Ferritin levels throughout childhood and metabolic syndrome in adolescent stage.

BACKGROUND AND AIM: Increased ferritin levels have been widely associated with cardiovascular risk in adults. Whether ferritin levels and their changes during childhood are related to metabolic syndrome (MetS) at adolescence is unknown. We aimed to evaluate these associations using levels of ferritin at 5, 10 and 16 years and their linear increases and patterns of sustained increased levels across childhood. METHODS AND RESULTS: There were four samples evaluated according to non-missing values for study variables at each stage (5 years: 562; 10 years: 381; and 16 years: 567 children; non-missing values at any stage: 379). MetS risk was evaluated as a continuous Z score. Patterns of sustained increased ferritin (highest tertile) and slope of the change of ferritin per year across the follow-up were calculated. Ferritin levels in the highest versus lowest tertile at five and 16 years were significantly positively associated with MetS risk Z score at adolescence in boys and these associations were unaffected by adjustment for covariates. Having high, compared to low/moderate ferritin level at 2 or more time periods between 5 and 16 years was related to higher Mets Z-score in boys only [e.g. 5-10 years adjusted-beta (95 %CI):0.26 (0.05-0.48),P < 0.05]. In girls, ferritin Z score at 10 and 16 years was positively and independently associated with HOMA-IR Z score. In girls, the slope of ferritin per year in the highest tertile was positively associated with MetS risk Z-score [adjusted-beta (95 %CI):0.21 (0.05-0.38),P < 0.05]. CONCLUSIONS: Ferritin levels throughout childhood are positively related to cardiometabolic risk in adolescence, with associations varying by sex.

Genetic determinants of BMI from early childhood to adolescence: the Santiago Longitudinal Study.

BACKGROUND: While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z-score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence. OBJECTIVES: We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS). METHODS: We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS). RESULTS: We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni-corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%). CONCLUSION: Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.

Greater early weight gain and shorter breastfeeding are associated with low adolescent adiponectin levels.

BACKGROUND: Early life factors can programme future risk for cardiovascular disease. OBJECTIVES: We explored associations between adolescent adiponectin levels and concomitant metabolic alteration and also looked at the association between early life factors and adolescent adiponectin levels. METHODS: We studied a longitudinal cohort of low-income to middle-income Chilean adolescents who were enroled in an infancy iron-deficiency anaemia preventive trial and follow-up studies at the Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile. In the 577 adolescents who were assessed as part of the 16-year follow-up, we evaluated independent associations between adiponectin levels and metabolic disturbances during adolescence. We also assessed the association between early life factors [short breastfeeding {<6 months} and infancy weight gain] and adolescent adiponectin levels. RESULTS: Participants were 16.8 years old (16.4-18.1), 48% female and 38% overweight/obese. Adolescent adiponectin levels were inversely associated with metabolic disturbances: altered homeostatic model assessment of insulin resistance and high-density lipoprotein cholesterol [odds ratios {95% confidence interval} = 0.87 {0.79-0.95}, p-value = 0.002, and 0.90 {0.87-0.94}, p-value < 0.001, respectively], adjusting for sex and fat mass index. Early life factors were independently associated with adolescent adiponectin levels, which decreased 0.88 ug mL-1 per each unit increase in weight-for-age z-score between 0 and 6 months and was 1.58 ug mL-1 lower among participants with short breastfeeding. CONCLUSIONS: Higher adolescent adiponectin levels were independently associated with lower odds of metabolic disturbances. Greater weight gain during infancy and shorter breastfeeding were associated with lower adolescent adiponectin levels, supporting research indicating early life as a window of opportunity for prevention of later cardiovascular alterations. © 2017 World Obesity Federation.

Obesity leads to declines in motor skills across childhood.

