinal Tolerance: A Multicenter, Prospective, Observational Cohort Study in China.

To study feeding tolerance in infants fed formula with increased sn-2 palmitate and oligofructose (sn-2+OF) in a real-world setting, healthy Chinese infants were enrolled in this 48-day observational study on their current feeding regimens: exclusively breastfed (BF; n = 147), exclusively sn-2+OF formula-fed (FF; n = 150), or mixed-fed with breast milk and sn-2+OF formula (MF; n = 163). Throughout the study, incidence (90% confidence interval) of hard stools was ≤2.1% (0.0-5.3) in FF and 0.8% (0.0-3.5) in MF, with no hard stools in BF. Incidence of watery stools was ≤5.0% (1.0-9.2) in FF and ≥5.1% (2.4-9.3) in MF and BF. Gastrointestinal tolerance scores, although low in all groups (lower scores indicating better tolerance), were slightly higher (P ≥ .03) in FF (17.5 ± 4.8) and MF (18.2 ± 5.0) versus BF (16.3 ± 3.2) at mid-study; this difference disappeared at study end. Overall, low incidences of hard and watery stools and good feeding tolerance were observed in infants fed sn-2+OF formula.

Nutrient intake and dietary patterns in children 2.5-5 years of age with picky eating behaviours and low weight-for-height.

BACKGROUND AND OBJECTIVES: Picky eating behaviours are common in young children and may adversely affect dietary intake. This study examined the adequacy of dietary patterns and nutrient intake in preschool-aged children in China and Hong Kong with picky eating behaviours and weight-for-height in the lowest quartile of the WHO Growth Standards. METHODS AND STUDY DESIGN: Dietary intake was assessed using baseline 3-day food records from a multicenter, randomized trial in Chinese children (N=151) ages 2.5-5 years characterized as picky eaters by their parents and with weight-for-height <=25th percentile of the WHO Growth Standards. Nutrient intakes were calculated using validated dietary analysis software and compared with age-appropriate Chinese Recommended Nutrient Intakes (RNIs). Dietary patterns were compared with Hong Kong Food Pyramid recommendations. RESULTS: Median daily energy intake was 25% lower than the age-appropriate RNI, while median intakes of calcium, iron, zinc, and vitamins C and E ranged from 52%-73% of the RNI. Vitamin D intake was only 37% of the RNI. Total fat and sodium intakes exceeded recommendations by 10% and 56%, respectively, while >16% of daily energy was derived from foods in the sweets/beverages/snack and the fats/oils groups. Almost 75% of the children met the recommended daily servings of meat/meat substitutes and nearly half met the recommendation for daily servings of fruit. Fewer met the recommendations for daily servings of vegetables (14.7%), milk/milk products (6.3%), and grains and cereals (6.3%). CONCLUSIONS: Young children with picky eating behaviours and low weight-for-height had suboptimal dietary patterns and were at risk for significant dietary and nutrient insufficiencies.

Infant feeding and health-related quality of life in healthy Chinese infants: results from a prospective, observational cohort study.

BACKGROUND: Infant feeding regimens, including breastfeeding, formula-feeding, or a combination of the two, may influence infant health-related quality of life (HRQOL). However, few studies have examined this association. METHODS: This prospective cohort study assessed HRQOL in relation to three parent-selected feeding regimens: exclusively breastfed (n = 136), exclusively study formula-fed (n = 140), and mixed-fed with study formula and breast milk (n = 151). Healthy Chinese infants were enrolled at their first normally scheduled well infant clinic visit at age 42 days (study day 1). Parents independently chose their infants' feeding regimens prior to recruitment into the study, with infants in the formula and mixed-fed groups already consuming an infant formula enriched with α-lactalbumin and increased sn-2 palmitate and oligofructose. The Infant and Toddler Quality of Life Questionnaire, which includes six infant-focused and three parent-focused concepts, was used to assess HRQOL at day 1 and at a follow-up visit 48 days later. Scores for each concept ranged from 0 to 100. Parent quality of life (assessed using the Mental Component Summary score of the SF-12v2 Health Survey) was included in the ANCOVA model to adjust for its potential effect on parent's perception of infant HRQOL. RESULTS: HRQOL concept scores were high in all three study groups at both visits (mean scores 71-95). Day 1 HRQOL scores were not significantly different between groups. At day 48, 5 of 9 HRQOL scores were not significantly different between groups. However, scores for Temperament and Moods, General Health Perceptions and Parent Impact-Time were slightly but statistically significantly lower in the formula-fed group (mean scores 75-86; all p ≤ 0.01) compared to the breastfed (78-90) and mixed-fed (77-91) groups. Day 48 Parent Impact-Emotional scores were also significantly lower by a small margin (4 points; p = 0.003) in the formula-fed group compared with the breastfed group. CONCLUSIONS: HRQOL was high in this population of healthy infants, with only a few small differences in HRQOL concept scores observed between breastfed, formula-fed and mixed-fed infants. These results indicate favorable physical, mental, and social well-being in these infants and parents. Assessment of infant HRQOL is therefore feasible and provides valuable insight into parental perceptions of their child's health and well-being. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01370967 .

