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It is under debate how preferential perfusion of the brain (brain-sparing) in fetal growth restriction (FGR) relates to long-term neurodevelopmental outcome. Epigenetic modification of neurotrophic genes by altered fetal oxygenation may be involved. To explore this theory, we performed a follow-up study of 21 FGR children, in whom we prospectively measured the prenatal cerebroplacental ratio (CPR) with Doppler sonography. At 4 years of age, we tested their neurodevelopmental outcome using the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and the Behavior Rating Inventory of Executive Function. In addition, we collected their buccal DNA to determine the methylation status at predefined genetic regions within the genes hypoxia-inducible factor-1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), erythropoietin (EPO), EPO-receptor (EPOR), brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor, type 2 (NTRK2) by pyrosequencing. We found that FGR children with fetal brain-sparing (CPR n = 8) demonstrated a trend (0.05 < p < 0.1) toward hypermethylation of HIF1A and VEGFA at their hypoxia-response element (HRE) compared with FGR children without fetal brain-sparing. Moreover, in cases with fetal brain-sparing, we observed statistically significant hypermethylation at a binding site for cyclic adenosine monophophate response element binding protein (CREB) of BDNF promoter exon 4 and hypomethylation at an HRE located within the NTRK2 promoter (both p VEGFA was associated with a poorer Performance Intelligence Quotient, while hypermethylation of BDNF was associated with better inhibitory self-control (both p

To determine the long-term cognitive outcomes in children who underwent intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP).Prospective cohort study.This single-center study enrolled 186 children between 3 and 6 years of age and included 101 children in the final analysis: premature without ROP (group 1), ROP not needing treatment (group 2), IVB monotherapy (group 3), IVB plus laser therapy (group 4), and laser monotherapy (group 5). The Full-Scale Intelligence Quotient (FSIQ) was evaluated by the Wechsler Preschool and Primary Scale of Intelligence Test at baseline and then annually for 1-2 years and compared among groups.The age at cognitive evaluation was 4.5-4.9 years at baseline and 6.1-7.0 years at the last follow-up. The FSIQ was comparable among the groups at both time points (P = .08 and .50, respectively). Severe cognitive impairment (FSIQ70) was more common in group 4 at baseline (4%, 22%, 13%, 33%, and 0% in groups 1-5, respectively; P = .03) but did not differ among the groups at the last follow-up (6%, 0%, 4%, 22%, and 0%; P = .22). After adjusting for sex, Apgar score, neonatal adverse events, and days on mechanical ventilation, IVB was not associated with FSIQ either at baseline or at the last follow-up.At 4.5 to beyond 6 years of age, children who underwent IVB monotherapy had comparable cognitive outcomes compared to the other premature children without prior IVB. Children who underwent IVB plus laser showed higher severe cognitive impairment at 4.5 years of age.

Background This study is part of a multicountry matched-cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI) of children exposed to invasive group B Streptococcus (iGBS). The specific objective of this paper is to compare NDI across domains of iGBS survivors with a matched non iGBS group in our population. Methods Survivors of iGBS in a South Indian hospital were identified and recruited between January 2020 and April 2021. Cases were compared with age- and gender-matched non iGBS children. Participants were assessed using Bayley Scales of Infant and Toddler Development–3rd edition (BSID-III), Wechsler Preschool and Primary Scale of Intelligence–4th edition (WPPSI-IV), Wechsler Intelligence Scale for Children–5th edition (WISC-V), Child Behavior Checklist (CBCL), and Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2), depending on age. Results Our cohort comprised 35 GBS-exposed and 65 matched non iGBS children, aged 1–14 years. The iGBS-exposed group had 17 (48.6%) children with impairment in ≥1 domain compared to 25 (38%) in the non iGBS group (unadjusted OR, 1.51; 95% CI, .65–3.46), 9 (26%) children with “multi-domain impairment” compared to 10 (15.4%) in the non iGBS group (unadjusted OR, 1.90; 95% CI, .69–5.24), and 1 (2.9%) child with moderate to severe impairment compared to 3 (4.6%) in the non iGBS group (unadjusted OR, .60; 95% CI, .06–6.07). In the iGBS group, more children had motor impairments compared with the non iGBS group (unadjusted OR, 10.7; 95% CI, 1.19–95.69; P = .034). Conclusions Children with iGBS seem at higher risk of developing motor impairments compared with a non iGBS group.

The Wechsler Preschool and Primary Scale of Intelligence, 4th ed. includes two measures of working memory normed on children 2;6–7;7. The present analyses of the typically developing children (N = 1,591, 812 female, 779 male, with an ethnic distribution approximating the United States) provide new, theoretically important information about these working memory tasks, Picture Memory and Zoo Locations. These new analyses establish developmental trends, individual-difference properties, and cognitive task properties. They show comparable developmental trends for the two tasks, but Picture Memory picks up more individual-difference variation and is more sensitive to knowledge. This analysis of normed tasks starting very young makes possible new methods for research on the early stages of childhood working memory development, about which little is currently known.

The Wechsler Preschool and Primary Scale of Intelligence – Fourth Edition Australian and New Zealand Standardised Edition (WPPSI-IVA&NZ) is one of the most widely used intelligence assessments for ...

It has frequently been asserted that females have higher verbal abilities than males. A review of studies of sex differences in verbal abilities in the Wechsler tests shows there was no difference of Verbal IQ on the WPPSI for 4 to 6 year olds. On the WISC for 6 to 16 year olds, males obtained a higher median than females on the Verbal IQ of .16d, and in the WAIS tests for adults males obtained a higher median score than females of .28d. Males obtained higher average scores than females on the Information, Vocabulary, Arithmetic, Comprehension and Similarities subtests of WISC and WAIS.

OBJECTIVE To assess diagnostic accuracy of 36-week anthropometric weight, length, and head circumference

This study longitudinally characterized the developmental status, growth, and body composition of children who were fed human milk (breastfed, BF), cow’s milk-based (MF), or soy protein-based (SF) infant formula from 3 to 12 months. Standardized anthropometrics and dual-energy X-ray absorptiometry were used to characterize growth and body composition at 3, 6, 9, 12, 24, 36, 48, 60, and 72 months (NCT00616395). Preschool Language Scale-3, Children’s Memory Scale Index (CMS), and Wechsler Preschool and Primary Scale of Intelligence were administered at age 72 months. Mixed-effects models adjusting for gestational age, birth weight, child race and sex, parental education, and maternal IQ were performed. Body Mass index (BMI) was significantly lower between 24 and 72 months in BF children compared to SF children. At 3 and 6 months, BF infants had significantly higher fat mass (FM) than SF infants, whereas BF children had significantly lower FM at 36 and 48 months than SF children. Delayed Recognition Index of the CMS was higher for SF than for MF participants (p = 0.009). There was no other significant difference in developmental outcomes between groups. In conclusion, BF, MF, and SF support adequate growth and development up to age 6 years.

