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Variability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment.To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years.We conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA).Maternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes).Maternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions.

Background Millions of children fail to meet their developmental potential and experience mental health concerns globally. Evidence is mixed on whether growth beyond the first 1000 d of life influences intellectual functioning and mental health in school-age children. Objectives We examined associations of childhood growth before and after the first 1000 d of life with child intellectual functioning and mental health at age 6-7 y. Methods We used data from a follow-up of a randomized controlled trial of preconception supplementation (PRECONCEPT study) in Vietnam. A total of 5011 women participated in the study and 1579 children were born during 2012-2014. At age 6-7 y, child intellectual functioning was assessed using the Wechsler Intelligence Scale for Children, and mental health concerns were measured using the Strengths and Difficulties Questionnaire. Multivariable linear models were used to examine the independent association of child size at age 2 y [height-for-age z-score (HAZ) and body-mass-index z-score (BMIZ)] and conditional measures of linear and ponderal growth between the ages of 2 and 7 y. Results HAZ at 2 y was positively associated with the Full-Scale Intelligence Quotient (β = 1.4; 95% CI: 0.5, 2.2 points) and its subdomains, namely Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index (β = 1.0-1.4 points). Higher HAZ at 2 y was associated with lower overall mental health concerns (β = -0.24; 95% CI: -0.47, -0.01) and peer problems (β = -0.08; 95% CI: -0.17, -0.01). Faster height gain between 2 and 7 y was associated with higher total intellectual functioning (β = 0.9; 95% CI: 0.02, 1.8) and fewer emotional issues (β = -0.09; 95% CI: -0.18, -0.01). BMIZ at 2 y was not associated with intellectual functioning but was marginally associated with higher conduct and peer problems. Conditional weight gain between 2 and 7 y was not associated with child intellectual functioning or mental health in young school-age children. Conclusions Child linear growth both during and beyond the first 1000 d is positively associated with intellectual functioning and mental health during the early school-age years.

Background Although there is growing evidence on the role of preconception nutrition for birth outcomes, very few studies have evaluated the long-term effects of nutrition interventions during the preconception period on offspring cognitive outcomes. Objective We evaluate the impact of preconception weekly multiple micronutrients (MMs) or iron and folic acid (IFA) supplementation compared with folic acid (FA) alone on offspring intellectual functioning at age 6-7 y. Methods We followed 1599 offspring born to women who participated in a double-blinded randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements containing either 2800 μg FA only, 60 mg iron and 2800 μg FA, or MMs (15 micronutrients including IFA) from baseline until conception, followed by daily prenatal IFA supplements until delivery. We used the Wechsler Intelligence Scale for Children to measure full-scale IQ (FSIQ) and 4 related domains of intellectual functioning [Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores] at 6-7 y. Group comparisons were done using ANOVA tests for all children and the subgroup born to women who consumed the supplements ≥26 wk before conception (per-protocol analyses). Results The final sample with data at 6-7 y (n = 1321) was similar for baseline maternal and offspring birth characteristics and age at follow-up by treatment group. Compared with the offspring in the FA group, those in the MM group had higher FSIQ (β = 1.7; 95% CI: 0.1, 3.3), WMI (β = 1.7; 95% CI: 0.2, 3.2), and PSI (β = 2.5; 95% CI: 0.9, 4.1). Similar findings were observed in the per-protocol analyses. There were no significant differences by treatment group for VCI and PRI. Conclusions Preconception supplementation with MMs improved certain domains of intellectual functioning at age 6-7 y compared with FA. These findings suggest the potential for preconception micronutrient interventions to have long-term benefits for offspring cognition.

Nationally, school-based mental health (SBMH) is seen as an avenue to increase access to children’s mental health services and promote mental health awareness. The current article describes the imp...

Background:The Institute of Nutrition of Central America and Panama (INCAP) Longitudinal Study provides a unique opportunity to examine the role of nutrition in cognitive functioning over time, controlling for other sociocultural factors.Objective:This article describes results of analyses carried out in the INCAP Longitudinal Study on relationships between early childhood nutritional status and supplementation with concurrent and subsequent cognitive development in childhood and adolescence/young adulthood.Methods:Articles were chosen for review that addressed this topic from the original and 1988 follow-up studies; 41 articles were reviewed and key results summarized for relationships between early nutrition and cognition in infancy, early childhood, and adolescence/young adulthood.Results:Overall, results suggest strong relationships between indicators of a child’s early nutritional status and motor and cognitive development in infancy and through the preschool years, continuing into adolescence/young adulthood, particularly for males. Nutritional supplementation during gestation through 2 years of age was associated with improvements in motor development and small, but consistent improvements in cognitive development during infancy and preschool years, with similar results of greater magnitude found with cognitive functioning in adolescence and young adulthood. Findings remain strong after controlling for various sociocultural factors (eg, socioeconomic status [SES]) and schooling. Among adolescents, significant interactions were found with SES and years of school attained; differences in performance favored Atole over Fresco children, with greatest differences for participants of low SES and those with higher levels of schooling.Conclusions:Results support the need for programs to address unmet nutritional requirements among at-risk mothers and children and potential beneficial effects for human cognitive development.

