Melbourne School of Psychological Sciences - Research Publications
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ItemNo Preview AvailableHigh Postnatal Growth Hormone Levels Are Related to Cognitive Deficits in a Group of Children Born Very Preterm(ENDOCRINE SOC, 2015-07)CONTEXT AND OBJECTIVES: Little is known regarding the influence of GH on brain development, especially in infants born very preterm (VP; <30 weeks' gestation). Preterm infants are thought to have higher levels of GH in the first days of life compared with full-term infants. VP infants experience cognitive difficulties in childhood and have a diffuse pattern of structural brain abnormalities. This study aimed to explore the relationship between postnatal GH concentrations following VP birth and its association with cognitive functioning and brain volumes at age 7 years. METHODS: Eighty-three infants born VP had GH concentrations measured at eight time points postnatally, and 2- and 6-week area under the curve (AUC) summary measures were calculated. Followup at age 7 years included neuropsychological assessment and brain magnetic resonance imaging. Univariable and multivariable regression modeling were used where AUC for GH was the main predictor of neurodevelopmental outcome at age 7 years. RESULTS: Univariable modeling revealed that higher GH levels (2-week AUC) were related to poorer performance on a verbal working memory (P = .04) and shifting attention task (P = .01). These relationships persisted on multivariable modeling and when the 6-week AUC was analyzed; working memory (P = .03), immediate spatial memory (P = .02), and delayed spatial memory (P = .03) deficits were found. Higher GH levels were also associated with larger amygdala volumes after adjustment for potential confounders (P = .002, 2-week AUC; P = .03, 6-week AUC). CONCLUSIONS: Higher postnatal GH levels may potentially contribute to the documented neurodevelopmental abnormalities seen in children born VP at school age.
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ItemRegional white matter microstructure in very preterm infants: Predictors and 7 year outcomes(ELSEVIER MASSON, CORPORATION OFFICE, 2014-03)The aims of this study were to investigate regional white matter microstructural differences between very preterm (VPT) (<30 weeks' gestational age and/or <1250 g) and full term (FT) (≥37 weeks' gestational age) infants at term corrected age with diffusion tensor imaging, and to explore perinatal predictors of diffusion measures, and the relationship between regional diffusion measures and neurodevelopmental outcomes at age 7 years in VPT children. Mean (MD) (p = .003), axial (AD) (p = .008), and radial diffusivity (RD) (p = .003) in total white matter were increased in VPT compared with FT infants, with similar fractional anisotropy (FA) in the two groups. There was little evidence that group-wise differences were specific to any of the 8 regions studied for each hemisphere. Perinatal white matter abnormality and intraventricular hemorrhage (grade III or IV) were associated with increased diffusivity in the white matter of VPT infants. Higher white matter diffusivity measures of the inferior occipital and cerebellar region at term-equivalent age were associated with increased risk of impairments in motor and executive function at 7 years in VPT children, but there was little evidence for associations with IQ or memory impairment. In conclusion, myelination is likely disrupted or delayed in VPT infants, especially those with perinatal brain abnormality (BA). Altered diffusivity at term-equivalent age helps explain impaired functioning at 7 years. This study defines the nature of microstructural alterations in VPT infant white matter, assists in understanding the associated risk factors, and is the first study to reveal an important link between inferior occipital and cerebellar white matter disorganization in infancy, and executive and motor functioning 7 years later.
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ItemNo Preview AvailablePsychiatric outcomes at age seven for very preterm children: rates and predictors(WILEY, 2013-07)BACKGROUND: Uncertainty remains about the rate of specific psychiatric disorders and associated predictive factors for very preterm (VPT) children. The aims of this study were to document rates of psychiatric disorders in VPT children aged 7 years compared with term born children, and to examine potential predictive factors for psychiatric diagnoses in VPT children. METHODS: Participants were 177 VPT and 65 term born children. Perinatal medical data were collected, which included brain abnormalities detected using magnetic resonance imaging. The Infant-Toddler Social-Emotional Assessment (ITSEA) and Strengths and Difficulties Questionnaire (SDQ) were administered at 2 and 5 years respectively. At 7 years of age, the Developmental and Well-being Assessment (DAWBA) was used to indicate psychiatric diagnoses. RESULTS: Compared with term born children, VPT children had three times the odds of meeting criteria for any psychiatric diagnosis at age 7 years (odds ratio 3.03; 95% confidence interval 1.23, 7.47, p = .02). The most common diagnoses were anxiety disorders (11% VPT, 8% term), attention-deficit/hyperactivity disorder (10% VPT, 3% term) and autism spectrum disorder (4.5% VPT, 0% term). For VPT children, those with severe global brain abnormalities (p = .02), those who displayed social-emotional problems at age 5 (p = .000) and those with higher social risk at age 7 (p = .001) were more likely to meet criteria for a psychiatric illness at age 7. CONCLUSIONS: Compared with term born children, VPT children have higher rates of psychiatric diagnoses at early school age, predicted by neonatal brain abnormalities, prior social-emotional problems and social factors.
