Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of preterm infants. In a large prospective longitudinal cohort study of 202 preterm and 36 term infants, MR scans at term equivalent were undertaken for volumetric estimates of cortical and deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF within 8 parcellated regions for each hemisphere of the brain. Perinatal correlates analysed in relation to regional brain structure included gender, gestational age, intrauterine growth restriction, bronchopulmonary dysplasia, white matter injury (WMI) and intraventricular haemorrhage. Results revealed region-specific reductions in brain volumes in preterm infants compared with term controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8--2.3%), sensorimotor (-11.6%; -18.2--5.0%), orbitofrontal (-30.6%; -49.8--11.3%) and premotor (-7.6%; -14.2--0.9%) regions. Within the sensorimotor and orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly within the parieto-occipital and subgenual regions. CSF (ventricular and extracerebral) was doubled in volume within the superior regions in preterm infants compared with term controls. Cerebral WMI and intrauterine growth restriction were both associated with a more posterior reduction in brain volumes, whereas bronchopulmonary dysplasia was associated with a more global reduction across all regions. In contrast degree of immaturity was not related to regional brain structure among preterm infants. In summary, preterm birth is associated with regional cerebral tissue reductions, with the adverse pattern varying between risk factors. These findings add to our understanding of the potential pathways leading to altered brain structure and outcome in the preterm infant.

Brain volume is a determinant of head size at term. Microcephaly is associated with a reduction of brain tissue volumes, especially deep nuclear gray matter, which suggests a selective vulnerability. Poor postnatal head growth in preterm infants becomes more evident by 2 years and is strongly associated with poor neurodevelopmental outcome and cerebral palsy.

IMPORTANCE Moderate and late preterm (MLPT) births comprise most preterm infants. Therefore, long-term developmental concerns in this population potentially have a large public health influence. While there are increasing reports of developmental problems in MLPT children, detail is lacking on the precise domains that are affected. OBJECTIVE To compare neurodevelopment and social-emotional development between MLPT infants and term-born control infants at age 2 years. DESIGN, SETTING, AND PARTICIPANTS This investigation was a prospective longitudinal cohort study at a single tertiary hospital. Participants were MLPT infants (32-36 weeks' completed gestation) and healthy full-term controls (Ն37 weeks' gestation) recruited at birth. During a 3-year period between December 7, 2009, and November 7, 2012, MLPT infants were recruited at birth from the neonatal unit and postnatal wards of the Royal Women's Hospital, Melbourne, Australia. The term control recruitment extended to March 26, 2014. The dates of the data developmental assessments were February 23, 2012, to April 8, 2016. EXPOSURE Moderate and late preterm birth.MAIN OUTCOMES AND MEASURES Cerebral palsy, blindness, and deafness assessed by a pediatrician; cognitive, language, and motor development assessed using the Bayley Scales of Infant Development-Third Edition (developmental delay was defined as less than −1 SD relative to the mean in controls in any domain of the scales); and social-emotional and behavioral problems assessed by a parent questionnaire (Infant Toddler Social Emotional Assessment). Outcomes were compared between birth groups using linear and logistic regression, adjusted for social risk. RESULTSIn total, 198 MLPT infants (98.5% of 201 recruited) and 183 term-born controls (91.0% of 201 recruited) were assessed at 2 years' corrected age. Compared with controls, MLPT children had worse cognitive, language, and motor development at age 2 years, with adjusted composite score mean differences of −5.3 (95% CI, −8.2 to −2.4) for cognitive development, −11.4 (95% CI, −15.3 to −7.5) for language development, and −7.3 (95% CI, −10.6 to −3.9) for motor development. The odds of developmental delay were higher in the MLPT group compared with controls, with adjusted odds ratios of 1.8 (95% CI, 1.1-3.0) for cognitive delay, 3.1 (95% CI, 1.8-5.2) for language delay, and 2.4 (95% CI, 1.3-4.5) for motor delay. Overall social-emotional competence was worse in MLPT children compared with controls (t statistic mean difference, −3.6 (95% CI, −5.8 to −1.4), but other behavioral domains were similar. The odds of being at risk for social-emotional competence were 3.9 (95% CI, 1.4-10.9) for MLPT children compared with controls.CONCLUSIONS AND RELEVANCE Moderate and late preterm children exhibited developmental delay compared with their term-born peers, most marked in the language domain. This knowledge of developmental needs in MLPT infants will assist in targeting surveillance and intervention.