Background:Craniosynostosis is defined as a premature fusion of one or more cranial sutures. Several studies have revealed cognitive deficits in some children who had undergone surgery to treat craniosynostosis. However, no general distinction has been drawn in the cognitive abilities between the various types of craniosynostosis. The purpose of the present study was to analyze if there is a difference in cognitive and motor function among the different types of non-syndromic craniosynostosis in preschool children.Methods:Twenty-seven children with different types of non-syndromic craniosynostosis were assessed using the Wechsler Preschool and Primary Scale of Intelligence – Third Edition, as well as the Quantitative, Memory and Motor scales of McCarthy Scales of Children’s Abilities (MSCA). The children were aged between 3 and 5 years and 11 months. The various types of craniosynostosis were compared.Results:The unicoronal synostosis group performed significantly worse than the multisuture synostosis group on the MSCA Motor scale. No differences in cognitive functions were found between the various types of craniosynostosis.Conclusions:Children with unicoronal synostosis may experience impaired motor skills and screening of their motor ability is recommended.

PurposeHigher serum estradiol levels occur in women undergoing assisted reproductive technology (ART) owing to ovarian stimulation. Here, we investigated the association between maternal serum estradiol levels and the intellectual development of offspring conceived with ART.MethodsA total of 204 singletons born after fresh embryo transfer were recruited for this cohort study. Among them, 102 children were born from mothers with high serum estradiol levels (> 12,000 pmol/L) on the day that human chorionic gonadotropin was administered. Another 102 children, matched by gestational age and age of the children, were recruited as controls from mothers with low serum estradiol (≤ 12,000 pmol/L). The Wechsler Preschool and Primary Scale of Intelligence was used to evaluate the intellectual development of the children.ResultsChildren from mothers with higher serum estradiol levels scored lower in the verbal intelligence quotient (IQ) tests and verbal comprehension than children whose mothers had lower estradiol levels. The main difference between the two groups was in verbal subtests including information, vocabulary, and sorting. Partial correlation analysis revealed that the logarithm of maternal serum estradiol level negatively correlated with verbal IQ, performance IQ, and full scale IQ.ConclusionOur data demonstrate that a high maternal serum estradiol level may negatively associate the verbal ability of children conceived via ART.

Background: Cognitive deficits after perinatal brain lesion in preterm infants are among the most common neurodevelopmental disturbances. The relationship between structural changes on at term magnetic resonance imaging (MRI) and cognitive deficits in the preschool age should be a special focus due to timely intervention. The aim of this study was to correlate qualitative and quantitative MRI parameters of perinatal brain lesion in preterm children, on early neonatal MRI and follow up MRI, with general and specific cognitive functions in the preschool age. Methods: Twenty-one preterm infants with verified perinatal lesions based on clinical and ultrasound data underwent a brain MRI at term-equivalent age and a second MRI between 3 and 5 years of age. Qualitative and quantitative MRI analyses were done. All subjects underwent cognitive assessment (3–5 years) using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Developmental Neuropsychological Assessment (NEPSY-II). Results: Results show that many structural changes on at term MRI and on follow up MRI in preterm born children moderately correlate with specific cognitive deficits in preschool age. At term equivalent MRI, white matter changes and cortical thickness correlate to general and specific cognitive functions in infants born preterm. By analyzing follow up MRI at preschool age, structural changes of different white matter segments, corpus callosum, cortical thickness and lobe volume correlate to some specific cognitive functions. Conclusion: Besides general cognitive delay, specific cognitive deficits in preterm children should be targeted in research and intervention, optimally combined with MRI scanning, providing timely and early intervention of cognitive deficits after perinatal brain lesion. Our results, as well as previously published results, suggest the importance of detailed preschool neuropsychological assessment, prior to enrolment in the school system. Although preliminary, our results expand our understanding of the relationship between early brain developmental lesions and cognitive outcome following premature birth. Key Words: cognitive deficit, MRI, perinatal lesion, premature infants, preschool age

Abstract Background The implementation of genomic testing in pregnancy means that couples have access to more information about their child’s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. Methods This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old’s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. Discussion This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. Trial registration ACTRN12620000446965p; Registered on April 6, 2020.

Introduction The clinical complications of congenital hypothyroidism such as brain disorders are very subtle and are not recognizable in infancy period. They are recognizable when it is too late for treatment or prevention. General screening of newborns is effective in diagnosing congenital hypothyroidism and initiating initial treatment. The aim of this study is to compare the physical and mental growth pattern of children with congenital hypothyroidism with healthy ones. Methods This case–control study was performed on 34 patients and 68 healthy children who were matched in terms of inclusion and exclusion criteria. Children development screening test (ASQ), children development assessment test (Bayley), preschool Wechsler intelligence scale (WPPSI) and age and steps questionnaire of emotional social development (ASQ-SE) were completed by trained questioners. Data were analyzed using STATA software. Results The results indicated that there was no significant difference between the mean of verbal (P = 0.77), non-verbal (P = 0.81) and general (P = 0.66) IQ in permanent and transient patients and healthy individuals. Also, there was no significant difference between the mean of different ranges of ASQ test (including communication, delicate and large movements, problem solving and social) at 12 months and 42 months (P P = 0.42) and expressive (P = 0.38) categories. The difference was significant in the perceptual (P = 0.011), large (P = 0.03) and delicate (P = 0.04) movements categories. Conclusion This study emphasized on the high effectiveness of neonate hypothyroidism screening program, so that the difference between 3.5 years old children with and without this disease has decreased significantly. Early diagnosis of the patients, while creating beneficial effects for patients and increasing quality of life, cause reduction in the long-term costs of the health system.

The WISC-R was standardized on a representative sample of Greek school children for the age range 13 - 15 in Greece. (Number of children tested in each age group was 100, total 300.). The reliabilities of the Scale are equivalent to the Americanone in the subtests and I.Q.s, ranging for T.Q.s from 0.89 to 0.93 for the Verbal Scale, from 0.83 to 0.9*1 for the Performance Scale, and from 0.92 to O.96 for the Full Scale. The validities obtained in this study between the WISC-R andteachers ratings range from O.38 to 0.62 for the 13-year-old group,from O.3O to Ο.55 for the l4-year-old group and from 0.1*1 to O.Wfor the 15-year-old group. Furthermore the intercorrelations, sex differences, age differences were found. The order of difficulty of the"items is not the same as that which is given in the WISC-R manual for each subtest, the majority of items are easier for the boys. Item validity as a whole as measuredby the biserial correlation coefficient is satisfactory for the majority of items, but the tetrachoric correlation is low. The factor analysis of this study supports the opinion of Wechsler that there is a general intelligence and his dichotomy into Verbal and Performance Scales. Our results show that general intelligence decreases as age increases. All the correlations on the socioeconomic level of the family for the 13 and 14-year-old groupswere significant at the 0.01 level. Negative correlations were found between family size and intelligence scores on all Scales for all ages. The urban children had higher I.Q.s than their rural counterparts. The better educated fathers and mothers tend to have children with higher I.Q.s. The correlation obtained for the 13 and 14-year-old groups are significant at the 0.01 level.

