Time after a peak-pesticide use period and neurobehavior among ecuadorian children and adolescents: The ESPINA study.

BACKGROUND: Limited evidence exists regarding transient neurobehavioral alterations associated with episodic pesticide exposures or agricultural pesticide spray periods. We previously observed that children examined soon after a pesticide spray period (the Mother's Day flower harvest [MDH]) had lower neurobehavioral performance than children examined later. The present study builds on our previous work by incorporating longitudinal analyses from childhood through adolescence. METHODS: We examined participants in agricultural communities in Ecuador (ESPINA study) during three periods: July-August 2008 (N = 313, 4-9-year-olds); April 2016 (N = 330, 11-17-year-olds); July-October 2016 (N = 535, 11-17-year-olds). Participants were examined primarily during a period of low floricultural production. Neurobehavior was assessed using the NEPSY-II (domains: Attention/Inhibitory Control, Language, Memory/Learning, Visuospatial Processing, and Social Perception). Linear regression and generalized linear mixed models were used to examine cross-sectional and longitudinal associations between examination date (days) after the MDH and neurobehavioral outcomes, adjusting for demographic, anthropometric, and socio-economic variables. RESULTS: Participants were examined between 63 and 171 days after the MDH. Mean neurobehavioral domain scores ranged from 1.0 to 17.0 (SDrange = 2.1-3.1) in 2008 and 1.0 to 15.5 (SDrange = 2.0-2.3) in 2016. In cross-sectional analyses (2016 only; N = 523), we found significant or borderline positive associations between time after the MDH and Attention/Inhibitory Control (difference/10 days [ß] = 0.22 points [95% CI = 0.03, 0.41]) and Language (ß = 0.16 points [95% CI = -0.03, 0.34]). We also observed positive, longitudinal associations (2008-2016) with Attention/Inhibitory Control (ß = 0.19 points [95% CI = 0.04, 0.34]) through 112 days after the harvest and Visuospatial Processing (ß = 3.56, ß-quadratic = -0.19 [95% CI: -0.29, -0.09]) through 92 days. CONCLUSIONS: Children examined sooner after the harvest had lower neurobehavioral performance compared to children examined later, suggesting that peak pesticide spray seasons may transiently affect neurobehavior followed by recovery during low pesticide-use periods. Reduction of pesticide exposure potential for children during peak pesticide-use periods is advised.

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.

Eating in the Absence of Hunger and Obesity Among Adolescents in Santiago, Chile.

In reports among mostly, US, white, preschool and young school-age children eating in the absence of hunger (EAH) has been positively related to adiposity, with some support for a sex-specific relationship. There is considerable interest in EAH and obesity in populations at risk for obesity-like populations of countries that have undergone rapid development. We assessed adolescents (n = 679) after an overnight fast with anthropometry and an EAH paradigm beginning with an ad lib pre-load meal. Participants reported satisfaction and perceived ability to eat more food, and then proceeded to a room with freely available snacks where they were permitted to eat ad lib for 20 min. Adolescents were 16.8 years old, 52% male, and 14% with obesity. Median preload meal kcal consumption was 602 (IQR 474-746). Additional calories were consumed at the EAH snack by 47.6%. Among those who ate snack, 155 additional calories were consumed (IQR 78-283). Adolescents with obesity had 0.61 (95% CI 0.37-0.99) reduced odds of eating at the EAH snack adolescents without obesity. Adolescents with obesity were also less likely to eat above the median total calories compared to adolescents without obesity (OR = 0.59, 95% CI 0.36-0.96). A sex by obesity interaction term was not significant in any model. Obesity was related to eating behavior in our sample of Chilean adolescents, however not in the direction we hypothesized. Adolescents with obesity were less likely to eat additional calories in the EAH paradigm and ate fewer total calories compared to adolescents without obesity.

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.

Breastfeeding as the sole source of milk for 6 months and adolescent bone mineral density.

