Longitudinal Structural and Diffusion-Weighted Neuroimaging of Young Children Born Preterm.

BACKGROUND: Children born preterm are at risk for diffuse injury to subcortical gray and white matter. METHODS: We used a longitudinal cohort study to examine the development of subcortical gray matter and white matter volumes, and diffusivity measures of white matter tracts following preterm birth. Our participants were 47 children born preterm (24 to 32 weeks gestational age) and 28 children born at term. None of the children born preterm had significant neonatal brain injury. Children received structural and diffusion weighted magnetic resonance imaging scans at ages five, six, and seven years. We examined volumes of amygdala, hippocampus, caudate nucleus, putamen, thalamus, brainstem, cerebellar white matter, intracranial space, and ventricles, and volumes, fractional anisotropy, and mean diffusivity of anterior thalamic radiation, cingulum, corticospinal tract, corpus callosum, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, temporal and parietal superior longitudinal fasciculus, and uncinate fasciculus. RESULTS: Children born preterm had smaller volumes of thalamus, brainstem, cerebellar white matter, cingulum, corticospinal tract, inferior frontal occipital fasciculus, uncinate fasciculus, and temporal superior longitudinal fasciculus, whereas their ventricles were larger compared with term-born controls. We found no significant effect of preterm birth on diffusivity measures. Despite developmental changes and growth, group differences were present and similarly strong at all three ages. CONCLUSION: Even in the absence of significant neonatal brain injury, preterm birth has a persistent impact on early brain development. The lack of a significant term status by age interaction suggests a delayed developmental trajectory.

Design of the FRESH-DOSE study: A randomized controlled noninferiority trial evaluating a guided self-help family-based treatment program for children with overweight or obesity.

Overweight and obesity affect 45% of children and increases the risk for several negative health sequelae. Family-Based Behavioral Treatment (FBT) is the most efficacious treatment for child weight management and consists of nutrition and physical activity education, behavior change skills and parenting skills training. FBT is time and staff intensive and can include 20, 60-min separate groups for parents and children, as well as 20-min behavior coaching sessions to help problem solve barriers to implementing the skills learned and individualize the program. Guided self-help (GSH) therapies involve providing families a manual to review independently and brief coaching sessions by an interventionist to facilitate adherence. We developed a GSH version of FBT (gshFBT) which provides a manual to both parents and children and includes 14, 20-min coaching sessions over 6-months. The current study randomized 150 children (mean age = 10.1 years (SD = 1.38); mean BMI% = 97.3% (SD = 2.84); mean BMIz = 2.09 (SD = 0.40); 49% female; 43% Hispanic) and one of their parents (mean age = 41.8 years (SD = 6.52); mean BMI = 32.0 (SD = 7.24); 87.3% female; 43% Hispanic) to either a group-based FBT program or a gshFBT program. Assessments are conducted at baseline, post-treatment (6 months), 6-month follow-up (12 months) and 12-month follow-up (18 months). Primary outcomes are child weight change (BMIz) and cost effectiveness. Recruitment occurred between May 2017 and October 2021 and follow-up assessments are underway. Given the public health concern for children with obesity and the low level of access to FBT, gshFBT could prove extremely useful to provide intervention to a greater proportion of the population.

Fetal alcohol spectrum disorders and access to regional center services in San Diego County.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are developmental disabilities that are estimated to occur in 2-5% of elementary school children and that negatively impact a child's ability to function without support. Timely diagnosis-informed interventions are crucial to optimizing the developmental trajectory of children with FASD. The true prevalence of FASD among children receiving services for developmental disabilities is unknown. METHODS: An FASD prevalence study was carried out between 2011 and 2014 among a sample of 5- to 7-year-old children who were receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Children whose parent or caregiver consented were evaluated using the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study assessment protocol and classification criteria. RESULTS: Among 216 eligible caregiver-child dyads, 44 completed assessments that were sufficient to obtain a classification for FASD, including fetal alcohol syndrome (FAS), partial FAS, alcohol-related neurodevelopmental disorder, or no fetal alcohol spectrum disorder. Fifteen children were classified as meeting the criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1000 (6.9%) among all eligible children was estimated. None of the children classified as FASD were receiving services because of an FASD diagnosis, and none had previously been diagnosed with FASD. Autism was the most common qualifying diagnosis for which children classified as FASD were receiving services. CONCLUSIONS: The 6.9% prevalence estimate among Regional Center clients was higher than the prevalence estimate of 2.3% in the same community among 5- to 7-year-old children in the general population, though the estimate was based on only 20% of eligible dyads. All children in the sample were receiving Regional Center services for another diagnosis. Barriers to eligibility for services for children with FASD may lead to less than optimum care for these children. Study findings support the facilitation of access to developmental services for children with FASD.

