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Objective: To examine 5-year outcomes in children enrolled in a pilot randomized controlled trial of a high loading dose of caffeine after preterm birth., Study Design: Seventy-four very low birth weight neonates were randomized within the first 24 h of life to receive a high (80 mg/kg) or standard (20 mg/kg) loading dose of caffeine citrate. At 5 years of age, we conducted standardized neurodevelopmental tests and collected parent reports of child socioemotional problems., Result: Seventy-four percent of survivors returned for follow up. Children obtained similar scores on neurodevelopmental and socioemotional evaluations. There was no difference in the incidence of any neurodevelopmental delay after controlling for confounding factors., Conclusion: Five-year follow up of a pilot trial of high loading dose caffeine citrate documented no profound impacts on childhood neurodevelopment or socioemotional outcome., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The cingulum bundle (CB), specifically the dorsal anterior portion of the CB, plays an important role in psychiatric illnesses; however, its role during early development is unclear. This study investigated whether neonatal white matter microstructure in the CB and its subregions is associated with subsequent preterm behavioral phenotype symptoms (internalizing, inattention, and social deficits) in very preterm (VPT) children., Methods: Diffusion magnetic resonance imaging data were obtained on a 3T scanner in 138 sleeping nonsedated neonates: 55 full-term neonates (gestational age ≥ 36 weeks) and 83 VPT neonates (gestational age < 30 weeks). The CB was tracked using probabilistic tractography and split into anterior and posterior portions. When children were 5 years of age, parents (n = 80) and teachers (n = 63) of VPT children completed questionnaires of preterm behavioral phenotype symptoms. Linear regression models were used to relate measures of neonatal CB microstructure and childhood preterm behavioral phenotype symptoms (n = 56 parent report, n = 45 teacher report)., Results: Mean diffusivity in the anterior and posterior CB was increased in VPT neonates compared with full-term neonates. Increased fractional anisotropy and decreased mean diffusivity in the right anterior CB, but not in the posterior CB, were related to increased preterm behavioral phenotype symptoms in VPT children as reported by parents and teachers., Conclusions: Aberrations in the anterior portion of the right CB may underlie the early development of the preterm behavioral phenotype. This finding provides the foundation for future mechanistic and therapeutic investigations into the role of the anterior cingulum in the development of psychopathology in VPT infants., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (© 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.)

Objective: Preterm children are at greater risk for psychiatric disorders, including anxiety disorders and attention-deficit/hyperactivity disorder (ADHD), than their term-born peers. Prior research has focused primarily on children born at early gestational ages. Less is known about the rate of psychiatric disorders among late preterm or early term children. In addition, whether a history of maternal depression also associated with prematurity has an impact on the risk for psychiatric disorders remains underexplored., Method: Preschoolers between ages 3 and 6 years (N = 306) were recruited for a study examining preschool depression that included healthy and disruptive preschoolers. Preschoolers were placed in the following groups: late preterm (34-36 weeks, n = 39), early term (37-39 weeks, n = 78), and full term (40-41 weeks, n = 154). DSM-IV psychiatric disorders were assessed via the Preschool Age Psychiatric Assessment. Maternal history of psychiatric disorders was assessed using the Family Interview for Genetic Studies., Results: Late preterm children had higher rates of any Axis I psychiatric diagnosis (odds ratio = 3.18, 95% confidence interval = 1.09-4.76) and of any anxiety disorder (odds ratio = 3.74, 95% confidence interval = 1.59-8.78) than full term children after adjusting for gender, ethnicity, family income, and IQ. There were no differences in rates of psychiatric diagnoses between early term and full term children. A history of maternal depression mediated the relationship between late preterm birth and anxiety disorders in preschoolers., Conclusions: Late preterm children were at increased risk for anxiety disorders at preschool age. A history of maternal depression mediated this association. Findings confirm the extension of the risk of psychiatric disorders associated with prematurity to the late preterm group, and suggest that maternal depression may play a key role in this risk trajectory., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Preterm children are at risk for social-emotional difficulties, including autism and attention-deficit/hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via magnetic resonance imaging (MRI) at term-equivalent postmenstrual age (TEA), to later social-emotional difficulties., Method: MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birth weight <1,250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. A total of 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy and apparent diffusion coefficient. Social-emotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5 years., Results: Higher apparent diffusion coefficient in the right orbitofrontal cortex was associated with social-emotional problems at age 5 years (peer problems, p < .01). In females, smaller hippocampal volume was associated with increased hyperactivity (p < .01), peer problems (p < .05), and SDQ total score (p < .01). In males, a smaller frontal region was associated with poorer prosocial (p < .05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had social-emotional problems in similar domains at age 2 and those who did not., Conclusions: Early alterations in regional cerebral development in very preterm infants relate to specific deficits in social-emotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.