Little is known regarding the relationship between early life factors and bone mineral density (BMD). We found a positive association between breastfeeding for at least 6 months, without formula supplementation, and whole body adolescent BMD z-score. INTRODUCTION: The aim of the study is to assess the role of breastfeeding BF on adolescent bone mineral density (BMD) in a cohort prospectively followed since infancy. METHODS: We studied 679 participants from an infancy iron deficiency anemia preventive trial in Santiago, Chile, followed to adolescence. Breast and bottle feeding were ascertained weekly from 4 to 12 months. At 16 years, whole body BMD was assessed by DEXA. Using linear regression, we evaluated associations between BF duration and BF as the sole source of milk and adolescent BMD z-score, adjusting for possible infancy, adolescent, and background confounders. RESULTS: Mean birth weight and length were 3.5 (0.3) kg and 50.7 (1.6) cm. For at least 6 months, BF was the sole source of milk for 26.3% and with supplementation for 36.7%. For 37%, BF was provided for less than 6 months. Mean 16-year BMD z-score was 0.25 (1.0). Covariates included male sex, birth length, and gestational age. BF as the sole source of milk ≥6 months, compared to BF < 6 months, was associated with higher adolescent BMD z-score adjusting for covariates (ß = 0.29, p < 0.05). Mixed BF was not significantly related to adolescent BMD z-score (ß = 0.06, p = 0.47). For every 30 days of BF as the sole source of milk, adolescent BMD z-score increased by 0.03 (p = 0.01). CONCLUSION: BF without formula supplementation for at least 6 months was associated with higher adolescent BMD z-score and a suggestive trend in the same direction for BMD suggests that exclusivity and duration of BF may play a role in adolescent bone health.

Low muscle mass is associated with cardiometabolic risk regardless of nutritional status in adolescents: A cross-sectional study in a Chilean birth cohort.

BACKGROUND: Increased cardiometabolic risk (CMR) is documented in obese and non-obese adolescents with low muscular fitness. However, the association of low muscle mass (LMM) with CMR, independent of weight status, has not been examined. We analyzed the relationship of LMM with CMR in adolescents, regardless of their weight status. MATERIALS AND METHODS: Observational study in 660 adolescents. BMI, waist circumference (WC), arterial blood pressures (ABP) were measured. Total fat mass (TFM), total lean tissue (TLT), and appendicular skeletal muscle mass (ASM) were estimated (DXA). Fasting lipid profile, glucose, and insulin were measured. HOMA-IR was estimated. Metabolic Syndrome (MetS) was diagnosed (AHA/NHLBI/IDF). ROC analysis was performed to find the optimal cutoffs of TLT percentage for MetS diagnosis. Values below these cutoffs defined LMM. ANCOVA examined the association of LMM with selected cardiometabolic biomarkers. RESULTS: In both sexes, TLT showed better sensitivity and specificity than ASM for MetS diagnosis. In males and females, TLT of 66.1% and 56.3%, respectively, were the optimal cutoff for MetS diagnosis. In the sample, 17.3% of males and 23.7% of females had LMM. In both sexes, adolescents with LMM had significantly higher values of WC, ABP, TG, TC/HDL, HOMA-IR, and MetS z-score than non-LMM participants. Adolescents with LMM, regardless nutritional status, had significantly increased values of MetS z-score, ABP, TG, TC/HDL-chol, and HOMA-IR than non-obese non-LMM adolescents. Adolescents having both obesity and LMM had the unhealthiest CMR profile. CONCLUSION: In adolescents, LMM was associated with higher CMR, regardless of nutritional status. In obese adolescents, LMM increased obesity-associated CMR.

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.

Healthy Chilean Adolescents with HOMA-IR ≥ 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors.

OBJECTIVE: To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. METHODS: In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. RESULTS: Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. CONCLUSIONS: In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk.

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.

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.

Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child.

The Food and Drug Administration licensed a live-virus varicella vaccine (Varivax; Merck & Co Inc, West Point, PA) in March 1995. Prelicensure adverse events were minimal; however, since licensure and increased vaccine use, rare previously undetected risks have arisen. Presented here is the clinical course of a previously undiagnosed, human immunodeficiency virus-infected boy who developed dissemination of the vaccine strain of varicella zoster after immunization. chickenpox, human immunodeficiency virus, pneumonia, encephalopathy, varicella vaccine, adverse events, dissemination.

A stepwise approach to evaluation of undernutrition and failure to thrive.

The primary care physician is key to evaluating children who are undernourished or failing to thrive. The comprehensive stepwise approach to evaluation is simple and effective. Positive outcomes can be expected.

The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p.

