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Male partner involvement (MPI) during the prenatal and postnatal periods has been proven to have a beneficial effect on infant development. Infants born to HIV seropositive mothers with lacking or no prenatal and postnatal male partner support may be at a higher risk for adverse developmental outcomes. This study examined the effect of MPI on cognitive, communicative, fine, and gross motor development in 160 infants born to HIV seropositive mothers attending Prevention of Mother-to-Child Transmission of HIV (PMTCT) services in rural South Africa. Results of the bivariate logistic regression showed that both prenatal (OR 1.13; 95% CI 1.01, 1.26; p

OBJECTIVES: A major issue in the rehabilitation of children with cochlear implants (CIs) is unexplained variance in their language skills, where many of them lag behind children with normal hearing (NH). Here, we assess links between generative language skills and the perception of prosodic stress, and with musical and parental activities in children with CIs and NH. Understanding these links is expected to guide future research and toward supporting language development in children with a CI. DESIGN: Twenty-one unilaterally and early-implanted children and 31 children with NH, aged 5 to 13, were classified as musically active or nonactive by a questionnaire recording regularity of musical activities, in particular singing, and reading and other activities shared with parents. Perception of word and sentence stress, performance in word finding, verbal intelligence (Wechsler Intelligence Scale for Children (WISC) vocabulary), and phonological awareness (production of rhymes) were measured in all children. Comparisons between children with a CI and NH were made against a subset of 21 of the children with NH who were matched to children with CIs by age, gender, socioeconomic background, and musical activity. Regression analyses, run separately for children with CIs and NH, assessed how much variance in each language task was shared with each of prosodic perception, the child's own music activity, and activities with parents, including singing and reading. All statistical analyses were conducted both with and without control for age and maternal education. RESULTS: Musically active children with CIs performed similarly to NH controls in all language tasks, while those who were not musically active performed more poorly. Only musically nonactive children with CIs made more phonological and semantic errors in word finding than NH controls, and word finding correlated with other language skills. Regression analysis results for word finding and VIQ were similar for children with CIs and NH. These language skills shared considerable variance with the perception of prosodic stress and musical activities. When age and maternal education were controlled for, strong links remained between perception of prosodic stress and VIQ (shared variance: CI, 32%/NH, 16%) and between musical activities and word finding (shared variance: CI, 53%/NH, 20%). Links were always stronger for children with CIs, for whom better phonological awareness was also linked to improved stress perception and more musical activity, and parental activities altogether shared significantly variance with word finding and VIQ. CONCLUSIONS: For children with CIs and NH, better perception of prosodic stress and musical activities with singing are associated with improved generative language skills. In addition, for children with CIs, parental singing has a stronger positive association to word finding and VIQ than parental reading. These results cannot address causality, but they suggest that good perception of prosodic stress, musical activities involving singing, and parental singing and reading may all be beneficial for word finding and other generative language skills in implanted children.

BackgroundThe jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs.MethodsData were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs.ResultsCompared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1–2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98–1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19–2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose–response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported.ConclusionThe findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs.

Several chemical compounds are resistant to degradation and end up in the food chain. One group of these chemicals is poly-chlorinated biphenyls (PCBs) which are used as flame retardants and plasticizers. Although PCBs were banned several decades ago, PCBs are still found in environmental media, including in the body of humans. PCBs are transferred from mother to fetus via the placenta during pregnancy. Considering that the prenatal period is a sensitive period during which essential developmental processes take place, exposure to environmental chemicals might have considerable and permanent consequences for outcomes in later life.The aim of this review is to provide an update on the latest insights on the effects of prenatal exposure to PCBs on neurological, sexual and pubertal development in children. We give an overview of recent literature, and discuss it in the light of the findings in a unique Dutch birth cohort, with data on both neurological and pubertal development into adolescence.The findings in the studies included in this review, together with the findings in the Dutch cohort, demonstrate that prenatal exposure to PCBs can interfere with normal child development, not only during the perinatal period, but up to and including adolescence. Higher prenatal exposure to PCBs was found to be both negatively and positively associated with neurodevelopmental outcomes. Regarding pubertal development, higher prenatal PCB exposure was found to be associated with more advanced pubertal development, also in the Dutch cohort, whereas other studies also found delayed pubertal development. These findings raise concern regarding the effects of man-made chemical compounds on child development. They further contribute to the awareness of how environmental chemical compounds can interfere with child development and negatively influence healthy ageing.

BACKGROUND: Evolving evidence suggests that vegetation surrounding schools is beneficial to children's academic performance, however vehicle emissions are adversely related. Little is known about concurrent impacts of vegetation and vehicle emissions on academic performance. This study examined associations of vegetation and vehicle emissions near urban Australian primary schools with children's academic performance.METHODS: Vegetation within schoolyards and Euclidean buffers (100, 300 and 1000m) was assessed using the Normalised Difference Vegetation Index (NDVI). Weighted road density (WRD) was computed for each buffer as a vehicle emissions proxy. Cross-sectional associations and mediating pathways between vegetation and vehicle emissions and standardised average academic scores in Literacy (Reading, Writing, Language Conventions) and Mathematics for Grades 3 and 5 attending 3745 primary schools in urban areas (population ≥10,000) of Australia in 2018 were assessed using generalised linear models adjusted for school socio-educational status.RESULTS: Significant positive associations were found between vegetation and Reading in Grades 3 and 5, Mathematics in Grade 3 (all buffers), Writing in Grade 3 (100 and 300m), and Language Conventions in Grades 3 and 5 (most buffers). Increased vehicle emissions were negatively associated with Reading and Mathematics in Grades 3 and 5 (most buffers), and Language Conventions in Grade 3 (300 and 1000m) and Grade 5 (100-1000m). Within 300m, vehicle emissions partially mediated associations between vegetation with Mathematics in Grade 3 (proportion mediated, 21%), Reading and Language Conventions in Grade 5 (15%, 37% respectively).CONCLUSIONS: Our findings contribute to growing evidence that vegetation around primary schools is associated with higher achievement in Literacy and Mathematics, with partial mediation by vehicle emissions. Future studies should conduct on-site measurement of vehicle emissions and audit vegetation around schools to confirm findings and inform urban/school planners and school leaders on designing and modifying school environments to support learning.