Background Little is known about associations of psychological and mental well-being with cognitive and socioemotional factors in low and middle-income countries, particularly among vulnerable populations born in adverse environments that may restrict developmental potential. This study aimed to examine the cognitive and socioemotional correlates of psychological well-being and mental health in a cohort of Guatemalan adults born in contexts of poverty and malnutrition. Methods From Dec 2017 to Apr 2019, data were collected from 704 women and 564 men ages 40–57 years living in four rural villages in eastern Guatemala and Guatemala City. We measured latent domains of psychological well-being, spirituality and religion, emotional support, and executive function using Confirmatory Factor Analysis (CFA). Under a Structural Equation Modeling framework, we examined intercorrelations among latent domains and observed measures of intelligence and mental health. Results CFA supported the construct validity of factor structures in this population. Correlations of psychological well-being with spirituality and religion were moderate in women (r = 0.68, p r = 0.70, p r = 0.23, p r = 0.34, and r = 0.15, respectively; p r = 0.35, and r = 0.25, respectively; p r = 0.09, p r = 0.18, p r = 0.09, p r = 0.32 and r = 0.35, in women and men respectively; p Conclusions Of all examined factors, spirituality and religion made the greatest contribution to psychological well-being. These findings support the notion that in populations experiencing difficult circumstances, religion can perhaps make a greater contribution to well-being and aid coping. More research is needed to examine mediators of this association.

The prevalence of mental health concerns is growing worldwide, along with lack of access to and receipt of needed treatment. Current gaps in treatment provision have led to exploring alternative methods of prevention, with research linking nutrition and mental health, of particular relevance in low- and middle-income countries, with a high prevalence of undernutrition.To examine whether exposure to a protein-energy nutritional supplement during the first 1000 d of life decreased odds of mental distress in adulthood among men and women in Guatemala compared with receiving a low energy-no protein supplement or supplementation outside the 1000-d window.Data from participants (n = 1249) in a longitudinal cohort protein-energy supplementation trial (early-life, supplementation data from 1969 to 1977, ages 0-7 y; life course, outcome data from 2017-2018 follow-up, ages 40-57 y) were analyzed for associations between nutrition in the first 1000 d and mental distress in adulthood (WHO Self-Reporting Questionnaire 20 [SRQ-20]), controlling for early-life variables and current life stress; life course variables (e.g. education) were examined as potential mediators of this relation. Generalized linear mixed models and zero-inflated Poisson generalized linear mixed models were utilized.Both partial and full supplementation with Atole during the first 1000 d were associated with 63% (95% CI: 0.16, 0.87) and 56% (95% CI: 0.19, 1.03) lower odds, respectively, of experiencing mental distress in adulthood. Results did not differ by sex. These inverse relations remained relatively unchanged (partial OR = 0.34 [95% CI: 0.14, 0.83]; full OR = 0.38 [95% CI: 0.16, 0.92]) after controlling for early-life and life course variables, including life stress.Protein-energy supplementation during the first 1000 d of life in Guatemala, where undernutrition is prevalent, may reduce the prevalence of later mental distress in adulthood. This effect appears to occur directly, rather than indirectly, through pathways of life course variables such as education, wealth, and marital status.

Objective We study how life course objective socioeconomic position (SEP) predicts subjective social status (SSS) and the extent to which SSS mediates the association of objective SEP with nutritional status and mental health outcomes. Methods We use data from participants of the INCAP Longitudinal Study 1969–2018 (n = 1258) from Guatemala. We use the MacArthur ladder for two measures of SSS - perceived community respect and perceived economic status. We estimate the association of SSS with health outcomes after adjusting for early life characteristics and life course objective SEP (wealth, schooling, employment) using linear regression. We use path analysis to study the extent of mediation by SSS on the health outcomes of body mass index (BMI; kg/m2), psychological distress (using the WHO Self-Reported Questionnaire; SRQ-20) and happiness, using the Subjective Happiness Scale (SHS). Results Median participant rating was 5 [IQR: 3–8] for the perceived community respect and 3 [IQR: 1–5] for the perceived economic status, with no differences by sex. Objective SEP in early life and adulthood were predictive of both measures of SSS in middle adulthood as well as health outcomes (BMI, SRQ-20 and SHS). Perceived community respect (z-scores; 1 z = 3.1 units) was positively associated with happiness (0.13, 95 % CI: 0.07, 0.19). Perceived economic status (z-scores; 1 z = 2.3 units) was inversely associated with psychological distress (−0.28, 95 % CI: −0.47, −0.09). Neither measure of SSS was associated with BMI. Neither perceived community respect nor perceived economic status attenuated associations of objective SEP with health outcomes on inclusion as a mediator. Conclusions Subjective social status was independently associated with happiness and psychological distress in middle adulthood after adjusting for objective SEP. Moreover, association of objective SEP with health was not mediated by SSS, suggesting potentially independent pathways., Highlights • Subjective social status (SSS) is a self-appraisal of one's objective measures of socio-economic position (SEP; such as education and wealth) and social identity relative to their community. • Perceived community respect and perceived economic status were positively associated with happiness and inversely associated with psychological distress respectively. • Neither measure of SSS were associated with body mass index. • The associations of objective SEP measures with health outcomes were not attenuated after adjusting for SSS, suggesting independent pathways.

