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Objective: To examine profiles of distress of mothers of preterm infants in the neonatal intensive care unit (NICU) and relate profiles to maternal and child outcomes at child age 5 years., Method: A racially and economically diverse sample of mothers (n = 94; 39% African American, 52% White) of preterm infants (≤30 weeks of gestation) completed validated questionnaires assessing depression, anxiety (state and trait), NICU stress, and life stress at NICU discharge of their infant. Mothers reported on their own and their children's symptomatology at child age 5. A latent profile analysis was conducted to categorize maternal symptomatology., Results: Latent profile analysis yielded 4 distinct maternal profiles: low symptomatology, high NICU stress, high depression and anxiety, and high state anxiety. Social determinants of health factors including age, education, neighborhood deprivation, and infant clinical risk distinguished the profiles. Mothers in the high depression and anxiety profile reported more anxiety and life stress at follow-up and reported their children experienced more anxious/depressed symptoms., Conclusion: Existing literature has gaps related to examining multiple dimensions of NICU distress and understanding how patterns of mood/affective symptoms, life stressors, and related social determinants of health factors vary across mothers. In this study, one specific profile of maternal NICU distress demonstrated enduring risks for poorer maternal and child mental health outcomes. This new knowledge underscores sources of disparate health outcomes for mothers of preterm infants and the infants themselves. Universal screening is needed to identify at-risk dyads for poor health outcomes in need of individualized interventions that address both maternal and child well-being., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the study was to describe and contrast the brain development and outcome among very preterm infants that were and were not exposed to surgery requiring general anesthesia prior to term equivalent age (TEA)., Methods: Preterm infants born ≤30 weeks' gestation who did (n = 25) and did not (n = 59) have surgery requiring general anesthesia during the preterm period were studied. At TEA, infants had MRI scans performed with measures of brain tissue volumes, cortical surface area, Gyrification Index, and white matter microstructure. Neurodevelopmental follow-up with the Bayley Scales of Infant and Toddler Development, Third Edition was undertaken at 2 years of corrected age. Multivariate models, adjusted for clinical and social risk factors, were used to compare the groups., Results: After controlling for clinical and social variables, preterm infants exposed to surgical anesthesia demonstrated decreased relative white matter volumes at TEA and lower cognitive and motor composite scores at 2-year follow-up. Those with longer surgical exposure demonstrated the greatest decrease in white matter volumes and lower cognitive and motor outcomes at age 2 years., Conclusions: Very preterm infants who required surgery during the preterm period had lower white mater volumes at TEA and worse neurodevelopmental outcome at age 2 years., Impact: In very preterm infants, there is an association between surgery requiring general anesthesia during the preterm period and reduced white mater volume on MRI at TEA and lower cognitive and motor composite scores at age 2 years. It is known that the very preterm infant's brain undergoes rapid growth during the period corresponding to the third trimester. The current study suggests an association between surgery requiring general anesthesia during this period and worse outcomes.

Objective: Previous studies suggest that maternal postpartum mental health issues may have an impact on parenting and child development in preterm infants, but have often not measured symptomatology in the neonatal intensive care unit (NICU) or followed families through early childhood. This study examines how maternal depressive symptoms and stress in the NICU are related to parenting behaviors at age 5 years, in mothers of children born very preterm (at ≤30 weeks' gestation)., Method: This longitudinal study followed a diverse sample of 74 very preterm children and their mothers. Maternal depression and stress were assessed in the NICU. At age 5, mother-child dyads were observed and coded for maternal intrusiveness, negativity, sensitivity, and positivity. Other covariates, including maternal and child intelligence, maternal education, income-to-needs ratio, maternal depression at age 5 years, and child sex were included in multivariate analyses., Results: The interaction between maternal NICU stress and NICU depression for intrusiveness and negativity indicates that greater NICU depression was associated with more intrusiveness under medium or high levels of NICU stress, and more negativity under high levels of NICU stress. Furthermore, greater NICU depression was associated with less sensitivity, over and above other covariates., Conclusion: Findings suggest that early maternal peripartum depression and stress in the NICU can have lasting impacts on multiple parenting behaviors, highlighting the need for screening and targeted interventions in the NICU., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Despite advances in antenatal and neonatal care, preterm birth remains a leading cause of neurological disabilities in children. Infants born prematurely, particularly