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.Polygenic risk scores are nearing a level of differentiation required for their clinical utility in risk prediction in populations with high-risk rare pathogenic genetic variants.

This article reconsiders the role of social origin in health selection by examining whether parental education moderates the association between early health and educational attainment and whether health problems mediate the intergenerational transmission of education. We used longitudinal register data on Finns born in 1986–1991 (n = 352,899). We measured the completion of secondary and tertiary education until age 27 and used data on hospital care and medication reimbursements to assess chronic somatic conditions, frequent infections, and mental disorders at ages 10–16. We employed linear probability models to estimate the associations between different types of health problems and educational outcomes and to examine moderation by parental education, both overall in the population and comparing siblings with and without health problems. Finally, we performed a mediation analysis with g-computation to simulate whether a hypothetical eradication of health problems would weaken the association between parental and offspring education. All types of health problems reduced the likelihood of secondary education, but mental disorders were associated with the largest reductions. Among those with secondary education, there was further evidence of selection to tertiary education. High parental education buffered against the negative impact of mental disorders on completing secondary education but exacerbated it in the case of tertiary education. The simulated eradication of health problems slightly reduced disparities by parental education in secondary education (up to 10%) but increased disparities in tertiary education (up to 2%). Adolescent health problems and parental education are strong but chiefly independent predictors of educational attainment. Electronic supplementary material The online version of this article (10.1007/s13524-020-00919-y) contains supplementary material, which is available to authorized users.

Background Exposure to green space has beneficial effects on several cognitive and behavioral aspects. However, to our knowledge, no study addressed intelligence as outcome. We investigated whether the level of urbanicity can modify the association of residential green space with intelligence and behavior in children. Methods and findings This study includes 620 children and is part of the East Flanders Prospective Twin Survey (EFPTS), a registry of multiple births in the province of East Flanders, Belgium. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) in 620 children (310 twin pairs) between 7 and 15 years old. From a subset of 442 children, behavior was determined based on the Achenbach Child Behavior Checklist (CBCL). Prenatal and childhood residential addresses were geocoded and used to assign green space indicators. Mixed modeling was performed to investigate green space in association with intelligence and behavior while adjusting for potential confounding factors including sex, age, parental education, neighborhood household income, year of assessment, and zygosity and chorionicity. We found that residential green space in association with both intelligence and behavior in children was modified by the degree of urbanicity (p < 0.001). In children living in an urban environment, multivariable adjusted mixed modeling analysis revealed that an IQR increment of residential green space (3,000-m radius) was associated with a 2.6 points (95% CI 1.4–3.9; p < 0.001) higher total intelligence quotient (IQ) and 2.0 points (95% CI −3.5 to −0.4; p = 0.017) lower externalizing behavioral score. In children residing in a rural or suburban environment, no association was found. A limitation of this study is that no information was available on school location and the potential for unmeasured confounding (e.g., time spend outdoors). Conclusions Our results indicate that residential green space may be beneficial for the intellectual and the behavioral development of children living in urban areas. These findings are relevant for policy makers and urban planners to create an optimal environment for children to develop their full potential., Esmée M Bijnens and colleagues reveal beneficial effects of a green environment on a child's development and behaviour., Author summary Why was this study done? This study examines residential surrounding green space in association with intelligence and behavior in a study area that includes a spectrum of urban to rural environments. Previous studies mainly focused on urban areas, whereas only a few studies have explored differences in the effect of green space on cognition in nonurban settings. Understanding the health disparities that exist between urban and rural environments is essential for maintaining and improving human well-being in a rapidly urbanizing world. What did the researchers do and find? This longitudinal birth cohort study of twins assessed intelligence in 620 children between 7 and 15 years old. Our results indicate that residential green space is especially beneficial for intellectual and behavioral development of children living in an urban environment. What do these findings mean? We show that low residential green space in urban children is associated with a “shift” towards a higher incidence of low IQ demonstrating the public health impact of our findings.

Physical activity and motor competence (MC) have been considered to be closely related and prevent childhood obesity. The aim of the study was two-fold: to examine MC measured with two different tools in relation to individual, family, and environmental correlates and to investigate gender differences in MC. The Test of Gross Motor Development-Third Edition (TGMD-3) was administered to three- to seven-year-old children (n = 945), while the K&ouml, rperkoordinationstest f&uuml, r Kinder (KTK) was also used for five- to seven-year-old children (n = 444). The parent questionnaire (n = 936) included questions about individual (e.g., participation in organized sports), family (e.g., parents&rsquo, education level), and environmental (e.g., access to sports facilities) correlates. The children&rsquo, s temperament was assessed using the Colorado Childhood Temperament Inventory (CCTI) questionnaire. Data were analyzed using one-way analysis of variance and linear mixed-effects regression models. The regression models explained 57% and 38% of the variance in TGMD-3 and KTK, respectively. Individual correlates, including older age, more frequent participation in sports, and specific temperament traits of activity and attention span-persistence, were the strongest predictors for better MC. Small gender differences were found in both assessment tools, albeit in a different manner. In conclusion, socioecological correlates of MC in young children are multidimensional, and individual correlates appear to be the most important predictors of MC. Importantly, the correlates can differ according to the MC assessment tools.