Do aggregate, multimodal structural neuroimaging measures replicate regional developmental differences observed in highly cited cellular histological studies?

Influential investigations of postmortem human brain tissue showed regional differences in tissue properties at early phases of development, such as between prefrontal and primary sensory cortical regions. Large-scale neuroimaging studies enable characterization of age-related trajectories with much denser sampling of cortical regions, assessment ages, and demographic variables than postmortem tissue analyses, but no single imaging measure perfectly captures what is measured with histology. Using publicly available data from the Pediatric Imaging, Neurocognition, and Genetics (PING) study, including 951 participants with ages ranging from 3 to 21 years, we characterized cortical regional variability in developmental trajectories of multimodal brain imaging measures. Multivariate analyses integrated morphometric and microstructural cortical surface measures. To replicate foundational histological work showing delayed synapse elimination in middle frontal gyrus relative to primary sensory areas, we tested whether developmental trajectories differ between prefrontal and visual or auditory cortex. We extended this to a whole-cortex analysis of interregional differences, producing cortical parcellations with maximally different developmental trajectories. Consistent with the general conclusions of postmortem analyses, our imaging results suggest that prefrontal regions show a protracted period of greater developmental change; however, they also illustrate the challenges of drawing conclusions about the relative maturational phases of different brain regions.

Self-regulation task in young school age children born preterm: Correlation with early academic achievement.

BACKGROUND: Children born preterm are at risk for difficulties in executive function (EF), however there are limited tools to assess EF in young children and it is not fully understood how these early deficits are related to emerging academic skills. AIMS: To examine (a) early EF differences in young children born preterm, (b) how a measure of behavioral self-regulation correlates with other measures of EF in children born preterm, and (c) how this measure relates to academic outcomes in children born preterm. STUDY DESIGN: Longitudinal cohort study. SUBJECTS: Thirty-three healthy children born preterm (25-32 weeks gestation) and 14 children born full term were assessed before starting kindergarten at age 5 and again at ages 6 and 7 years. OUTCOME MEASURES: Each assessment included a measure of behavioral self-regulation, the Head Toes Knees Shoulders task (HTKS), performance-based measures of EF, parent rating scales of EF and behavior problems, a measure of motor ability, and academic measures. RESULTS: Children born preterm performed worse on all measures of self-regulation, EF, parent-report, academic outcomes, and motor ability across time. The HTKS had weak to moderate correlations with parent-report and performance-based measures of EF, moderate to strong correlations with academic performance, and was not correlated with motor ability. CONCLUSION: This study shows the predictive value of early EF measures on functional academic outcomes and their potential as targets of effective interventions in this high-risk population.

Person Ability Scores as an Alternative to Norm-Referenced Scores as Outcome Measures in Studies of Neurodevelopmental Disorders.

Although norm-referenced scores are essential to the identification of disability, they possess several features which affect their sensitivity to change. Norm-referenced scores often decrease over time among people with neurodevelopmental disorders who exhibit slower-than-average increases in ability. Further, the reliability of norm-referenced scores is lower at the tails of the distribution, resulting in floor effects and increased measurement error for people with neurodevelopmental disorders. In contrast, the person ability scores generated during the process of constructing a standardized test with item response theory are designed to assess change. We illustrate these limitations of norm-referenced scores, and relative advantages of ability scores, using data from studies of autism spectrum disorder and creatine transporter deficiency.

Cognitive functions mediate the effect of preterm birth on mathematics skills in young children.