Background Very preterm children generally perform poorly in executive functions and particularly in working memory. Adaptive training tasks encouraging these children to work continuously on their personal working memory capacity can be very useful. Above all in preschool-age children, several cognitive training programs focused on improving working memory capacity. Cogmed is a computerized visuospatial cognitive training program that improves working memory in children and adolescents with attention-deficit/hyperactivity disorder. The main objective is to assess the long-term effects (18 months) of cognitive training (Cogmed) on visuospatial processing in preschool-age very preterm children with working memory impairment. Methods The EPIREMED study is a prospective, randomized, controlled, multicentric trial nested in a population based epidemiological survey. An intervention group (Cogmed cognitive training) and a control group (standard care management) will compare children aged 5½ to 6 years, born between 24- and 34-weeks’ gestational age, with a global intelligence quotient > 70 and a working memory index Discussion This project’s primary goal is to demonstrate the necessity of early visuospatial memory assessment within the vulnerable population of very preterm children, and to prove the feasibility and efficacy of computerized cognitive training using online software programs. A better global neuropsychological development improvement (visuospatial processing and other far transfer) can be expected with an improvement in learning and decreased behavioral problems. In the long term, these improvements might also reduce those global costs linked to the consequences of extreme prematurity. Trial registration NCT02757794 (registered on 2nd May 2016 at ClinicalTrial.gov).

Intelligence quotient (IQ) is commonly measured in child development studies, while adaptive behavior is less frequently considered. Given its associations with functional outcomes in children with neurodevelopmental disabilities, adaptive behavior may be a useful outcome in general population samples, as well. This study aimed to compare social and environmental correlates of adaptive behavior vs. IQ in a sample of preschoolers exposed to the Flint water crisis (N= 184). Mother–child dyads were recruited from the community and administered a comprehensive battery to obtain information about child neurodevelopmental functioning, including direct assessment of IQviathe Wechsler Preschool and Primary Scale of Intelligence and assessment of parent-reported adaptive functioningviathe Vineland Adaptive Behavior Scales. Multiple social environmental factors were explored as potential correlates of child outcomes (i.e., IQ and adaptive behavior), and robust correlates were identified using a data-driven approach [i.e., least absolute shrinkage and selection operator (LASSO) regression]. We then examined associations between the LASSO-selected predictors and IQ and adaptive behavior while controlling for child age, child sex, and maternal age. Children in this sample showed relative strength in adaptive behaviors, with scores in the adequate range, while average IQs fell in the low-average range. Adaptive behavior was significantly associated with maternal nurturance practices, while IQ was associated with the maternal education level. Implications for the use of adaptive behavior as an outcome measure in studies of children at an increased risk for neurodevelopmental problems are discussed.

Polybrominated diphenylethers (PBDEs) are persistent organic pollutants (POPs), they are considered endocrine disruptors and can bioaccumulate in nature, and in living tissue. Human exposure to and the presence of PBDEs in human samples is of concern due to their potential health risks. Young children are one of the most vulnerable populations to PBDE's potential health effects. Ninety-one serum samples of 6-year-old children, residing in a contaminated location, due to former production of polychlorinated biphenyls (PCBs), were analysed to examine children's exposure to PBDEs in Slovakia. Median serum concentrations found for individual PBDE congeners BDE-28+33, −47, −99, −100, −153, −154 and −183 were 0.015, 0.184, 0.079, 0.046, 0.176, 0.014, and 0.097 ng g−1 lipid weight, respectively. Children's preschool maturity was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) test. In multivariate analyses BDE-153 serum concentrations were significantly inversely associated with WPPSI-III composite score (p = 0.011, β = −23.6), while adjusting for PCB-153 and sex. Significant negative associations were observed for BDE-153 serum concentrations (p = 0.002, β = −29.8) and WPPSI-III composite score, after controlling for PCB-118 and sex. Negative associations were also observed for BDE-47, BDE-100 and BDE-153, with different individual WPPSI subtest scores, after adjustment with PCB-153 and/or PCB-118 and sex. Serum concentrations of PCB-153 and PCB-118 were not statistically significantly associated with WPPSI-III composite score and individual subtest scores. These findings demonstrate adverse effects of PBDE serum exposure on preschool maturity of children, and PBDEs potentially negative impact on child neuropsychological development.

Differences in Conflict-Based Play Behavior, Socio-Emotional and Cognitive Development of Preterm Children Compared to Full-Term Children at Preschool Age Preterm children are at increased risk for socio-emotional and cognitive developmental difficulties at preschool age. This study investigates whether preterm children (n = 50) at the age of five years show different socio-emotional competencies in conflict situations and in the corresponding conflict resolution capacity in comparison to full-term children (n = 50). For this purpose, the MacArthur Story Stem Battery was used as the central examination method. In addition, parents completed the Strengths and Difficulties Questionnaire to obtain information about the children's behavior; moreover, the Wechsler Preschool and Primary Scale of Intelligence - Third Edition was applied to examine cognitive development. The parental reports did not reveal any behavioral differences between preterm and term children. However, significant group differences regarding their play behavior were detected. In their narratives, preterm children included content themes of interpersonal conflict and dysregulation more frequently compared to term born controls. Concerning empathic and moral themes and narrative coherence, no group difference could be detected. This could indicate that preterm children show no clinically manifest behavioral disorders at preschool age, but differences concerning intrapsychic experience compared to controls. In addition, preterm children had significantly lower IQ scores than term-born controls. Gestational age was a significant predictor of IQ and hyperactivity and attention problems. The results clarify the need for long term clinical follow up of preterm children and should be used to provide more specific care and support.

Objective To evaluate the clinical usefulness of the Korean Developmental Screening Test (K-DST) via comparison with Korean Ages and Stages Questionnaire (K-ASQ) for the diagnosis of developmental delay in pediatric patients. Methods The K-DST and K-ASQ were used to screen pediatric patients who visited the hospital for evaluation and diagnosis of delayed development. Korean Bayley Scales of Infant Development-II (K-BSID-II) or Korean Wechsler Preschool and Primary Scale of Intelligence III (K-WPPSI-III) were used for the standardized assessment. Moreover, the final clinical diagnosis was confirmed by three expert physicians (rehabilitation doctor, psychiatrist, and neurologist). The sensitivity and specificity of each screening tool for the final diagnosis were investigated and correlated with standardized assessments. Results A total of 145 pediatric consultations were conducted, which included 123 developmental disorders (40 autism spectrum disorders, 46 global developmental delay/intellectual disability, and 37 developmental language disorders) and another 22 that were not associated with any such disorders. The sensitivity and specificity of K-DST based on the final clinical diagnosis were 82.9% and 90.9%, respectively, which were not significantly different from that of K-ASQ (83.7% and 77.3%). Both K-DST and K-ASQ showed good correlation with K-BSID-II and K-WPPSI-III. No significant difference was found between the K-DST and K-ASQ measures. Conclusion K-DST is an excellent screening tool and is expected to replace K-ASQ with high validity.

