Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities.

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.

Relationship between insulin and Netrin-1/DCC guidance cue pathway regulation in the prefrontal cortex of rodents exposed to prenatal dietary restriction.

Fetal restriction (FR) alters insulin sensitivity, but it is unknown how the metabolic profile associated with restriction affects development of the dopamine (DA) system and DA-related behaviors. The Netrin-1/DCC guidance cue system participates in maturation of the mesocorticolimbic DA circuitry. Therefore, our objective was to identify if FR modifies Netrin-1/DCC receptor protein expression in the prefrontal cortex (PFC) at birth and mRNA in adulthood in rodent males. We used cultured HEK293 cells to assess if levels of miR-218, microRNA regulator of DCC, are sensitive to insulin. To assess this, pregnant dams were subjected to a 50% FR diet from gestational day 10 until birth. Medial PFC (mPFC) DCC/Netrin-1 protein expression was measured at P0 at baseline and Dcc/Netrin-1 mRNA levels were quantified in adults 15 min after a saline/insulin injection. miR-218 levels in HEK-293 cells were measured in response to insulin exposure. At P0, Netrin-1 levels are downregulated in FR animals in comparison to controls. In adult rodents, insulin administration results in an increase in Dcc mRNA levels in control but not FR rats. In HEK293 cells, there is a positive correlation between insulin concentration and miR-218 levels. Since miR-218 is a Dcc gene expression regulator and our in vitro results show that insulin regulates miR-218 levels, we suggest that FR-induced changes in insulin sensitivity could be affecting Dcc expression via miR-218, impacting DA system maturation and organization. As fetal adversity is linked to nonadaptive behaviors later in life, this may contribute to early identification of vulnerability to chronic diseases associated with fetal adversity.

Thrifty-Eating Behavior Phenotype at the Food Court - Programming Goes Beyond Food Preferences.

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS). Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data. Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples. Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases.

Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis / Deficiência de vitamina D em pacientes pediátricos que fazem uso de fármacos antiepilépticos - revisão sistemática com metanálise

Abstract Objectives: To measure the prevalence of vitamin D deficiency (through the 25-hydroxyvitamin D metabolite) in pediatric patients using antiepileptic drugs. Source of data: Meta-analysis of studies identified through search in the PubMed, Embase, LILACS, and Cochrane Library databases, on February 19, 2019. Summary of data: A total of 748 articles were identified, 29 of which were relevant to the objectives of this study. The prevalence of vitamin D deficiency found was 0.32 (95% CI = 0.25-0.41; I 2 = 92%, p < 0.01). In the subgroup analyses, the most significant results were observed in the group of patients using cytochrome P450-inducing antiepileptic drugs, with a prevalence of 0.33 (95% CI = 0.21-0.47; I 2 = 86%, p < 0.01) and, considering the study design, in the subgroup of cohort studies, with a prevalence of 0.52 (95% CI = 0.40-0.64; I 2 = 76%, p < 0.01). Conclusions: Taking into account the deleterious effects of vitamin D deficiency on the bone health of individuals using antiepileptic drugs, it is suggested to include in their care 25-hydroxyvitamin D monitoring, cholecalciferol supplementation, and treatment of the deficiency, when present.

Resumo Objetivos: Mensurar a prevalência de deficiência de vitamina D (através do metabólito 25-hidroxivitamina D) em pacientes pediátricos em uso de fármacos antiepilépticos. Fonte dos dados: Metanálise de estudos identificados por meio de pesquisa nas bases de dados Pubmed, Embase, LILACS e Cochrane em 19 de fevereiro de 2019. Síntese dos dados: Foram identificados 748 artigos, dos quais 29 mostraram-se relevantes aos objetivos deste estudo. A prevalência de deficiência de vitamina D encontrada foi de 0,32 (IC 95% = 0,25-0,41) (I2 = 92%, p < 0,01). Nas análises por subgrupos, os resultados mais expressivos foram observados no grupo de pacientes em uso de fármacos antiepilépticos indutores do citocromo P450, que apresentou prevalência de 0,33 (IC 95% = 0,21-0,47) (I2 = 86%, p < 0,01). Considerou-se o delineamento dos estudos, no subgrupo de estudos de coorte, com prevalência de 0,52 (IC 95% = 0,40-0,64) (I2 = 76%, p < 0,01). Conclusões: Levando-se em consideração os efeitos deletérios da deficiência de vitamina D na saúde óssea dos sujeitos em uso de fármacos antiepilépticos, sugere-se incluir em seu atendimento, o monitoramento de 25-hidroxivitamina D, suplementação com colecalciferol e tratamento de deficiência quando existente.

Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis.

OBJECTIVES: To measure the prevalence of vitamin D deficiency (through the 25-hydroxyvitamin D metabolite) in pediatric patients using antiepileptic drugs. SOURCE OF DATA: Meta-analysis of studies identified through search in the PubMed, Embase, LILACS, and Cochrane Library databases, on February 19, 2019. SUMMARY OF DATA: A total of 748 articles were identified, 29 of which were relevant to the objectives of this study. The prevalence of vitamin D deficiency found was 0.32 (95% CI=0.25-0.41; I2=92%, p<0.01). In the subgroup analyses, the most significant results were observed in the group of patients using cytochrome P450-inducing antiepileptic drugs, with a prevalence of 0.33 (95% CI=0.21-0.47; I2=86%, p<0.01) and, considering the study design, in the subgroup of cohort studies, with a prevalence of 0.52 (95% CI=0.40-0.64; I2=76%, p<0.01). CONCLUSIONS: Taking into account the deleterious effects of vitamin D deficiency on the bone health of individuals using antiepileptic drugs, it is suggested to include in their care 25-hydroxyvitamin D monitoring, cholecalciferol supplementation, and treatment of the deficiency, when present.

Intrauterine growth restriction increases impulsive behavior and is associated with altered dopamine transmission in both medial prefrontal and orbitofrontal cortex in female rats.

Recent studies have implicated a role for impulsivity in the altered eating behaviors and the increased risk for obesity consistently associated with intrauterine growth restriction (IUGR). Changes in dopamine transmission within prefrontal areas are believed to contribute to these adverse outcomes. Here we investigated the impulsive behavior toward a delayed reward and evaluated dopamine levels and its receptors in the medial prefrontal (mPFC) and orbitofrontal (OFC) cortex of female adult rats exposed to IUGR. From day 10 of pregnancy and until birth, Sprague-Dawley dams received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, all pups were adopted by Adlib mothers, generating the groups Adlib/Adlib (control) and FR/Adlib (intrauterine growth-restricted). Adult impulsive behavior was evaluated using a Tolerance to Delay of Reward Task. In vivo dopamine responses to sweet food intake were measured by voltammetry, and D1, D2 and DAT levels were accessed by Western Blot. Animals from FR group showed a pronounced aversion to delayed rewards. DA response to sweet food was found to be blunted in the mPFC of FR animals, whereas in the OFC, the DA levels appear to be unaffected by reward consumption. Moreover, FR animals presented reduced D1 receptors in the OFC and a later increase in the mPFC D2 levels. These findings suggest that IUGR female rats are more impulsive and that the associated mechanism involves changes in the dopamine signaling in both the mPFC and OFC.

Perceived maternal care is associated with emotional eating in young adults.

