Household socioeconomic status relates to specific hippocampal subfield volumes across development.

The hippocampus is composed of cytoarchitecturally distinct subfields that support specific memory functions. Variations in total hippocampal volume across development have been linked to socioeconomic status (SES), a proxy for access to material resources, medical care, and quality education. High childhood household SES is associated with greater cognitive abilities in adulthood. Currently, it is not known whether household SES differentially impacts specific hippocampal subfield volumes. We assessed susceptibility of subfields to variations in household SES across development in a sample of 167 typically developing 5- to 25-year-old. Bilateral cornu ammonis (CA) 1-2, combined CA3-dentate gyrus (DG), and subiculum (Sub) volumes were measured by highly reliable manual segmentation of high-resolution T2-weighted images and adjusted for intracranial volume. A summary component score of SES measures (paternal education, maternal education, and income-to-needs ratio) was used to examine variability in volumes across ages. We did not identify age-related differences in any of the regional volumes, nor did age modify SES-related effects. Controlling for age, larger volumes of CA3-DG and CA1-2 were associated with lower SES, while Sub volume was not. Overall, these findings support the specific impact of SES on CA3-DG and CA1-2 and highlight the importance of considering environmental influences on hippocampal subfield development.

Meta-Analysis of Hippocampal Volume and Episodic Memory in Preterm and Term Born Individuals.

Preterm birth (< 37 weeks gestation) has been associated with memory deficits, which has prompted investigation of possible alterations in hippocampal volume in this population. However, existing literature reports varying effects of premature birth on hippocampal volume. Specifically, it is unclear whether smaller hippocampal volume in preterm-born individuals is merely reflective of smaller total brain volume. Further, it is not clear if hippocampal volume is associated with episodic memory functioning in preterm-born individuals. Meta-analysis was used to investigate the effects of premature birth on hippocampal volume and episodic memory from early development to young adulthood (birth to 26). PubMed, PsychINFO, and Web of Science were searched for English peer-reviewed articles that included hippocampal volume of preterm and term-born individuals. Thirty articles met the inclusion criteria. Separate meta-analyses were used to evaluate standardized mean differences between preterm and term-born individuals in uncorrected and corrected hippocampal volume, as well as verbal and visual episodic memory. Both uncorrected and corrected hippocampal volume were smaller in preterm-born compared to term-born individuals. Although preterm-born individuals had lower episodic memory performance than term-born individuals, the limited number of studies only permitted a qualitative review of the association between episodic memory performance and hippocampal volume. Tested moderators included mean age, pre/post-surfactant era, birth weight, gestational age, demarcation method, magnet strength, and slice thickness. With this meta-analysis, we provide novel evidence of the effects of premature birth on hippocampal volume.

Cumulative Antenatal Risk and Kindergarten Readiness in Preterm-Born Preschoolers.

A suboptimal intrauterine environment is thought to increase the probability of deviation from the typical neurodevelopmental trajectory, potentially contributing to the etiology of learning disorders. Yet the cumulative influence of individual antenatal risk factors on emergent learning skills has not been sufficiently examined. We sought to determine whether antenatal complications, in aggregate, are a source of variability in preschoolers' kindergarten readiness, and whether specific classes of antenatal risk play a prominent role. We recruited 160 preschoolers (85 girls; ages 3-4 years), born ≤336/7 weeks' gestation, and reviewed their hospitalization records. Kindergarten readiness skills were assessed with standardized intellectual, oral-language, prewriting, and prenumeracy tasks. Cumulative antenatal risk was operationalized as the sum of complications identified out of nine common risks. These were also grouped into four classes in follow-up analyses: complications associated with intra-amniotic infection, placental insufficiency, endocrine dysfunction, and uteroplacental bleeding. Linear mixed model analyses, adjusting for sociodemographic and medical background characteristics (socioeconomic status, sex, gestational age, and sum of perinatal complications) revealed an inverse relationship between the sum of antenatal complications and performance in three domains: intelligence, language, and prenumeracy (p = 0.003, 0.002, 0.005, respectively). Each of the four classes of antenatal risk accounted for little variance, yet together they explained 10.5%, 9.8%, and 8.4% of the variance in the cognitive, literacy, and numeracy readiness domains, respectively. We conclude that an increase in the co-occurrence of antenatal complications is moderately linked to poorer kindergarten readiness skills even after statistical adjustment for perinatal risk.