Rationale Early-life nutrition interventions in low and middle-income countries have demonstrated long-term benefits on cognitive skills, however, their influence on socioemotional outcomes has not been fully explored. Moreover, the mediating processes through which nutrition intervention effects operate and are maintained over time are understudied. Methods We followed-up a cohort of Guatemalan adults who participated as children in a community randomized food-supplementation trial. We examined associations of exposure to nutritional supplementation from conception to age 2 years with executive function (measured using three sub-tests of the NIH Toolbox Cognition Battery) and psychological well-being (measured using two sub-scales of the NIH Toolbox Emotion Battery) at ages 40–57 years (n = 1268). We used structural equation modeling to investigate the mediating role of psychosocial stimulation (measured in childhood using parent reports and ratings of home environments), cognitive ability (measured at ages 26–42 years using standardized tests), and executive function on the association of early-life exposure to nutritional supplementation with adult psychological well-being (n = 1640). Results We found positive but inconsistent associations of nutritional supplementation in childhood with executive function and psychological well-being in adulthood. Psychosocial stimulation, cognitive ability, and executive function did not mediate the association of early-life nutritional supplementation with adult psychological well-being. We found strong and positive associations of psychosocial stimulation in childhood with cognitive ability, executive function, and psychological well-being in adulthood. Moreover, we observed no interaction of exposure to nutritional supplementation and psychosocial stimulation in childhood with cognitive and psychological well-being outcomes in adulthood. Conclusion Our findings suggest that childhood nutrition interventions have long-lasting effects on cognitive ability and psychological well-being outcomes., Highlights • We assess the influence of early-life nutrition on neurodevelopmental outcomes. • We use a theoretical approach to examine mediators of the association. • We found no mediators of the association of early-life nutrition with adult psychological well-being. • Psychosocial stimulation is strongly associated with neurodevelopmental outcomes. • Improved child nutrition is positively associated with adult psychological well-being.

Background: Maternal health and nutrition play a crucial role in early child growth and development. However, little is known about the benefits of preconception micronutrient interventions beyond the role of folic acid (FA) and neural tube defects.Objective: We evaluated the impact of weekly preconception multiple micronutrient (MM) or iron and folic acid (IFA) supplementation on child growth and development through the age of 2 y compared with FA alone.Methods: We followed 1599 offspring born to women who participated in a randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements that contained either 2800 μg FA, 60 mg Fe and 2800 μg FA, or 15 MMs including IFA, from baseline until conception followed by daily prenatal IFA supplements until delivery. Child anthropometry was measured at birth and at 3, 6, 12, 18, and 24 mo. Child development was measured with the use of the Bayley Scales for Infant Development III at 24 mo.Results: The groups were similar for baseline maternal and offspring birth characteristics. At 24 mo of age, the offspring in the IFA group had significantly higher length-for-age z scores (LAZs) (0.14; 95% CI: 0.03, 0.26), reduced risk of being stunted (0.87; 95% CI: 0.76, 0.99), and smaller yearly decline in LAZs (0.10; 95% CI: 0.04, 0.15) than the offspring in the FA group. Similar trends were found for the offspring in the MM group compared with the FA group for LAZs (0.10; 95% CI: -0.02, 0.22) and the risk of being stunted (0.88; 95% CI: 0.77, 1.01). Offspring in the IFA group had improved motor development (P = 0.03), especially fine motor development (0.41; 95% CI: 0.05, 0.77), at the age of 24 mo, but there were no differences for measures of cognition or language.Conclusions: Preconception supplementation with IFA improved linear growth and fine motor development at 2 y of age compared with FA. Future studies should examine whether these effects persist and improve child health and schooling. The trial was registered at clinicaltrials.gov as NCT01665378.

Measuring executive function (EF) among adults is important, as the cognitive processes involved in EF are critical to academic achievement, job success and mental health. Current evidence on measurement and structure of EF largely come from Western, Educated, Industrialized, Rich and Democratic (WEIRD) countries. However, measuring EF in low-and-middle-income countries (LMICs) is challenging, because of the dearth of EF measures validated across LMICs, particularly measures that do not require extensive training, expensive equipment, or professional administration. This paper uses data from three LMIC cohorts to test the feasibility, validity and reliability of EF assessment in adults using three sub-tests (representing key components of EF) of the NIH Toolbox Cognitive battery. For each cohort, all three EF measures (inhibition, flexibility and working memory) loaded well onto a unidimensional latent factor of EF. Factor scores related well to measures of fluid intelligence, processing speed and schooling. All measures showed good test-retest reliability across countries. This study provides evidence for a set of sound measures of EF that could be used across different cultural, language and socio-economic backgrounds in future LMIC research. Furthermore, our findings extend conclusions on the structure of EF beyond those drawn from WEIRD countries.

