Genetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some?

There is wide variation in how individuals perceive the chemosensory attributes of liquid formulations of ibuprofen, encompassing both adults and children. To understand personal variation in the taste and chemesthesis properties of this medicine, and how to measure it, our first scientific strategy centered on utilizing trained adult panelists, due to the complex and time-consuming psychophysical tasks needed at this initial stage. We conducted a double-blind cohort study in which panelists underwent whole-genome-wide genotyping and psychophysically evaluated an over-the-counter pediatric medicine containing ibuprofen. Associations between sensory phenotypes and genetic variation near/within irritant and taste receptor genes were determined. Panelists who experienced the urge to cough or throat sensations found the medicine less palatable and sweet, and more irritating. Perceptions varied with genetic ancestry; panelists of African genetic ancestry had fewer chemesthetic sensations, rating the medicine sweeter, less irritating, and more palatable than did those of European genetic ancestry. We discovered a novel association between TRPA1 rs11988795 and tingling sensations, independent of ancestry. We also determined for the first time that just tasting the medicine allowed predictions of perceptions after swallowing, simplifying future psychophysical studies on diverse populations of different age groups needed to understand genetic, cultural-dietary, and epigenetic factors that influence individual perceptions of palatability and, in turn, adherence and the risk of accidental ingestion.

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.

Glutamic Acid Intake by Formula-Fed Infants: Are Acceptable Daily Intakes Feasible?

PURPOSE: The 2017 European Food Safety Authority (EFSA) recommendation of an acceptable daily intake (ADI) of 30 mg glutamic acid/kg bw/d 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 formulas (EHF); the formulas differed in glutamic acid content (262.4 mg/100ml, CMF; 436.2 mg/100ml, EHF). METHODS: The infants ( n = 141) were randomized to be fed either CMF or EHF. Daily intakes were determined from weighed bottle methods and/or prospective diet records, and body weights and lengths were measured on 15 occasions from 0.5 to 12.5 months. The trial was registered on http://www. CLINICALTRIALS: gov/ as trial registration number NCT01700205 on 3 October 2012. RESULTS: 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/d from 0.5 to 12.5 months. CONCLUSIONS: Faced with the knowledge that the EFSA health-based guidance value (ADI) was not based on actual intake data and did not account for the primary energy sources during infancy, EFSA may reconsider the scientific literature on growing children's intakes from human milk, infant formula, and the complementary diet to provide parents and health care providers with revised guidelines.

Infant factors that impact the ecology of human milk secretion and composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 3.

Infants drive many lactation processes and contribute to the changing composition of human milk through multiple mechanisms. This review addresses the major topics of milk removal; chemosensory ecology for the parent-infant dyad; the infant's inputs into the composition of the human milk microbiome; and the impact of disruptions in gestation on the ecology of fetal and infant phenotypes, milk composition, and lactation. Milk removal, which is essential for adequate infant intake and continued milk synthesis through multiple hormonal and autocrine/paracrine mechanisms, should be effective, efficient, and comfortable for both the lactating parent and the infant. All 3 components should be included in the evaluation of milk removal. Breastmilk "bridges" flavor experiences in utero with postweaning foods, and the flavors become familiar and preferred. Infants can detect flavor changes in human milk resulting from parental lifestyle choices, including recreational drug use, and early experiences with the sensory properties of these recreational drugs impact subsequent behavioral responses. Interactions between the infant's own developing microbiome, that of the milk, and the multiple environmental factors that are drivers-both modifiable and nonmodifiable-in the microbial ecology of human milk are explored. Disruptions in gestation, especially preterm birth and fetal growth restriction or excess, impact the milk composition and lactation processes such as the timing of secretory activation, adequacy of milk volume and milk removal, and duration of lactation. Research gaps are identified in each of these areas. To assure a sustained and robust breastfeeding ecology, these myriad infant inputs must be systematically considered.

Sodium Intake Tracked from Infancy and Salt Taste Preference during Adolescence: Follow-up of a Randomized Controlled Field Trial in Brazil.