Validation of a Parent Report Questionnaire: The Infant Gastrointestinal Symptom Questionnaire.

OBJECTIVE: To evaluate the reliability and validity of the Infant Gastrointestinal Symptom Questionnaire (IGSQ), a tool to assess feeding tolerance in infants. METHODS: Qualitative methods were used to develop IGSQ content across 5 symptom clusters, yielding a 13-item index of parent-reported infant digestion and elimination behaviors over the prior 7 days. Classical psychometric methods evaluated factor structure, interrater and retest reliability, and validity in 4 prospective studies of 836 infants. RESULTS: Interrater and retest reliability were acceptable to good. IGSQ Index score was highly correlated (r = 0.89) with daily parent reports. IGSQ scores were significantly different between infants whose parents planned to switch formulas because of perceived feeding problems and those without parental concerns. CONCLUSIONS: The IGSQ is a practical, reliable, and valid method for assessment of infant gastrointestinal-related behaviors. Its use in clinical studies can provide empirical evidence to advance parent education regarding both normal and clinically meaningful feeding-related behaviors.

Effect of an α-lactalbumin-enriched infant formula supplemented with oligofructose on fecal microbiota, stool characteristics, and hydration status: a randomized, double-blind, controlled trial.

AIMS: To evaluate the impact of oligofructose (OF)-supplemented infant formula on fecal microbiota, stool characteristics, and hydration. METHODS: Ninety-five formula-fed infants were randomized to α-lactalbumin-enriched control formula (CF) or identical formula with 3.0 g/L OF (EF) for 8 weeks; 50 infants fed human milk (HM) were included. RESULTS: Eighty-four infants completed the study, 70 met per-protocol criteria. Over 8 weeks, bifidobacteria increased more in EF than CF group (0.70 vs. 0.16 log10 bacterial counts/g dry feces, P = .008); EF was not significantly different from HM group (P = .32). EF group stool consistency was intermediate between CF and HM groups; at week 8, EF group had softer stools than CF (5-point scale: 1 = hard, 5 = watery; consistency score 3.46 vs. 2.82, P = .015) without significant differences in stool frequency. Physician-assessed hydration status was normal for all infants. CONCLUSIONS: Infant formula with 3.0 g/L OF promoted bifidobacteria growth and softer stools without adversely affecting stool frequency or hydration.

Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term infants fed infant formulas containing high sn-2 palmitate with or without oligofructose: a double-blind, randomized clinical trial.

BACKGROUND: Formula-fed (FF) infants often have harder stools and higher stool concentrations of fatty acid soaps compared to breastfed infants. Feeding high sn-2 palmitate or the prebiotic oligofructose (OF) may soften stools, reduce stool soaps, and decrease fecal calcium loss. METHODS: We investigated the effect of high sn-2 palmitate alone and in combination with OF on stool palmitate soap, total soap and calcium concentrations, stool consistency, gastrointestinal (GI) tolerance, anthropometrics, and hydration in FF infants. This double-blind trial randomized 165 healthy term infants 25-45 days old to receive Control formula (n = 54), formula containing high sn-2 palmitate (sn-2; n = 56), or formula containing high sn-2 palmitate plus 3 g/L OF (sn-2+OF; n = 55). A non-randomized human milk (HM)-fed group was also included (n = 55). The primary endpoint, stool composition, was determined after 28 days of feeding, and was assessed using ANOVA accompanied by pairwise comparisons. Stool consistency, GI tolerance and hydration were assessed at baseline, day 14 (GI tolerance only) and day 28. RESULTS: Infants fed sn-2 had lower stool palmitate soaps compared to Control (P = 0.0028); while those fed sn-2+OF had reduced stool palmitate soaps compared to both Control and sn-2 (both P < 0.0001). Stool total soaps and calcium were lower in the sn-2+OF group than either Control (P < 0.0001) or sn-2 (P < 0.0001). The HM-fed group had lower stool palmitate soaps, total soaps and calcium (P < 0.0001 for each comparison) than all FF groups. The stool consistency score of the sn-2+OF group was lower than Control and sn-2 (P < 0.0001), but higher than the HM-fed group (P < 0.0001). GI tolerance was similar and anthropometric z-scores were <0.2 SD from the WHO growth standards in all groups, while urinary hydration markers were within normal range for all FF infants. CONCLUSIONS: Increasing sn-2 palmitate in infant formula reduces stool palmitate soaps. A combination of high sn-2 palmitate and OF reduces stool palmitate soaps, total soaps and calcium, while promoting softer stools. TRIAL REGISTRATION: This study was registered on http://www.clinicaltrials.gov: number NCT02031003.

