In utero aspirin exposure and child neurocognitive development: A propensity score-matched analysis.

OBJECTIVE: To evaluate the association between a short-period, high-dose in utero aspirin exposure and child neurocognitive development. DESIGN: A propensity score-matched analysis of a multicentre prospective cohort study. SETTING: The US Collaborative Perinatal Project (1959-1976). POPULATION: A total of 50 565 singleton live births with maternal information. METHODS: We performed a propensity score matching to balance maternal characteristics between women with and without aspirin exposure. Inverse probability-weighted marginal structural models were used to estimate associations between aspirin exposure and child neurocognitive assessments. MAIN OUTCOME MEASURES: Child neurocognitive development was assessed using the Bayley Scales at 8 months, the Stanford Binet Intelligence Scale at 4 years, and the Wechsler Intelligence Scale and Wide-Range Achievement Test (WRAT) at 7 years. RESULTS: Children exposed to aspirin in utero were associated with an 8%-16% reduced risk of having suspect/abnormal or below-average scores in most neurocognitive assessments. A trend of lower risks of having suspect/abnormal or below-average scores was further observed in children with in utero aspirin exposure for more than 7 days, particularly on Bayley Mental (relative risk [RR] 0.82, 95% CI 0.74-0.92), WRAT Reading (RR 0.88, 95% CI 0.78-0.98) and WRAT Arithmetic tests (RR 0.76, 95% CI 0.66-0.86). This association was mainly observed in the second trimester of pregnancy. CONCLUSIONS: In utero aspirin exposure was associated with improved child neurocognitive development in a prospective cohort study. Further studies are warranted to evaluate the impact of long-period and low-dose in utero aspirin exposure on child short- and long-term neurodevelopment.

The promise and pitfalls of a strength-based approach to child poverty and neurocognitive development: Implications for policy.

There has been significant progress in understanding the effects of childhood poverty on neurocognitive development. This progress has captured the attention of policymakers and promoted progressive policy reform. However, the prevailing emphasis on the harms associated with childhood poverty may have inadvertently perpetuated a deficit-based narrative, focused on the presumed shortcomings of children and families in poverty. This focus can have unintended consequences for policy (e.g., overlooking strengths) as well as public discourse (e.g., focusing on individual rather than systemic factors). Here, we join scientists across disciplines in arguing for a more well-rounded, "strength-based" approach, which incorporates the positive and/or adaptive developmental responses to experiences of social disadvantage. Specifically, we first show the value of this approach in understanding normative brain development across diverse human environments. We then highlight its application to educational and social policy, explore pitfalls and ethical considerations, and offer practical solutions to conducting strength-based research responsibly. Our paper re-ignites old and recent calls for a strength-based paradigm shift, with a focus on its application to developmental cognitive neuroscience. We also offer a unique perspective from a new generation of early-career researchers engaged in this work, several of whom themselves have grown up in conditions of poverty. Ultimately, we argue that a balanced strength-based scientific approach will be essential to building more effective policies.

Role of one-carbon nutrient intake and diabetes during pregnancy in children's growth and neurodevelopment: A 2-year follow-up study of a prospective cohort.

BACKGROUND & AIMS: Both maternal metabolic dysregulation, e.g., gestational diabetes mellitus (GDM), and maternal supply of nutrients that participate in one-carbon (1C) metabolism, e.g., folate, choline, betaine, and vitamin B12, have been demonstrated to influence epigenetic modification such as DNA methylation, thereby exerting long-lasting impacts on growth and development of offspring. This study aimed to determine how maternal 1C nutrient intake was associated with DNA methylation and further, development of children, as well as whether maternal GDM status modified the association in a prospective cohort. METHODS: In this study, women with (n = 18) and without (n = 20) GDM were recruited at 25-33 weeks gestation. Detailed dietary intake data was collected by 3-day 24-h dietary recall and nutrient levels in maternal blood were also assessed at enrollment. The maternal-child dyads were invited to participate in a 2-year follow-up during which anthropometric measurement and the Bayley Scales of Infant and Toddler Development™ Screening Test (Third Edition) were conducted on children. The association between maternal 1C nutrients and children's developmental outcomes was analyzed with a generalized linear model controlling for maternal GDM status. RESULTS: We found that children born to mothers with GDM had lower scores in the language domain of the Bayley test (p = 0.049). Higher maternal food folate and choline intakes were associated with better language scores in children (p = 0.01 and 0.025, respectively). Higher maternal food folate intakes were also associated with better cognitive scores in children (p = 0.002). Higher 1C nutrient intakes during pregnancy were associated with lower body weight of children at 2 years of age (p < 0.05). However, global DNA methylation of children's buccal cells was not associated with any maternal 1C nutrients. CONCLUSIONS: In conclusion, higher 1C nutrient intake during pregnancy was associated with lower body weight and better neurodevelopmental outcomes of children. This may help overcome the lower language scores seen in GDM-affected children in this cohort. Studies in larger cohorts and with a longer follow-up duration are needed to further delineate the relationship between prenatal 1C nutrient exposure, especially in GDM-affected pregnancies, and offspring health outcomes.

