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 (≥37 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 delaywas 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. Results In 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 (tstatistic 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.

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.

OBJECTIVE. Extremely preterm birth is associated with adverse neurodevelopmental sequelae. Head circumference has been used as a measure of brain growth. There are limited data relating head circumference to MRI. The purpose of this work was to establish the relationship between head circumference with brain MRI at term-equivalent age and to relate head circumference with neurodevelopmental outcome at 2 years. PATIENTS AND METHODS. Two hundred and twenty-seven preterm infants (birth weight of <1250 g or <30 weeks’ gestation) were recruited. Head circumference was measured at birth, term, and 2 years’ corrected age, and z scores were computed. Microcephaly was defined as a head circumference z score of less than −2 SDs for age and gender. MRI scans at term (n = 214) were graded for white and gray matter abnormalities, and segmented volumes were calculated for different tissue types. Outcome at 2 years’ corrected age (n = 202) included scores on the Bayley Scales of Infant Development II. RESULTS. Microcephaly increased from 7.5% at term to 29.7% at 2 years. There was no significant relationship between head circumference and white or gray matter abnormalities on MRI. There was a strong correlation between head circumference and brain volume at term. At term, microcephalic infants had significantly decreased volumes for total brain tissue and most segmented volumes compared with infants with normal head circumference, but only deep nuclear gray matter volume remained significantly lower when adjusted for total intracranial volume. At 2 years, microcephaly was associated with poorer cognitive and motor development and an increased rate of cerebral palsy. CONCLUSIONS. 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.

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.

Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal cortex, parietal cortex and the hippocampus. While the eligible sample consisted of 227 very preterm children who were born at the Royal Women's Hospital, Melbourne prior to 30 weeks gestation or weighing <1250 g, 156 children had complete data sets. Neonatal magnetic resonance images of the brain were obtained at term equivalent age and subsequently parcellated into eight sub-regions, while the hippocampus was manually segmented. The relationship between brain volumes for these regions and performance on a working memory task (delayed alternation) at 2 years of age was examined. Very preterm children who perseverated on the working memory task had significantly smaller hippocampal volumes than very preterm children who exhibited intact working memory, even after adjusting for relevant perinatal, sociodemographic and developmental factors. Preterm children appear to have altered hippocampal volumes by discharge from hospital which may have a lasting impact on working memory function.