BACKGROUND: Poor motor skills have been consistently linked with a higher body weight in childhood, but the causal direction of this association is not fully understood. This study investigated the temporal ordering between children's motor skills and weight status at 5 and 10 years. METHODS: Participants were 668 children (54% male) who were studied from infancy as part of an iron deficiency anaemia preventive trial and follow-up study in Santiago, Chile. All were healthy, full-term and weighing 3 kg or more at birth. Cross-lagged panel modelling was conducted to understand the temporal precedence between children's weight status and motor proficiency. Analyses also examined differences in gross and fine motor skills among healthy weight, overweight, and obese children. RESULTS: A higher BMI at 5 years contributed to declines in motor proficiency from 5 to 10 years. There was no support for the reverse, that is, poor motor skills at 5 years did not predict increases in relative weight from 5 to 10 years. Obesity at 5 years also predicted declines in motor proficiency. When compared with normal weight children, obese children had significantly poorer total and gross motor skills at both 5 and 10 years. Overweight children had poorer total and gross motor skills at 10 years only. The differences in total and gross motor skills among normal weight, overweight and obese children appear to increase with age. There were small differences in fine motor skill between obese and non-obese children at 5 years only. CONCLUSIONS: Obesity preceded declines in motor skills and not the reverse. Study findings suggest that early childhood obesity intervention efforts might help prevent declines in motor proficiency that, in turn, may positively impact children's physical activity and overall fitness levels.

Inhibitory control in otherwise healthy overweight 10-year-old children.

BACKGROUND: Preventing obesity is a worldwide public health priority. In vulnerable children living in obesogenic environments, with easy access to high-caloric food, alterations in inhibitory control functions might favor excessive food intake and affect energy regulation. We hypothesized that overweight/obese children would present lower inhibitory control in comparison to normal weight children. METHODS: We measured inhibitory control functions in 93 otherwise healthy overweight/obese and 92 normal weight 10-year-old children using the Stroop test and the Go/No-Go task. Event-related potentials were recorded during the Go/No-Go task. RESULTS: Overweight/obese children showed slower reaction times (1248.6 ms (95% confidence interval (CI): 1182.9-1314.3) vs 1149.0 ms (95% CI: 1083.0-1215.1)) on the Stroop test, higher reaction time variability (0.25 (95% CI: 0.22-0.27) vs 0.21 (95% CI: 0.19-0.24)) on the Go/No-Go task and decreased P300 amplitude (4.1 µV (95% CI: 3.0-5.2) vs 6.4 µV (95% CI: 5.2-7.6)) on event-related potentials compared with normal weight children. CONCLUSIONS: Our results indicate altered inhibitory control functions in otherwise healthy overweight/obese children, which might contribute to their excessive food consumption.

Night time sleep macrostructure is altered in otherwise healthy 10-year-old overweight children.

OBJECTIVE: Epidemiological evidence shows an inverse relationship between sleep duration and overweight/obesity risk. However, there are few polysomnographic studies that relate the organization of sleep stages to pediatric overweight (OW). We compared sleep organization in otherwise healthy OW and normal-weight (NW) 10-year-old children. SUBJECTS: Polysomnographic assessments were performed in 37 NW and 59 OW children drawn from a longitudinal study beginning in infancy. Weight and height were used to evaluate body mass index (BMI) according to international criteria. Non-rapid eye movement (NREM) sleep (stages N1, N2 and N3), rapid eye movement (REM) sleep (stage R) and wakefulness (stage W) were visually scored. Sleep parameters were compared in NW and OW groups for the whole sleep period time (SPT) and for each successive third of it using independent Student's t-tests or nonparametric tests. The relationship between BMI and sleep variables was evaluated by correlation analyses controlling for relevant covariates. RESULTS: The groups were similar in timing of sleep onset and offset, and sleep period time. BMI was inversely related to total sleep time (TST) and sleep efficiency. OW children showed reduced TST, sleep efficiency and stage R amount, but higher stage W amount. In analysis by thirds of the SPT, the duration of stage N3 episodes was shorter in the first third and longer in the second third in OW children as compared with NW children. CONCLUSIONS: Our results show reduced sleep amount and quality in otherwise healthy OW children. The lower stage R amount and changes involving stage N3 throughout the night suggest that OW in childhood is associated with modifications not only in sleep duration, but also in the ongoing night time patterns of NREM sleep and REM sleep stages.

Satiety responsiveness and eating behavior among Chilean adolescents and the role of breastfeeding.