Early-life matters: The role of fetal adrenal steroids in the relationship between cytokines within the placental circulation and cognitive development among infants in the Philippines.

Prenatal exposure to inflammation is related to the risk for cognitive impairment in offspring. However, mechanisms underlying the link between inflammatory cytokines at the maternal-fetal interface and human cognitive development are largely unknown. This study addressed this research gap by examining whether i) cytokines within the placenta are associated with different domains of neurocognitive development during infancy, and ii) if DHEA-S in cord blood mediates these associations. We also explored the role of early-life socioeconomic status (SES) in moderating the effect of fetal adrenal steroids on cognitive development in low- and middle-income country contexts. A cohort of 242 mother-infant dyads in Leyte, the Philippines participated in the study and all of them were followed from early pregnancy until 12-months. Concentrations of pro- and anti-inflammatory cytokines in the placenta, and DHEA-S in cord blood collected at delivery were evaluated. The multifactorial aspects of the infant's cognitive functioning were assessed based on the Bayley Scales of Infant Development, third edition (BSID-III). We used Structural Equation Modelling (SEM) with an orthogonal rotation to examine associated paths among latent variables of pro- and anti-inflammatory cytokines in the placenta, fetal neuroendocrine factors, and cognitive development. Pathway analyses showed that both pro- and anti-inflammatory cytokines in the placenta were indirectly related to cognitive (p < 0.05) and language developmental outcomes (p < 0.1) via DHEA-S in cord blood among the low SES group. Yet, we found no statistically significant indirect effect of pro- or anti-inflammatory cytokines on neurocognitive development among the high SES sub-sample. This study extends our understanding of how early-life socioeconomic conditions modify biological pathways underlying the relationship between prenatal factors and postpartum cognitive development.

Teoría de la mente en niños con trastorno por déficit de atención/hiperactividad / Theory of mind in children with attention deficit hyperactivity disorder

Introducción: La teoría de la mente (TM) está involucrada en la cognición social, ya que evalúa nuestra capacidad para atribuir estados mentales a los demás con el fin de predecir y explicar el comportamiento. En la bibliografía, se ha observado que los niños con trastorno por déficit de atención/hiperactividad (TDAH) muestran algunas alteraciones en la TM en comparación con los niños sin problemas de neurodesarrollo. Nuestro objetivo en este estudio fue comparar la TM en dos grupos: niños en edad escolar con desarrollo normal y niños en edad escolar con TDAH. Sujetos y métodos: Se reclutó a 35 niños con edades comprendidas entre los 6 y los 12 años: 17 con TDAH y 18 sin problemas de neurodesarrollo. La TM se evaluó utilizando un método de evaluación validado para la población portuguesa: Tortuga en la Isla-Batería de Evaluación de Funciones Ejecutivas en Niños. Resultados: Obtuvimos dos grupos comparables en cuanto a datos sociodemográficos. No hubo diferencias significativas entre los dos grupos en cuanto a la TM. Conclusiones: La evaluación de la TM en niños portugueses no reveló alteraciones significativas en esta habilidad cognitiva en niños con TDAH.(AU)