In this article we describe the origins of the subtests that appear on the modern Stanford-Binet Intelligence Scales (SB5), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV), Wechsler Intelligence Scale for Children (WISC-V), and Wechsler Adult Intelligence Scale (WAIS-IV). We found that the majority of these subtest formats were first created in 1908 or earlier and that only three have been created since 1980. We discuss the implications of these findings, which are that (1) many subtests have lengthy research histories that support their use in measuring intelligence; (2) many subtests have formats that predate modern theories of test creation, cognitive psychology, and intelligence; and (3) the history of many subtests is more complex than psychologists probably realize.

An adapted version of the Wechsler Preschool and Primary Scale of Intelligence—Third Edition (WPPSI-III) was administered to assess cognitive functioning among 1,253 5-year-old children from the Malnutrition and Enteric Disease (MAL-ED) study—an international, multisite study investigating multiple aspects of child development. In this study, the factor structure and invariance of the WPPSI-III were examined across seven international research sites located in Bangladesh, Brazil, India, Nepal, Pakistan, South Africa, and Tanzania. Using a multiple indicator multiple cause (MIMIC) modeling approach, the findings supported the validity of a fluid reasoning dimension (comprised of block design, matrix reasoning, and picture completion subscales) across each of the seven sites, although the scores were noninvariant. Accordingly, these scores are recommended for research purposes and understanding relationships between variables but not for mean comparisons or clinical purposes.

The landmark findings of the Mother–Infant Transaction Program (MITP) showing improved neurodevelopment of preterm infants following parent-sensitivity training delivered in the neonatal intensive care unit have not been consistently replicated. This study evaluated an MITP-type intervention in terms of neurobehavioural development to preschool age. A randomised controlled trial involved 123 very preterm and extremely preterm infants allocated to either a parent-sensitivity intervention (PremieStart, n = 60) or to standard care (n = 63). When children were 2 and 4.5 years corrected age, parents completed the Child Behavior Checklist (CBCL). General development was assessed at 2 years with the Bayley Scales of Infant Development (Bayley-III). At 4.5 years, cognitive functioning was assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and executive functioning with the NEPSY-II. There were no significant between-group differences in behaviour problems at 2 or 4.5 years, general development at 2 years, or cognitive and executive functioning at 4.5 years. Advances in the quality of neonatal intensive care may mean that MITP-type interventions now have limited additional impact on preterm infants’ long-term neurobehavioural outcomes. The gestational age of infants and the exact timing of intervention may also affect its efficacy.

Testrezension WPPSI-IV Wechsler Preschool And Primary Scale of Intelligence – Fourth Edition D. Wechsler, Bearbeiter der deutschen Fassung: F. Petermann & M. Daseking, unter Mitarbeit von F. Walter (2018)

Aim: This study determined whether cognitive outcomes differed between very preterm (VPT) and extremely preterm (EPT) children who were monolingual or multilingual when they reached the corrected ages of two and five years. Methods: The data were collected at the Emma Children's Hospital, Amsterdam, The Netherlands, as part of our national neonatal follow-up programme and comprised 325 VPT/EPT children born between January 1, 2007 and January 1, 2012. The study used the Third Editions of the Bayley Scales of Infant and Toddler Development and the Wechsler Preschool and Primary Scale of Intelligence. Results: We compared 234 monolingual children, 65 multilingual children who spoke Dutch and at least one foreign language at home and 26 multilingual children who didn't speak Dutch at home. The best performers on the cognitive scale at two years of age and the verbal subscales at five years of age were the monolingual children, followed by the children who spoke Dutch and at least one foreign language at home, then the children who only spoke foreign languages at home. Conclusion: In our study cohort from The Netherlands, multilingualism lowered the cognitive and verbal outcomes of VPT/EPT children at the corrected ages of two and five years.

Prenatal, perinatal, and postnatal factors have been shown to shape neurobiological functioning and alter the risk for mental disorders later in life. The gut microbiome is established early in life, and interacts with the brain via the brain-immune-gut axis. However, little is known about how the microbiome relates to early-life cognitive functioning in children. The present study, where the fecal microbiome of 380 children was characterized using 16s rDNA and metagenomic sequencing aimed to investigate the association between the microbiota and cognitive functioning of children at the age of 45 months measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Overall the microbiome profile showed a significant association with cognitive functioning. A strong correlation was found between cognitive functioning and the relative abundance of an unidentified genus of the family Enterobacteriaceae. Follow-up mediation analyses revealed significant mediation effects of the level of this genus on the association of maternal smoking during pregnancy and current cigarette smoking with cognitive function. Metagenomic sequencing of a subset of these samples indicated that the identified genus was most closely related to Enterobacter asburiae. Analysis of metabolic potential showed a nominally significant association of cognitive functioning with the microbial norspermidine biosynthesis pathway. Our results indicate that alteration of the gut microflora is associated with cognitive functioning in childhood. Furthermore, they suggest that the altered microflora might interact with other environmental factors such as maternal cigarette smoking by acting as a mediator between maternal smoking and child cognitive function. Interventions directed at altering the microbiome should be explored in terms of improving cognitive functioning in young children. Overall the microbiome profile showed a significant association with cognitive functioning. A strong correlation was found between cognitive functioning and the relative abundance of an unidentified genus of the family Enterobacteriaceae. Follow-up mediation analyses revealed significant mediation effects of the level of this genus on the associations of maternal smoking during pregnancy and current maternal smoking with cognitive functioning. Metagenomic sequencing of a subset of these samples indicated that the identified genus was most closely related to Enterobacter asburiae. Our results indicate that alteration of the gut microflora is associated with cognitive functioning in childhood. Furthermore, they suggest that the altered microflora might interact with other environmental factors such as maternal cigarette smoking by acting as a mediator between those factors and child cognitive function. Interventions directed at altering the microbiome should be explored in terms of improving cognitive functioning in young children.

Maternal gestational inflammation from infection, obesity, depression, and adverse childhood experiences negatively affects offspring cognitive development. Choline is a key nutrient in fetal brain development. We investigated whether higher maternal plasma choline concentrations have a positive association with offspring cognition, specifically processing speed, in the presence of inflammation. Forty-eight children were evaluated at 4 years of age. Processing Speed Composite Score on the Wechsler Preschool & Primary Scales of Intelligence was the principal outcome. Maternal C-reactive protein (CRP), a marker of inflammation, and choline plasma concentration had been measured at 16 weeks’ gestation. Choline concentrations >7.07μM were compared to lower levels. Mothers with lower choline levels reported more depression and stress. Head circumference was larger for neonates of mothers with higher choline levels. In analyses with maternal CRP, higher maternal choline was associated with higher offspring Processing Speed Composite Scores for both sexes. For males, higher maternal choline competed with the negative association of maternal CRP on Processing Speed. Higher Processing Speed was related to the child’s behavioral ratings, with fewer Withdrawn Problems on the Child Behavior Checklist 11/2-5 years at 4 years and higher Infant Behavior Questionnaire Orienting/Regulation at 3 months of age, consistent with persistent developmental effects. Higher processing speed and decreased problems in social withdrawal are positively associated with prenatal maternal choline. Both lower processing speed and social withdrawal problems are precursors to later mental difficulties. Choline supplementation in pregnancy may mitigate effects of maternal inflammation that contribute to problems in offspring’s’ cognition and behavior.