OBJECTIVE: To determine patterns of satiety responsiveness and its relationship to eating in the absence of hunger (EAH), in a cohort of adolescents. We also assessed whether sex, body mass index and duration of breastfeeding, during infancy, predicted satiety responsiveness and eating behavior at 16 years. METHODS: Adolescents (n=576) from a longitudinal cohort, which began as an iron deficiency anemia preventive trial, participated in an unlimited breakfast after an overnight fast, and reported satiety response on a visual analog scale after the meal, followed by an EAH procedure. Height, weight and body composition were measured before breakfast. Latent profile analysis generated profiles that captured individual differences in satiety responsiveness. Multivariable regressions, adjusted for potential confounders, evaluated the association between: (1) satiety responsiveness and EAH, and (2) breastfeeding in infancy, satiety responsiveness and EAH in adolescence. RESULTS: Participants were on average 16.7-year old, 48% female, 37% overweight/obese and 76% were breastfed as the sole source of milk for <6 months. We found three latent profiles of satiety responsiveness: 1: 'responsive' (49%); 2: 'not responsive' (41%); 3: 'still hungry' (10%). Participants in the 'not responsive' or 'still hungry' profile were more likely to eat during the EAH procedure (odds ratio (OR)=2.5, 95% confidence interval (CI)=1.8-3.6). Being breastfed for <6 months was related to higher odds of being in the 'not responsive' or 'still hungry' profile (OR=1.8, 95% CI=1.2-2.6) and EAH (OR=2.2, 95% CI=1.4-3.3). Satiety responsiveness was not influenced by sex and overweight/obesity. CONCLUSION: After an ad libitum meal, we found varied satiety responses, which related to EAH. Furthermore, shorter breastfeeding duration was associated with poorer satiety response and higher consumption during an EAH procedure. Understanding if breastfeeding influences the development of satiety responsiveness and eating behavior may be important in an era characterized by abundant calorie-dense foods and a plethora of environmental cues promoting consumption.

Motor activity and intra-individual variability according to sleep-wake states in preschool-aged children with iron-deficiency anemia in infancy.

BACKGROUND: A chronic or acute insult may affect the regulatory processes that guide motor and behavioral performance, leading to increased intra-individual variability (IIV). Increased variability is often interpreted as an indication of regulatory dysfunction. Iron plays an important role in the regulatory processes of the nervous system and affects motor activity. To our knowledge, no study has examined the long-lasting patterns and IIV of motor activity following iron-deficiency anemia in human infants. AIMS: This study compared 48-h motor activity and variability in preschool-aged children with or without iron-deficiency anemia (IDA) in infancy. METHODS: Motor activity was recorded through actigraphs during two week-days in 47 4-year-old Chilean children (23 former IDA and 24 non-anemic in infancy). All were given oral iron as infants. Sleep-wake states were identified by means of automated software. The frequency of movement units per minute was determined for each waking/sleep state during the individual day and night periods; data were examined in blocks of 15 min. Analyses of mean frequency and duration and intra-individual variability were conducted using multivariate mixed models. RESULTS: For daytime sleep, former IDA children were more active without a difference in the total duration. They also spent less time awake throughout the individual day period. Motor activity intra-individual variability was higher in former IDA children. CONCLUSIONS: The findings suggest that IDA in infancy sets the stage for long lasting dysfunction in the neural processes regulating sleep-wake states and spontaneous motor activity patterns.

Postnatal Growth Patterns in a Chilean Cohort: The Role of SES and Family Environment.

Objective. This study examined how family environmental characteristics served as mediators in the relationship between socioeconomic conditions and infant growth in a cohort of Chilean infants. Methods. We studied 999 infants, born between 1991 and 1996, from a longitudinal cohort which began as an iron deficiency anemia preventive trial. SES (Graffar Index), the Life Experiences Survey, and the Home Observation for Measurement of the Environment (HOME) were assessed in infancy. Using path analysis, we assessed the relationships between the social factors, home environment, and infant growth. Results. During the first year, weight and length gain averaged 540 grams/month and 6.5 cm/month, respectively. In the path analysis model for weight gain, higher SES and a better physical environment were positively related to higher maternal warmth, which in turn was associated with higher average weight gain. Higher SES was directly related to higher average length gain. Conclusions. In our cohort, a direct relationship between SES and length gain developed during infancy. Higher SES was indirectly related to infant weight gain through the home environment and maternal warmth. As the fastest growing infants are at risk for later obesity, new strategies are needed to encourage optimal rather than maximal growth.