Age-associated increase in mnemonic strategy use is linked to prefrontal cortex development.

Memory functioning undergoes dynamic changes between childhood and adulthood. Spontaneous use of elaborative strategies, which can enhance the recall of information, expands with age and contributes to age-associated improvement in memory functioning. Findings from lesion and neuroimaging studies suggest that the ability to use elaborative strategies is dependent upon intact functioning of the prefrontal cortex (PFC), particularly the dorsolateral PFC region. Because the PFC undergoes protracted maturation, we examined whether age difference in the structure of the PFC is correlated with age-associated increase in strategy use. Here, we investigated the relationship between PFC volume and spontaneous strategy use in a sample of 120 participants aged 5-25 years. We assessed semantic clustering during recall with a standardized word-list recall task (California Verbal Learning Task children's version, CVLT-C) and computed PFC regional volumes from participants' structural brain images. We observed an age-associated increase in the use of semantic clustering and an age-associated decrease in volumes of the PFC. Further, we found that smaller PFC volume was linked to increased use of semantic clustering. Importantly, the volume of the right dorsolateral PFC partially explained the relation between age and the use of semantic clustering. These findings suggest that PFC maturation supports the development of strategy use and lends further support for the notion that brain-behavior relations change across development.

Socioeconomic status and hippocampal volume in children and young adults.

An individual's socioeconomic status (SES) is often viewed as a proxy for a host of environmental influences. SES disparities have been linked to variance in brain structures particularly the hippocampus, a neural substrate of learning and memory. However, it is unclear whether the association between SES and hippocampal volume is similar in children and adults. We investigated the relationship between hippocampal volume and SES in a group of children (n = 31, age 8-12 years) and a group of young adults (n = 32, age 18-25 years). SES was assessed with four indicators that loaded on a single factor, therefore a composite SES scores was used in the main analyses. Hippocampal volume was measured using manual demarcation on high resolution structural images. SES was associated with hippocampal volume in the children, but not in adults, suggesting that in childhood, but not adulthood, SES-related environmental factors influence hippocampal volume. In addition, hippocampal volume, but not SES, was associated with scores on a memory task, suggesting that net effects of postnatal environmental factors, captured by SES, are more distal determinants of memory performance than hippocampal volume. Longitudinal investigation of the association between SES, hippocampal volume and cognitive functioning may further our understanding of the putative neural mechanisms underlying SES-related environmental effects on cognitive development.

Neuropsychological Functioning in Preterm-Born Twins and Singletons at Preschool Age.

OBJECTIVES: A limited body of research is available on the relationships between multiplicity of birth and neuropsychological functioning in preterm children who were conceived in the age of assisted reproductive technology and served by the modern neonatal intensive care unit. Our chief objective was to evaluate whether, after adjustment for sociodemographic factors and perinatal complications, twin birth accounted for a unique portion of developmental outcome variance in children born at-risk in the surfactant era. METHODS: We compared the neuropsychological functioning of 77 twins and 144 singletons born preterm (<34 gestational weeks) and served by William Beaumont Hospital, Royal Oak, MI. Children were evaluated at preschool age, using standardized tests of memory, language, perceptual, and motor abilities. RESULTS: Multiple regression analyses, adjusting for sociodemographic and perinatal variables, revealed no differences on memory or motor indices between preterm twins and their singleton counterparts. In contrast, performance of language and visual processing tasks was significantly lower in twins despite reduced perinatal risk in comparison to singletons. Effect sizes ranged from .33 to .38 standard deviations for global language and visual processing ability indices, respectively. No significant group by sex interactions were observed, and comparison of first-, or second-born twins with singletons yielded medium effect sizes (Cohen's d=.56 and .40, respectively). CONCLUSIONS: The modest twin disadvantage on language and visual processing tasks at preschool-age could not be readily attributable to socioeconomic or perinatal variables. The possibility of biological or social twinning-related phenomena as mechanisms underlying the observed performance gaps are discussed. (JINS, 2016, 22, 865-877).

Physical growth in the neonatal intensive-care unit and neuropsychological performance at preschool age in very preterm-born singletons.