In the first 2–3 years of life, the gut microbiota of infants quickly becomes diverse and rich. Disruptions in the evolving gut microbiota during this critical developmental period can impact brain development. Communication between the microbiota, gut and brain is driven by hormonal and neural regulation, as well as immune and metabolic pathways, however, our understanding of how the parallel developments that may underlie this communication are limited. In this paper, we review the known associations between the gut microbiota and brain development and brain function in early life, speculate on the potential mechanisms involved in this complex relationship and describe how nutritional intervention can further modulate the microbiota and, ultimately, brain development and function.

BackgroundLower intelligence quotient (IQ) has frequently been reported in patients with schizophrenia. However, it is unclear whether IQ declines (further) after illness onset and what the familial contribution is to this change. Therefore, we investigate IQ changes during the course of illness in patients with non-affective psychosis, their siblings and controls.MethodsData are part of the longitudinal Genetic Risk and Outcome of Psychosis (GROUP) study in the Netherlands and Belgium. Participants underwent three measurements, each approximately 3 years apart. A total of 1022 patients with non-affective psychosis [illness duration: 4.34 (s.d.= 4.50) years], 977 of their siblings, and 565 controls had at least one measure of IQ (estimated from four subtests of the WAIS-III).ResultsAt baseline, IQ was significantly lower in patients (IQ = 97.8) and siblings (IQ = 108.2;p< 0.0001) than in controls (IQ = 113.0;p< 0.0001), and in patients as compared with siblings (p< 0.0001). Over time, IQ increased in all groups. In siblings, improvement in IQ was significantly more pronounced (+0.7 points/year) than in patients (+0.5 points/year;p< 0.0001) and controls (+0.3 points/year;p< 0.0001). IQ increase was not significantly correlated with improvement in (sub)clinical outcome in any of the groups.ConclusionsDuring the first 10 years of the illness, IQ increases to a similar (and subtle) extent in a relatively high-functioning group of schizophrenia patients and controls, despite the lower IQ in patients at baseline. In addition, the siblings’ IQ was intermediate at baseline, but over time the increase in IQ was more pronounced.

The aims of this study were to 1) assess the predictive value of psychological assessment at five years of age on the need for educational support in very preterm children, and 2) report the neuropsychological profile of very preterm children at eleven years of age and risk factors for poorer neuropsychological functions. A cohort of 167 very preterm children was included (birth weight???1500?g and/or gestational age

Environment, physical activity (PA) and motor development are tightly interwoven during childhood. We examined the associations of environmental factors with motor competence (MC) in children. Children (N = 945, 50.1% boys, age = 3–7 years, mean = 5.4 years) from 37 childcare centres in the Southern (n = 17), Central (n = 13) and Northern Finland (n = 7) participated. The environmental factors comprised the geographical location (Southern, Central and Northern Finland) and residential density (metropolitan area, city, rural area and countryside) of the childcare centres’ based on postal codes and the national population density registry. MC was measured using the Test of Gross Motor Development (TGMD)-3, as well as by quantifying time spent outdoors and participation in organised sports via parental questionnaire. It was found that children from the countryside had better MC and spent most time outdoors, while children from the metropolitan area most frequently engaged in organised sports. Gender comparisons revealed that girls outperformed boys in locomotor skills, while boys were better in object control skills, had higher TGMD-3 score and spent more time outdoors. Time spent outdoors and participation in organised sports were associated positively with MC, but not in children from the countryside. In conclusion, higher population density was associated with lower MC and less time spent outdoors. The findings suggest that versatile outdoor environments may support motor development through PA. View Full-Text Keywords: children; motor competence; environment; geographical location; residential density; outdoor time; participation in sports

Fragmented sleep is common in infancy. Although night awakening is known to decrease with age, in some infants night awakening is more persistent and continues into older ages. However, the influence of fragmented sleep on development is poorly known. In the present study, the longitudinal relationship between fragmented sleep and psychomotor development (Bayley Scales of Infant and Toddler Development [Bayley-III]; Bayley, 2009) was investigated in infants with (≥3 night awakenings, n = 81) and without fragmented sleep (≤1 night awakening, n = 70) within the CHILD-SLEEP birth cohort at 8 and 24 months of age. Differences in parent-reported (Brief Infant Sleep Questionnaire [BISQ]) sleep parameters were studied at 8, 18, and 24 months of age. Group differences in night awakening were stable across all assessment points. Infants with fragmented sleep slept less in total than infants without fragmented sleep and they did not compensate their nocturnal sleep during daytime. Additionally, infants with fragmented sleep spent more time awake at night than infants without fragmented sleep. However, psychomotor development did not differ between infants with and without fragmented sleep at 8 or 24 months of age. Our findings indicate that early onset fragmented sleep did not have a negative effect on psychomotor development within the first 2 years despite the differences in sleep length among infants with and without fragmented sleep. In the future, more specific domains of cognitive development and various factors affecting sleep fragmentation should be taken into account when studying the developmental effects of night awakening in infancy. (PsycINFO Database Record