Twenty-four-hour motor activity in human infants with and without iron deficiency anemia.

Iron deficiency anemia (IDA) is a very common nutritional problem that alters motor activity. The aim of this study was to compare 24-h motor activity in the home in healthy 6-month-old infants with and without IDA. Activity was assessed via actigraphs on the leg during 24 continuous hours in 17 Chilean infants with IDA and 18 with normal hemoglobin levels. All infants were given oral iron, and activity was reassessed at 12 and 18 months. The frequency of movement units per minute was determined for each waking/sleep state during the day and night, and the duration of each state was computed. At 6 months of age, there were no differences between anemic and nonanemic infants in time per state. However, infants with IDA showed an overall increase in motor activity compared to controls. These differences were no longer observed at 12 and 18 months of age. Increased activity during the period of IDA raises the issue of a shared underlying mechanism with restless legs syndrome, a sensorimotor dysfunction where iron deficiency increases the severity of the symptoms and iron supplementation ameliorates them. Due to previous findings of decreased motor activity in the laboratory at 12 months during the waking time surrounding an afternoon nap, we also compared those data to a nap in the home. Infants with IDA were less active in the laboratory than in the home. The home versus laboratory results suggest that contextual factors affect the motor activity of IDA infants to a larger extent than controls.

Spontaneous motor activity in human infants with iron-deficiency anemia.

This study compared spontaneous motor activity in 6-month-old Chilean infants with or without iron-deficiency anemia (IDA) who were otherwise healthy. Activity was assessed in conjunction with polysomnographic recording during an afternoon nap in 11 infants with IDA and 15 with normal hemoglobin levels. All infants were given oral iron, and activity was reassessed at 12 and 18 months. Using actigraphs placed on the ankle, the frequency of movement units per minute was determined for each waking/sleep state. The total amount of time infants were in an alert-active state before and after the nap was used to calculate the proportion of movements/minute of waking. There were no differences between anemic and nonanemic infants in total recording time, duration of sleep, or motor activity during sleep. However, infants with IDA showed reduced motor activity during waking at all ages. The magnitude of the differences increased at 12 and 18 months. Thus, IDA was associated with reduced motor activity in infants even after iron treatment. It will be important to confirm these results in a larger sample and to determine the 24-h pattern of motor activity, since reduced motor activity may limit infants' opportunities to explore and learn from the social and physical environment.

Prevention of iron-deficiency anemia: comparison of high- and low-iron formulas in term healthy infants after six months of life.

OBJECTIVES: For bottle-fed babies or nursing infants who receive milk supplements, the American Academy of Pediatrics recommends the use of iron-fortified infant formula. Because these recommendations have not been universally adopted, the hematologic effects of currently available low-iron formulas need to be determined. STUDY DESIGN: Healthy Chilean 6-month-old infants (without iron-deficiency anemia, born at term weighing > or 3.0 kg) who were totally or partially weaned from the breast were randomly allocated in a double-blind fashion to receive high-iron (n = 430) or low-iron formula (n = 405), containing an average of 12.7 mg/L or 2.3 mg/L, respectively, of elemental iron as ferrous sulfate. Iron status was determined at 12 months. RESULTS: The prevalence of iron-deficiency anemia was not different in the high- and low-iron groups (2.8% versus 3.8%, p = 0.35). Nevertheless, infants receiving high-iron formula had somewhat higher levels of hemoglobin and serum ferritin, greater mean cell volumes, and lower erythrocyte protoporphyrin levels (p < 0.005). CONCLUSIONS: Although high-iron formulas are more efficacious in improving iron status, currently available low-iron formulas may prevent iron-deficiency anemia in selected healthy, term infant populations with otherwise poor sources of dietary iron after 6 months of life. Formulas with relatively small amounts of iron appear to prevent iron-deficiency anemia. We speculate that the optimal level of iron fortification likely lies somewhere between the current levels in high- and low-iron formulas.

Iron-deficiency anemia and infant development: effects of extended oral iron therapy.

