Alice C. Burnett

Contribution of brain size to IQ and educational underperformance in extremely preterm adolescents.

Objectives Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (<28weeks) and term-born (≥37weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. Methods Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. Results Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. Conclusions EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP.

Quality of Life at Age 18 Years after Extremely Preterm Birth in the Post-Surfactant Era

OBJECTIVES To assess the self-reported quality of life, health status, self-esteem, and functional outcomes at age 18 years of extremely preterm (EP; <28 weeks gestation) or extremely low birth weight (ELBW; birth weight <1000 g) adolescents born in 1991-1992 compared with normal birth weight (birth weight >2499 g) controls, and, within the EP/ELBW cohort, to assess whether these outcomes are related to gestational age or birth weight. STUDY DESIGN Self-reported measures of quality of life, health status, self-esteem, and functional outcomes were obtained at age 18 years from a geographic cohort of all survivors born EP/ELBW in 1991-1992 in the state of Victoria, Australia, along with matched normal birth weight controls. RESULTS Data were available from 194 EP/ELBW and 148 control adolescents. EP/ELBW adolescents reported similar overall quality of life, health status, and self-esteem as controls (P > .05). Birth at younger gestational age or lower birth weight were not related to poorer quality of life within the EP/ELBW cohort (P > .05). EP/ELBW adolescents reported less physical activity (OR, 0.5; 95% CI, 0.3-0.8; P < .01), sexual activity (OR, 0.6; 95% CI, 0.4-0.9; P = .01), and alcohol intake (OR, 0.5; 95% CI, 0.3-0.8; P = .01) compared with controls. Other aspects of risk-taking behavior were similar in the 2 groups (P > .05). CONCLUSION EP/ELBW individuals born after the introduction of exogenous surfactant are transitioning well into young adulthood, despite the fact that more of the tiniest and most immature infants survive than ever before. They report similar quality of life, self-esteem, and social and risk-taking behaviors as controls.

Executive function outcome in preterm adolescents

Preterm birth (PT) and low birthweight (LBW) are risk factors for cognitive, academic, and behavioral difficulties. Executive functioning, which is an umbrella term encompassing higher-order problem-solving and goal-oriented abilities, may help to understand these impairments. This review article examines executive functioning in PT and LBW children, with a specific focus on adolescence and the functional consequences of executive dysfunction in this age group. We have focused on adolescence as it is a critical period for brain, cognitive and social-emotional development, and a period of increased autonomy, independence and reliance on executive functioning. While more longitudinal research is required, there is evidence demonstrating that the PT/LBW population is at increased risk for impairments across all executive domains. Emerging evidence also suggests that executive dysfunction may partly explain poorer academic and social-emotional competence in PT/LBW adolescents. In conclusion, PT/LBW adolescents exhibit poorer executive functioning, and close surveillance is recommended for high-risk individuals.

Biological and Social Influences on Outcomes of Extreme-Preterm/Low-Birth Weight Adolescents

BACKGROUND AND OBJECTIVES: The importance of biological versus social influences on long-term outcomes of extremely preterm children is debatable. The goal of this study was to determine the relative contributions of biological and social exposures to outcomes into adolescence in extremely preterm survivors, hypothesizing that biological exposures would be more important early, but social exposures would dominate later. METHODS: The study included 298 consecutive survivors born at <28 weeks’ gestation or weighing <1000 g in Victoria, Australia (during 1991–1992), and 262 normal birth weight (>2499 g) control subjects who were used to standardize outcomes for the preterm group. Cognitive ability was assessed at 2, 5, 8, and 18 years of age. Academic achievement was assessed at 8 and 18 years of age. RESULTS: The differences between the preterm and control groups for cognitive and academic scores remained relatively constant over time. The biological variables most associated with worse outcomes within the extremely preterm group were intraventricular hemorrhage and postnatal corticosteroid therapy. Of the social variables, being reared in a multilingual household was disadvantageous early, with social class and maternal education becoming more important for later outcomes. The strength of the biological associations mostly equaled or exceeded those of social exposures, even in late adolescence. CONCLUSIONS: Contrary to expectations, several perinatal biological exposures had large and persistent adverse associations with cognitive and academic outcomes among extremely preterm survivors. As expected, some social variables assumed increasing importance in later years but mostly did not diminish or exceed the important biological associations.

Executive Function in Adolescents Born <1000 g or <28 Weeks: A Prospective Cohort Study

BACKGROUND AND OBJECTIVES: Extremely preterm (EP; <28 weeks) birth and extremely low birth weight (ELBW; <1000 g) are risk factors for poor cognitive outcomes, including in executive function (EF; higher-order cognitive skills necessary for goal-directed, adaptive functioning and important for academic and behavioral-emotional outcomes). We aimed to (1) extend the limited data on EF in EP/ELBW survivors in adolescence compared with normal birth weight controls, and (2) determine changes in EF between ages 8 and 17 years in both groups. METHODS: Two hundred twenty-eight EP/ELBW and 166 control adolescents (mean age, 17 years) from a prospective geographical cohort were assessed with multiple EF tasks, and parent- and self-ratings of behavioral EF. The Rey Complex Figure and Behavior Rating Inventory of Executive Function parent report were also administered at age 8 years, enabling examination of change in scores between childhood and adolescence. RESULTS: EP/ELBW adolescents performed more poorly than controls in verbal processing speed, attentional control, cognitive flexibility, and goal-setting (effect sizes, −0.7 to −0.2 SD), but not psychomotor reaction time. Group differences were of similar magnitude across tasks. From childhood to late adolescence, EP/ELBW children improved their accuracy of the Rey Complex Figure copy more than controls. According to parents, executive behaviors were largely stable over time in both groups. CONCLUSIONS: Adolescents born EP/ELBW have poorer EF skills across multiple domains than controls. From childhood to late adolescence, different aspects of EF improved, but others did not, underscoring the need for multidomain, longitudinal assessments in this high-risk population.