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ItemNo Preview AvailableFree Thyroxine Levels After Very Preterm Birth and Neurodevelopmental Outcomes at Age 7 Years(AMER ACAD PEDIATRICS, 2014-04)BACKGROUND AND OBJECTIVES: Preterm infants commonly have transient hypothyroxinemia of prematurity after birth, which has been associated with deficits in general intellectual functioning, memory, attention, and academic achievement. However, research has predominantly focused on thyroxine levels in the first 2 weeks of life and outcomes are limited to the preschool period. Our objective was to evaluate the relationships between free thyroxine (fT₄) levels over the first 6 weeks after very preterm (VPT) birth with cognitive functioning and brain development at age 7 years. METHODS: A total of 83 infants born VPT (<30 weeks' gestation) had fT₄ concentrations measured postnatally and 2- and 6-week area under the curve (AUC) summary measures were calculated. Follow-up at age 7 years included a neuropsychological assessment and brain MRI. Univariable and multivariable regression modeling was used where AUC for fT₄ was the main predictor of neurodevelopmental outcome at age 7 years. RESULTS: Multivariable modeling revealed that higher, not lower, postnatal fT₄ levels (2-week AUC) were associated with poorer cognitive performances at age 7 years on tasks of verbal learning (P = .02), verbal memory (P = .03), and simple reaction time (P < .001). A similar pattern of results was found when the 6-week AUC was examined. No significant associations between postnatal fT₄ levels and brain volumes at age 7 years were identified. CONCLUSIONS: Results are contradictory to previous observations and suggest that after adjustment for confounders, higher postnatal fT₄ levels in VPT infants, rather than lower levels, may be a marker of adverse neuropsychological development in childhood.
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ItemNo Preview AvailableVisual Processing in Adolescents Born Extremely Low Birth Weight and/or Extremely Preterm(AMER ACAD PEDIATRICS, 2013-09)BACKGROUND AND OBJECTIVES: Ocular growth and development differs between preterm and term-born infants and may cause long-term negative consequences for visual function, but contemporary data on long-term visual outcomes in representative samples of the highest risk extremely low birth weight (ELBW, <1000 g birth weight) or extremely preterm (EP, <28 weeks' gestation) survivors are lacking. Our objective was to compare visual functioning between ELBW/EP and normal birth weight (NBW, >2499 g birth weight) control adolescents. METHODS: Geographically determined cohort study of 228 consecutive ELBW/EP survivors born in the state of Victoria in 1991 and 1992, and 166 randomly selected NBW controls assessed between 14 and 20 years of age. Visual acuity, stereopsis, convergence, color perception, and visual perception were assessed and contrasted between groups. RESULTS: ELBW/EP subjects had significantly worse visual acuity with habitual correction in both the left and right eyes, and for the best eye (P < .001). The ELBW/EP adolescents also exhibited poorer stereopsis, odds ratio (OR) 3.22 (95% confidence interval [CI] 1.78 to 5.84), and convergence, OR 2.76 (CI 1.32 to 5.75) than controls, and more problems with visual perception, OR 3.09 (CI 1.67 to 5.71) after habitual correction. CONCLUSIONS: Despite advances in medical care improving the survival rate of high-risk ELBW/EP infants, visual morbidity is still relatively high compared with controls in late adolescence.