Background: The Early Learning Outcomes Measure (ELOM) assesses early learning programme outcomes in children aged 50-69 months. ELOM assesses gross motor development (GMD), fine motor coordination and visual motor integration (FMC & VMI), emergent numeracy and mathematics (ENM), cognition and executive functioning (CEF), and emergent literacy and language (ELL). Content and construct validity, reliability and cross-cultural fairness have been established. Aim: To establish the test-retest reliability and concurrent validity of the ELOM. Setting: Low income preschool and Grade R children. Methods: In study one, Test-retest reliability was investigated in a convenience sample of 49 English and isiXhosa speaking preschool children (Mean age = 60.77 months, SD = 3.70) tested and retested one week apart. In study two, concurrent validity was investigated in a convenience sample of 62 children (Mean age = 75.05 months, SD = .75). ELOM performance was compared with that on the Wechsler Preschool and Primary Scale of Intelligence Fourth Edition (WPPSI-IV). Results: Test-retest reliability was established for ELOM Total score ( r = .90, p < .001). The concurrent validity of ELOM Total and the WPPSI-IV Full Scale Composite scores was established ( r = .64, p < .001). FMC & VMI, CEF, and ELL domains correlated significantly with their corresponding WPPSI-IV indices: visual spatial, fluid reasoning, processing speed, working memory, and verbal comprehension. Conclusion: The findings of both psychometric studies contribute further to the reliability and validity of the ELOM.

Existing empirical evidence suggests that the prevalence of undernutrition in remote and poor, rural areas is still high among Chinese children. While evidence reveals that undernutrition may detrimentally affect child development, studies focusing on rural Chinese preschoolers are sparse. Using the baseline survey of a preschool’s free nutritious lunch pilot program, this study examined the relationship between child undernutrition and developmental outcomes among a preschool-aged sample in poor, rural areas of China. We conducted the baseline survey in Hunan province in south central China in September 2018. A total of 1293 preschoolers living in two (then) nationally designated poverty counties in rural Hunan served as our study sample. Children’s nutritional statuses were measured using height-for-age z-score, weight-for-age z-score, and anemia, while their cognitive and socio-emotional skills were assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and Strengths and Difficulties Questionnaire (SDQ), respectively. We find that 33% of sample preschoolers were anemic, whereas the incidences of stunting and wasting were 11% and 2%, respectively. About 54% of the sample children had delay in at least one of the developmental domains measured in this study. Our findings provide suggestive evidence supporting that children from certain backgrounds tend to experience worse nutritional and developmental outcomes than their counterparts. After controlling for socioeconomic status, we observed that both anemia and stunting were negatively associated with children’s cognitive performance, however, they were not associated with socio-emotional performance. As such, this study suggests that free lunch programs have the potential to change children’s developmental trajectory in preschool. We believe that our results will contribute to the debate surrounding whether the nutritious lunch program in China should be expanded to the preschool education level.

IntroductionDocosahexaenoic acid (DHA) is an omega-3 (n-3) fatty acid that accumulates into neural tissue during the last trimester of pregnancy, as the fetal brain is undergoing a growth spurt. Infants born Methods and analysisN3RO was a randomised controlled trial of enteral DHA supplementation (60 mg/kg/day) or a control emulsion (without DHA) in 1273 infants born In this follow-up at 5 years’ corrected age, a predefined subset (n=655) of children from five Australian sites will be invited to attend a cognitive assessment with a psychologist. Children will be administered the Wechsler Preschool and Primary Scale of Intelligence (fourth edition) and a measure of inhibitory control (fruit stroop), while height, weight and head circumference will be measured.The primary outcome is full-scale IQ. To ensure 90% power, a minimum of 592 children are needed to detect a four-point difference in IQ between the groups.Research personnel and families remain blinded to group assignment.Ethics and disseminationThe Women’s and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/17/WCHN/187). Caregivers will give informed consent prior to taking part in this follow-up study. Findings of this study will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberACTRN12612000503820.

Many school feeding programs target child hunger, nutritional deficiencies, attendance, and education outcomes but often do not examine their effects on cognitive development. In this cluster-randomized controlled trial, we tested the effects of adding a morning snack to a school lunch program on the fluid intelligence of 951 children ages 4 to 6 years. While there were no significant effects on development overall, the morning snack improved short-term memory (STM) and total score on the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) among children from the lowest quartile of household expenditures (STM: 0.35SD, p = 0.020; WPPSI-IV: 0.65SD, p = 0.087), and those whose mothers completed secondary school or less (STM: 0.35SD, p = 0.002; total WPPSI-IV: 0.81SD, p = 0.011). For at risk preschoolers, school snack programs may help meet their developmental needs.

Objective To assess the effect of transabdominal amnioinfusion or no intervention on long‐term outcomes in children born after second‐trimester prelabour rupture of the membranes (PROM between 16+0/7–24+0/7 weeks) and oligohydramnios. Population Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL‐III (NTR3492). Methods Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires. Main outcome measures Neurodevelopmental outcomes were measured. Mild delay was defined as −1 standard deviation (SD), severe delay as −2 SD. Healthy long‐term survival was defined as survival without neurodevelopmental delay or respiratory problems. Results In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval [CI] 0.60–1.22). Follow‐up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long‐term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53–11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long‐term survivor. Conclusions In this small sample of women suffering second‐trimester PROM and oligohydramnios, amnioinfusion did not improve long‐term outcomes. Overall, 71% of survivors had no neurodevelopmental delay. Tweetable abstract Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention., Tweetable abstract Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention.

Background Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with adverse neurodevelopmental outcomes in children, but evidence remains mixed regarding sex differences in this association. Objective To examine the prospective association between prenatal PBDE exposure and cognitive ability in young children, as well as potential sex differences. Methods The study was conducted in a multi-site Canadian pregnancy cohort recruited in 2008–11. PBDEs were measured in maternal plasma samples collected early in pregnancy. Cognitive ability was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) in children at age 3 years (mean = 3.4). Multiple linear regression was used to analyze the association between maternal PBDE plasma concentrations (lipid-standardized and log10-transformed) and Verbal, Performance, and Full Scale IQ scores on the whole sample and stratified by sex, adjusting for confounders. Results The sample was composed of 592 children (291 boys and 301 girls). A tenfold increase in maternal blood PBDE concentration (sum of BDE-47, −99, −100, and −153) was associated with lower Full Scale scores in boys (−3.4 points; 95% CI: −7.0, 0.1), after adjusting for confounders. BDE-47 was the congener with the highest concentrations in maternal blood and a tenfold increase in exposure was associated with significantly lower Full Scale IQ scores in boys (−4.4 points; 95% CI: −7.9, −0.9), after adjusting for confounders. Verbal and Performance IQ scores were similarly associated with PBDE exposure. Maternal blood PBDE concentrations were not associated with IQ scores in girls. Conclusions Prenatal exposure to background levels of PBDEs, especially BDE-47, was associated with lower IQ scores in boys, but not in girls. Our results support that exposure to PBDEs during early development may be sex-dependent and detrimental to a child’s neurodevelopmental trajectory.