Randomized controlled trial to compare growth parameters and nutrient adequacy in children with picky eating behaviors who received nutritional counseling with or without an oral nutritional supplement.

In this study, changes in growth parameters and nutrient intake were compared in Chinese children (ages 30-60 months) with picky eating (PE) behaviors and weight-for-height ≤25th percentile, who were randomized to receive nutrition counseling alone (NC; n = 76) or with a nutritional milk supplement (NC + NS; n = 77) for 120 days. Increases in weight-for-height z-scores were significantly greater in the NC + NS group at days 30 and 90 and over the entire study period (all P < 0.05), but not at day 120. Increases in weight-for-age z-scores were significantly greater in the NC + NS group at day 90 (P = 0.025) and over the entire study period (P = 0.046). Mean intakes of energy, protein, carbohydrate, docosahexaenoic acid, arachidonic acid, calcium, phosphorous, iron, zinc, and vitamins A, C, D, E, and B6 were significantly higher in the NC + NS group at days 60 and 120 (all P < 0.01). Thus, in young children with PE behaviors, nutritional supplementation given as an adjunct to NC resulted in greater improvements in nutrient intake compared with NC alone. Growth parameters differed between groups at several timepoints during the study, but not at day 120.

Effects of term infant formulas containing high sn-2 palmitate with and without oligofructose on stool composition, stool characteristics, and bifidogenicity.

OBJECTIVES: Levels of stool fatty acid soaps and beneficial bacteria differ between formula-fed and breast-fed infants; addition of specific formula ingredients may reduce these differences. This study evaluated the effects of a term infant formula containing high sn-2 palmitate term infant formula (sn-2) or an identical formula supplemented with oligofructose (OF) at 2 concentrations (sn-2+3 g/L OF, sn-2+5 g/L OF) on stool composition, stool characteristics, and fecal bifidobacteria. METHODS: Healthy, term formula-fed infants 7 to 14 days old (n = 300) were randomized in a double-blind manner to receive standard formula (control), sn-2, sn-2+3 g/L OF, or sn-2+5 g/L OF for 8 weeks. Human milk (HM)-fed infants (n = 75) were studied in parallel. Stool samples were collected from all subjects at week 8 for fatty acid soaps and mineral content, and from a subset at baseline and week 8 for bifidobacteria. Stool characteristics were assessed via 3-day diary. RESULTS: The sn-2 group had 46% less stool soap palmitate (P < 0.001) and softer stools than control (20% more mushy soft stools, P = 0.026; 50% fewer formed stools, P = 0.003). Addition of OF resulted in even fewer formed stools versus control (65% fewer for sn-2+3 g/L OF, 79% fewer for sn-2+5 g/L OF), with 5 g/L OF more closely resembling that of HM-fed infants. Both sn-2 (P < 0.05) and sn-2 with OF groups (P < 0.01) had significantly higher fecal bifidobacteria concentrations than control at week 8, not differing from HM-fed infants. CONCLUSIONS: High sn-2-palmitate formulas led to reduced stool soaps, softer stools, and increased bifidobacteria, whereas addition of OF further improved stool consistency. Those modifications brought outcomes in formula-fed infants closer to that in HM-fed infants.

Body-composition assessment in infancy: air-displacement plethysmography compared with a reference 4-compartment model.