Background: Effective interventions to promote healthy sodium intakes require understanding factors driving liking for salt taste. Objectives: To examine effects of an early feeding intervention among low-income mothers on their children's energy and sodium intake and salt taste preferences at 12 years; and to identify age-related changes in dietary sodium sources. Methods: Secondary analyses were conducted on dietary intake and taste preference data collected from children in a longitudinal trial (NCT00629629). Mothers randomized to the intervention group received counseling on healthy eating practices for 1 year postpartum; the control group received no counseling. Two-day dietary recalls were obtained at 1 year (intervention end) and at 4-, 8-, and 12-year follow-up visits, from which foods were categorized as unprocessed, processed, or ultra-processed. At the 12-year visit, children's most preferred concentration of salt was measured using a validated, forced-choice, paired-comparison tracking method, and pubertal stage was self-assessed. Results: The intervention group had reduced energy intake compared with controls in all food categories at 1 year (P = 0.04) but not at the other time points. Sodium intake from processed foods increased from 4 to 12 years and from ultra-processed foods from 1 to 4; intake from unprocessed foods decreased from 1 to 8 year (all P < 0.01). At 12 years, children in early stages of puberty (Tanner stages 1-3; P = 0.04) or in the ≥75th percentile of sodium intake (P < 0.01) preferred significantly higher concentrations of salt than the other children. Conclusions: Both dietary intake of sodium and early puberty were associated with preferences for higher salt concentrations. Childhood and adolescence are important periods for understanding how experience and growth shape diet by changing salt taste. Clinical Trial Registration: This manuscript reports secondary analysis of data collected in trial NCT00629629 (2001-3) and follow-up [https://clinicaltrials.gov/ct2/show/NCT00629629?term=NCT00629629&draw=2&rank=1].

Factors Affecting BMI Changes in Mothers during the First Year Postpartum.

We tested the hypotheses that mothers of infants who exclusively breastfed would differ in the trajectories of postpartum BMI changes than mothers of infants who exclusively formula fed, but such benefits would differ based on the maternal BMI status prepregnancy (primary hypothesis) and that psychological eating behavior traits would have independent effects on postpartum BMI changes (secondary hypothesis). To these aims, linear mixed-effects models analyzed measured anthropometric data collected monthly from 0.5 month (baseline) to 1 year postpartum from two groups of mothers distinct in infant feeding modality (Lactating vs. Non-lactating). While infant feeding modality group and prepregnancy BMI status had independent effects on postpartum BMI changes, the benefits of lactation on BMI changes differed based on prepregnancy BMI. When compared to lactating women, initial rates of BMI loss were significantly slower in the non-lactating women who were with Prepregnancy Healthy Weight (ß = 0.63 percent BMI change, 95% CI: 0.19, 1.06) and with Prepregnancy Overweight (ß = 2.10 percent BMI change, 95% CI: 1.16, 3.03); the difference was only a trend for those in the Prepregnancy Obesity group (ß = 0.60 percent BMI change, 95% CI: -0.03, 1.23). For those with Prepregnancy Overweight, a greater percentage of non-lactating mothers (47%) gained ≥ 3 BMI units by 1 year postpartum than did lactating mothers (9%; p < 0.04). Psychological eating behavior traits of higher dietary restraint, higher disinhibition, and lower susceptibility to hunger were associated with greater BMI loss. In conclusion, while there are myriad advantages to lactation, including greater initial rates of postpartum weight loss regardless of prepregnancy BMI, mothers who were with overweight prior to the pregnancy experienced substantially greater loss if they breastfed their infants. Individual differences in psychological eating behavior traits hold promise as modifiable targets for postpartum weight management.

The Macronutrient Composition of Infant Formula Produces Differences in Gut Microbiota Maturation That Associate with Weight Gain Velocity and Weight Status.