ObjectivesTo assess the association of head circumference (HC) DesignIn a prospective cohort, semiautomatically segmented TCV and manually segmented white matter injury (WMI) volumes were obtained. Multivariable regressions were used to study the association of HC and TCV with neurodevelopmental outcomes, accounting for birth gestational age, WMI and postnatal illness.SettingParticipants born in 2006–2013 at British Columbia Women’s Hospital were recruited.Patients168 neonates had HC measurements at birth and discharge and MRI at term-equivalent age (TEA). 143 children were assessed at 4.5 years.Main outcome measuresMotor, cognitive and language outcomes at 4.5 years were assessed using the Movement Assessment Battery for Children Second Edition (M-ABC) and Wechsler Preschool and Primary Scale of Intelligence Third Edition Full Scale IQ (FSIQ) and Verbal IQ (VIQ).ResultsSmall birth HC was associated with lower M-ABC and FSIQ scores. In children with small birth HC, small discharge HC was associated with lower M-ABC, FSIQ and VIQ scores, while normal HC at discharge was no longer associated with adverse outcomes. HC strongly correlated with TCV at TEA. TCV did not correlate with outcomes.ConclusionsSmall birth HC is associated with poorer neurodevelopment, independent of postnatal illness and WMI. Normalisation of HC during NICU care appears to moderate this risk.

Over the last two decades, heart centres have developed strategies to meet the neurodevelopmental needs of children with congenital heart disease. Since the publication of guidelines in 2012, cardiac neurodevelopmental follow-up programmes have become more widespread. Local neurodevelopmental programmes, however, have been developed independently in widely varying environments. We sought to characterise variation in structure and personnel in cardiac neurodevelopmental programmes. A 31-item survey was sent to all member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. Multidisciplinary teams at each centre completed the survey. Responses were compiled in a descriptive fashion. Of the 29 invited centres, 23 responded to the survey (79%). Centres reported more anticipated neurodevelopment visits between birth and 5 years of age (median 5, range 2–8) than 5–18 years (median 2, range 0–10) with 53% of centres lacking any standard for routine neurodevelopment evaluations after 5 years of age. Estimated annual neurodevelopment clinic volume ranged from 85 to 428 visits with a median of 16% of visits involving children >5 years of age. Among responding centres, the Bayley Scales of Infant and Toddler Development and Wechsler Preschool and Primary Scale of Intelligence were the most routinely used tests. Neonatal clinical assessment was more common (64%) than routine neonatal brain imaging (23%) during hospitalisation. In response to clinical need and published guidelines, centres have established formal cardiac neurodevelopment follow-up programmes. Centres vary considerably in their approaches to routine screening and objective testing, with many centres currently focussing their resources on evaluating younger patients.

BACKGROUND:Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings.METHODS:Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence). Markers of socioeconomic status, infection, illness, dietary intake and status, anthropometry, and maternal factors were also assessed. Trajectories of development were determined by latent class-mixed models, and factors associated with class membership were examined by discriminant analysis.RESULTS:Five trajectory groups of cognitive development are described. The variables that best discriminated between trajectories included presence of stimulating and learning resources in the home, emotional or verbal responsivity of caregiver and the safety of the home environment (especially at 24 and 60 months), proportion of days (0–24 months) for which the child had diarrhea, acute lower respiratory infection, fever or vomiting, maternal reasoning ability, mean nutrient densities of zinc and phytate, and total energy from complementary foods (9–24 months).CONCLUSIONS:A supporting and nurturing environment was the variable most strongly differentiating the most and least preferable trajectories of cognitive development. In addition, a higher quality diet promoted cognitive development while prolonged illness was indicative of less favorable patterns of development.

BACKGROUND: Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings. METHODS: Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence). Markers of socioeconomic status, infection, illness, dietary intake and status, anthropometry, and maternal factors were also assessed. Trajectories of development were determined by latent class-mixed models, and factors associated with class membership were examined by discriminant analysis. RESULTS: Five trajectory groups of cognitive development are described. The variables that best discriminated between trajectories included presence of stimulating and learning resources in the home, emotional or verbal responsivity of caregiver and the safety of the home environment (especially at 24 and 60 months), proportion of days (0–24 months) for which the child had diarrhea, acute lower respiratory infection, fever or vomiting, maternal reasoning ability, mean nutrient densities of zinc and phytate, and total energy from complementary foods (9–24 months). CONCLUSIONS: A supporting and nurturing environment was the variable most strongly differentiating the most and least preferable trajectories of cognitive development. In addition, a higher quality diet promoted cognitive development while prolonged illness was indicative of less favorable patterns of development.

The theoretical, quantitative, and qualitative characteristics of five commonly used cognitive tests for preschoolers were reviewed and evaluated. These tests included the Woodcock-Johnson IV Tests of Cognitive Abilities (WJ IV COG; Schrank, McGrew, & Mather, 2014), the Wechsler Preschool and Primary Scale of Intelligence – Fourth Edition (WPPSI-IV; Wechsler, 2012a), the Differential Ability Scales – Second Edition (DAS-II; Elliott, 2007a), the Stanford-Binet Intelligence Scales – Fifth Edition (SB5; Roid, 2003a), and the Kaufman Assessment Battery for Children – Second Edition: Normative Update (KABC-II:NU; Kaufman & Kaufman, 2018b). Although the DAS-II and KABC-II emerged as the most well-rounded of the five cognitive tests evaluated, all of the tests have their strengths and limitations. The authors suggest that examiners and practitioners know the characteristics of each of these tests before selecting one for use with preschool children to maximize their utility, interpret them accurately, and provide meaningful recommendations to parents, teachers, and other professionals.

Objectives: To assess the role of fetal brain-sparing and postnatal cerebral oxygen saturation (rcSO2) as determinants of long-term neurodevelopmental outcome following fetal growth restriction (FGR). Methods: This was a prospective follow-up study of an FGR cohort of 41 children. Prenatally, the presence of fetal brain-sparing (cerebroplacental ratio < 1) was assessed by Doppler ultrasound. During the first two days after birth, rcSO2 was measured with near-infrared spectroscopy. At 4 years of age, intelligence (IQ points), behavior (T-scores), and executive function (T-scores) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Child Behavior Checklist, and Behavior Rating Inventory of Executive Function—Preschool Version, respectively. Using linear regression analyses, we tested the association (p < 0.05) between brain-sparing/rcSO2 and normed neurodevelopmental scores. Results: Twenty-six children (gestational age ranging from 28.0 to 39.9 weeks) participated in the follow-up at a median age of 4.3 (range: 3.6 to 4.4) years. Autism spectrum disorder was reported in three children (11.5%). Fetal brain-sparing was associated with better total and externalizing behavior (betas: −0.519 and −0.494, respectively). RcSO2 levels above the lowest quartile, particularly on postnatal day 2 (≥ 77%), were associated with better total and internalizing behavior and executive functioning (betas: −0.582, −0.489, and −0.467, respectively), but also lower performance IQ (beta: −0.530). Brain-sparing mediated some but not all of these associations. Conclusions: In this FGR cohort, fetal brain-sparing and high postnatal rcSO2 were—independently, but also as a reflection of the same mechanism—associated with better behavior and executive function. Postnatal cerebral hyperoxia, however, was negatively associated with brain functions responsible for performance IQ.