OBJECTIVE: To determine whether extended oral iron therapy corrects lower developmental test scores in infants with iron-deficiency anemia. STUDY DESIGN: Double-blind, controlled trial in Costa Rica involving 32 12- to 23-month-old infants with iron-deficiency anemia and 54 nonanemic control subjects. Anemic infants were treated with orally administered iron for 6 months; half the nonanemic children were treated with iron and half with placebo. Developmental test scores and hematologic status were evaluated before treatment, after 3 months, and after 6 months. RESULTS: Iron-deficient anemic infants received lower mental test scores than nonanemic infants at all three time points (p < 0.05 pretreatment and at 3 months, p = 0.07 at 6 months). There were no significant differences in motor test scores. More of the anemic infants were rated as unusually tearful and unhappy. Anemic infants came from families with lower maternal education and less support for child development and were less likely to be breast fed, were weaned earlier, and consumed more cow milk. CONCLUSIONS: Lower mental test scores persisted in infants with iron-deficiency anemia despite extended oral iron therapy and an excellent hematologic response. Iron-deficiency anemia may serve as a marker for a variety of nutritional and family disadvantages that may adversely affect infant development.

Using the HOME inventory with infants in Costa Rica.

PIP: It has been established through several decades of research that children's home environments significantly influence their development. Many researchers have also been interested in expanding research beyond indirect measures of the home environment, such as socioeconomic status, to help understand the nature of specific environmental mechanisms which influence early behavior and cognitive development. The Home Observation for Measurement of the Environment (HOME) Inventory was developed to meet these needs. Specifically, HOME measures the quality of stimulation in a child's early family environment. Almost all studies of the approach's reliability and validity have been conducted with US samples. HOME is, however, being used in other countries. The authors report their findings from a study of whether the psychometric properties of HOME based upon US samples parallel those found in Costa Rica, and whether HOME discriminates between Costa Rican environments with different associations to child health and development. Focus centers upon the infant/toddler version of the HOME Inventory. HOME data for 183 healthy Costa Rican infants were compared to the original HOME standardization sample from Little Rock, Arkansas. The study found the HOME Inventory to be helpful in identifying children at risk for delayed development in this Latin American sample. Lower HOME scores related to a shorter duration of breastfeeding and differentiated children with iron deficiency anemia in infancy, a condition associated with long-lasting developmental disadvantage.^ieng

No evidence of developmental III effects of low-level lead exposure in a developing country.

Despite substantial controversy regarding the blood levels at which lead adversely affects neurobehavioral development, public health policy in some industrialized countries is prescribing ever more stringent screening criteria for all ages. This study addressed the question of ill effects of lead exposure at the new lower levels, specifically during the late infancy period, which has been targeted for maximum surveillance in pediatric practice. The sample of 184 participants consisted of 12- to 23-month-old healthy infants and toddlers who participated in a community-based study in a developing Central American country (Costa Rica) where extensive family and developmental information was collected. The mean infant blood lead level was 11.0 micrograms/dL, ranging from 5.4 to 37.0 micrograms/dL. Lead levels were not related to the Mental or Psychomotor Developmental Index of the Bayley Scales of Infant Development. When the children were 5 years old, they were reevaluated with complete physical and psychological testing. Blood lead levels in infancy did not predict any of the developmental outcome measures. Thus, among a group of healthy toddlers in a developing country, no ill effects on development of low blood lead levels were observed.

Iron deficiency anemia and iron therapy effects on infant developmental test performance.

The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind randomized controlled community-based study of 191 Costa Rican infants, 12 to 23 months of age, with various degrees of iron deficiency. The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron. Appropriate placebo-treated control infants were also tested. Infants with iron deficiency anemia showed significantly lower mental and motor test scores, even after considering factors relating to birth, nutrition, family background, parental IQ, and the home environment. After 1 week, neither IM nor oral iron treatments differed from placebo treatment in effects on scores. After 3 months, lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected (36%). However, significantly lower mental and motor test scores persisted among the majority of initially anemic infants (64%) who had more severe or chronic iron deficiency. Although no longer anemic, they still showed biochemical evidence of iron deficiency after 3 months of treatment. These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting, depending on the timing, severity, or chronicity of iron deficiency anemia in infancy.