IntroductionOptimal early childhood development is an international priority. Risks during pregnancy and early childhood have lasting effects because growth is rapid. We will test whether a complex intervention addressing multiple modifiable risks: maternal nutrition, mental health, parenting capabilities, infant health and development and gender-based violence, is effective in reducing deficient cognitive development among children aged two in rural Vietnam.Methods and analysisThe Learning Clubs intervention is a structured programme combining perinatal stage-specific information, learning activities and social support. It comprises 20 modules, in 19 accessible, facilitated groups for women at a community centre and one home visit. Evidence-informed content is from interventions to address each risk tested in randomised controlled trials in other resource-constrained settings. Content has been translated and culturally adapted for Vietnam and acceptability and feasibility established in pilot testing.We will conduct a two-arm parallel-group cluster-randomised controlled trial, with the commune as clustering unit. An independent statistician will select 84/112 communes in Ha Nam Province and randomly assign 42 to the control arm providing usual care and 42 to the intervention arm. In total, 1008 pregnant women (12 per commune) from 84 clusters are needed to detect a difference in the primary outcome (Bayley Scales of Infant and Toddler Development Cognitive Score Ethics and disseminationMonash University Human Research Ethics Committee (Certificate Number 20160683), Melbourne, Victoria, Australia and the Institutional Review Board of the Hanoi School of Public Health (Certificate Number 017-377IDD- YTCC), Hanoi, Vietnam have approved the trial. Results will be disseminated through a comprehensive multistranded dissemination strategy including peer-reviewed publications, national and international conference presentations, seminars and technical and lay language reports.Trial registration numberACTRN12617000442303; Pre-results.

AimsTo investigate while accounting for health at birth 1) associations between health problems during childhood, measured as hospitalizations, and school achievement in the final year of compulsory school, measured as overall grade points and eligibility for upper secondary education, 2) if and how gender moderates the association between health problems and school achievement, 3) if and how the timing of a health problem during childhood is associated with later school achievement.MethodsAnalyzes were performed on a population-based cohort (n = 115 196) born in 1990 in Sweden (51.3% boys, 48.7% girls) using data from several national registries. Multiple linear regression and logistic regression were used to analyze associations between study variables.ResultsOverall grade points and eligibility for continuation to upper secondary school were lower for individuals exposed to hospitalizations. Only the association between hospitalizations and overall grade points was moderated by gender and only for ages 13-16 years. Exposure close to actual grading had worst outcomes.ConclusionsHealth problems, measured through hospitalizations, was significantly associated with lower school achievements among Swedish children. Girls exposed to health problems requiring hospitalizations had relatively poorer school achievements as compared to boys. Health problems requiring hospitalization during junior high school had the greatest negative association with final achievement at compulsory school.

BACKGROUND: Supplementation of formula with bovine milk fat globule membranes has been shown to narrow the gap in immunological and cognitive development between breast-fed and formula-fed infants. METHOD: In a double-blinded randomized controlled trial 160 formula-fed infants received an experimental formula (EF), supplemented with bovine milk fat globule membranes, or standard formula until 6 months of age. A breast-fed reference group was recruited. Lipidomic analyses were performed on plasma and erythrocyte membranes at 6 months and on serum at 4 and 12 months of age. RESULTS: At 6 months of age, we observed a significant separation in the plasma lipidome between the two formula groups, mostly due to differences in concentrations of sphingomyelins (SM), phosphatidylcholines (PC), and ceramides, and in the erythrocyte membrane lipidome, mostly due to SMs, PEs and PCs. Already at 4 months, a separation in the serum lipidome was evident where SMs and PCs contributed. The separation was not detected at 12 months. CONCLUSIONS: The effect of MFGM supplementation on the lipidome is likely part of the mechanisms behind the positive cognitive and immunological effects of feeding the EF previously reported in the same study population.