Background:There are several potential mechanisms linking breastfeeding with enhanced neurodevelopment in infancy. Breast milk contains long chain polyunsaturated fatty acids which are structural lipids critical for retina and cortical brain development in early life.Objectives:The aim of this study was to assess the relationship between breastfeeding and the intellectual development. Methods:A retrospective study involving 350 preschool children( aged two years and six months till the age of five years) attending Kafr El-Khadra family health unit ,El Bagour district, Menoufia governorate, Egypt during the period of data collection (three months). They were subjected to a semistructured questionnaire from the mothers and their intellectual development were assessed using Wechsler Preschool and Primary Scale questionnaire for children 2013(WPPSI) Results:This study revealed that out of 350 studied preschool children, 154 children (44%) had an average intelligence quotient (IQ) while 4 children (1.1%) had an extremely low IQ and one child (0.3%) had very superior IQ. There were high statistically significant difference in IQ of studied children as regard exclusivity of breastfeeding and types of feeding either artificially or breast feeding (P value

BACKGROUND: A relationship between motor performance and cognitive functioning is increasingly being recognized. Yet, little is known about the precise nature of the relationship between both domains, especially in early childhood.AIMS: To identify distinct constellations of motor performance, executive functioning (EF), and verbal ability in preschool aged children; and to explore how individual and contextual variables are related to profile membership.METHODS AND PROCEDURES: The sample consisted of 119 3- to 4-year old children (62 boys; 52%). The home based assessments consisted of a standardized motor test (Movement Assessment Battery for Children - 2), five performance-based EF tasks measuring inhibition and working memory, and the Receptive Vocabulary subtest from the Wechsler Preschool and Primary Scale of Intelligence Third Edition. Parents filled out the Behavior Rating Inventory of Executive Function - Preschool version. Latent profile analysis (LPA) was used to delineate profiles of motor performance, EF, and verbal ability. Chi-square statistics and multinomial logistic regression analysis were used to examine whether profile membership was predicted by age, gender, risk of motor coordination difficulties, ADHD symptomatology, language problems, and socioeconomic status (SES).OUTCOMES AND RESULTS: LPA yielded three profiles with qualitatively distinct response patterns of motor performance, EF, and verbal ability. Quantitatively, the profiles showed most pronounced differences with regard to parent ratings and performance-based tests of EF, as well as verbal ability. Risk of motor coordination difficulties and ADHD symptomatology were associated with profile membership, whereas age, gender, language problems, and SES were not.CONCLUSIONS AND IMPLICATIONS: Our results indicate that there are distinct subpopulations of children who show differential relations with regard to motor performance, EF, and verbal ability. The fact that we found both quantitative as well as qualitative differences between the three patterns of profiles underscores the need for a person-centered approach with a focus on patterns of individual characteristics.

BACKGROUND AND OBJECTIVES: Children born very preterm (VPT) are at high risk of cognitive impairment that impacts their educational and social opportunities. This study examined the predictive accuracy of assessments at 2, 4, 6, and 9 years in identifying preterm children with cognitive impairment by 12 years. METHODS: We prospectively studied a regional cohort of 103 children born VPT (≤32 weeks’ gestation) and 109 children born term from birth to corrected age 12 years. Cognitive functioning was assessed by using age-appropriate, standardized measures: Bayley Scales of Infant Development, Second Edition (age 2); Wechsler Preschool and Primary Scale of Intelligence (ages 4 and 6); and Wechsler Intelligence Scale for Children, Fourth Edition (ages 9 and 12). RESULTS: By 12 years, children born VPT were more likely to have severe (odds ratio 3.9; 95% confidence interval 1.1–13.5) or any (odds ratio 3.2; 95% confidence interval 1.8–5.6) cognitive impairment compared with children born term. Adopting a severe cognitive impairment criterion at age 2 under-identified 44% of children born VPT with later severe impairment, whereas a more inclusive earlier criterion identified all severely affected children at 12 years. Prediction improved with age, with any delay at age 6 having the highest sensitivity (85%) and positive predictive value (66%) relative to earlier age assessments. Inclusion of family-social circumstances further improved diagnostic accuracy. CONCLUSIONS: Cognitive risk prediction improves with age, with assessments at 6 years offering optimal diagnostic accuracy. Intervention for children with early mild delay may be beneficial, especially for those raised in socially disadvantaged family contexts.

Background Accumulating evidence suggests that breastfeeding exclusivity and duration are positively associated with child cognition. This study investigated whether DNA methylation, an epigenetic mechanism modified by nutrient intake, may contribute to the link between breastfeeding and child cognition. The aim was to quantify the relationship between global DNA methylation and cognition and behavior at 4 years of age. Methods Child behavior and cognition were measured at age 4 years using the Wechsler Preschool and Primary Scale of Intelligence, third version (WPPSI‐III), and Child Behavior Checklist (CBC). Global DNA methylation (%5‐methylcytosines (%5mC)) was measured in buccal cells at age 4 years, using an enzyme‐linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. Results Data were collected from 73 children recruited from the Women and Their Children's Health (WATCH) study. No statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05), though the estimates of effect were consistently negative. Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p, This study quantified the relationship between global DNA methylation and cognition and behavior at 4 years of age. Data were collected from 73 children indicated no statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05). Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p

Despite the undisputed benefits of combination antiretroviral therapy (cART), perinatally acquired human immunodeficiency virus (PHIV) children on treatment often present with a spectrum of neurological deficits known as HIV-associated neurocognitive impairment. Even higher CD4 cell count does not seem to prevent the development of neurocognitive impairment in children with PHIV. While CD4 cell count has shown to have the greatest prognostic value, its association with neurocognitive abilities remains to be clarified. This study aimed at determining the correlation between plasma CD4+ lymphocyte and neurocognitive function in children with PHIV on cART. In total, 152 purposively recruited hospital-based sample of children with PHIV on cART, aged 3 years to 7 years 6 months (mean age, 63.13 months), underwent neurocognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Immunological status of each child was based on the plasma CD4+ lymphocyte levels. The mean CD4+ lymphocyte cell count at the time of neurocognitive assessment was 1,259.85 cells/mm3 (mean range, 139-2,717 cells/mm3), with significant age difference on CD4+ lymphocyte count levels [F (2, 149) = 13.58, p = 0.000]. CD4+ lymphocyte counts was significantly correlated with subdomains of neurocognitive function scores of task that measures working memory, processing speed, and perceptual reasoning. Global cognitive ability (Full Scale Intellectual Quotient) had no significant association with immunological status of the children. The findings support an association between immunological status of PHIV infection and executive function task. These neurocognitive faculties are critical for learning, school readiness and success in early childhood, and ultimately treatment adherence in adolescence. The need for early identification of neurodevelopment deficits in children, even when on cART, is crucial because early psychosocial and neurorehabilitative interventions can lead to better outcome for children with PHIV.