Introduction: Theory of mind (TM) is involved in social cognition, as it evaluates our ability to impute our mental states to the others in order to predict and explain behaviour. In the literature, it has been noticed that children with attention deficit hyperactivity disorder (ADHD) show some impairments of TM when compared with children not neurodevelopmental impaired. Our goal in this study was to compare the TM in two groups: schooler children with normal development and schooler children with ADHD. Subjects and methods: A total of 35 children, aged between 6 and 12 years, were recruited: 17 with ADHD and 18 not neurodevelopmental impaired. TM was evaluated using an assessment method validated for the Portuguese population: Turtle on the Island-Battery of Assessment of Executive Functions in Children. Results: We obtained two comparable groups concerning sociodemographic data. There were no significant differences between the two groups regarding TM. Conclusion: The TM assessment in Portuguese children did not reveal significant impairment regarding this cognitive skill in children with ADHD.(AU)

The impact of air pollution on neurocognitive development: Adverse effects and health disparities.

Air pollution is recognized as a major public health concern. The number of deaths related to ambient air pollution has increased in recent years and is projected to continue rising. Additionally, both short- and long-term air pollution exposure has been linked with deleterious effects on neurocognitive function and development. While air pollution poses as a threat to everyone, people of color and individuals of lower socioeconomic status are often exposed to elevated levels of air pollution as a function of systemic racism and classism. Further, given additional disparities in access to healthcare and other compounding stressors, adverse effects of air pollution on neurocognitive health are exacerbated among individuals who hold marginalized identities-making effects both less likely to be detected and treated. This review examines evidence of the effects of air pollution on neurocognitive development across the lifespan and incorporates an environmental justice perspective to highlight disparities in air pollution exposure across race and socioeconomic status. Last, upon the reviewed evidence, limitations of past research and recommendations for policy are discussed.

Early life adversity jointly regulates body-mass index and working memory development.

Previous work has proposed that balancing energy expenditure towards body and brain development in an optimal fashion results in a negative relationship between somatic and neurocognitive growth during development. An important issue, largely overlooked so far, is the extent to which this energetic trade-off is influenced by early life environmental factors. In this study, we estimated the association between neurocognitive (measured by working memory ability) and somatic (measured by body-mass index) developmental trajectories, while taking into account multiple dimensions of early life adversity. Results of our initial growth curve model were consistent with this brain-body trade-off in both girls and boys. In a subsequent model, we showed that early life adversity had positive associations with somatic and negative associations with neurocognitive growth trajectories, although the direct negative coupling between them remained consistent. Finally, a multidimensional adversity model, separating the effects of deprivation, threat and unpredictability, revealed that the dimension of deprivation-reflecting lack of access to resources and cognitive stimulation-contributed the most to both somatic and neurocognitive growth patterns. These results suggest that the way individuals balance energy between these two biological constructs during development is partly linked to environmental influences through phenotypic plasticity.

Stability of executive function in children born at risk of neonatal hypoglycemia.

Executive function plays an important role in promoting learning and social-emotional development in children. Neonatal hypoglycemia associates with executive function difficulties at 4.5 years, but little is known about the development of executive function over time in children born at risk of neonatal hypoglycemia. We aimed to describe the stability of executive function from early to mid-childhood in children born at risk of neonatal hypoglycemia and its association with neonatal hypoglycemia. Participants in a prospective cohort study of infants born at risk for neonatal hypoglycemia were assessed at ages 2, 4.5, and 9-10 years. We assessed executive function with batteries of performance-based and questionnaire-based measures, and classified children into one of four stability groups (persistent typical, intermittent typical, intermittent difficulty, and persistent difficulty) based on dichotomized scores (typical versus low at each age). Multinomial logistic regression was used to determine the associations between neonatal hypoglycemia and executive function stability groups. Three hundred and nine children, of whom 197 (64%) experienced neonatal hypoglycemia were assessed. The majority of children had stable and typical performance-based (63%) and questionnaire-based (68%) executive function across all three ages. Around one-third (30-36%) of children had transient difficulties, and only a few (0.3-1.9%) showed persistent difficulties in executive function at all ages. There was no consistent evidence of an association between neonatal hypoglycemia and the stability of executive function. Neonatal hypoglycemia does not appear to predict a specific pattern of development of executive function in children born at risk.