Children born preterm are at risk for cognitive deficits and lower academic achievement. Notably, mathematics achievement is generally most affected. Here, we investigated the cognitive functions mediating early mathematics skills and how these are impacted by preterm birth. Healthy children born preterm (gestational age at birth < 33 weeks; n = 51) and children born full term (n = 27) were tested at ages 5, 6, and 7 years with a comprehensive battery of tests. We categorized items of the TEMA-3: Test for Early Mathematics Abilities Third Edition into number skills and arithmetic skills. Using multiple mediation models, we assessed how the effect of preterm birth on mathematics skills is mediated by spatial working memory, inhibitory control, visual-motor integration, and phonological processing. Both number and arithmetic skills showed group differences, but with different developmental trajectories. The initial performance gap observed in the preterm children decreased over time for number skills but increased for arithmetic skills. Phonological processing, visual-motor integration, and inhibitory control were poorer in children born preterm. These cognitive functions, particularly phonological processing, had a mediating effect on both types of mathematics skills. These findings help define and chart the trajectory of the specific cognitive skills directly influencing math deficit phenotypes in children born very preterm. This knowledge provides guidance for targeted evaluation and treatment implementation.

Variations in brain morphometry among healthy preschoolers born preterm.

BACKGROUND: Preterm birth is associated with an increased risk of neonatal brain injury, which can lead to alterations in brain maturation. Despite being born without the most significant medical consequences of preterm birth, infants born early remain at increased risk for subtle brain injury that affects future neurodevelopment and functioning. AIMS: To investigate the gray matter morphometry measures of cortical thickness, cortical surface area, and sulcal depth using MRI at 5 years of age in healthy children born preterm. STUDY DESIGN: Cohort study. SUBJECTS: Participants were 52 children born preterm (<33 weeks gestational age) and 37 children born full term. OUTCOME MEASURES: Cortical segmentation and calculation of morphometry measures were completed using FreeSurfer version 5.3.0 and compared between groups using surface-based, voxel-wise analyses. RESULTS: The preterm group had a significantly thinner cortex in temporal and parietal regions while cortical thickness was significantly larger within occipital and inferior frontal regions. Surface area was significantly reduced within the fusiform gyrus. Sulcal depth was significantly lower within the posterior parietal and inferior temporal regions but greater in the middle temporal and medial parietal regions. CONCLUSIONS: Regional differences were found between preschoolers born preterm and full term in cortical thickness, surface area, and sulcal depth. Cortical thickness differences primarily overlapped with regions found in previous studies of older children and adults. Differences in sulcal depth may represent additional areas of maturational differences in preterm children. These findings likely represent a combination of delayed maturation and permanent alterations caused by the perinatal processes associated with preterm birth.

Fetal Alcohol Spectrum Disorders in a Pacific Southwest City: Maternal and Child Characteristics.

BACKGROUND: There are limited data on the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers from the general population in the United States. METHODS: During the 2012 and 2013 academic years, first-grade children in a large urban Pacific Southwest city were invited to participate in a study to estimate the prevalence of FASD. Children who screened positive on weight, height, or head circumference ≤25th centile or on parental report of developmental concerns were selected for evaluation, along with a random sample of those who screened negative. These children were examined for dysmorphology and neurobehavior and their mothers or collateral sources were interviewed. Children were classified as fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), or No FASD. RESULTS: A total of 854 children were evaluated; 5 FAS, 44 pFAS, 44 ARND, and 761 No FASD. Children with FAS or pFAS were more likely to have dysmorphic features, and 32/49 (65.3%) of those met criteria for neurobehavioral impairment on cognitive measures with or without behavioral deficits. In contrast, 28/44 (63.6%) of children with ARND met criteria on behavioral measures alone. Mothers of FASD children were more likely to recognize pregnancy later, be unmarried, and report other substance use or psychiatric disorders, but did not differ on age, socioeconomic status, education, or parity. Mothers of FASD children reported more drinks/drinking day each trimester. The risk of FASD was elevated with increasing number of drinks/drinking day prior to pregnancy recognition, even at the level of 1 drink per day (adjusted odds ratio 3.802, 95% confidence interval 1.634, 8.374). CONCLUSIONS: Data from this general population sample in a large urban region in the United States demonstrate the variability of expression of FASD and point to risk and protective factors for mothers in this setting.