Background Delayed motor development may occur in children with Down syndrome, cerebral palsy, general developmental delay or children born preterm. It limits the child's exploration of the environment and can hinder cognitive and social-emotional development. Literature suggests that task-specific training, such as locomotor treadmill training, facilitates motor development. Objectives To assess the effectiveness of treadmill interventions on locomotor development in children with delayed ambulation or in pre-ambulatory children (or both), who are under six years of age and who are at risk for neuromotor delay. Search methods In May 2017, we searched CENTRAL, MEDLINE, Embase, six other databases and a number of trials registers. We also searched the reference lists of relevant studies and systematic reviews. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs that evaluated the effect of treadmill intervention in the target population. Data collection and analysis Four authors independently extracted the data. Outcome parameters were structured according to the International Classification of Functioning, Disability and Health model. Main results This is an update of a Cochrane review from 2011, which included five trials. This update includes seven studies on treadmill intervention in 175 children: 104 were allocated to treadmill groups, and 71 were controls. The studies varied in population (children with Down syndrome, cerebral palsy, developmental delay or at moderate risk for neuromotor delay); comparison type (treadmill versus no treadmill; treadmill with versus without orthoses; high- versus low-intensity training); study duration, and assessed outcomes. Due to the diversity of the studies, only data from five studies were used in meta-analyses for five outcomes: age of independent walking onset, overall gross motor function, gross motor function related to standing and walking, and gait velocity. GRADE assessments of quality of the evidence ranged from high to very low. The effects of treadmill intervention on independent walking onset compared to no treadmill intervention was population dependent, but showed no overall effect (mean difference (MD) -2.08, 95% confidence intervals (CI) -5.38 to 1.22, 2 studies, 58 children; moderate-quality evidence): 30 children with Down syndrome benefited from treadmill training (MD -4.00, 95% CI -6.96 to -1.04), but 28 children at moderate risk of developmental delay did not (MD -0.60, 95% CI -2.34 to 1.14). We found no evidence regarding walking onset in two studies that compared treadmill intervention with and without orthotics in 17 children (MD 0.10, 95% CI -5.96 to 6.16), and high- versus low-intensity treadmill interventions in 30 children with Down syndrome (MD -2.13, 95% -4.96 to 0.70). Treadmill intervention did not improve overall gross motor function (MD 0.88, 95% CI -4.54 to 6.30, 2 studies, 36 children; moderate-quality evidence) or gross motor skills related to standing (MD 5.41, 95% CI -1.64 to 12.43, 2 studies, 32 children; low-quality evidence), and had a negligible improvement in gross motor skills related to walking (MD 4.51, 95% CI 0.29 to 8.73, 2 studies, 32 children; low-quality evidence). It led to improved walking skills in 20 ambulatory children with developmental delay (MD 7.60, 95% CI 0.88 to 14.32, 1 study) and favourable gross motor skills in 12 children with cerebral palsy (MD 8.00, 95% CI 3.18 to 12.82). A study which compared treadmill intervention with and without orthotics in 17 children with Down syndrome suggested that adding orthotics might hinder overall gross motor progress (MD -8.40, 95% CI -14.55 to -2.25). Overall, treadmill intervention showed a very small increase in walking speed compared to no treadmill intervention (MD 0.23, 95% CI 0.08 to 0.37, 2 studies, 32 children; high-quality evidence). Treadmill intervention increased walking speed in 20 ambulatory children with developmental delay (MD 0.25, 95% CI 0.08 to 0.42), but not in 12 children with cerebral palsy (MD 0.18, 95% CI -0.09 to 0.45). Authors' conclusions This update of the review from 2011 provides additional evidence of the efficacy of treadmill intervention for certain groups of children up to six years of age, but power to find significant results still remains limited. The current findings indicate that treadmill intervention may accelerate the development of independent walking in children with Down syndrome and may accelerate motor skill attainment in children with cerebral palsy and general developmental delay. Future research should first confirm these findings with larger and better designed studies, especially for infants with cerebral palsy and developmental delay. Once efficacy is established, research should examine the optimal dosage of treadmill intervention in these populations.

Christoph Völter was supported by a scholarship of the German National Academic Foundation. Planning defined as the predetermination of a sequence of actions towards some goal is crucial for complex problem solving. To shed light on the evolution of executive functions, we investigated the ontogenetic and phylogenetic origins of planning. Therefore, we presented all four great apes species (N = 12) as well as 4- and 5-year-old human preschoolers (N = 24) with a vertical maze task. To gain a reward placed on the uppermost level of the maze, subjects had to move the reward to the bottom through open gaps situated at each level of the maze. In total, there were ten gaps located over three of the maze's levels, and free passage through these gaps could be flexibly blocked using multiple traps. Due to the decision tree design of the maze, the subjects had to plan their actions depending on the trap configuration up to two steps ahead to successfully retrieve the reward. We found that (1) our measure of planning was negatively correlated with age in nonhuman apes, (2) younger apes as well as 5-year-old children planned their moves up to two steps ahead whereas 4-year-olds were limited to plan one step ahead, and (3) similar performance but different underlying limitations between apes and children. Namely, while all species of nonhuman apes were limited by a lack of motor control, human children exhibited a shortage in shifting their attention across a sequence of subgoals. (C) 2013 Elsevier B.V. All rights reserved. Postprint

CONTEXT: Developmental outcomes of very preterm (gestational age ≤32 weeks) or very low birth weight ( OBJECTIVE: To determine the validity of early developmental assessments in predicting school-age cognitive deficits. DATA SOURCES: PubMed. STUDY SELECTION: English-language studies reporting at least 2 serial developmental/cognitive assessments on the same population, 1 between ages 1 and 3 years and 1 at ≥5 years. DATA EXTRACTION: For each study, we calculated the sensitivity, specificity, and positive and negative predictive values of early assessment for cognitive deficit (defined as test scores 1 SD below the population mean). Pooled meta-analytic sensitivity and specificity were estimated by using a hierarchical summary receiver operator characteristic curve. RESULTS: We included 24 studies (n = 3133 children). Early assessments were conducted at 18 to 40 months and generally involved the Bayley Scales of Infant Development or the Griffiths Mental Development Scales; 11 different cognitive tests were used at school-age assessments at 5 to 18 years. Positive predictive values ranged from 20.0% to 88.9%, and negative predictive vales ranged from 47.8% to 95.5%. The pooled sensitivity (95% confidence interval) of early assessment for identifying school-age cognitive deficit was 55.0% (45.7%–63.9%) and specificity was 84.1% (77.5%–89.1%). Gestational age, birth weight, age at assessment, and time between assessments did not explain between-study heterogeneity. LIMITATIONS: The accuracy of aggregated data could not be verified. Many assessment tools have been superseded by newer editions. CONCLUSIONS: Early developmental assessment has poor sensitivity but good specificity and negative predictive value for school-age cognitive deficit.