[Mental health of children conceived after assisted reproductive treatment]. / La santé mentale des enfants issus de procréation médicalement assistée.

The prevalence of infertility and the use of assisted reproductive treatment (ART) have been increasing worldwide in recent years. It appeared relevant to conduct a literature review on the safety of these techniques regarding the neurodevelopment and mental health of children and adolescents especially after in vitro fertilization. ART represents obstetrical risk factors. However, the published results are reassuring on the neurodevelopmental level as well as on the cognitive, psychomotor and language levels and on the behavioral and emotional levels among children and adolescents resulting from ART.

Le taux d'infertilité et le recours à la procréation médicalement assistée (PMA) sont en constante augmentation au cours des dernières années. Il est apparu pertinent de réaliser une revue de littérature sur la sécurité de ces techniques (en particulier de la fécondation in vitro) sur le neuro-développement et la santé mentale des enfants et adolescents. Les techniques de PMA représentent des facteurs de risque obstétricaux. En revanche, les résultats publiés sont rassurants sur le neuro-développement tant au niveau cognitif, psychomoteur et langagier qu'au niveau comportemental et émotionnel au sein des enfants et adolescents issus de PMA.

Long-term neurodevelopment in children with resected congenital lung abnormalities.

To determine whether children who underwent resection of a congenital lung abnormality (CLA) are at higher risk for neurodevelopmental impairments than peers in the general population. The study population consisted of children born between 1999-2018 who underwent resection of a symptomatic CLA. Neurocognitive development (intelligence, memory, attention, visuospatial processing, executive functioning) and motor function of this population are monitored through our structured, prospective longitudinal follow-up program at the ages of 30 months, 5, 8, and 12 years. We compared study population scores with Dutch norm values using one-sample t-tests and one-sample binominal proportion tests. Forty-seven children were analyzed. The 8-year-olds showed significant impairments in sustained attention through the Dot Cancellation Test (mean z-scores -2.4; [-4.1; -0.8], p = 0.006 and -7.1; [-12.8; -1.4], p = 0.02 for execution speed and fluctuations respectively). Visuospatial memory was impaired at 8 years, though only in 1 out of 3 assessment tools (Rey Complex Figure Test z-scores (-1.0; [-1.5; -0.5], p < 0.001). Further neurocognitive outcomes were unimpaired at all tested ages. Regarding motor function outcomes, mean z-scores of total motor functioning were unimpaired across assessed ages. However, at 8 years, significantly more children than expected had definite motor problems (18% vs 5%, 95% CI [0.052; 0.403], p = 0.022).   Conclusion: This evaluation reveals impairment in some subtests of sustained attention, visuospatial memory and motor development. However, globally, normal neurodevelopmental outcomes were found throughout childhood. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning. What is Known: • In general, surgically managed CLA cases seldom suffer from long-term surgery-related morbidity and show favorable lung function. What is New: • Long-term neurocognitive and motor function outcome appear unimpaired within surgically managed CLA cases. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning.

Iodine Deficiency, Maternal Hypothyroxinemia and Endocrine Disrupters Affecting Fetal Brain Development: A Scoping Review.

This scoping review critically discusses the publications of the last 30 years on the impact of mild to moderate iodine deficiency and the additional impact of endocrine disrupters during pregnancy on embryonal/fetal brain development. An asymptomatic mild to moderate iodine deficiency and/or isolated maternal hypothyroxinemia might affect the development of the embryonal/fetal brain. There is sufficient evidence underlining the importance of an adequate iodine supply for all women of childbearing age in order to prevent negative mental and social consequences for their children. An additional threat to the thyroid hormone system is the ubiquitous exposure to endocrine disrupters, which might exacerbate the effects of iodine deficiency in pregnant women on the neurocognitive development of their offspring. Ensuring adequate iodine intake is therefore essential not only for healthy fetal and neonatal development in general, but it might also extenuate the effects of endocrine disruptors. Individual iodine supplementation of women of childbearing age living in areas with mild to moderate iodine deficiency is mandatory as long as worldwide universal salt iodization does not guarantee an adequate iodine supply. There is an urgent need for detailed strategies to identify and reduce exposure to endocrine disrupters according to the "precautional principle".