The Prevalence of Fetal Alcohol Spectrum Disorders in An American Indian Community.

The prevalence of fetal alcohol spectrum disorders (FASD) differs among populations and is largely unknown among minority populations. Prevalence and characterization of FASD is necessary for prevention efforts and allocation of resources for treatment and support. However, prevalence data are lacking, including among many minority populations. The aim of this study was to obtain an FASD prevalence estimate in a Southern California American Indian community employing active case-ascertainment. In 2016, American Indian children aged 5-7 years and their caregivers were recruited in collaboration with Southern California Tribal Health Clinic. Children were assessed using physical examinations and neurobehavioral testing. Parent or guardian interviews assessed child behavior and prenatal exposures including alcohol. Of 488 children identified as eligible to participate, 119 families consented and 94 completed assessments to allow a classification for FASD. Participating children (n = 94) were an average of 6.61 ± 0.91 years old and half were female. Most interviews were conducted with biological mothers (85.1%). Less than one third (29.8%) of mothers reported consuming any alcohol in pregnancy and 19.1% met study criteria for risky alcohol exposure prior to pregnancy recognition. Overall 20 children met criteria for FASD, resulting in an estimated minimum prevalence of 41.0 per 1000 (4.1%). No cases of fetal alcohol syndrome (FAS) were identified; 14 (70.0%) met criteria for alcohol related neuro- developmental disorder (ARND). Minimum prevalence estimates found in this sample are consistent with those noted in the general population.

Partial Jacobsen syndrome phenotype in a patient with a de novo frameshift mutation in the ETS1 transcription factor.

Jacobsen syndrome (OMIM #147791) is a rare contiguous gene disorder caused by deletions in distal 11q. The clinical phenotype is variable and can include dysmorphic features, varying degrees of intellectual disability, behavioral problems including autism and attention deficit hyperactivity disorder, congenital heart defects, structural kidney defects, genitourinary problems, immunodeficiency, and a bleeding disorder due to impaired platelet production and function. Previous studies combining both human and animal systems have implicated several disease-causing genes in distal 11q that contribute to the Jacobsen syndrome phenotype. One gene, ETS1, has been implicated in causing congenital heart defects, structural kidney defects, and immunodeficiency. We performed a comprehensive phenotypic analysis on a patient with congenital heart disease previously found to have a de novo frameshift mutation in ETS1, resulting in the loss of the DNA-binding domain of the protein. Our results suggest that loss of Ets1 causes a "partial Jacobsen syndrome phenotype" including congenital heart disease, facial dysmorphism, intellectual disability, and attention deficit hyperactivity disorder.

Mathematics ability and related skills in preschoolers born very preterm.

Children born very preterm (VPT) are at risk for academic, behavioral, and/or emotional problems. Mathematics is a particular weakness and better understanding of the relationship between preterm birth and early mathematics ability is needed, particularly as early as possible to aid in early intervention. Preschoolers born VPT (n = 58) and those born full term (FT; n = 29) were administered a large battery of measures within 6 months of beginning kindergarten. A multiple-mediation model was utilized to characterize the difference in skills underlying mathematics ability between groups. Children born VPT performed significantly worse than FT-born children on a measure of mathematics ability as well as full-scale IQ, verbal skills, visual-motor integration, phonological awareness, phonological working memory, motor skills, and executive functioning. Mathematics was significantly correlated with verbal skills, visual-motor integration, phonological processing, and motor skills across both groups. When entered into the mediation model, verbal skills, visual-motor integration, and phonological awareness were significant mediators of the group differences. This analysis provides insights into the pre-academic skills that are weak in preschoolers born VPT and their relationship to mathematics. It is important to identify children who will have difficulties as early as possible, particularly for VPT children who are at higher risk for academic difficulties. Therefore, this model may be used in evaluating VPT children for emerging difficulties as well as an indicator that if other weaknesses are found, an assessment of mathematics should be conducted.

Development of a Brief Screening Tool for Early Literacy Skills in Preschool Children.