BACKGROUND: Up to 4% of children are born following assisted reproduction techniques (ART) yet relatively little is known on neurodevelopmental outcome of these children after 18 months of age. Only a limited number of long-term follow-up studies with adequate methodological quality have been reported. Our aim was to evaluate the effects of ovarian hyperstimulation, IVF laboratory procedures and a history of subfertility on neurological condition at 2 years. METHODS: Singletons born after controlled ovarian hyperstimulation IVF (COH-IVF, n=66), modified natural cycle IVF (MNC-IVF, n=56), natural conception in subfertile couples (Sub-NC, n=87) and in fertile couples (reference group, n=101) were assessed (using Hempel approach) by neurological examination at 2 years of age. This resulted in a neurological optimality score (NOS), a fluency score and the prevalence of minor neurological dysfunction (MND). Primary outcome was the fluency score, as fluency of movements is easily affected by subtle dysfunction of the nervous system. RESULTS: Fluency score, NOS and prevalence of MND were similar in COH-IVF, MNC-IVF and Sub-NC children. However, the fluency score (P

Long-chain PUFA (LCPUFA) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy, but uncertainty exists regarding effects after 6 months. The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age. A prospective, double-blind, randomised control study was performed in two groups of healthy term infants: a control group with standard formula (n 169) and a LCPUFA-supplemented group (LF; n 146). A breast-fed group (BF; n 159) served as a reference. At age 9 years, children were neurologically assessed according to Touwen, resulting in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction (MND). Information on potential confounders was collected at enrolment and follow-up. Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders. Attrition (28 %) was selective: drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months. Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups. Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children. In conclusion, LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age. The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants.

OBJECTIVE: The goal was to determine whether the quality of general movements (GMs) for preterm children had predictive value for cognitive development at school age. METHODS: In this prospective cohort study, 60 preterm infants (gestational age, median: 30.0 weeks [range: 25–33 weeks]; birth weight, median: 1130 g [range: 595–1800 g]) without cerebral palsy were studied. The quality of GMs was assessed prospectively as normal or abnormal, from video recordings that were made at regular intervals until 17 weeks after term. At 7 to 11 years, intelligence was tested by using the Wechsler Intelligence Scale for Children III, Dutch version. Total IQ (TIQ), verbal IQ (VIQ), and performance IQ (PIQ) scores were calculated. RESULTS: The median TIQ was 93 (range: 67–113), VIQ 96 (range: 68–117), and PIQ 92 (range: 65–119). Fifteen children (25%) had low TIQ scores ( CONCLUSIONS: The quality of GMs during the early postterm period is a marker for intelligence at school age. Abnormal GMs during the early postterm period may reflect injury or developmental disruptions of brain areas involved in cognitive development.

In manual search tasks designed to assess infants' knowledge of the object concept, why does search for objects hidden by darkness precede search for objects hidden by visible occluders by several months? A graded representations account explains this decalage by proposing that the conflicting visual input from occluders directly competes with object representations, whereas darkness merely weakens representations. This study tests the prediction that representations of objects hidden by darkness are strong enough for infants to bind auditory cues to them and support search, whereas representations of objects hidden by occluders are not. Six-and-half-month-olds were presented with audible or silent objects that remained visible, became hidden by darkness, or became hidden by a visible occluder. Search required engaging in the same means- end action in all conditions. As predicted, auditory cues increased search when objects were hidden by darkness but not when they were hidden by a visible occluder. Results are discussed in the context of different facets of object concept development highlighted by graded representations perspectives and core knowledge perspectives and in relation to other work on multimodal object representations.

Objective: Response inhibition and attention processing in 5- to 7-year-old children with or without symptoms of attention-deficit hyperactivity disorder (ADHD) were examined.Methods: Twelve children with ADHD symptoms and 15 control children performed a CPT-AX task. Behavioral Measures of inattention and impulsivity and ERP measures of conflict monitoring and inhibition (Nogo-N2 and Nogo-P3), cue-orientation and prestimulus target expectation (CUe-P2 and P3) and response preparation (CNV) were collected.Results: ADHD children detected fewer targets and had higher Inattention scores accompanied by reduced centro-parietal Cue- and Go-P3 activity. Occipital CNV amplitude was larger in ADHD children. At fronto-central leads, strong and comparable fronto-parietal Nogo-N2 effects were found in both groups, whereas the Nogo-P3 was only marginally significant in both groups.Conclusions: The attenuated Cue- and Go-P3 effects in the ADHD-symptom group are interpreted as early signs of delayed attention development, resulting in less preparation and less alertness to detect significant events. Whereas the Nogo-N2 effects were interpreted as signs of comparable levels of conflict processing in both groups, the small Nogo-P3 suggests that inhibitory processing is still immature at this age.Significance: The present Study shows that specific attention problems can already be detected in the behavior and brain activity of 5- to 7-year-old children with symptoms of ADHD performing a CPT-AX task, and might be better indicators for the risk of developing ADHD than impulsivity measures. (c) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All Fights reserved.

The present review addresses the effect of pre- and postnatal supplementation of nutrition with long-chain polyunsaturated fatty acids (LCPUFA) on neurodevelopmental outcome. The few studies which addressed the effect of prenatal LCPUFA status or prenatal LCPUFA supplementation suggest that a better prenatal arachidonic acid (AA) and doxosahexaenoic acid (DHA) status might be related to a better neurodevelopmental outcome until at least 18 months of age. A review of the few randomized controlled trials on formula supplementation with LCPUFA in preterm infants did not provide evidence for a significant beneficial effect of LCPUFA on developmental outcome. A review of the trials on formula supplementation with LCPUFA in term infants revealed that supplementation with LCPUFA, in particularly supplementation with ≥0.30% DHA, has a beneficial effect on neurodevelopmental outcome until 4 months. The studies could not demonstrate a consistent positive effect beyond that age. It was concluded that the relatively subtle effects of LCPUFA supplementation on neurodevelopmental outcome do not only depend on dosage but also on the gestational period during which the nutritional components are supplied: supplementation prior to term seems to have more effect than that after term.