We studied the associations between early postnatal growth gains and neuropsychological outcome in very preterm-born children. Specifically, we wished to establish whether relationships exist between gains in head circumference (relative to gains in body-weight or length), from birth to hospital discharge, and intellectual, language, or motor, performance at preschool age. We used data from 127 preschoolers, born <33 weeks, all graduates of the William Beaumont Hospital Neonatal Intensive-Care Unit (NICU) in Royal Oak, MI. Cognitive, motor, and language outcomes were evaluated using the Wechsler Preschool and Primary Scales of Intelligence-Revised, Peabody Developmental Scales - 2(nd) Edition, and the Preschool Language Scale - 3(rd) Edition, respectively. Differences between Z-scores at birth and hospital discharge, calculated for three anthropometric measures (head circumference, weight, length), were variables of interest in separate simultaneous multiple regression procedures. We statistically adjusted for sex, socioeconomic status, birth weight, length of hospitalization, perinatal complications, and intrauterine growth. Examination of the relationships between anthropometric indices and outcome measures revealed a significant association between NICU head growth and global intelligence, with the Z-difference score for head circumference accounting for a unique portion of the variance in global intelligence (ηp(2) =.04). Early postnatal head growth is significantly associated with neuropsychological outcome in very preterm-born preschoolers. To conclude, despite its relative brevity, NICU stay, often overlapping with the end of 2(nd) and with the 3(rd) trimester of pregnancy, appears to be a sensitive developmental period for brain substrates underlying neuropsychological functions.

Postnatal growth and neuropsychological performance in preterm-birth preschoolers.

OBJECTIVE: Compromised postnatal growth is an important risk factor accounting for poorer neuropsychological performance of preterm children during the preschool years, yet its unique contribution to explaining outcome variance within this high risk group has yet to be determined. Therefore, we examined within a large preterm sample (1) the relationships between head growth, measured either at birth or preschool age, and outcome; (2) the relationships of binary versus dimensional head growth measures and performance; and (3) the unique contribution of preschool-age head growth, after adjustment for general physical development (indexed by stature), to variance in neuropsychological functioning. METHOD: We evaluated 264 preterm (<36 weeks) preschoolers, without severe handicaps, using cognitive, language, and motor skill measures. Multiple regression analyses, adjusting for sociodemographic factors and pre-, peri-, and postnatal confounds, were used to study associations between growth indices and performance. RESULTS: While suboptimal head growth classification at birth was significantly associated only with motor performance, suboptimal head growth at preschool age explained a significant portion of variance in intellectual and language measures (g = .46 to .60). Treating preschool head size as a continuous dimension yielded null results, however, with body-height explaining a significant portion of the variance across several domains. CONCLUSION: Among postnatal anthropometric indices, preschool stature, rather than head circumference, remains a consistent correlate of preschool outcome in preterm children, highlighting the contribution of general physical development to neuropsychological performance. Further investigation of the underlying mechanisms likely involves exploration of complex relationships between postnatal nutrition, growth hormone levels, body and brain development, and neuropsychological functioning.

Intrauterine growth and neuropsychological performance in very low birth weight preschoolers.

In this study we examined the association between intrauterine growth, indexed either as a categorical variable or continuous dimension, and neuropsychological outcome, in a very low birth weight (VLBW) sample of 143 preschoolers. When the commonly used split at the 10th percentile rank was applied to classify intrauterine growth restriction (IUGR), we found that the growth restricted group (n = 25) exhibited significantly poorer performance in the global motor domain, but not on any other neuropsychological measure. In contrast, when adequacy of intrauterine growth was indexed by standardized birth weight, a continuous dimension, this early risk factor explained a unique portion of the variance in global cognitive abilities and visuospatial skills, as well as in global, fine, and gross motor skills. These findings are consistent with recent magnetic resonance imaging data disclosing global neurodevelopmental changes in the brains of preterm infants with IUGR. When cases classified with IUGR (<10th percentile) were excluded, the relationship between adequacy of intrauterine growth and global cognitive abilities remained significant despite range restriction. Hence, an association between appropriateness of intrauterine growth and global intellectual outcome may be observed even within the population of VLBW preschoolers with adequate standardized birth weight.