Background Metformin is widely used in pregnancy to treat gestational diabetes mellitus and polycystic ovary syndrome (PCOS). Association between PCOS and developmental delay in offspring, and larger head circumference of metformin-exposed newborns has been reported. The objective of this study was to explore whether metformin exposure in utero had any effect on offspring cognitive function. Method The current study is a follow-up of two randomized, placebo-controlled studies which were conducted at 11 public hospitals in Norway In the baseline studies (conducted in 2000–2003, and 2005–2009), participants were randomized to metformin 1700 and 2000 mg/d or placebo from first trimester to delivery. There was no intervention in the current study. We invited parents of 292 children to give permission for their children to participate; 93 children were included (mean age 7.7 years). The follow-up study was conducted in 2014–2016. The Wechsler Preschool and Primary Scale of Intelligence version III and the Wechsler Intelligence Scale for Children version IV were applied for cognitive assessment. Androstenedione and testosterone were measured in maternal blood samples at four time-points in pregnancy. Results We found no difference in mean, full scale IQ in metformin (100.0 (SD 13.2)) vs. placebo-exposed (100.9 (SD 10.1)) children. There was an association between metformin exposure in utero and borderline intellectual function of children (full scale IQ between 70 and 85). Free testosterone index in gestational week 19, and androstenedione in gestational week 36 correlated positively to full scale IQ. Conclusions We found no evidence of long-term effect of metformin on average child cognitive function. The increase of borderline intellectual functioning in metformin-exposed children must be interpreted with caution due to small sample size. Trial registration The baseline study was registered on 12 September 2005 at the US National Institute of Health (ClinicalTrials.gov) # NCT00159536.

OBJECTIVE To study the association of prepregnancy body mass index (BMI) and gestational weight gain with child neurodevelopmental outcomes. METHODS We performed a secondary analysis of data from two parallel, multicenter, randomized, double-blind, placebo-controlled thyroxine replacement trials in pregnant women with either hypothyroxinemia or subclinical hypothyroidism who delivered at term. Body mass index was categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30 or greater). We also evaluated early (20 weeks of gestation or less), late (greater than 20 weeks of gestation), and total gestational weight gain and categorized gestational weight gain as inadequate, adequate, and excessive per 2009 Institute of Medicine guidelines. Neurodevelopmental outcomes included 5-year Wechsler Preschool and Primary Scale of Intelligence and 3-year Differential Ability Scales-II. Linear and logistic regression analyses were performed and adjusted for maternal age, race-ethnicity, education, insurance status, parity, smoking and alcohol use, thyroid status (subclinical hypothyroidism or hypothyroxinemia), treatment group, gestational age at delivery, and neonatal sex. RESULTS Of the 948 women included, 380 (40%), 305 (32%), and 263 (28%) had normal, overweight, and obese prepregnancy BMI, respectively. A total of 106 (11%), 212 (22%), and 630 (66%) of women had inadequate, adequate, and excessive total rates of gestational weight gain, respectively. Maternal differences among the BMI categories included race-ethnicity, education, insurance type, parity, and thyroid status (all P

Background: Lead exposure predicts altered neurodevelopment and lower intelligence quotient (IQ) in children, but few studies have examined this association in children who have relatively low blood lead concentrations. Objectives: To test the associations between blood lead concentrations and cognitive function in Canadian preschoolers, with a possible moderation by sex. Methods: The data were gathered from 609 mother-child pairs from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study. Lead was measured in umbilical and maternal blood, and in children's venous blood at age 3–4 years. Cognitive function was measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) at 3–4 years. We tested the relationship between WPPSI-III scores and blood lead concentrations with multiple linear regression, adding child sex as a moderator. Results: Median blood lead concentrations for the mother at 1st trimester and 3rd trimester of pregnancy, and for cord and child blood were 0.60 μg/dL, 0.58 μg/dL, 0.79 μg/dL and 0.67 μg/dL, respectively. We found no association between cord blood lead concentrations and WPPSI-III scores in multivariable analyses. However, cord blood lead concentrations showed a negative association with Performance IQ in boys but not in girls (B = 3.44; SE = 1.62; 95% CI: 0.82, 5.98). No associations were found between WPPSI-III scores and prenatal maternal blood or concurrent child blood lead concentrations. Conclusions: Prenatal blood lead concentrations below 5 μg/dL were still associated with a decline in cognitive function in this Canadian cohort, but only for boys. Keywords: Blood lead concentrations, Sex differences, Intelligence quotient, Canadian children

Background Pompe disease (PD) is a rare condition caused by mutations in gene encoding for the enzyme alpha-glucosidase, resulting in an abnormal intracellular accumulation of glycogen. The disease clinical spectrum ranges from severe infantile forms to adult-onset forms with minor limitations. Since 2000 enzyme replacement therapy (ERT) is available and disease natural history has changed, with prolonged survival and evidence of myopathic features. Methods In this study, we monitored disease progression up to three years in eight young patients with PD. Based on the literature data and the long term personal experience, we selected validated functional scales for neuromuscular disorders and compared the results to identify a simple and reliable protocol for the follow-up of children with PD. Moreover, we evaluated cognitive functions using developmental/cognitive tests. Results Based on study results, we suggest that motor functions in children with PD could be better assessed by Chop Intend, MFM20 (Motor Function Measure Scale for Neuromuscular Diseases 20) and NSAA (North Star Ambulatory Assessment), according to age and functional level. Evaluation should be completed with ROM (Range Of Motion) measurement, MRC (Medical Research Council) evaluation and 6MWT (6 Minute Walk test) when possible. Conclusions The proposed protocol seems to be reliable and should be done every six months, because of the progressive natural history of the disease, the rapid changes typical of developmental age and the need to document ERT effects. About cognitive functions, additional tests to classical intelligence scales (WISC, WPPSI) should be useful to better describe specific neuropsychological profile.

Initial participants were 79 children who were recruited from six preschool programs in the U.S. Full assessment data was available for 73 children (average age of 4 years 7 months), including demographic data (gender, ethnicity, financial need, language(s) spoken at home and special education status). Children׳s math, repeating patterning, spatial and verbal skills were assessed at the beginning of the pre-kindergarten year. Assessments included the brief version of the Research-Based Early Mathematics Assessment, two measures of repeating patterning skills, three measures of spatial skills (the Block Design subtest of the Wechsler Preschool and Primary Scale of Intelligence, the Position in Space subtest of the Developmental Test of Visual Perception, and a Corsi Block Tapping Task), the Picture Vocabulary Test from the NIH Toolbox app and a backward letter span task. Near the end of the school year, their math knowledge was re-assessed using the same math measure, as was their memory span (forward and backward digit span task from the Wechsler Intelligence Scale for Children). Findings on the relations between patterning, spatial and math skills are published elsewhere (Rittle-Johnson et al., 2018) [1].