Neighborhood air pollution is negatively associated with neurocognitive maturation in early adolescence.

The ability to maintain focus and process task-relevant information continues developing during adolescence, but the specific physical environmental factors that influence this development remain poorly characterized. One candidate factor is air pollution. Evidence suggests that small particulate matter and NO2 concentrations in the air may negatively impact cognitive development in childhood. We assessed the relationship between neighborhood air pollution and the changes in performance on the n-back task, a test of attention and working memory, in the Adolescent Brain Cognitive Development (ABCD) Study's baseline (ages 9-10) and two-year-follow-up releases (Y2, ages 11-12; n = 5,256). In the behavioral domain, multiple linear regression showed that developmental change in n-back task performance was negatively associated with neighborhood air pollution (ß = -.044, t = -3.11, p = .002), adjusted for covariates capturing baseline cognitive performance of the child, their parental income and education, family conflicts, and their neighborhood's population density, crime rate, perceived safety, and Area Deprivation Index (ADI). The strength of the adjusted association for air pollution was similar to parental income, family conflict, and neighborhood ADI. In the neuroimaging domain, we evaluated a previously published youth cognitive composite Connectome-based Predictive Model (ccCPM), and again found that decreased developmental change in the strength of the ccCPM from pre- to early adolescence was associated with neighborhood air pollution (ß = -.110, t = -2.69, p = .007), adjusted for the covariates mentioned above and head motion. Finally, we found that the developmental change in ccCPM strength was predictive of the developmental change in n-back performance (r = .157, p < .001), and there was an indirect-only mediation where the effect of air pollution on change in n-back performance was mediated by the change in the ccCPM strength (ßindirect effect = -.013, p = .029). In conclusion, neighborhood air pollution is associated with lags in the maturation of youth cognitive performance and decreased strengthening of the brain networks supporting cognitive abilities over time.

The Development of Cortical Responses to the Integration of Audiovisual Speech in Infancy.

In adults, the integration of audiovisual speech elicits specific higher (super-additive) or lower (sub-additive) cortical responses when compared to the responses to unisensory stimuli. Although there is evidence that the fronto-temporal network is active during perception of audiovisual speech in infancy, the development of fronto-temporal responses to audiovisual integration remains unknown. In the current study, 5-month-olds and 10-month-olds watched bimodal (audiovisual) and alternating unimodal (auditory + visual) syllables. In this context we use alternating unimodal to denote alternating auditory and visual syllables that are perceived as separate syllables by adults. Using fNIRS we measured responses over large cortical areas including the inferior frontal and superior temporal regions. We identified channels showing different responses to bimodal than alternating unimodal condition and used multivariate pattern analysis (MVPA) to decode patterns of cortical responses to bimodal (audiovisual) and alternating unimodal (auditory + visual) speech. Results showed that in both age groups integration elicits cortical responses consistent with both super- and sub-additive responses in the fronto-temporal cortex. The univariate analyses revealed that between 5 and 10 months spatial distribution of these responses becomes increasingly focal. MVPA correctly classified responses at 5 months, with key input from channels located in the inferior frontal and superior temporal channels of the right hemisphere. However, MVPA classification was not successful at 10 months, suggesting a potential cortical re-organisation of audiovisual speech perception at this age. These results show the complex and non-gradual development of the cortical responses to integration of congruent audiovisual speech in infancy.

Towards imaging the infant brain at play.

Infants' first-person experiences are crucial to early cognitive and neural development. To a vast extent, these early experiences involve play, which in infancy takes the form of object exploration. While at the behavioral level infant play has been studied both using specific tasks and in naturalistic scenarios, the neural correlates of object exploration have largely been studied in highly controlled task settings. These neuroimaging studies did not tap into the complexities of everyday play and what makes object exploration so important for development. Here, we review selected infant neuroimaging studies, spanning from typical, highly controlled screen-based studies on object perception to more naturalistic designs and argue for the importance of studying the neural correlates of key behaviors such as object exploration and language comprehension in naturalistic settings. We suggest that the advances in technology and analytic approaches allow measuring the infant brain at play with the use of functional near-infrared spectroscopy (fNIRS). Naturalistic fNIRS studies offer a new and exciting avenue to studying infant neurocognitive development in a way that will draw us away from our laboratory constructs and into an infant's everyday experiences that support their development.