This proof-of-principle study analyzed fecal samples from 30 infants who participated in a randomized controlled trial on the effects of the macronutrient composition of infant formula on growth and energy balance. In that study, infants randomized to be fed cow milk formula (CMF) had faster weight-gain velocity during the first 4 months and higher weight-for-length Z scores up to 11.5 months than those randomized to an isocaloric extensive protein hydrolysate formula (EHF). Here we examined associations among infant formula composition, gut microbial composition and maturation, and children's weight status. Fecal samples collected before and monthly up to 4.5 months after randomization were analyzed by shotgun metagenomic sequencing and targeted metabolomics. The EHF group had faster maturation of gut microbiota than the CMF group, and increased alpha diversity driven by Clostridia taxa. Abundance of Ruminococcus gnavus distinguished the two groups after exclusive feeding of the assigned formula for 3 months. Abundance of Clostridia at 3-4 months negatively correlated with prior weight-gain velocity and body weight phenotypes when they became toddlers. Macronutrient differences between the formulas likely led to the observed divergence in gut microbiota composition that was associated with differences in transient rapid weight gain, a well-established predictor of childhood obesity and other comorbidities.

Effects of Early Weight Gain Velocity, Diet Quality, and Snack Food Access on Toddler Weight Status at 1.5 Years: Follow-Up of a Randomized Controlled Infant Formula Trial.

This study followed children who participated in a feeding trial in which the type of randomized infant formula fed from 2 weeks significantly affected weight gain velocity during the first 4 months and weight-for-length Z (WLZ) scores up to 11.5 months. We focused on measures of anthropometry, dietary intakes, and parenting related to the provision of snack foods that were collected at the end of the trial (1 year) and the 1.5 years follow-up visit. We not only describe what toddlers are eating, but we also determined the independent and/or interactive effects of randomized formula group, early weight gain velocity, the nutrient content of the post-formula diet, and maternal snack food practices, on toddlers' weight status. Diet quality underwent drastic changes during this 6-month period. As infant formula disappeared from the diet, fruit and 100% fruit juice intake increased slightly, while intake of "What We Eat in America" food categories sweetened beverages and snacks and sweets more than doubled. Added sugars accounted for 5% of energy needs at 1 year and 9% at 1.5 years. Generalized linear mixed models revealed that, independent of the randomized formula group, greater velocities of weight gain during early infancy and lower access to snacks as toddlers predicted higher WLZ and a greater proportion of toddlers with overweight at 1.5 years. Energy and added sugar intake had no significant effects. These findings add to the growing body of evidence that unhealthy dietary habits are formed even before formula weaning and that, along with improving early diet, transient rapid weight gain and parental feeding practices are modifiable determinants that may reduce risks for obesity.

Psychophysical Tracking Method to Assess Taste Detection Thresholds in Children, Adolescents, and Adults: The Taste Detection Threshold (TDT) Test.

This paper describes a two-alternative, forced-choice, staircase, tracking procedure, called the Taste Detection Threshold (TDT) test, that provides a reliable measure of sweet, salty, and umami taste detection thresholds from childhood to adulthood. Advantages of the method include procedures that are identical for children and adults, thus allowing the determination of age-related and individual differences in taste perception, if any, and tasks that can be completed in a relatively short time frame, do not rely on continuous attention or require memorization, control for subjective response biases, and minimize the impact of language development. After a 1 hour fast, participants are presented with pairs of solutions; in each pair, one solution is water, and the other solution contains varying concentrations of the tastant. Using a whole-mouth tasting method, participants taste each solution (without swallowing and with rinsing between tastings) and then point to the solution with a taste or that tastes different from water. The concentration of the stimulus in the subsequent pair increases after a single incorrect response and decreases after two consecutive correct responses. A reversal occurs when the concentration sequence changes direction. The task is deemed completed after the occurrence of four reversals, provided there are a maximum of two dilution steps between two successive reversals, and the series of reversals do not form an ascending pattern. These additional criteria ensure greater reliability in outcomes. The TDT is then calculated as the geometric mean of the concentrations of the four reversals. This method has real-world relevance as it provides information on a dimension of taste perception that is independent of hedonics, and that can change with aging and certain disease states, making it a valuable psychophysical test.

Impact of early rapid weight gain on odds for overweight at one year differs between breastfed and formula-fed infants.