BACKGROUND: Preschool children develop early literacy skills (ELS) needed for reading acquisition. Screening for delayed ELS could trigger interventions to prevent reading problems. OBJECTIVE: To develop a brief screening test for ELS delays, the Early Literacy Skills Assessment Tool (ELSAT). METHODS: This study included 4-year-old, typically developing, English language-predominant children attending preschool. The ELSAT comprised 63 items relating to 3 main ELS domains and was piloted with 21 children. After we excluded items that were nondiscriminatory, 57 items remained and were administered to 96 children. Items were compared with reference measures of ELS (Get Ready to Read-Revised), and language (Peabody Picture Vocabulary Test-4 and Phonological Awareness from the Comprehensive Test of Phonological Processing-2). Within-domain reliability was calculated for each of the 3 ELS domains and item correlations between all ELSAT items and the reference measures were calculated. RESULTS: A final set of 10 items was retained that represented all 3 ELS domains and that maximized correlations with reference measures. Cronbach alpha for the refined 10-item ELSAT was 0.868; correlations between individual items and a composite of the reference measures ranged from 0.409 to 0.617 (all Ps < .01). In a receiver operating characteristic curve analysis, a cut-off score of ≤5 predicted a below-average score for any of the reference measures with sensitivity of 90%, specificity of 71.4%, and area under the curve of 0.872. CONCLUSIONS: The 10-item ELSAT shows strong psychometric properties and with further validation may prove valuable in screening preschool children for ELS delays.

Developmental differentiation of executive functions on the NIH Toolbox Cognition Battery.

OBJECTIVE: The NIH Toolbox Cognition Battery (NTCB) is a brief computerized method for evaluating neuropsychological functions in children, adolescents, and adults. We examined how performance on the 2 executive function measures of cognitive flexibility and inhibitory control was related to performance on the other NTCB measures across development. METHOD: Participants were 1,020 typically developing individuals between the ages of 3 and 21 from the Pediatric Imaging, Neurocognition, and Genetics Study who were divided into 5 age groups (3-6, 7-9, 10-13, 14-17, and 18-21). Scores were adjusted for sex, level of parental education, and family income. RESULTS: Although the correlations between the 2 executive function measures were moderate and consistent across age groups, their correlations with the other 5 cognitive measures were highest in the youngest age group and decreased across the older age groups. Exploratory factor analysis revealed that all NTCB measures loaded onto a single factor for the 3- to 6-year-olds. Across the older age groups, the executive function and processing speed measures loaded onto one factor, and the vocabulary knowledge, oral reading, and working memory measures loaded onto a second factor. CONCLUSIONS: These results indicate that younger children's performance on the NTCB is more intercorrelated and less differentiated, while performance on the NTCB executive function measures becomes more differentiated from performance on the other measures with development. These results support the hypothesis that executive functions become increasingly differentiated from other cognitive functions with development as the functional specialization of neural systems progresses throughout childhood and young adulthood. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Williams Syndrome neuroanatomical score associates with GTF2IRD1 in large-scale magnetic resonance imaging cohorts: a proof of concept for multivariate endophenotypes.

Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n = 38; validating, n = 60). We then associated this score with single nucleotide polymorphisms (SNPs) in the WS hemi-deleted region in five cohorts of neurologically and psychiatrically typical individuals (healthy European descendants, n = 1863). Among 110 SNPs within the 7q11.23 WS chromosomal region, we found one associated locus (p = 5e-5) located at GTF2IRD1, which has been implicated in animal models of WS. Furthermore, the genetic signals of neuroanatomical scores are highly enriched locally in the 7q11.23 compared with summary statistics based on regions of interest, such as hippocampal volumes (n = 12,596), and also globally (SNP-heritability = 0.82, se = 0.25, p = 5e-4). The role of genetic variability in GTF2IRD1 during neurodevelopment extends to healthy subjects. Our approach of learning MRI-derived phenotypes from clinical populations with well-established brain abnormalities characterized by known genetic lesions may be a powerful alternative to traditional region of interest-based studies for identifying genetic variants regulating typical brain development.

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities.