ObjectivesFew studies have used longitudinal data to study the development of cognition over the life course in low-income and middle-income countries. The objectives of this study were to assess predictors of cognitive development trajectories from 6 months through 7 years, and if these trajectories predicted adult cognitive function in a birth cohort from Guatemala.DesignWe analysed data from the INCAP Nutrition Supplementation Trial Longitudinal Study in Guatemala. Cognition was assessed at eight different time points between 6 months and 7 years. We derived childhood development trajectories using latent class growth analysis. We assessed predictors of the trajectories using ordinal logistic regression, and associations between childhood trajectories and adult non-verbal intelligence and literacy at age 18–52 years (mean±SD =42.7±6.4 years) using mixed models.SettingThe study was conducted in four Guatemalan villages.ParticipantsThe study included 927 participants from Guatemala with repeated measurements of cognitive function during the first 7 years of life.ResultsWe identified three trajectories of cognitive development (high: n=214, average: n=583, low: n=130). Participants whose mothers were taller (proportional log odds (PO)=0.03, 95% CI=0.01 to 0.06), had more years of schooling (PO=0.15, 95% CI=0.06 to 0.25), or lived in households with higher socioeconomic scores (PO=0.19, 95% CI=0.09 to 0.29) were more likely to follow higher trajectories. Childhood trajectories predicted adult non-verbal intelligence (high=18.4±0.3, average=14.6±0.53, low=11.4±0.9) and literacy (high=63.8±2.0, average=48.6±1.2, low=33.9± 2.6) scores.ConclusionsIn this sample from Guatemala, cognitive development trajectories from 6 months through 7 years were associated with adult non-verbal intelligence and literacy. These findings provide evidence of tracking of cognition over time in a transitioning low-income setting.

Docosahexanoic acid (DHA) is an important constituent of the brain. Evidence from well-designed intervention trials of the long-term benefits of increasing DHA intake during pregnancy has been sparse.We evaluated global cognition, behavior, and attention at age 5 y in the offspring of Mexican women who participated in a randomized controlled trial of prenatal DHA supplementation.A total of 1094 women were randomly assigned to receive 400 mg of either DHA or placebo/d from 18 to 22 wk of pregnancy until delivery. We assessed cognitive development and behavioral and executive functioning, including attention, in 797 offspring at age 5 y (82% of 973 live births) with the use of the McCarthy Scales of Children's Abilities (MSCA), the parental scale of the Behavioral Assessment System for Children, Second Edition (BASC-2), and the Conners' Kiddie Continuous Performance Test (K-CPT). We compared the groups on raw scores, T-scores, and standardized scores, as appropriate. We examined heterogeneity by the quality of the home environment, maternal intelligence, and socioeconomic status.There were no group differences for MSCA scores (P0.05), but the positive effect of the home environment at 12 mo on general cognitive abilities was attenuated in the DHA group compared with in the placebo group (P-interaction0.05). There were no differences between groups on the BASC-2. On the K-CPT, offspring in the DHA group showed improved mean ± SD T-scores compared with those of the placebo group for omissions (DHA: 47.6 ± 10.3; placebo: 49.6 ± 11.2; P0.01) with no differences (P0.05) for the other K-CPT scores or of the proportion who were clinically at risk of attention deficit hyperactivity disorders after Bonferroni correction for multiple comparisons.Prenatal exposure to DHA may contribute to improved sustained attention in preschool children. This trial was registered at clinicaltrials.gov as NCT00646360.

Background and objectives: Initiation and adherence are both critical challenges for micronutrient supplementation programs, especially during the preconceptional period. This study examines factors influencing initiation of supplement use and continued adherence among women participating in PRECONCEPT, a double-blind randomized controlled trial of preconception micronutrient supplementation. Methods: In-depth interviews were conducted with 39 participants during different periods (prepregnancy [n = 15], pregnancy [n = 8], postpartum [n = 8], and dropouts [n = 8]). We examined participants’ knowledge about nutritional needs and micronutrient deficiencies, individual experience with nutritional supplements, and perceived benefits and side effects of supplements. Four focus groups were conducted with 24 village health workers (VHWs) to collect information on VHWs’ perceptions of factors influencing participants’ adherence and logistics of supplement distribution. Influences on initiation and adherence were examined within the Health Belief Model framework. Results: Primary barriers to initiation of supplement use were low perceptions of severity of nutrient deficiencies and personal susceptibility. These are associated with low knowledge and awareness around deficiencies. Perceived seriousness and susceptibility varied by nutrient: high for iron during pregnancy but low for all other micronutrient deficiencies, including iron outside pregnancy. Continued maintained adherence to an initiated regimen was influenced by the woman’s perceptions of the health benefits of, and barriers to, regular supplement use. Conclusion: Initiation of supplement use was influenced by perceived susceptibility and severity of nutrient deficiencies, while maintained adherence to consistent use was influenced by perceived benefits and barriers. Recognizing the influences on each stage may help improve adherence and maximize positive effects of future interventions.