Maternal perinatal depression and child neurocognitive development: A relationship still to be clarified.

Pregnancy frequently is associated with emotional conditions such as anxiety and depression. Perinatal depression has an incidence of around 12%. Only recently researcher put the attention on the effects of pre- and postpartum psychopathology on infant neurocognitive development. Neurobiology studies indicate that perinatal maternal depression can significantly affect the structure and function of children's prefrontal cortex and modulate the development of cognitive abilities from intrauterine life. On the topic, the scientific literature appears ambiguous, reporting mixed results. Some studies have found no significant differences in developmental outcomes between prenatal and postpartum exposure to maternal depression, others have suggested a greater burden of depression in pregnancy than in postpartum, and still others have emphasized the role of chronicity of symptoms rather than the period of onset. Few studies have examined the effects of different developmental trajectories of maternal depression on children's neurocognitive outcomes. The assessment of maternal health has for years been limited to postpartum depression often neglecting the timing of onset, the intensity of symptoms and their chronicity. These aspects have received less attention than they deserve, especially in relation to the effects on children's neurocognitive development. The aim of this Perspective was to highlight inconsistencies and gaps that need to be filled in the approach to the study of this problem. Given the wide heterogeneity of data in the current literature, further studies are needed to clarify these interactions. This Perspective provides an overview of current progress, future directions, and a presentation of the authors' views on the topic.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas.

BACKGROUND: There is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. OBJECTIVE: To estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. METHODS: Concentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC - ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. RESULTS: The geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 µg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: -4.22, 3.36) for the 2nd, 6.50 (95%CI: -11.73, -1.27) for the 3rd, 5.42 (95%CI: -10.74, -0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: -7.90, -0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [-1.94 (95%CI: -3.18, -0.71)] and tAs [-1.61 (95%CI: -3.02, -0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. CONCLUSIONS: Our study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Robust determinants of neurocognitive development in children: evidence from the Pune Maternal Nutrition Study.

Neurocognitive development is a dynamic process over the life course and is influenced by intrauterine factors as well as later life environment. Using data from the Pune Maternal Nutrition Study from 1994 to 2008, we investigate the association of in utero, birth, and childhood conditions with offspring neurocognitive development in 686 participants of the cohort, at age 12 years. The life course exposure variables in the analysis include maternal pre-pregnancy size and nutrition during pregnancy, offspring birth measurements, nutrition and physical growth at age 12 years along with parental education and socio-economic status. We used the novel Bayesian Model Averaging (BMA) approach; which has been shown to have better predictive performance over traditional tests of associations. Our study employs eight standard neurocognitive tests that measure intelligence, working memory, visuo-conceptual and verbal learning, and decision-making/attention at 12 years of age. We control for nutritional-metabolic information based on blood measurements from the pregnant mothers and the children at 12 years of age. Our findings highlight the critical role of parental education and socio-economic background in determining child neurocognitive performance. Maternal characteristics (pre-pregnancy BMI, fasting insulin during pregnancy) and child height at 12 years were also robust predictors on the BMA. A range of early factors - such as maternal folate and ferritin concentrations during pregnancy, and child's head circumference at birth - remained important determinants of some dimensions of child's neurocognitive development, but their associations were not robust once we account for model uncertainty. Our results suggest that intrauterine influences on long- term neurocognitive outcomes may be potentially reversible by post-birth remediation. In addition to the current nutritional interventions, public health policy should also consider social interventions in children born into families with low socio-economic status to improve human capital.

The impact of early exposure to general anesthesia on visual and neurocognitive development.