Social cognition in Turner’s Syndrome

Turners Syndrome (TS), or X-monosomy, is a common chromosomal disorder in women, and provides a valuable paradigm to investigate genotypic contributions to social cognition. We review evidence suggesting that some facets of social cognition, particularly emotion recognition and gaze perception, are impaired in women with TS, despite the absence of a global social-processing impairment. Further, these deficits co-exist with neuroanatomical abnormalities of the amygdala and other regions implicated in social processing. A parallel is drawn between the non-verbal profile of sociocognitive dysfunction in TS and autism spectrum disorders, possibly underpinned by genomic imprinting effects. TS provides a unique opportunity to identify genetic, and particularly sex chromosome, influences on social cognition and behaviour.

Changing neurodevelopment at 8 years in children born extremely preterm since the 1990s

Despite improvements in survival with advances in care of EP infants, neurosensory outcomes at school age are not improving; indeed, academic performance may be deteriorating. BACKGROUND AND OBJECTIVE: Survival of extremely preterm (EP; <28 weeks’ gestation) infants has increased over the last 2 decades. Equivalent reductions in developmental morbidity in early childhood have not been consistently reported. The aim of this study was to determine trends in neurodevelopmental outcomes at 8 years of age of children born EP (22–27 completed weeks’ gestation) over the past 2 decades. METHODS: Population-based cohorts of all EP survivors born in the state of Victoria, Australia in 1991–1992, 1997, and 2005 were recruited at birth. At 8 years of age, general intelligence (IQ), academic achievement, and neurosensory status were assessed. Major neurosensory disability was defined as any of moderate or severe cerebral palsy, IQ <−2 SD relative to term controls, blindness, or deafness. RESULTS: Rates of major neurosensory disability were similar in all eras (1991–1992, 18%; 1997, 15%; 2005, 18%), as were rates of IQ <−2 SD, cerebral palsy, blindness, and deafness. Mean z scores for IQ were similar across eras, but there was some evidence that scores for academic achievement were lower in 2005 than in 1997, and the odds of having academic problems were higher in 2005 than in both earlier eras. These outcomes were not explained by differences in known perinatal care or sociodemographic variables between eras. CONCLUSIONS: Contrary to expectations, rates of major neurosensory disability have not improved, and academic performance is poorer at early school age in 2005 than in earlier eras for EP children born in the state of Victoria, Australia.

Association between Postnatal Dexamethasone for Treatment of Bronchopulmonary Dysplasia and Brain Volumes at Adolescence in Infants Born Very Preterm

Objectives To compare brain volumes in adolescents who were born extremely preterm (<28 weeks gestation) who had received postnatal dexamethasone, and to determine if there was a postnatal dexamethasone dose–response effect on brain volumes. Study design Geographical cohort study of extremely preterm adolescents born in 1991-1992 in Victoria, Australia. T1-weighted magnetic resonance imaging was performed at 18 years of age. Segmented and parcellated brain volumes were calculated using an automated segmentation method (FreeSurfer) and compared between groups, with and without adjustment for potential confounders. The relationships between total postnatal dexamethasone dose and brain volumes were explored using linear regression. Results Of the 148 extremely preterm participants, 55 (37%) had received postnatal dexamethasone, with a cumulative mean dose of 7.7 mg/kg. Compared with participants who did not receive postnatal dexamethasone, those who did had smaller total brain tissue volumes (mean difference −3.6%, 95% CI [−7.0%, −0.3%], P value = .04) and smaller white matter, thalami, and basal ganglia volumes (all P < .05). There was a trend of smaller total brain and white matter volumes with increasing dose of postnatal dexamethasone (regression coefficient −7.7 [95% CI −16.2, 0.8] and −3.2 [−6.6, 0.2], respectively). Conclusions Extremely preterm adolescents who received postnatal dexamethasone in the newborn period had smaller total brain tissue volumes than those who did not receive postnatal dexamethasone, particularly white matter, thalami, and basal ganglia. Vulnerability of brain tissues or structures associated with postnatal dexamethasone varies by structure and persists into adolescence.

Assessing developmental delay in early childhood — concerns with the Bayley-III scales

Abstract Objective: Early detection of children with developmental delay is crucial for determining which children require close surveillance and intervention services. For many decades, the Bayley Scales has been the most widely used objective measure of early developmental delay, both in clinical and research settings. Significant structural changes were incorporated in the most recent edition, the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). This article reviews the psychometric properties of the Bayley-III and investigates criticisms raised on the Bayley-III, namely that it overestimates developmental status and is a poor predictor of later functioning. Method: This critical review examines the literature on the Bayley-III, which was released in 2006. Results: The Cognitive, Language, and Motor composites of the Bayley-III overestimate development, resulting in an under-identification of children with developmental delay. A range of strategies have been proposed for dealing with the inflated scores on the Bayley-III, none of which are ideal. Evidence to date suggests that the Bayley-III is a poor predictor of later cognitive and motor impairments. Conclusions: The Bayley-III needs new norms, or alternatively, it may be time for a new edition of the Bayley Scales.

Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight

Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (>2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent‐reported metacognition scores overall (P = 0.008) and better self‐reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects. Hum Brain Mapp 36:1138–1150, 2015.