Maternal nutrition is important for fetal development, but its impact on the functional outcome of infants is still unclear. The present study investigated the effects of vitamin A and Fe supplementation during gestation on infant mental and psychomotor development. Mothers of infants from five villages in Indonesia were randomly assigned to supervised, double-blind supplementation once per week from approximately 18 weeks of pregnancy until delivery. Supplementation comprised 120 mg Fe + 500 μg folic acid with (n94) or without (n94) 4800 μg retinol in the form of retinyl acetate. Mothers of infants who participated in the national Fe+folic acid supplementation programme, but whose intake of supplements was not supervised, were recruited from four other villages (n88). The mental and psychomotor development of infants was assessed, either at 6 or 12 months of age, using the Bayley Scales of Infant Development (BSID). We found no impact of vitamin A supplementation on mental or psychomotor development of infants. In addition, infants whose mothers had received weekly Fe supplementation had similar mental and psychomotor indices as those whose mothers had participated in the governmental Fe supplementation programme. The study population was moderately Fe and vitamin A deficient. The size of the treatment groups was large enough to detect a mean difference of 10 points on the BSID, which is less than 1 sd (15 points) of the average performance of an infant on the BSID. In conclusion, the present study did not find an impact of weekly supplementation of 4800 RE vitamin A in addition to Fe during gestation on functional development of Indonesian infants. However, smaller improvements in development may be seen if studied in a larger and/or more deficient population.

We investigated the influence of early nutrition with and without long-chain polyunsaturated fatty acids (LCP) on later development of less than or equal to 2500 g newborns receiving preterm formula without LCP (n=75), preterm formula with 18:3 omega 6 and LCP omega 3 (at two doses; n=26) or their mother's own milk (n=27). All diets were given from birth to day 42. Erythrocytes (RBC) fatty-acid compositions were determined on day 42. Bayley's mental development (MDI) and psychomotor development (PDI) indices were assessed at 19 months. Multivariate regression analysis revealed that PDI was most strongly related to RBC 22:6 omega 3 in the cohort of 101 infants who received formula. The most consistent correlations were between development and early LCP omega 3 intake, and between development and parameters of RBC LCP omega 3 status day 42, in infants who received formula with 18:3 omega 6 and LCP omega 3. Development of formula-fed low-birthweight infants seems positively influenced by early dietary LCP omega 3. (C) 1999 Harcourt Publishers Ltd.

Survival of children with Down syndrome (DS) has improved considerably, but insight into their level of daily functioning upon entering adulthood is lacking. We collected cross-sectional data from a Dutch nationwide cohort of 322 DS adolescents aged 16-19 (response 62.8%) to assess the degree to which they master various practical and social skills, using the Dutch Social competence rating scale and the Children's Social Behavior Questionnaire. Up to 60% mastered some of the skills required for independent functioning, such as maintaining adequate standards of personal hygiene and preparing breakfast. Less than 10% had achieved basic skills such as basic cooking and paying in a shop. It is difficult for DS people to master all the skills necessary to live independently. Ninety percent of adolescents with DS experience significant problems in social functioning. (C) 2013 Elsevier Ltd. All rights reserved.

To evaluate the effect of iron intervention on physical growth in fetuses, infants, children, and adolescents up to 18 years of age, a systematic review with meta-analysis of randomized controlled trials (RCTs) was conducted. Structured electronic searches were conducted to February 2010 using MEDLINE, Embase, and the Cochrane Library databases. RCTs that included iron-fortified foods, iron-fortified formula, or iron supplements and in which height, weight, mid-arm circumference (MAC), head circumference, birth weight, or length of gestation was evaluated were analyzed for inclusion. In total, 21 RCTs in infants, children, and adolescents and 7 studies in pregnant women met the inclusion criteria. The overall pooled result (random-effects model) showed no significant effects of iron intervention on any of the parameters measured. To accommodate wide heterogeneity, studies were stratified according to dose of iron, duration of intervention, age, and baseline iron status. However, only doses of 40–66 mg of supplemental iron and intervention in children ≥ 6 years of age showed a slight but significant association with weight and MAC.

It takes >20 y before the human brain obtains its complex adult configuration. Most dramatic neurodevelopmental changes occur prenatally and early postnatally, including a major transformation in cortical organization 3-4 mo after term. The long-lasting changes have practical implications for studies evaluating the effect of prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids (LC-PUFAs). Whether studies of the effect of supplementation will reveal an effect not only depends on the dosage and duration of supplementation but also on 1) the timing of supplementation, 2) the age at which the outcome is assessed, 3) the application of age-specific sensitive neurodevelopmental tools, and 4) the functional domain evaluated. Studies of the effects of prenatal supplementation with docosahexaenoic acid (DHA) or fish oil have provided inconsistent results. However, maternal and neonatal concentrations of DHA and arachidonic acid are associated with improved outcomes in early infancy, and concentrations of DHA are associated with favorable neurodevelopmental outcome beyond early infancy. Studies of LC-PUFA supplementation in preterm infants have not shown evidence of a positive effect on neurodevelopmental outcome. Similar studies in fullterm infants have indicated that supplementation with 0.30% DHA (by wt) promotes neurodevelopmental outcome in early infancy, but positive effects on later outcome have not been shown. However, information on the effects on outcomes at school age or later is virtually absent. This article stresses the need for long-term longitudinal studies that apply age-specific, sensitive neurodevelopmental tools, which also take into account lifestyle habits, maternal prepregnancy nutritional status, and genetic variation in metabolism. Am J Clin Nutr 2011;94(suppl):1874S-9S.