Every year millions of children are exposed to general anesthesia while undergoing surgical and diagnostic procedures. In the field of ophthalmology, 44,000 children are exposed to general anesthesia annually for strabismus surgery alone. While it is clear that general anesthesia is necessary for sedation and pain minimization during surgical procedures, the possibility of neurotoxic impairments from its exposure is of concern. In animals there is strong evidence linking early anesthesia exposure to abnormal neural development. but in humans the effects of anesthesia are debated. In humans many aspects of vision develop within the first year of life, making the visual system vulnerable to early adverse experiences and potentially vulnerable to early exposure to general anesthesia. We attempt to address whether the visual system is affected by early postnatal exposure to general anesthesia. We first summarize key mechanisms that could account for the neurotoxic effects of general anesthesia on the developing brain and review existing literature on the effects of early anesthesia exposure on the visual system in both animals and humans and on neurocognitive development in humans. Finally, we conclude by proposing future directions for research that could address unanswered questions regarding the impact of general anesthesia on visual development.

The Early Motor Repertoire in Preterm Infancy and Cognition in Young Adulthood: Preliminary Findings.

OBJECTIVE: Preterm birth poses a risk to cognition during childhood. The resulting cognitive problems may persist into young adulthood. The early motor repertoire in infancy is predictive of neurocognitive development in childhood. Our present aim was to investigate whether it also predicts neurocognitive status in young adulthood. METHOD: We conducted an explorative observational follow-up study in 37 young adults born at a gestational age of less than 35 weeks and/or with a birth weight below 1200 g. Between 1992 and 1997, these individuals were videotaped up until 3 months' corrected age to assess the quality of their early motor repertoire according to Prechtl. The assessment includes general movements, fidgety movements (FMs), and a motor optimality score (MOS). In young adulthood, the following cognitive domains were assessed: memory, speed of information processing, language, attention, and executive function. RESULTS: Participants in whom FMs were absent in infancy obtained lower scores on memory, speed of information processing, and attention than those with normal FMs. Participants with aberrant FMs, that is, absent or abnormal, obtained poorer scores on memory, speed of information processing speed, attention, and executive function compared to peers who had normal FMs. A higher MOS was associated with better executive function. CONCLUSIONS: The quality of the early motor repertoire is associated with performance in various cognitive domains in young adulthood. This knowledge may be applied to enable the timely recognition of preterm-born individuals at risk of cognitive dysfunctions.

Assessment of aberrant DNA methylation two years after paediatric critical illness: a pre-planned secondary analysis of the international PEPaNIC trial.

Critically ill children requiring intensive care suffer from impaired physical/neurocognitive development 2 y later, partially preventable by omitting early use of parenteral nutrition (early-PN) in the paediatric intensive-care-unit (PICU). Altered methylation of DNA from peripheral blood during PICU-stay provided a molecular basis hereof. Whether DNA-methylation of former PICU patients, assessed 2 y after critical illness, is different from that of healthy children remained unknown. In a pre-planned secondary analysis of the PEPaNIC-RCT (clinicaltrials.gov-NCT01536275) 2-year follow-up, we assessed buccal-mucosal DNA-methylation (Infinium-HumanMethylation-EPIC-BeadChip) of former PICU-patients (N = 406 early-PN; N = 414 late-PN) and matched healthy children (N = 392). CpG-sites differentially methylated between groups were identified with multivariable linear regression and differentially methylated DNA-regions via clustering of differentially methylated CpG-sites using kernel-estimates. Analyses were adjusted for technical variation and baseline risk factors, and corrected for multiple testing (false-discovery-rate <0.05). Differentially methylated genes were functionally annotated (KEGG-pathway database), and allocated to three classes depending on involvement in physical/neurocognitive development, critical illness and intensive medical care, or pre-PICU-admission disorders. As compared with matched healthy children, former PICU-patients showed significantly different DNA-methylation at 4047 CpG-sites (2186 genes) and 494 DNA-regions (468 genes), with most CpG-sites being hypomethylated (90.3%) and with an average absolute 2% effect-size, irrespective of timing of PN initiation. Of the differentially methylated KEGG-pathways, 41.2% were related to physical/neurocognitive development, 32.8% to critical illness and intensive medical care and 26.0% to pre-PICU-admission disorders. Two years after critical illness in children, buccal-mucosal DNA showed abnormal methylation of CpG-sites and DNA-regions located in pathways known to be important for physical/neurocognitive development.