OBJECTIVES: While there is growing evidence on the role of preconception nutrition for birth outcomes, very few studies have evaluated the effects of nutrition interventions during the preconception period on child development. This study evaluates the impact of preconception weekly multiple micronutrients (MM) or iron and folic acid (IFA) supplementation compared to FA alone on child growth and development at age 6–7y. METHODS: We followed 1599 offspring born to women who participated in a randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements containing either 2800 μg FA only, 60 mg iron and 2800 μg FA, or MM (15 micronutrients including IFA), from baseline until conception; followed by daily prenatal IFA supplements until delivery. Child anthropometry and development were measured at 6–7y. Child development was measured using the Wechsler Intelligence Scale for Children IV®. Group comparisons were done using ANOVA or chi-square tests for both intention-to-treat (ITT) and per-protocol analyses (PP, women consumed supplements ≥26 wk before conception). RESULTS: The groups were similar for baseline maternal and offspring birth characteristics and age at follow-up. We found significant differences (P

This chapter deals with the interface between Syntax and Pragmatics by examining argument fronting in Old Irish non-poetic Glosses. Relying on lexical and contextual indicators of discourse function, three Information Structure patterns can be identified: aboutness topic; contrastive topic; and focus. Aboutness and contrastive topic are often resumed and do not mark relativization on the verb, suggesting that they are left dislocation structures. Focus is most commonly expressed through clefts, although clefts in Old Irish can be morphologically opaque. Modern Irish has all these structures besides a non-clefted focus structure, which is likely derived from interpreting morphologically opaque clefts as topicalization. In sum, this paper argues that Old Irish has a set of productive argument fronting positions with distinct and conventional information structural properties that can be analysed in terms of an articulated left periphery, and that these fronting positions are the direct ancestors of fronting positions in Modern Irish.

Background Prenatal exposure to environmental pollutants such as mold, lead, pesticides, tobacco, and air pollutants has been suggested to impair cognitive development. Evidence is needed from longitudinal studies to understand their joint impact on child development across time. Objective To study associations between exposure to indoor environmental pollutants or outdoor air pollution during pregnancy and offspring cognitive development trajectories through 7 years. Methods We included 718 Mexican mother-child pairs. Prenatal exposure to indoor environmental pollutants (mold, ventilation, pesticides, tobacco smoke, and use of vidiartred clay pots) was self-reported by the mothers and integrated into an index, or objectively measured in the case of outdoor air pollutants (nitrogen oxides, benzene, toluene, and xylene). Child global cognitive development was measured at 12, 18, 60, or 84 months. Using Latent Class Growth Analysis, we identified three developmental trajectories (positive = 108, average = 362, low = 248). We used multinomial logistic models to test associations between environmental pollutant score (EPS) or outdoor air pollutants, and cognitive development trajectories. Results After adjustment for sociodemographic covariates, EPS was associated with the average (OR = 1.26 95%CI = 1.01, 1.55) and low (OR = 1.41 95%CI = 1.11, 1.79) trajectories compared to positive; where a unit increase in EPS means an additional prenatal exposure to a pollutant. There was no association between outdoor air pollutants and cognitive development trajectories. Conclusion Children of women who reported higher exposure to indoor environmental pollutants during pregnancy were more likely to follow worse developmental trajectories through 7 years. These results support the development and testing of interventions to reduce exposure to environmental pollutants during pregnancy and early childhood as a potential strategy to improve long-term cognitive development.

The neuroimaging techniques available to observe ongoing brain activity during human cognition include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), event-related potentials (ERPs), magnetoencephalography (MEG) and event-related optical signaling (EROS). Additionally, brain activity can be disrupted temporarily via transcranial magnetic stimulation (TMS). Using these neuroimaging methods, both spatial and temporal precision are attainable in describing the underlying neural substrates that comprise human cognition. Great progress has been made in understanding the physiological basis of human thought with many exciting new frontiers opening up including understanding the genetics of human cognition and the neural basis of consciousness. Keywords: functional brain mapping; functional magnetic resonance imaging; positron emission tomography; haemodynamic response; cognitive neuroscience

Summary Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course.

Early childhood development plays a key role in a child's future health, educational success, and economic status. However, suboptimal early development remains a global challenge. This study examines the influences of quality of the home learning environment (HOME) and child stunting in the first year of life on child development. We used data collected from a randomized controlled trial of preconceptional micronutrient supplementation in Vietnam (n = 1,458). The Bayley Scales of Infant Development‐III were used to assess cognition, language, and motor development domains at 2 years. At 1 year, 14% of children were stunted, and 15%, 58%, and 28% of children lived in poor, medium, and high HOME environments, respectively. In multivariate generalized linear regression models, living in a high HOME environment was significantly associated with higher scores (0.10 to 0.13 SD) in each of the developmental domains. Stunted children scored significantly lower for cognitive, language, and motor development (−0.11 to −0.18), compared to nonstunted children. The negative associations between stunting on development were modified by HOME; the associations were strong among children living in homes with a poor learning environment whereas they were nonsignificant for those living in high‐quality learning environments. In conclusion, child stunting the first year of life was negatively associated with child development at 2 years among children in Vietnam, but a high‐quality HOME appeared to attenuate these associations. Early interventions aimed at improving early child growth as well as providing a stimulating home environment are critical to ensure optimal child development.