BACKGROUND: Early rapid weight gain (RWG) increases, whereas longer durations of breastfeeding decreases, odds for later obesity. OBJECTIVES: To determine the independent and interactive effects of early weight gain and diet on infant weight status trajectories and odds for overweight at 1 year. METHODS: We conducted secondary analysis on data from two longitudinal trials with repeated anthropometric measures. One trial consisted of predominantly or exclusively breastfed (BF, n = 97) infants, whereas the other consisted of exclusively formula-fed (FF, n = 113) infants. Weight-for-length z-score (WLZ) change from 0.5 to 4.5 months was used to categorize early weight gain as slow (<-0.67; SWG), normal (-0.67 to 0.67; NWG) or rapid (>0.67; RWG). Linear-mixed effects models were fit to examine the independent effects and interaction of early diet (BF, FF) and weight gain (SWG, NWG, RWG) groups on WLZ trajectories; logistic regression was used to assess odds for overweight at 1 year. RESULTS: While similar percentages (41%) of BF and FF infants experienced RWG, we found a significant diet × early weight gain group interaction (P < .001) on weight status. At 1 year, the WLZ of FF infants with RWG (1.57 ± 0.99) was twice that of BF infants with RWG (0.83 ± 0.92). Using BF infants with NWG as the reference group, FF infants with RWG had increased odds [OR: 25.3 (95% CI: 3.21, 199.7)] for overweight at 1 year, whereas BF infants with RWG did not. CONCLUSIONS: Early diet interacts with early weight gain and influences weight status trajectories and overweight risk at 1 year.

Relationship between Sucrose Taste Detection Thresholds and Preferences in Children, Adolescents, and Adults.

To address gaps in knowledge, our objectives were to (1) to determine whether there are age-related changes in sweet taste detection thresholds, as has been observed for sweet taste preferences, and (2) determine whether detection thresholds and taste preferences were significantly related to each other from childhood to adulthood. We combined data from studies that used the same validated psychophysical techniques to measure sucrose taste detection threshold and the most preferred sucrose concentration in children (n = 108), adolescents (n = 172), and adults (n = 205). There were significant effects of age group on both sucrose detection thresholds (p < 0.001) and most preferred sucrose concentration (p < 0.001). While children had higher sucrose detection thresholds than adolescents, who in turn tended to have higher detection thresholds than adults, both children and adolescent most preferred sucrose concentrations were higher than that of adults (all p < 0.05). Among each age group, and when combined, the lowest sucrose concentration detected was not significantly correlated with the most preferred sucrose concentration (all p > 0.18). These data provide further evidence that age-related changes in sucrose taste preferences that occur during adolescence cannot be explained by changes in taste sensitivity and that these two dimensions of sweet taste undergo distinct developmental trajectories from childhood to adulthood.

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].

Caregiver feeding practices and child weight outcomes: a systematic review.

BACKGROUND: As part of the USDA-Department of Health and Human Services Pregnancy and Birth to 24 Months Project, we conducted systematic reviews (SRs) on topics important for health and nutrition of young children. OBJECTIVES: The purpose of the present SR was to examine the relation between caregiver feeding practices in children from birth to 24 mo and child weight gain, size, and body composition. METHODS: A search of articles published from January 1980 to January 2017 in 4 databases identified 8739 references. Nutrition Evidence Systematic Review (NESR) analysts used the Nutrition Evidence Library Risk of Bias Assessment Tool to assess potential bias in the studies, and a Technical Expert Collaborative graded the body of evidence using the NESR grading rubric. RESULTS: Twenty-seven articles were included in this review (8 controlled trials, 19 longitudinal cohort studies). Moderate evidence from randomized controlled trials suggests that providing responsive feeding guidance to teach mothers to recognize and respond appropriately to children's hunger and satiety cues can lead to "normal" weight gain and/or "normal" weight status in children aged ≤2 y compared with children whose mothers did not receive responsive feeding guidance. Moderate evidence from longitudinal cohort studies indicates an association between maternal feeding practices and the child's weight status and/or weight gain, but the direction of effect has not been adequately studied. Restrictive feeding practices are associated with increased weight gain and higher weight status, and pressuring feeding practices are associated with decreased weight gain and lower weight status. Evidence suggests that a mother's feeding practices are related to concerns about her child's body weight. CONCLUSIONS: This review highlights the importance of the interaction between caregivers and infants and toddlers related to child feeding practices on children's weight outcomes. Research is needed on more diverse populations with consistent methodological app-roaches and objective measures.