INTRODUCTION: Early life adversity, including the perception of poor quality of maternal care, is associated with long-term metabolic and psychosocial consequences. The negative quality of mother/child relationship is associated with emotional overeating in young children, which is defined by eating in response to emotional arousal states such as fear, anger or anxiety. However, it is not known if this association persists through adolescence. Therefore, we aimed at verifying if maternal care during infancy can influence emotional eating in young adults. METHODS: Seventy-five adolescents, residents of Porto Alegre, who participated in the PROTAIA Program (anxiety disorder in childhood and adolescence program), answered the Parental Bonding Instrument (PBI - assessment of perceived maternal care), and the Dutch Eating Behavior Questionnaire (DEBQ). Regression analysis models were built to predict Emotional Eating, a domain of the DEBQ, using maternal care, gender, and anxiety as independent variables. RESULTS: The model was statistically significant when adjusted for potential confounders (r2 = 0.272; p < 0.0001). Emotional eating was significantly predicted by levels of maternal care, anxiety and gender (beta = -0.316; p = 0.006). CONCLUSION: The results demonstrated a negative association between the quality of maternal care and emotional eating in young adults, suggesting that the early environment could be involved on the development of eating disorders or on the differential eating behavior in adolescents with emotional disorders.

Decreased comfort food intake and allostatic load in adolescents carrying the A3669G variant of the glucocorticoid receptor gene.

BACKGROUND: The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. METHODS: One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. RESULTS: Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations, increased insulin sensitivity, and lower anxiety scores. Because of our unbalanced sample sizes (31/37 participants non-G allele carriers/total), our imaging data analysis failed to find whole brain-corrected significant results in between-group t-tests. CONCLUSION: These results highlight that a genetic variation in the GR gene is associated, at the cellular level, with significant reduction in GC sensitivity, which, at cognitive and behavioural levels, translates to altered food intake and emotional stress response. This genetic variant might play a major role in decreasing risk for metabolic and psychiatric diseases.

Alterations in the hypothalamic­pituitary­thyroid axis in animals submitted to early-life trauma

Introduction: Changes in maternal care can affect offspring's thyroid hormone T3 levels. Pups from highly caring mothers have higher levels of thyroid hormone T3. In humans, physical abuse in childhood is related to lower levels of T3 in adolescence. This study aimed at verifying if early-life trauma in rodents is correlated with T3 levels in adulthood. Methods: From the second day of life, litters of Wistar rats were subjected to reduced nesting material (Early­Life Stress-ELS) or standard care (Controls). In adult life, the animals were chronically exposed to standard diet or standard diet + palatable diet and plasma T3 levels were measured before and after the exposition to diet. Results: Thyroid hormone T3 levels in adult life correlated negatively with the licking and grooming (LG) scores in the ELS group. This correlation disappeared when the animals had the opportunity to choose between two diets chronically. Conclusion: The adverse environment affected maternal behavior and caused marks on the metabolism of the intervention group (T3), which were reverted by chronic palatable food consumption (AU)

Interaction between perceived maternal care, anxiety symptoms, and the neurobehavioral response to palatable foods in adolescents.

Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults.

Early life stress is associated with anxiety, increased stress responsivity and preference for "comfort foods" in adult female rats.

Chronic stress increases anxiety and encourages intake of palatable foods as "comfort foods". This effect seems to be mediated by altered function of the hypothalamic-pituitary-adrenal axis. In the current study, litters of Wistar rats were subjected to limited access to nesting material (Early-Life Stress group - ELS) or standard care (Control group) from postnatal day 2 to 9. In adult life, anxiety was assessed using the novelty-suppressed feeding test (NSFT), and acute stress responsivity by measurement of plasma corticosterone and ACTH levels. Preference for palatable foods was monitored by a computerized system (BioDAQ, Research Diets(®)) in rats receiving only regular chow or given the choice of regular and palatable diet for 30 days. ELS-augmented adulthood anxiety in the NSFT (increased latency to eat in a new environment; decreased chow intake upon return to the home cage) and increased corticosterone (but not ACTH) secretion in response to stress. Despite being lighter and consuming less rat chow, ELS animals ate more palatable foods during chronic exposure compared with controls. During preference testing, controls receiving long-term access to palatable diet exhibited reduced preference for the diet relative to controls exposed to regular chow only, whereas ELS rats demonstrated no such reduction in preference after prolonged palatable diet exposure. The increased preference for palatable foods showed by ELS animals may result from a habit of using this type of food to ameliorate anxiety.