BACKGROUND: A better understanding of the associations of early infant nutrition and growth with adult health requires accurate assessment of body composition in infancy. OBJECTIVE: This study evaluated the performance of an infant-sized air-displacement plethysmograph (PEA POD Infant Body Composition System) for the measurement of body composition in infants. DESIGN: Healthy infants (n = 49; age: 1.7-23.0 wk; weight: 2.7-7.1 kg) were examined with the PEA POD system. Reference values for percentage body fat (%BF) were obtained from a 4-compartment (4-C) body-composition model, which was based on measurements of total body water, bone mineral content, and total body potassium. RESULTS: Mean (+/- SD) reproducibility of %BF values obtained with the PEA POD system was 0.4 +/- 1.3%. Mean %BF obtained with the PEA POD system (16.9 +/- 6.5%) did not differ significantly from that obtained with the 4-C model (16.3 +/- 7.2%), and the regression between %BF for the 4-C model and that for the PEA POD system (R2 = 0.73, SEE = 3.7%BF) did not deviate significantly from the line of identity (y = x). CONCLUSIONS: The PEA POD system provided a reliable, accurate, and immediate assessment of %BF in infants. Because of its ease of use, good precision, minimum safety concerns, and bedside accessibility, the PEA POD system is highly suitable for monitoring changes in body composition during infant growth in both the research and clinical settings.

Child-specific thoracic gas volume prediction equations for air-displacement plethysmography.

OBJECTIVE: To develop child-specific thoracic gas volume (TGV) prediction equations for use in air-displacement plethysmography in 6- to 17-year-old children. RESEARCH METHODS AND PROCEDURES: Study 1 developed TGV prediction equations using anthropometric variables after completing a measured TGV and air-displacement plethysmography test in 224 healthy boys and girls (11.2 +/- 3.2 years, 45.3 +/- 18.7 kg, 149.9 +/- 18.5 cm). Study 2 cross-validated the prediction equations in a separate cohort of 62 healthy boys and girls (11.2 +/- 3.4 years, 44.2 +/- 15.3 kg, 149.4 +/- 19.3 cm). RESULTS: In Study 1 (development of TGV prediction equations), the quadratic relationship using height as the independent variable and the measured TGV as the dependent variable yielded the highest adjusted R(2) and the lowest SE of estimate in both genders, thus producing the following prediction equations: TGV = 0.00056 x H(2) - 0.12422 x H + 8.15194 (boys) and TGV = 0.00044 x H(2) - 0.09220 x H + 6.00305 (girls). In Study 2 (cross-validation), no significant difference between the predicted and measured TGVs (-0.018 +/- 0.377 liters) was observed. The regression between the measured TGV and the predicted TGV yielded a slope and intercept that did not significantly differ from the line of identity. Prediction accuracy was good as indicated by a high R(2) (0.862) and low SE of estimate (0.369 liters). DISCUSSION: The new child-specific TGV prediction equations accurately, precisely, and without bias estimated the actual TGV of 6- to 17-year-old children.

Validation of a new pediatric air-displacement plethysmograph for assessing body composition in infants.

BACKGROUND: The accurate measurement of body composition is useful in assessments of infant growth and nutritional status. OBJECTIVE: This study evaluated the reliability and accuracy of a new air-displacement plethysmography (ADP) system for body-composition assessment in infants. DESIGN: Between- and within-day reliability was assessed by comparing the percentage body fat (%BF) obtained on consecutive days and on the same day, respectively, in 36 full-term infants. Accuracy was assessed by comparing %BF measured with the use of ADP and %BF measured with the use of deuterium (2H2O) dilution in 53 infants. RESULTS: There were no significant differences in %BF between days (-0.50 +/- 1.21%BF) or within days (0.16 +/- 1.44%BF). Mean between- and within-day test-retest SDs of 0.69 and 0.72%BF, respectively, indicated excellent reliability. The %BF measurements obtained by using ADP were not significantly influenced by infant behavioral state. Mean %BF obtained by using ADP (20.32%BF) did not differ significantly from that obtained by using 2H2O dilution (20.39%BF), and the regression line [%BF(2H2O) = 0.851%BF (ADP) + 3.094] gave a high R2 (0.76) and a low SEE (3.26). The 95% limits of agreement between ADP and 2H2O (-6.84%BF, 6.71%BF) were narrower than those reported for other body-composition techniques used in infants. Individual differences between the 2 methods were not a function of body mass or fatness. CONCLUSION: ADP is a reliable and accurate instrument for determining %BF in infants, and it has the potential for use in both research and clinical settings.

Dietary pattern is associated with homocysteine and B vitamin status in an urban Chinese population.