Mental health problems in women and children represent a significant public health problem worldwide, especially in developing countries. The role of nutrition as a cost-effective approach in the prevention and management of these conditions has received recent attention, particularly nutrients such as iron, zinc, and n–3 (omega-3) fatty acids, which play a role in brain structure and function. The objective of this article was to review current evidence on the relation between n–3 fatty acids, especially docosahexaenoic acid (DHA), and maternal and child mental health disorders. Human studies published in English were identified from Medline databases (1966 to June 2008) by using key search terms and review articles. A summary of the role of DHA in the human brain is followed by a review of human studies, both observational and intervention trials, that examine the relation between n–3 fatty acids such as DHA and depression and child mental health disorders. Observational studies support a direct association between poor n–3 fatty acid status and increased risk of maternal depression and childhood behavioral disorders such as attention-deficit hyperactivity disorder (ADHD). However, evidence from intervention trials is weak. Most of the studies reviewed had small sample sizes and were conducted in clinically diagnosed samples, with no placebo-controlled groups. Little is known about the benefits of DHA in the prevention of maternal depression and ADHD. Large, well-designed, community-based prevention trials are needed.

Promotion of optimal growth while preventing the emergence of obesity in childhood requires an understanding of the dynamics over time of linear growth and weight for height. To assess long-term secular trends in height-for-age and BMI for age in children 1.00 was 21.1% in 1968 and 19.6% in 2005-7 (P > 0.05); for BMI 0.05). There have been long-term improvements in child growth, as measured by HAZ, without concurrent increases in BMI over successive generations of children.

Objective: To test the contribution of maternal depression during late infancy to physical activity in children 5 years later. Method: Children (n = 168) from very low-income households in semiurban Mexico were assessed as toddlers (15 months, Time 1) and at pre-school age (4- 6 years, Time 2). Child low activity level (

OBJECTIVE. Our goal was to assess the impact of “Baby-Friendly” hospital practices and other maternity-care practices experienced by mothers on breastfeeding duration. METHODS. This analysis of the Infant Feeding Practices Study II focused on mothers who initiated breastfeeding and intended prenatally to breastfeed for >2 months, with complete data on all variables (n = 1907). Predictor variables included indicators of 6 “Baby-Friendly” practices (breastfeeding initiation within 1 hour of birth, giving only breast milk, rooming in, breastfeeding on demand, no pacifiers, fostering breastfeeding support groups) along with several other maternity-care practices. The main outcome measure was breastfeeding termination before 6 weeks. RESULTS. Only 8.1% of the mothers experienced all 6 “Baby-Friendly” practices. The practices most consistently associated with breastfeeding beyond 6 weeks were initiation within 1 hour of birth, giving only breast milk, and not using pacifiers. Bringing the infant to the room for feeding at night if not rooming in and not giving pain medications to the mother during delivery were also protective against early breastfeeding termination. Compared with the mothers who experienced all 6 “Baby-Friendly” practices, mothers who experienced none were ∼13 times more likely to stop breastfeeding early. Additional practices decreased the risk for early termination. CONCLUSIONS. Increased “Baby-Friendly” hospital practices, along with several other maternity-care practices, improve the chances of breastfeeding beyond 6 weeks. The need to work with hospitals to implement these practices continues to exist, as illustrated by the small proportion of mothers who reported experiencing all 6 of the “Baby-Friendly” hospital practices measured in this study.

Attempts to understand determinants of anemia and iron deficiency have led researchers to examine the role of Helicobacter pylori infection. The current study assessed determinants of anemia and iron deficiency, including H. pylori, in Alaska Native children.In 1999, a population-based survey was conducted among 86 children (67% response rate), mean age of 43.7 months (standard deviation = 16.8 months). Samples of breath, stool, and venous blood were obtained from children for measures of anemia, iron deficiency, H. pylori, fecal blood loss, and current inflammation. Standardized interviews with parents provided information on demographics, illness, and intake of dietary iron, iron-absorption inhibitors, and enhancers.Of the 86 children studied, 17.4% were anemic and 38.6% were iron deficient. Forty-one percent of the cohort had H. pylori-specific IgG antibodies, 86% tested positive by the urea breath test (UBT), and 80% tested positive by the stool antigen test. Presence of H. pylori antibodies emerged as a significant risk factor for anemia and iron deficiency in adjusted analyses controlling for demographic factors, current inflammation, and antibiotic use. In contrast, children with positive UBT or stool antigen results were significantly less likely to have anemia or iron deficiency than those with negative results.Results from different measures of H. pylori may reflect different stages of infection. Relationships between H. pylori and anemia/iron deficiency may depend on the phase of infection measured, with serologic tests reflecting established H. pylori infection associated with anemia/iron deficiency, and UBT and stool antigen results reflecting an earlier stage of infection.