Neonatal respiratory dysfunction and neuropsychological performance at the preschool age: a study of very preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: The neuropsychological outcome of chronic lung disease (CLD) in the very preterm (VP) infant may be determined by a process involving chronic hypoxia, with superimposed acute hypoxic episodes, in the developing brain. We wished to study the differences in quality of outcome between VP preschoolers with and without history of the most common form of CLD in the preterm infant, bronchopulmonary dysplasia (BPD). We also examined the strength of association between BPD severity and neuropsychological outcome, with degree of severity defined according to the National Institute of Child Health and Human Development (NICHD) National Heart, Lung and Blood Institute (NHLBI) Workshop categorical ranking scheme (Jobe & Bancalari, 2001) or in accord with dimensional views of severity of respiratory illness. METHOD: We evaluated the intellectual, language, and motor outcomes of 156, predominantly middle-class preschoolers with history of VP birth, with (n = 80) or without (n = 76) BPD. We used supplemental oxygen requirement or need for mechanical ventilation as indirect indexes of respiratory dysfunction. RESULTS: Following adjustment for potentially confounding sociodemographic variables and perinatal medical risk factors, we found no group differences in neuropsychological outcome based on categorical ranking of BPD severity. However, continuous measures of BPD severity accounted for a unique portion of the variance in fine motor performance (η²p = .05), while patent ductus arteriosus, a risk marker or antecedent of BPD, explained a unique portion of the variance in both receptive language (η²p = .048), and gross motor (η²p = .061) function. CONCLUSION: A significant, yet circumscribed, association was demonstrated between neonatal hypoxic risk, in the VP infant, and neuropsychological outcome assessed in the preschool years.

Extreme prematurity and neuropsychological outcome in the preschool years.

With the increasing survival of extremely preterm (EP) birth infants in the surfactant era, the longer-term outcome of infants born at the threshold of viability has become a vital topic of study. The goal of this investigation was twofold. First, while taking into account the influence of sociodemographic confounds, we wished to investigate neuropsychological outcome differences between two groups of EP preschoolers: 23-24 weeks (n = 20), and 25-26 weeks' (n = 21) gestation at delivery. Second, we wished to explore whether, within the population of EP preschoolers, gestational maturity accounts for a unique portion of the variance in neuropsychological outcome, over and above the variance explained by ante-, peri-, and neonatal complications, or treatment factors. The findings revealed group differences, ranging from .70 to .80 of a standard deviation in general intellectual abilities, nonverbal intelligence, and global motor performance, in favor of the more mature EP group. Additionally, gestational maturity was found to explain a unique portion of the variance in global intellectual and motor abilities. These findings are interpreted from the perspective that gestational age is an index of the vulnerability of the central nervous system to disruption of developmentally regulated processes.

Neurodevelopmental outcome in children born to mothers with hypertension in pregnancy: the significance of suboptimal intrauterine growth.

In this investigation of 45 children born to mothers with hypertension in pregnancy, our objective was to examine the role of a fetal risk factor (suboptimal intrauterine growth [SOIUG]) in determining developmental outcome. There were two groups of children: Group 1 (n=26; 10 males, 16 females; mean testing age 56.77 mo [SD 13.03], range 41-82 mo; mean gestational age 32.96 wks [SD 2.24], range 27-38 wks; mean birthweight 1,984.42g [SD 563], range 1,046-3,515g) without, and Group 2 (n=19; 6 males, 13 females; mean testing age 57.63 mo [SD 14.86], range 40-84 mo; mean gestational age 34.21 wks [SD 2.10], range 29-39 wks, mean birthweight 1,572g [SD 365], range 855-2,690g) with SOIUG. We found that SOIUG was associated with a significant reduction in cognitive and motor skills (p<0.05). Visuospatial (p<0.01) as well as motor skills (p<0.001) were linearly associated with the extent of intrauterine growth deficit when the latter was treated as a continuous variable. To conclude, an increase in intrauterine growth deficit is accompanied by a proportionate decline in quality of developmental outcome in children born to mothers with hypertension in pregnancy.

Influence of slight to moderate risk for birth hypoxia on acquisition of cognitive and language function in the preterm infant: a cross-sectional comparison with preterm-birth controls.

The cognitive and language performance of a group of 26 preterm-birth preschool and early school-age children with slight to moderate risk for perinatal hypoxia was compared with the performance of a preterm-birth comparison group of 26 children. Despite the relatively small discrepancy in degree of risk, the cognitive performance of the 2 groups diverged significantly. When data for children with known perinatal arterial pH were combined, a curvilinear (quadratic) regression model provided the best fit. Increasing acidosis was linearly related to decreases in cognitive skills, with the bend in the curve occurring well within the normal range of pH values. Hence, in the preterm infant, even minor risk for birth hypoxia may result in discernible deviation from the expected developmental trajectory.