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ItemNo Preview AvailableSchool-age Outcomes of Extremely Preterm or Extremely Low Birth Weight Children(AMER ACAD PEDIATRICS, 2013-04)OBJECTIVE: Research is required to monitor changes in the nature of neurobehavioral deficits in extremely preterm (EP) or extremely low birth weight (ELBW) survivors. This study examines cognitive, academic, and behavioral outcomes at age 8 years for a regional cohort of EP/ELBW children born in 1997. METHODS: The EP/ELBW cohort comprised all live births with a gestational age <28 weeks (EP) or birth weight <1000 g (ELBW) born in the state of Victoria, Australia, in 1997. Of 317 live births, 201 (63.4%) survived to 2 years of age.A term/normal birth weight (T/NBW) cohort was recruited comprising 199 infants with birthweights ≥2500 g or gestational age ≥37 weeks [corrected]. Measures of intellectual ability, educational achievement, and behavior were administered at age 8. RESULTS: Retention was 94% for the EP/ELBW group and 87% for the T/NBW group. The EP/ELBW group performed poorer than the T/NBW group on measures of IQ, educational achievement, and certain behavioral domains, even after adjustment for sociodemographic factors and exclusion of children with neurosensory impairment. The rate of any neurobehavioral impairment was elevated in the EP/ELBW group (71% vs 42%), and one-half of subjects had multiple impairments. The outcomes for those with <750 g birth weight or <26 weeks' gestational age were similar to those with a birth weight of 750 to 999 g or a gestational age of 26 to 27 weeks, respectively. CONCLUSIONS: Despite ongoing improvements in the management of EP/ELBW infants, the rate of neurobehavioral impairment at school-age remains too high relative to controls.
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ItemNo Preview AvailableDoes the Bayley-III Motor Scale at 2 years predict motor outcome at 4 years in very preterm children?(WILEY-BLACKWELL, 2013-05)AIM: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) for later motor outcome. METHOD: Ninety-six infants (49 males, 47 females) born at less than 30 weeks' gestation admitted to two tertiary hospitals in Melbourne, Australia, were assessed with the Bayley-III Motor Scale at 2 years' corrected age and were classified as suspect or definite motor impairment if they scored less than -1 or -2 standard deviations respectively, relative to the test mean. At 4 years' corrected age, children completed Movement Assessment Battery for Children - Second Edition (MABC-2); for the total motor score, cut-offs of not more than the 15th were used to classify motor development and cut-offs of not more than the 15th centile were classified as having a significant movement difficulty. RESULTS: Of the 96 children assessed at both ages, at 2 years 9% had suspect and 4% had definite motor impairment; however, by 4 years, rates had increased to 22% and 19% respectively. The specificity of the Bayley-III for motor impairments for later motor outcome was excellent (ranging from 94 to 100% for cerebral palsy [CP] and 97 to 100% for motor impairment), although the sensitivity was low (ranging from 67 to 83% for CP and 18 to 37% for motor impairment); many children with later impairment were not identified by the Bayley-III. INTERPRETATION: The Bayley-III Motor Scale at 2 years underestimates later rates of motor impairment, particularly in the absence of CP at 4 years on the MABC-2 total motor score in children born at less than 30 weeks' gestational age.
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ItemNo Preview AvailableGeneral Movements in Very Preterm Children and Neurodevelopment at 2 and 4 Years(AMER ACAD PEDIATRICS, 2013-08)OBJECTIVE: Although ~50% of very preterm (VP) children have neurodevelopmental impairments, early prediction of infants who will experience problems later in life remains a challenge. This study evaluated the predictive value of general movements (GM; spontaneous and endogenous movements) at 1 and 3 months' corrected age for neurodevelopment at 2 and 4 years of age in VP children. METHODS: At 1 and 3 months' corrected age, infants born <30 weeks' gestation had GM assessed as normal or abnormal. Motor, cognitive, and language development at 2 years was assessed by using the Bayley Scales of Infant and Toddler Development, Third Edition. At 4 years, cognitive and language outcomes were assessed by using the Differential Ability Scale-Second Edition and motor outcomes with the Movement Assessment Battery for Children-Second Edition; a diagnosis of cerebral palsy was documented. RESULTS: Ninety-nine VP infants were recruited, with 97% and 88% of survivors followed up at age 2 and 4 years, respectively. Abnormal GM at 1 month were associated with worse motor outcomes at 2 and 4 years but not language or cognitive outcomes. Abnormal GM at 3 months were associated with worse motor, cognitive, and language outcomes at both 2 and 4 years. Overall, GM at 1 month demonstrated better sensitivity to impairments at 2 and 4 years, whereas GM at 3 months had better specificity and were more accurate overall at distinguishing between children with and without impairment. CONCLUSIONS: Abnormal GM in VP infants, particularly at 3 months postterm, are predictive of worse neurodevelopment at ages 2 and 4 years.
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ItemNo Preview AvailableAssociation between Postnatal Dexamethasone for Treatment of Bronchopulmonary Dysplasia and Brain Volumes at Adolescence in Infants Born Very Preterm(MOSBY-ELSEVIER, 2014-04)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.