Importance: Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples. Objective: To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States. Design, Setting, and Participants: Active case ascertainment methods using a cross-sectional design were used to assess children for fetal alcohol spectrum disorders between 2010 and 2016. Children were systematically assessed in the 4 domains that contribute to the fetal alcohol spectrum disorder continuum: dysmorphic features, physical growth, neurobehavioral development, and prenatal alcohol exposure. The settings were 4 communities in the Rocky Mountain, Midwestern, Southeastern, and Pacific Southwestern regions of the United States. First-grade children and their parents or guardians were enrolled. Exposures: Alcohol consumption during pregnancy. Main Outcomes and Measures: Prevalence of fetal alcohol spectrum disorders in the 4 communities was the main outcome. Conservative estimates for the prevalence of the disorder and 95% CIs were calculated using the eligible first-grade population as the denominator. Weighted prevalences and 95% CIs were also estimated, accounting for the sampling schemes and using data restricted to children who received a full evaluation. Results: A total of 6639 children were selected for participation from a population of 13 146 first-graders (boys, 51.9%; mean age, 6.7 years [SD, 0.41] and white maternal race, 79.3%). A total of 222 cases of fetal alcohol spectrum disorders were identified. The conservative prevalence estimates for fetal alcohol spectrum disorders ranged from 11.3 (95% CI, 7.8-15.8) to 50.0 (95% CI, 39.9-61.7) per 1000 children. The weighted prevalence estimates for fetal alcohol spectrum disorders ranged from 31.1 (95% CI, 16.1-54.0) to 98.5 (95% CI, 57.5-139.5) per 1000 children. Conclusions and Relevance: Estimated prevalence of fetal alcohol spectrum disorders among first-graders in 4 US communities ranged from 1.1% to 5.0% using a conservative approach. These findings may represent more accurate US prevalence estimates than previous studies but may not be generalizable to all communities.

Cortical morphology of the pars opercularis and its relationship to motor-inhibitory performance in a longitudinal, developing cohort.

This study investigates the relationship between variability in cortical surface area and thickness of the pars opercularis of the inferior frontal gyrus and motor-inhibitory performance on a stop-signal task in a longitudinal, typically developing cohort of children and adolescents. Linear mixed-effects models were used to investigate the hypotheses that (1) cortical thinning and (2) a relatively larger cortical surface area of the bilateral pars opercularis of the inferior frontal gyrus would predict better performance on the stop-signal task in a cohort of 110 children and adolescents 4-13 years of age, with one to four observations (totaling 232 observations). Cortical thickness of the bilateral opercular region was not related to inhibitory performance. However, independent of age, gender, and total cortical surface area, relatively larger cortical surface area of the bilateral opercular region of the inferior frontal gyrus was associated with better motor-inhibitory performance. Follow-up analyses showed a significant effect of surface area of the right pars opercularis, but no evidence for an effect of area of left pars opercularis, on motor-inhibitory performance. These findings are consistent with the previous work in adults showing that cortical morphology of the pars opercularis is related to inhibitory functioning. It also expands upon this literature by showing that, in contrast to earlier work highlighting the importance of cortical thickness of this region in adults, relative cortical surface area of the pars opercularis may be related to developing motor-inhibitory functions during childhood and adolescence. Relationships between cortical phenotypes and individual differences in behavioral measures may vary across the lifespan.

A Randomized Clinical Trial of Umbilical Cord Milking vs Delayed Cord Clamping in Preterm Infants: Neurodevelopmental Outcomes at 22-26 Months of Corrected Age.

OBJECTIVE: To compare the effect of umbilical cord milking vs delayed cord clamping (DCC) on neurodevelopmental and health outcomes in very preterm infants at 22-26 months of corrected age. STUDY DESIGN: Neurodevelopmental outcomes at 2 years of age were assessed using the Bayley Scales of Infant Development, third edition, and a standardized neurologic examination. Data regarding pulmonary morbidities, neurosensory impairments, and hospitalizations were obtained by parental interview. Intention-to-treat was used for primary analyses. RESULTS: Of the 197 infants enrolled in the original study there were 15 deaths, 5 in the umbilical cord milking group and 10 in DCC group. Of the remaining infants, 135 (74%) were assessed at 22-26 months of corrected age. Demographics in umbilical cord milking (n = 70) and DCC (n = 65) groups were similar. Infants randomized to umbilical cord milking at birth had significantly higher cognitive and language composite scores, and were less likely to have a cognitive composite score of <85 (4% vs 15%; P = .04). Motor function was similar in both groups. There were no differences in the incidences of mild or moderate to severe neurodevelopmental impairment, hearing or visual impairments, pulmonary morbidities, or rehospitalizations between the 2 groups. CONCLUSIONS: Infants randomized to umbilical cord milking had higher language and cognitive scores compared with those randomized to DCC. There was no difference in rates of mild or moderate to severe neurodevelopmental impairment. TRIAL REGISTRATION: clinicaltrials.gov: NCT01434732.