Micronutrient malnutrition has been associated with maternal depressive symptoms (MDS), but little is known about the effects of pre-conceptual micronutrient supplementation. We examined the effects of pre-conceptual micronutrient supplementation on MDS during pregnancy and postpartum using data from a double-blind controlled trial (PRECONCEPT) in which 5011 Vietnamese women were randomized to receive weekly supplements containing either a) multiple micronutrients MM b) iron and folic acid IFA or c) folic acid FA until conception, followed by daily IFA supplements through delivery. Maternal depression was assessed using CES-D at baseline and 12 m post-partum and the EPDS during pregnancy and 3 m postpartum. The proportion of women ever experiencing elevated MDS during pregnancy (n=1616), postpartum (n= 1465) was 17.8% and 5.4%, respectively. No significant differences were seen by treatment. Among women at risk for depression at baseline (CES > 10; n=157), 29.1 and 30.1% experiencing elevated MDS during p...

Gene therapy for dominant-negative disorders presents a more difficult challenge than gene therapy for recessive disorders, since even partial replacement of a protein for a recessive disorder can reverse symptoms. Osteogenesis imperfecta (OI) has frequently served as a model disorder for dominant-negative defects of structural proteins. The disease is caused by mutations in type I collagen (COL1A1), the major structural component of bone, skin and other connective tissues. The severity of the phenotype is largely dependent on the ratio of normal to mutant type I procollagen synthesized by cells. Recently, attempts have been made to develop strategies for cell and gene therapies using the adult stem cells from bone marrow referred to as mesenchymal stem cells or marrow stromal cells (MSCs). In this study, we used MSCs from a patient with type III OI who was heterozygous for an IVS 41A+4C mutation in COL1A1. A hybrid genomic / cDNA construct of COL1A1 was transfected into the MSCs and the transfectants were expanded over a 200-fold. Transfected MSCs showed increased expression of the wild-type mRNA and protein. In vitro assays demonstrated that the transfected cells more efficiently differentiated into mineralizing cells. The results indicated that it is possible to overexpress COL1A1 cDNA in OI MSCs and thereby to correct partially the dominant-negative protein defect.

Expression of telomerase activity presumably is involved in maintaining self-replication and the undifferentiated state of stem cells. Adult mouse bone marrow mesenchymal stem cells (mMSCs) are multipotential cells capable of differentiating into a variety of lineage cell types, including adipocytes and chondrocytes. Here we show that the lacking telomerase of mMSC lose multipotency and the capacity to differentiate. Primary cultures of mMSCs were obtained from both telomerase knockout (mTR−/−) and wild-type (WT) mice. The MSCs isolated from mTR−/− mice failed to differentiate into adipocytes and chondrocytes, even at early passages, whereas WT MSCs were capable of differentiation. Consistent with other cell types, late passages mTR−/−MSCs underwent senescence and were accompanied by telomere loss and chromosomal end-to-end fusions. These results suggest that in addition to its known role in cell replication, telomerase is required for differentiation of mMSCs in vitro. This work may be significant for further potentiating adult stem cells for use in tissue engineering and gene therapy and for understanding the significance of telomerase expression in the process of cell differentiation.

Background: In the United States, since a substantial percentage of mothers are not breastfeeding, research is needed to assess important influences on breastfeeding. The current study assessed the impact on breastfeeding of the perceived attitudes of health care providers about infant feeding. Methods: A longitudinal mail survey (1993–1994) was administered to 1620 women prenatally through 12 months postpartum; the current study focused on the prenatal and neonatal periods (66% response rate). The outcome variable was failure to breastfeed beyond 6 weeks. Predictor variables were the mother's perceptions of her prenatal physician's and hospital staff's attitudes on infant feeding. Analysis controlled for mother's prenatal breastfeeding intentions, father's feeding preference, and demographic and psychosocial variables. Results: Forty-one percent of the mothers were not breastfeeding at 6 weeks postpartum. Substantial percentages of mothers reported that physicians and hospital staff expressed a preference for breastfeeding (38% and 57%, respectively), or expressed no preference (61% and 42%, respectively), whereas few favored formula feeding. Adjusted analyses indicated that “no preference” by hospital staff was a significant risk factor for failure to breastfeed beyond 6 weeks. “No preference” by physicians did not significantly influence breastfeeding outcome in these analyses. Further analyses indicated that the effects of perceived hospital staff attitudes were only present for mothers who intended prenatally to breastfeed for 2 months or less. Conclusions: Many women did not report receiving positive breastfeeding messages from their health caregivers and hospital staff. A perceived neutral attitude from the hospital staff is related to not breastfeeding beyond 6 weeks, especially among mothers who prenatally intended to breastfeed for only a short time. (BIRTH 30:2 June 2003)

In comparison to explicit learning, implicit learning is hypothesized to be a phylogenetically older form of learning that is important in early developmental processes (e.g., natural language acquisition, socialization)and relatively impervious to individual differences in age and IQ. We examined implicit learning in a group of children and adults (9.49 years of age)with Williams syndrome (WS)and in a comparison group of typically developing individuals matched for chronological age. Participants were tested in an artificial-grammar learning paradigm and in a rotor-pursuit task. For both groups, implicit learning was largely independent of age. Both groups showed evidence of implicit learning but the comparison group outperformed the WS group on both tasks. Performance advantages for the comparison group were no longer significant when group differences in working memory or nonverbal intelligence were held constant.