Influence of maternal diet on flavor transfer to amniotic fluid and breast milk and children's responses: a systematic review.

BACKGROUND: Maternal diet during pregnancy and lactation may provide the earliest opportunity to positively influence child food acceptance. OBJECTIVE: Systematic reviews were completed to examine the relation among maternal diet during pregnancy and lactation, amniotic fluid flavor, breast-milk flavor, and children's food acceptability and overall dietary intake. DESIGN: A literature search was conducted in 10 databases (e.g., PubMed, Embase, Cochrane, and CINAHL) to identify articles published from January 1980 to June 2017. Data from each included study were extracted, risk of bias assessed, evidence synthesized qualitatively, conclusion statements developed, and strength of the evidence graded. RESULTS: Eleven and 15 articles met a priori criteria for inclusion to answer questions related to maternal diet during pregnancy and lactation, respectively. CONCLUSIONS: Limited but consistent evidence indicates that flavors (alcohol, anise, carrot, garlic) originating from the maternal diet during pregnancy can transfer to and flavor amniotic fluid, and fetal flavor exposure increases acceptance of similarly flavored foods when re-exposed during infancy and potentially childhood. Moderate evidence indicates that flavors originating from the maternal diet during lactation (alcohol, anise/caraway, carrot, eucalyptus, garlic, mint) transmit to and flavor breast milk in a time-dependent manner. Moderate evidence indicates that infants can detect diet-transmitted flavors in breast milk within hours of a single maternal ingestion (alcohol, garlic, vanilla, carrot), within days after repeated maternal ingestion (garlic, carrot juice), and within 1-4 mo postpartum after repeated maternal ingestion (variety of vegetables including carrot) during lactation. Findings may not generalize to all foods and beverages. Conclusions cannot be drawn to describe the relationship between mothers' diet during either pregnancy or lactation and children's overall dietary intake.

Repeated exposure to food and food acceptability in infants and toddlers: a systematic review.

BACKGROUND: Repeated exposure has been found to be an effective strategy to increase acceptability of foods in older children and adults, but little is known about its effectiveness in the birth to 24-mo population. OBJECTIVES: This systematic review was conducted to examine the effects of repeated exposure to a single or multiple foods on acceptance of those or other foods among infants and toddlers. METHODS: A search was conducted for peer-reviewed articles related to food acceptability, flavor, taste, and infants and toddlers in 12 databases (e.g., PubMed, Embase, Cochrane, and CINAHL) with a date range of January 1980 to July 2017. The Nutrition Evidence Library (NEL) Bias Assessment Tool was used to assess potential bias in the included studies, and the NESR grading rubric was used to grade evidence supporting the conclusion statement. RESULTS: From the 10,844 references obtained, 21 studies (19 controlled trials and 2 longitudinal cohort studies) published from 1980 to 2015 were included in this review. Moderate evidence indicates that tasting a single vegetable or fruit or multiple vegetable(s) or fruit(s) 1 food per day for 8-10 or more days is likely to increase acceptability of an exposed food (indicated by an increase in intake or faster rate of feeding after comparison with before the exposure period) in infants and toddlers 4-24 mo old. The effect of repeated exposure on acceptability is likely to generalize to other foods within the same food category but not foods from a different food category. Findings are based on the effects of repeated exposure to mostly vegetables with some findings on repeated exposure to fruits. CONCLUSION: This review advances the understanding of early food experiences and the development of food acceptability. Additional research is needed using diverse foods and textures with a focus on the transition to table foods.