Severe combined immunodeficiency disease (SCID) consists of a group of heterogeneous genetic disorders. The most severe phenotype, T-B- SCID, is inherited as an autosomal recessive trait and is characterized by a profound deficiency of both T cell and B cell immunity. There is a uniquely high frequency of T-B- SCID among Athabascan-speaking Native Americans (A-SCID). To localize the A-SCID gene, we conducted a genomewide search, using linkage analysis of approximately 300 microsatellite markers in 14 affected Athabascan-speaking Native American families. We obtained conclusive evidence for linkage of the A-SCID locus to markers on chromosome 10p. The maximum pairwise LOD scores 4.53 and 4.60 were obtained from two adjacent markers, D10S191 and D10S1653, respectively, at a recombination fraction of straight theta=.00. Recombination events placed the gene in an interval of approximately 6.5 cM flanked by D10S1664 and D10S674. Multipoint analysis positioned the gene for the A-SCID phenotype between D10S191 and D10S1653, with a peak LOD score of 5.10 at D10S191. Strong linkage disequilibrium was found in five linked markers spanning approximately 6.5 cM in the candidate region, suggesting a founder effect with an ancestral mutation that occurred sometime before 1300 A.D.

Child abuse or osteogenesis imperfecta: how can we tell?

Osteogenesis imperfecta may be difficult to differentiate from nonaccidental trauma. Social history may prejudice the physician in favor of or against considering the diagnosis of child abuse. Three cases of osteogenesis imperfecta that were initially diagnosed as nonaccidental trauma are presented. The availability of biochemical analysis of type I collagen was instrumental in confirming the diagnosis of osteogenesis imperfecta in all three cases.

A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.

A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.

Comparison of active and combined passive/active immunization of Navajo children against Haemophilus influenzae type b.

In a high risk Navajo population we compared the immunogenicity of a new Haemophilus influenzae type b mutant-diphtheria toxic conjugate vaccine (HbOC) with simultaneous active (HbOC) and passive immunization with bacterial polysaccharide immunoglobulin prepared from adults immunized with H. influenzae b, pneumococcal and meningococcal vaccines. Only 7 of 26 (27%) 2-month-olds had an increase in H. influenzae b capsular polysaccharide antibody after a single dose of HbOC, a proportion similar to that of saline controls (9 of 25, 36%). After a second HbOC dose at 4 months 88% had antibody concentrations of 0.15 microgram or more, and after a third dose at 6 months all had antibody levels greater than or equal to 0.15 microgram/ml. The group receiving both HbOC and bacterial polysaccharide immunoglobulin at 2 months uniformly had H. influenzae b CP antibody concentrations of greater than or equal to 0.15 microgram/ml at 4 months (P less than 0.001 relative to "HbOC alone" group) and subsequently responded similarly to second and third doses of HbOC vaccine as did also the "HbOC alone" group. We conclude that combined passive/active immunization with bacterial polysaccharide immunoglobulin and HbOC at 2 months maintains antibody at concentrations thought to be protective (greater than or equal to 0.15 microgram/ml) without interfering with the active antibody response to second and third doses of HbOC at 4 and 6 months of age.

In vitro half-life of 14-C-tryptamine in whole blood of drug-free chronic schizophrenic patients.

The authors found higher in vitro 14C-tryptamine half-lives in the blood of 10 drug-free chronic schizophrenic patients than in the blood of 13 mentally normal control subjects. This finding was negatively correlated for both groups with platelet MAO activity. Repeated determinations of in vitro 14C-tryptamine half-lives over a period of 5 months were positively correlated for the patients, although some blood samples showed statistically significant variability.

Effects of various neuroleptics on rabbit hyperthermia induced by N, N-Dimethyltryptamine (DMT) and d-amphetamine.

The effects of various neuroleptics were studied on N, N-dimethyltryptamine (DMT, 3.2 mg/kg) and d-amphetamine (3.2 mg/kg) induced hyperthermia in the rabbit. Complete dose-effect curves were obtained. The order of potency for antagonism of DMT-induced hyperthermia was: methiothepin greater than octoclothepin greater than or equal to oxyprothepin greater than perathiepin greater than dokloxythepin greater than mianserine greater than loxapine greater than oxypertine greater than chlorpromazine greater than pipamperone greater than fluphenazine greater than thiothixene greater than haloperidol greater than molindone. The order of potency for antagonism of d-amphetamine hyperthermia was: haloperidol greater than chlorpromazine greater than oxypertine greater than octoclothepin and methiothepin. For these five drugs, the order of potency for antagonism of amphetamine hyperthermia was the reverse of the order for antagonism of DMT hyperthermia. Methiothepin reduced d-amphetamine-induced hyperthermia effectively at a very high dose (0.32 mg/kg) and variably at lower doses. The results indicate that neuroleptics differ markedly in their specificity of antagonism of DMT and d-amphetamine which may act through different neurotransmitter mechanisms (tryptaminergic vs. adrenergic).