Objective We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age. Design Randomized placebo double-blind controlled trial. Settings Cuernavaca, Mexico. Participants and Methods We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment. Interventions or Main Exposures 400 mg/day of algal DHA. Outcome Measures Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores. Results Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation. Conclusions Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments. Trial Registration Clinicaltrials.gov NCT00646360

Objective To determine the relative validity of three food frequency questionnaires (FFQs) compared with results from 24-hour dietary recalls for measuring dietary intakes in Guatemalan schoolchildren. Design A cross-sectional study of primary caregivers (mothers or grandmothers) of 6–11 year-old children. Caregivers completed one of three constructed FFQs to measure the child’s dietary consumption in the last week: FFQ1 did not incorporate portion sizes; FFQ2 provided portion sizes; and FFQ3 incorporated pictures of median portion sizes. During the same week, each caregiver also completed three 24-hour dietary recalls. Results from the FFQ were compared with corresponding results from the 24-hour dietary recalls. Setting Santa Catarina Pinula, peri-urban Guatemala City. Subjects Caregivers (n = 145) of 6–11 year-old children: 46 completed FFQ1, 49 completed FFQ2, and 50 completed FFQ3. Results The mean values for all nutrients obtained from the 24-hour dietary recall were lower than for those obtained from the FFQs, excluding folic acid in FFQ3, cholesterol and zinc in FFQ2, and cholesterol, folic acid, magnesium, potassium, sodium, and zinc in FFQ1. Energy-adjusted Pearson correlation coefficients ranged from 0.07 (protein) to 0.54 (cholesterol) for FFQ1 and from 0.05 to 0.74 for FFQ2 and FFQ3. Agreement by both methods (FFQ and 24-hour dietary recalls) of classifying children into the same or adjacent quartiles of energy-adjusted nutrient consumption ranged from 62.0% for cholesterol to 95.9% for vitamin B12 across all three FFQs. Conclusions Our FFQs had moderate to good relative validity in measuring energy and nutrient intakes for 6–11 year-old Guatemalan children. More evidence is needed to evaluate their reproducibility and applicability in similar populations.

Using a set of natural coiled-coil proteins as models, a series of recombinant proteins were designed and expressed in E. coli. These proteins contain a consensus coiled-coil sequence as a framework into which were incorporated positively or negatively charged residues at selected positions. A mixed-site genetic strategy was used to generate DNA fragments encoding over 4,000 different combinations of charged residues within the coiled-coil motif. A subset of these genes was used to produce recombinant coiled-coil proteins with well-defined variations in charge pattern and composition. Variants of each sequence containing a unique cysteine at the C-terminus were oxidized to the disulfide-linked dimer, and characterization of their physical properties support the proposed parallel orientation of protein chains. In all cases, equilibrium populations of dimeric and tetrameric structures were observed under physiological conditions, with dimer-to-tetramer dissociation constants in the range of 50-190 riM. Significant differences in complex stability were seen with different charge patterns. Contrary to expectations, no linear relationship was observed between net ionic interaction and any measure of complex stability, arguing that a more subtle set of rules governs these interactions. This work has revealed two important aspects of coiled-coil interactions: the observed relationship between charge interactions and complex stability shows considerable nonlinearity, and the presence of higher order interactions in coiled-coil motifs may be more widespread than is currently suspected. The relationships described here have broad relevance, especially in the areas of protein folding, protein-based materials design, antibody-antigen and receptor-ligand interactions, and rational drug design.

BackgroundThe associations among dietary zinc intakes and biomarkers of zinc status are unknown in apparently healthy children at high risk for zinc deficiency.ObjectiveTo assess associations among zinc-related parameters in a sample of Guatemalan school-aged children.MethodsWe assessed total dietary intakes and biomarkers of zinc status before and after receiving 6 months of zinc supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years. Most of the children also received zinc-fortified milk from a government program that started shortly after the trial began. We assessed associations between zinc intakes and serum zinc, alkaline phosphatase (ALP), and albumin.ResultsAt baseline, the prevalence of serum zinc < 65 μg/dL and dietary zinc intake below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9 and ≥ 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson correlations between serum zinc concentration and dietary zinc intake, serum ALP, and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes were observed in 1.2% and 0.0% of children in the zinc-supplemented group and 4.0% and 34.1% in the placebo group, respectively. Pearson correlations between serum zinc concentration and total zinc intake, serum ALP, and serum albumin were 0.10, 0.06, and −0.11 in the zinc-supplemented group and −0.04, 0.05, and 0.01 in the placebo group, respectively.ConclusionsZinc intake was inconsistently associated with markers of serum zinc concentration. Zinc fortification or supplementation attenuated the associations.