Repeated Exposure to Low-Sodium Cereal Affects Acceptance but Does not Shift Taste Preferences or Detection Thresholds of Children in a Randomized Clinical Trial.

BACKGROUND: Although salt taste preference is malleable in adults, no research to date has focused on children, whose dietary sodium intake exceeds recommended intake and whose salt taste preferences are elevated. OBJECTIVE: This proof-of-principle trial determined whether 8-wk exposure to low-sodium cereal (LSC) increased children's acceptance of its taste and changed their salty and sweet taste preferences. METHODS: Children (n = 39; ages 6-14 y; 67% female) were randomly assigned to ingest LSC or regular-sodium cereal (RSC) 4 times/wk for 8 wk. The cereals, similar in sugar (3 g/cup compared with 2 g/cup) and energy content (100 kcal/cup) yet different in sodium content (200 mg sodium/cup compared with 64 mg sodium/cup), were chosen based on taste evaluation by a panel of children. Mothers completed daily logs on children's cereal intake. At baseline and after the exposure period, taste tests determined which cereal children preferred and measured children's most preferred amount of salt (primary outcomes), and most preferred amount of sucrose and salt taste detection thresholds (secondary outcomes). Repeated measures ANOVAs were conducted on primary and secondary outcomes, and generalized estimating equations were conducted on amount of cereal ingested at home over time. RESULTS: Both treatment groups accepted and ate the assigned cereal throughout the 8-wk exposure. There were no group × time interactions in salt detection thresholds (P = 0.32) or amount of salt (P = 0.30) and sucrose (P = 0.77) most preferred, which were positively correlated (P = 0.001). At baseline and after the exposure, the majority in both groups preferred the taste of the RSC relative to LSC (P > 0.40). CONCLUSIONS: Children showed no change in salt preference but readily ate the LSC for 8 consecutive weeks. Findings highlight the potential for reducing children's dietary salt intake by incorporating low-sodium foods in the home environment without more preferred higher-salt versions of these foods. This trial was registered at clinicaltrials.gov as NCT02909764.

Exposure to a slightly sweet lipid-based nutrient supplement during early life does not increase the level of sweet taste most preferred among 4- to 6-year-old Ghanaian children: follow-up of a randomized controlled trial.

BACKGROUND: The impact of feeding a slightly sweet nutrient supplement early in life on later sweet taste preference is unknown. OBJECTIVE: We tested the hypothesis that the level of sucrose most preferred by 4-6-y-old children exposed to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not be higher than that of children never exposed to LNS. DESIGN: We followed up children born to women (n = 1,320) who participated in a randomized trial in Ghana. In one group, LNS was provided to women on a daily basis during pregnancy and the first 6 mo postpartum and to their infants from age 6 to 18 mo (LNS group). The control groups received daily iron and folic acid or multiple micronutrients during pregnancy and the first 6 mo postpartum, with no infant supplementation (non-LNS group). At age 4-6 y, we randomly selected a subsample of children (n = 775) to assess the concentration of sucrose most preferred using the Monell 2-series, forced-choice, paired-comparison tracking procedure. We compared LNS with non-LNS group differences using a noninferiority margin of 5% weight/volume (wt/vol). RESULTS: Of the 624 children tested, most (61%) provided reliable responses. Among all children, the mean ± SD sucrose solution most preferred (% wt/vol) was 14.6 ± 8.6 (LNS group 14.9 ± 8.7; non-LNS group 14.2 ± 8.4). However, among children with reliable responses, it was 17.0 ± 10.2 (LNS group 17.5 ± 10.4; non-LNS group 16.5 ± 10.0). The upper level of the 95% CI of the difference between groups did not exceed the noninferiority margin in either the full sample or those with reliable responses, indicating that the LNS group did not have a higher sweet preference than the non-LNS group. CONCLUSION: Exposure to a slightly sweet nutrient supplement early in life did not increase the level of sweet taste most preferred during childhood. This trial was registered at clinicaltrials.gov as NCT00970866.

Type of infant formula increases early weight gain and impacts energy balance: a randomized controlled trial.