Children born preterm and of very low birth weight are at increased risk of learning difficulties and educational under-achievement. However, little is known about the specific neuropsychological problems facing these children or their neurological basis. Using prospective longitudinal data from a regional cohort of 92 preterm and 103 full-term children, this study examined relations between term MRI measures of cerebral injury and structural brain development and children's subsequent performance on an object working memory task at the age of 2 years. Results revealed clear between-group differences, with preterm children having greater difficulty encoding new information in working memory than term control children. Within the preterm group, task performance at the age of 2 years was related to both qualitative MRI measures of white matter (WM) injury and quantitative measures of total and regional brain volumes assessed at term equivalent. Bilateral reductions in total tissue volumes (%region) of the following cerebral regions were specifically related to subsequent working memory performance: dorsolateral prefrontal cortex, sensorimotor, parietooccipital and premotor. Associations between total cerebral tissue volumes at term (adjusted and unadjusted for intracranial volume) persisted even after the effects of WM injury were taken into account. This suggests that early disturbance in cerebral development may have an independent adverse impact on later working memory function in the preterm infant. These findings add to our understanding of the neuropathological pathways associated with later executive dysfunction in the very preterm infant.

Objectives To determine the associations of breast milk intake after birth with neurological outcomes at term equivalent and 7 years of age in very preterm infants Study design We studied 180 infants born <30 weeks’ gestation or <1250 grams birth weight enrolled in the Victorian Infant Brain Studies cohort from 2001–2003. We calculated the number of days on which infants received >50% of enteral intake as breast milk from 0–28 days of life. Outcomes included brain volumes measured by magnetic resonance imaging at term equivalent and 7 years of age, and cognitive (IQ, reading, mathematics, attention, working memory, language, visual perception) and motor testing at years. We adjusted for age, sex, social risk,7 and neonatal illness in linear regression. Results A greater number of days on which infants received >50% breast milk was associated with larger deep nuclear gray matter volume at term equivalent age (0.15 cc/day, 95% CI 0.05, 0.25); and with better performance at age 7 years on IQ (0.5 points/day, 95% CI 0.2, 0.8), mathematics (0.5, 95% CI 0.1, 0.9), working memory (0.5, 95% CI 0.1, 0.9), and motor function (0.1, 95% CI 0.0, 0.2) tests. No differences in regional brain volumes at 7 years in relation to breast milk intake were observed. Conclusion Predominant breast milk feeding in the first 28 days of life was associated with larger deep nuclear gray matter volume at term equivalent age and better IQ, academic achievement, working memory, and motor function at 7 years of age in very preterm infants.

Hippocampal volumes were reduced in PT infants exposed to several perinatal events but were preserved in PT infants without these exposures. Smaller PT hippocampal volumes were indirectly associated with delayed development at 2 years.

The aim of this study was to relate altered corpus callosum (CC) integrity in 106 very preterm (VPT) infants (<30 weeks’ gestational age or <1250 g birth weight) at term equivalent to perinatal predictors and neurodevelopmental outcomes at two years. T1 and diffusion magnetic resonance images were obtained. The CC was traced, and divided into six sub-regions for cross-sectional area and shape analyses. Fractional anisotropy, mean, axial and radial diffusivity was sampled within the CC, and probabilistic tractography performed. Perinatal predictors were explored. The Bayley Scales of Infant Development (BSID-II) was administered at two years. Intraventricular hemorrhage was associated with a smaller genu and altered diffusion values within the anterior and posterior CC of VPT infants. White matter injury was associated with widespread alterations to callosal diffusion values, especially posteriorly, and radial diffusivity was particularly elevated, indicating altered myelination. Reduced CC tract volume related to lower gestational age, particularly posteriorly. Reduced posterior callosal skew was associated with postnatal corticosteroid exposure. This more circular CC was associated with delayed cognitive development. Higher diffusivity, particularly in splenium tracts, was associated with impaired motor development. This study elucidates perinatal predictors and adverse neurodevelopmental outcomes associated with altered callosal integrity in VPT infants.

The corpus callosum is the largest white matter tract, important for interhemispheric communication. The aim of this study was to investigate and compare corpus callosum size, shape and diffusion characteristics in 106 very preterm infants and 22 full-term infants. Structural and diffusion magnetic resonance images were obtained at term equivalent. The corpus callosum was segmented, cross-sectional areas were calculated, and shape was analyzed. Fractional anisotropy, mean, axial and radial diffusivity measures were obtained from within the corpus callosum, with additional probabilistic tractography analysis. Very preterm infants had significantly reduced callosal cross sectional area compared with term infants (p=0.004), particularly for the mid-body and posterior sub-regions. Very preterm callosi were more circular (p=0.01). Fractional anisotropy was lower (p=0.007) and mean (p=0.006) and radial (p=0.001) diffusivity values were higher in very preterm infants' callosi, particularly at the anterior and posterior ends. The volume of tracts originating from the corpus callosum was reduced in very preterm infants (p=0.001), particularly for anterior mid-body (p=0.01) and isthmus tracts (p=0.04). This study characterizes callosal size, shape and diffusion in typically developing infants at term equivalent age, and reports macro-and micro-structural abnormalities as a result of prematurity.