Academic Achievement Deficits and Their Neuropsychological Correlates in Children Born Extremely Preterm.

OBJECTIVE: The purpose of this study was to examine the risks associated with learning disabilities (LDs) in a large sample of children born extremely preterm. We predicted higher than expected rates of LD, particularly in math, and children with LD in math, reading, or both would have lower intelligence quotients (IQs) and specific patterns of neuropsychological deficits. METHODS: We evaluated academic achievement, rates of LD, and their neuropsychological correlates in the Extremely Low Gestational Age Newborns (ELGANs) Study cohort of 10-year-old children born at 23 to 27 weeks gestational age. Primary analyses focused on children without intellectual disability (verbal IQ > 70 and nonverbal IQ > 70; N = 668). Low achievement was defined as a standard score ≤85 on the reading or math measures. RESULTS: The risk of low math achievement scores (27%) was 1.5 times higher than the risk of low reading achievement scores (17%). Children were classified as having LD based on low achievement criteria in reading only (RD, 6.4% of sample), math only (MD, 16.2%), both reading and math (RD/MD, 8.3%), or no reading or math disabilities (No LD, 69.1%). Although all 3 LD groups had multiple neuropsychological weaknesses compared with the No LD group, the RD and MD groups had different patterns of neuropsychological impairment. CONCLUSION: These children from the ELGAN cohort had higher than expected rates of LD, particularly in mathematics, even after taking socioeconomic status into consideration. These results indicate specific cognitive weaknesses that differ between extremely preterm children with RD and MD.

Academic Difficulties in Children with Prenatal Alcohol Exposure: Presence, Profile, and Neural Correlates.

BACKGROUND: Academic achievement was evaluated in children with heavy prenatal alcohol exposure to determine potential strengths and weaknesses, evaluate the utility of different definitions for identifying low academic performance, and explore the neural correlates that may underlie academic performance. METHODS: Children (8 to 16 years) were assessed using the WIAT-II. Patterns of performance were examined in 2 subject groups: children with heavy prenatal alcohol exposure (n = 67) and controls (n = 61). A repeated-measures MANCOVA examining group differences on academic domain (reading, spelling, math) scores was conducted. Post hoc comparisons examined within-group profiles. Numbers and percentage of children with low achievement were calculated using several criteria. In a subsample (n = 42), neural correlates were analyzed using FreeSurfer v5.3 to examine relations between cortical structure (thickness and surface area) and performance. RESULTS: The alcohol-exposed group performed worse than controls on all domains and had a unique academic profile, supported by a significant group × academic domain interaction (p < 0.001). For the alcohol-exposed group, math reasoning was significantly lower than numerical operations, which was significantly lower than spelling and word reading. Over half of the alcohol-exposed group (58.2%) demonstrated low achievement on 1 or more academic domains. The number and percentage of children meeting criteria for low achievement varied based on the domain and definition used. The imaging analysis identified several surface area clusters that were differentially related to math (L superior parietal and R lateral/middle occipital) and spelling (bilateral inferior and medial temporal) performance by group, with no relations for the other academic domains. Generally, scores improved as surface area decreased in controls, whereas no relation or a positive relation was observed in the alcohol-exposed group. CONCLUSIONS: Alcohol-exposed children demonstrated deficits in academic performance across domains and definitions, with a relative weakness in math functioning. Atypical brain development may contribute to these impairments in academic achievement. Understanding academic difficulties can assist in advocating effectively for alcohol-exposed children.