Background: Millions of infants are fed breast milk substitutes, and the type of infant formula can impact weight gain patterns. Objective: We conducted a randomized controlled trial to determine the direct impact of 2 types of infant formula (cow milk formula, CMF; extensively protein hydrolyzed formula, EHF) on growth and energy balance. Design: A racially diverse group of formula-fed infants (n = 113) were randomly assigned to either CMF or EHF from the age of 0.75 to 12.5 mo. At each monthly visit, anthropometric measures were obtained to determine growth z scores and weight gain velocity, and to categorize early weight gain patterns as rapid or nonrapid. Also, diet records were collected to determine energy from formula and other sources. Comprehensive assessments of energy balance (intake, expenditure, loss) were made at 0.75, 3.5, and 12.5 mo. Results: Beginning 3 wk after randomization, CMF infants had significantly higher weight, but not length, z scores than did EHF infants, and this persisted after solid foods complemented the formula diet. On average, weight gain velocity from 0.75 to 4.5 mo was within the range of typically growing infants for both groups, yet velocity was 3.9 g/d greater for CMF infants (P = 0.002), who were more likely to be classified as an early rapid weight gainer, than EHF infants (46% compared with 18%; P = 0.007). Early differences in energy intake and fecal loss, yielding greater energy available for deposition among CMF infants, contributed to the differential weight gain patterns. There were no significant differences between the formula treatment groups in total energy expenditure or sleeping energy expenditure. Conclusions: Among healthy infants, the type of formula impacted on early rapid weight gain patterns owing to energy intake and loss mechanisms. Research is needed to identify the macronutrients and other compositional constituents in EHF and breast milk that promote satiation and healthy weight gain during sensitive periods of development. This trial was registered at clinicaltrials.gov as: NCT01700205.

Use of Adult Sensory Panel to Study Individual Differences in the Palatability of a Pediatric HIV Treatment Drug.

PURPOSE: The recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra® [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes. METHODS: As a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients. Panelists rated taste sensations using generalized labeled magnitude scales to determine genotype-phenotype relationships. Several months later, the panelists were retested to assess response reliability. FINDINGS: Not all panelists had the same sensory experience when tasting Kaletra. Palatability ratings varied widely, from moderate like to strongest imaginable dislike, and were reliable over time. The more irritating and bitter Kaletra tasted, the more disliked by the panelist. The more they disliked the taste of Kaletra, the more they disliked the taste of its excipient ethanol and the bitter stimulus denatonium. Those who experienced less bitter and sweeter taste sensations had a different genetic signature than the other panelists. Bitterness and irritation ratings of Kaletra varied by the orphaned bitter receptor gene (TAS2R60), whereas sweetness ratings of Kaletra varied according to the cold receptor gene (TRPM8), which is activated by menthol, an excipient of Kaletra. Neither genotype related to ratings for ethanol or denatonium, however. IMPLICATIONS: The use of a sensory panel holds promise as a first step in determining the nature of individual differences in the palatability of existing pediatric drug formulations and sources of variation. In this era of personalized medicine, the need is great to develop psychophysical tools to determine which drugs will show variation in acceptance by children and whether patterns of individual variation in taste as assessed by adults mirror those of young patients. ClinicalTrials.gov identifier: NCT01841710.

The Relationship between Infant Facial Expressions and Food Acceptance.

PURPOSE OF REVIEW: To highlight the range of methodological approaches used to objectively measure hedonic responses to taste stimuli during the first year of life and how these behavioral responses change with experience. Challenges inherent to this type of research are discussed. RECENT FINDINGS: Although newborns display characteristic orofacial reactivity to four of the five basic tastes, the facial expressions made and the amount of food consumed can be modified by experience: children learn to like what they are fed. In some cases changes in facial responses are concordant with infant consumption, whereas in other cases facial reactivity follows changes in intake. SUMMARY: Together with ingestive measurements, precise and objective measurements of orofacial reactivity provide an understanding of how early experiences shift the hedonic tone of the taste of foods, the foundation of dietary preferences.