The present study compared the gross motor skills of 7- to 12-year-old children with learning disabilities (n = 104) with those of age-matched typically developing children (n = 104) using the Test of Gross Motor Development-2. Additionally, the specific relationships between subsets of gross motor skills and academic performance in reading, spelling, and mathematics were examined in children with learning disabilities. As expected, the children with learning disabilities scored poorer on both the locomotor and object-control subtests than their typically developing peers. Furthermore, in children with learning disabilities a specific relationship was observed between reading and locomotor skills and a trend was found for a relationship between mathematics and object-control skills: the larger children's learning lag, the poorer their motor skill scores. This study stresses the importance of specific interventions facilitating both motor and academic abilities. (C) 2011 Elsevier Ltd. All rights reserved.

It takes more than 20 years before the human brain obtains its complex, adult configuration. Most dramatic developmental changes occur prenatally and early postnatally. During development, long-chain polyunsaturated fatty acids (LCPUFA) such as doxosahexaenoic acid (DHA) and arachidonic acid (AA) are accreted in the brain. Since breastfeeding is associated with a better developmental outcome than formula feeding, and human milk in contrast to traditional standard formula contains LCPUFA, the question arose whether LCPUFA supplementation of infant formula may promote the neurodevelopmental outcome. The current paper reviews the evidence available in full-term infants. It concludes that postnatal supplementation of formula with LCPUFA is associated with a beneficial effect on short-term neurodevelopmental outcome. However, no evidence is available that LCPUFA supplementation enhances neurodevelopmental outcome in full-term infants beyond the age of four months. Nevertheless, it should be realized that very limited information is available on the effect of LCPUFA supplementation on neurodevelopmental outcome at school age or later. It is conceivable that effects of LCPUFA supplementation first emerge or re-emerge at school age when more complex neural functions are expressed.

The aim of this paper is to evaluate correlative magnetic resonance imaging (MRI) and histological parameters of development of cortical afferents during pathfinding and target selection in transient fetal cerebral laminas in human fetuses and preterm infants. The transient fetal subplate zone, situated between the fetal white matter (i.e. intermediate zone) and the cortical plate, is the crucial laminar compartment for development of thalamocortical and corticocortical afferents. The prolonged coexistence of transient (endogenously active) and permanent (sensory-driven) circuitry within the transient fetal zones is a salient feature of the fetal and preterm cortex ; this transient circuitry is the substrate of cerebral functions in preterm infants. Another transient aspect of organization of developing fibre pathways is the abundance of extracellular matrix and guidance molecules in periventricular crossroads of projection and corticocortical pathways. Both the subplate zone and periventricular crossroads are visible on MRI in vivo and in vitro. Hypoxic-ischaemic lesions of periventricular crossroads are the substrate for motor, sensory, and cognitive deficits after focal periventricular leukomalacia (PVL). Lesions of distal portions of the white matter and the subplate zone are the substrate for diffuse PVL. The neuronal elements in transient fetal zones form a developmental potential for plasticity after perinatal cerebral lesions.

This study examined motor control in 61 early and continuously treated patients with phenylketonuria (PKU) and 69 control participants, aged 7 to 14 years. The pursuit task demanded concurrent planning and execution of unpredictable movements, whereas the tracking task required a highly automated circular movement that could be planned in advance. PKU patients showed significantly poorer motor control in both tasks compared with control participants. Deficits were particularly observed for younger patients (age

The presence of minor neurological dysfunction is associated with behavioural and cognitive development at school age. We have previously shown a relation between minor neurological dysfunction and perinatal disorders, especially abnormal neonatal neurological condition. We have now investigated the relation between breastfeeding and long-term neurological development. We studied 135 breastfed (for greater than or equal to 3 weeks) and 391 formula-fed children, born at term in the University Hospital Groningen between 1975 and 1979. A standard neonatal neurological examination was used to classify the infants as normal (247), slightly abnormal (213), or frankly abnormal (66). At 9 years of age the children were reexamined. In 1993 their mothers were asked to complete a questionnaire about how the children were fed as infants. After adjustment for obstetric, perinatal, neonatal neurological, and social differences, a small advantageous effect of breastfeeding on neurological status at 9 years of age was found (odds ratio for neurological non-normality 0.54 [95% Cl 0.30-0.97]). Although a retrospective design cannot lead to definite conclusions, our data suggest a beneficial effect of breastfeeding on postnatal neurological development. Longer-chain polyunsaturated fatty acids, which are present in breast-milk but not in most formula-milks, may have a role since they are vital for brain development.

INTRODUCTION: In developing countries, severe undernutrition in early childhood is associated with increased mortality and morbidity, and 10-40% of hospital admissions. The current study aimed to elicit maternal perceptions of factors that contribute to severe undernutrition among children in a rural Kenyan community in order to identify appropriate and acceptable targeted interventions. METHODS: The study consisted of 10 focus group discussions (FGDs) of between eight and ten mothers each, in a rural coastal community in Kenya. A grounded theory approach was used to analyse the FGD data. RESULTS: In all FGDs 'financial constraints' was the main reason given for severe undernutrition of children. The mothers reported the additional factors of inadequate food intake, ill health, inadequate care of children, heavy workload for mothers, inadequate control of family resources by women and a lack of resources for generating income for the family. The mothers also reported their local cultural belief that severe malnutrition was due to witchcraft and the violation of sexual taboos. CONCLUSIONS: The mothers in the study community recognised multiple aetiologies for severe undernutrition. A multidisciplinary approach is needed address the range of issues raised and so combat severe undernutrition. Suggested interventions include poverty alleviation, medical education and psychosocial strategies. The content and approach of any program must address the need for variability, determined by individual and local needs, concerns, attitudes and beliefs.