Evaluation of genomic factors and early childhood stimulation on intelligence in children from a Brazilian birth cohort: The primary role of independent factors.

BACKGROUND: Childhood cognitive abilities are a predictor of health outcomes and adult income potential. Identifying factors associated with childhood intelligence and their interactions is essential in behavioral research. We assessed the impact of genetic variants and early child stimulation (ECS) on child intelligence and examined their possible interaction as potential modifiers of IQ in a population-based longitudinal study. METHODS: Participants of the 2004 Pelotas Birth Cohort study (N = 4231) underwent intelligent quotient (IQ) by WISC-III assessment at 6 years of age. At 24 and 48-months, mothers answered five ECS marker questions, whose sum was used to create a score. The polygenic score for intelligence (IQ-PGS) was constructed from the GWAS-weighted estimate of cognition. Association was assessed using multiple linear regression models adjusted for maternal, family, and child confounding variables. To explore the possible influence of skin color and ethnoracial classification, the regression models were stratified according to the skin color variable, as a sensitivity analysis. RESULTS: In the adjusted analysis, IQ-PGS (ß = 0.79, 95% confidence interval [95% CI] 0.26;1.31) as well as ECS (ß = 2.34; 95% CI: 1.76;2.92) were associated with IQ in this sample. The association between IQ-PGS and IQ was significant only in the white Brazilian group in the sensitivity analysis. However, there was no interaction between IQ-PGS and ECS on IQ (p(IQ-PGS x ECS) = 0.46). CONCLUSIONS: ECS did not modify the impact of genetic potential on intellectual development during childhood, suggesting that genetic factors and ECS exert independent effects on the IQ levels of children.

Physical Activity and Chronic Stress in Early Life: Findings From the 2015 Pelotas (Brazil) Birth Cohort.

BACKGROUND: The association of physical activity through early childhood on children's chronic stress still is unclear. Therefore, the aim of the present study is to test the association of physical activity through early childhood (1-4 y) with chronic stress, measured by hair cortisol at age 4. METHODS: Longitudinal study including children from the 2015 Pelotas (Brazil) Birth Cohort. Cortisol at age 4 was measured using a hair sample, which provided cortisol concentration from the past months. Physical activity was measured using accelerometers at 1, 2, and 4 years. Linear regression models were used to assess the association between physical activity and chronic stress. Trajectory models were also applied to examine chronic stress in relation to physical activity patterns throughout early childhood. RESULTS: Children with valid physical activity and hair cortisol data were included in the analyses (N = 1475). Three groups of physical activity trajectories between 1 and 4 years were identified: low, medium, and high. No association between physical activity at 1, 2, and 4 years and chronic stress at age 4 was observed. However, children in the "high" physical activity trajectory presented low cortisol concentration; the magnitude of the regression coefficient was slightly larger in girls (ß = -0.125; 95% confidence interval, -0.326 to 0.074) than boys (ß = -0.051; 95% confidence interval, -0.196 to 0.09). CONCLUSION: There was no clear association between physical activity and chronic stress in early childhood. Trajectories models suggest that higher activity throughout early childhood may positively impact chronic stress; however, more studies are needed to confirm that hypothesis.

Second generation of the 1993 birth cohort, Pelotas (Brazil): Aims, design, preliminary results.

BACKGROUND AND AIMS: Longitudinal cohort studies examining different generations can explain how health problems can be transmitted through genetic and environmental mechanisms and their effects on the health of offspring. This study aimed to present the design and to describe the characteristics of the baseline sample of a second generation cohort. METHODS: The 93Cohort-II is a dynamic prospective cohort composed of a second generation from the original 1993 Pelotas Birth Cohort (offspring), whose parents had their last follow-up at 22 years old. Biological parents were asked to answer questions addressing the type of birth, general health status, family composition, dietary habits, breastfeeding habits, and child-caregiver(s), among others, and the children's anthropometric measurements were evaluated. RESULTS: Of 1650 children identified, 1212 were evaluated (response rate, 73.4%), and 21 died before the baseline assessment. The age of the offspring ranged from 0 to 10 years (mean [±SD], 2.9 ± 2.1 years); most children (65.6%) lived with both parents and were born to young mothers and poor families. One-third of the children were breastfed until 6 months of age, one-half were born by cesarean section, 63.9% had used medication in the previous 15 days, 26.4% experienced hospitalization at least once since birth, and 14% had no updated vaccination; asthma/bronchitis (20.4%) and bronchiolitis (13.4%) were the most frequently reported diseases. More than 60% consumed ultra-processed foods, and the prevalence of overweight among those <5 and ≥6 years of age was 10.2% and 18.9%, respectively. The mean total Child Behavior Checklist score was 44.1 ± 23.61 (≥16 months), and the mean intellectual quotient score in children ≥6 years of age was 97.9 ± 15.4. CONCLUSION: Despite the difficulties in conducting intergenerational cohort studies, the results of the present investigation provide evidence supporting the feasibility of performing these types of studies in middle-income countries.

Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles.

Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocyte-lineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.