To identify existing dietary patterns and examine associations between these patterns and plasma homocysteine and B vitamin concentrations in an urban Chinese population living in Beijing (n = 119), dietary information was collected with a food frequency questionnaire designed for this population. Plasma homocysteine and B vitamin concentrations were examined. Food group variables, expressed as percentages of total energy intake, were entered into cluster analysis to define three distinct dietary pattern groups. The prevalence of high homocysteine (>11 micromol/L for women and 12 micromol/L for men), was 31.9%; of low folate (<6.8 nmol/L), 36.2%; of low vitamin B-12 (<221 pmol/L), 36.9%; and of low vitamin B-6 (<30 nmol/L), 16.0%. The three dietary patterns derived were defined by relatively greater intake of 1) fruit and milk, 2) red meat and 3) refined cereals. More than 40% of subjects in the refined cereals group had high plasma homocysteine and low plasma folate concentrations, and 67% had low plasma vitamin B-12 concentrations. Those following the refined cereals pattern were 4 and 5.2 times more likely to have high homocysteine and low vitamin B-12 concentrations, respectively, relative to the fruit and milk dietary pattern group (P < 0.01), after adjustment for potential confounders. High intake of refined cereals was associated with low B vitamin and high homocysteine concentrations, whereas the pattern high in fruit and milk was associated with the lowest homocysteine. Dietary patterns appear to play an important role in the micronutrient and homocysteine status of these Chinese adults.

Relative influence of diet and physical activity on body composition in urban Chinese adults.

BACKGROUND: The relative influence of diet and physical activity on body fatness remains uncertain. OBJECTIVE: The objective of the study was to investigate associations of dietary variables and physical activity with body fatness in urban Chinese adults. DESIGN: We conducted a cross-sectional study in 130 weight-stable men and women aged 35-49 y. Subjects were selected from upper and lower tertiles of dietary fat and physical activity on the basis of screening questionnaires. Dietary intake was assessed by weighed food intake, physical activity level (PAL) was calculated as the ratio of predicted total energy expenditure (TEE) to predicted resting energy expenditure, and body composition was measured with the use of (2)H(2)O. Reported energy intake and predicted TEE were validated against TEE determined with the use of (2)H(2)(18)O (n = 73). RESULTS: Body fatness was positively associated with dietary variety (ie, variety of ingredients) (partial r = 0.186, P = 0.039) and frequency of consuming restaurant foods (partial r = 0.237, P = 0.001) and negatively associated with PAL (partial r = -0.307, P = 0.001) in a multiple regression analysis that controlled for sex and confounders. The combined variance accounted for by dietary variety and restaurant food consumption (9.1%) was equivalent to that for PAL (9.4%). Neither dietary fat nor energy density predicted body fatness, but dietary energy density predicted within-subject day-to-day variation in reported energy intake (P < 0.001). CONCLUSIONS: Dietary variety, frequency of restaurant food consumption, and PAL significantly predicted body fatness in urban Chinese adults, but dietary fat did not. These findings support previous studies in US adults and suggest that dietary variables other than fat have an important influence on adult body composition.

Field methods for body composition assessment are valid in healthy chinese adults.

There is little information on the accuracy of simple body composition methods in non-Western populations. We determined the percentage of body fat (%BF) by isotope dilution [oxygen-18 (H(2)(18)O) and deuterium oxide ((2)H(2)O)] and anthropometry in 71 healthy, urban Chinese adults aged 35-49 y [body mass index (BMI) 18-35 kg/m(2)]. The accuracy of several prediction equations for assessment of %BF from skinfold measurements was evaluated against %BF determined by H(2)(18)O dilution. We also assessed the relationship between BMI and %BF, and the fat-free mass (FFM) hydration coefficient for our population. All skinfold equations yielded means within approximately 2%BF of H(2)(18)O-derived %BF. However, on the basis of residual plot analysis and the 95% confidence interval (CI) for the mean difference between methods, the equations of Durnin and Womersley (for assessment of body density from skinfolds) coupled with that of Brozek et al. (for assessment of %BF from body density) provided the most valid assessment for individuals. In addition, the FFM hydration coefficient averaged 0.734 +/- 0.002 (SEM), indicating that the usually assumed value of 0.732 is appropriate for this population. Finally, although BMI had high specificity (90%) for classifying individuals as having body fat within the normal range (<24%BF for men, and <35%BF for women), it had poor sensitivity (66%) for identifying individuals as having high body fat. We conclude that compared with H(2)(18)O dilution, skinfold thickness can provide an accurate and reliable assessment of body composition in healthy Chinese adults. Furthermore, using the equation of Brozek et al. may be preferable to using Siri's equation to predict %BF from body density in populations in which individuals have >30%BF.