those delivered at the earliest gestational ages, commonly demonstrate increased rates of impairment across multiple neurodevelopmental domains. Indeed, the current literature establishes that preterm birth is a leading risk factor for cerebral palsy, is associated with executive function deficits, increases risk for impaired receptive and expressive language skills, and is linked with higher rates of co-occurring attention deficit hyperactivity disorder, anxiety, and autism spectrum disorders. These same infants also demonstrate elevated rates of aberrant cerebral structural and functional connectivity, with persistent changes evident across advanced magnetic resonance imaging modalities as early as the neonatal period. Emerging findings from cross-sectional and longitudinal investigations increasingly suggest that aberrant connectivity within key functional networks and white matter tracts may underlie the neurodevelopmental impairments common in this population., Main Body: This review begins by highlighting the elevated rates of neurodevelopmental disorders across domains in this clinical population, describes the patterns of aberrant structural and functional connectivity common in prematurely-born infants and children, and then reviews the increasingly established body of literature delineating the relationship between these brain abnormalities and adverse neurodevelopmental outcomes. We also detail important, typically understudied, clinical, and social variables that may influence these relationships among preterm children, including heritability and psychosocial risks., Conclusion: Future work in this domain should continue to leverage longitudinal evaluations of preterm infants which include both neuroimaging and detailed serial neurodevelopmental assessments to further characterize relationships between imaging measures and impairment, information necessary for advancing our understanding of modifiable risk factors underlying these disorders and best practices for improving neurodevelopmental trajectories in this high-risk clinical population.

Objective: Alterations in the normal developmental trajectory of amygdala resting state functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants, and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years., Method: Resting state fMRI data were obtained shortly after birth from 65 FT infants (gestational age [GA] ≥36 weeks) and 57 VPT infants (GA <30 weeks) at term equivalent. Voxelwise correlation analyses were performed using individual-specific bilateral amygdala regions of interest. Total internalizing symptoms and the behavioral inhibition, depression/withdrawal, general anxiety, and separation distress subdomains were assessed in a subset (n = 44) at age 2 years using the Infant Toddler Social Emotional Assessment., Results: In FT and VPT infants, the amygdala demonstrated positive correlations with subcortical and limbic structures and negative correlations with cortical regions, although magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years with regional specificity consistent with known pathophysiology in older populations: connectivity with the anterior insula related to depressive symptoms, with the dorsal anterior cingulate related to generalized anxiety, and with the medial prefrontal cortex related to behavioral inhibition., Conclusion: Amygdala rs-FC is well established in neonates. Variability in regional neonatal amygdala rs-FC predicted internalizing symptoms at 2 years, suggesting that risk for internalizing symptoms may be established in neonatal amygdala functional connectivity patterns., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Recent resting-state functional MRI investigations have demonstrated that much of the large-scale functional network architecture supporting motor, sensory and cognitive functions in older pediatric and adult populations is present in term- and prematurely-born infants. Application of new analytical approaches can help translate the improved understanding of early functional connectivity provided through these studies into predictive models of neurodevelopmental outcome. One approach to achieving this goal is multivariate pattern analysis, a machine-learning, pattern classification approach well-suited for high-dimensional neuroimaging data. It has previously been adapted to predict brain maturity in children and adolescents using structural and resting state-functional MRI data. In this study, we evaluated resting state-functional MRI data from 50 preterm-born infants (born at 23-29weeks of gestation and without moderate-severe brain injury) scanned at term equivalent postmenstrual age compared with data from 50 term-born control infants studied within the first week of life. Using 214 regions of interest, binary support vector machines distinguished term from preterm infants with 84% accuracy (p<0.0001). Inter- and intra-hemispheric connections throughout the brain were important for group categorization, indicating that widespread changes in the brain's functional network architecture associated with preterm birth are detectable by term equivalent age. Support vector regression enabled quantitative estimation of birth gestational age in single subjects using only term equivalent resting state-functional MRI data, indicating that the present approach is sensitive to the degree of disruption of brain development associated with preterm birth (using gestational age as a surrogate for the extent of disruption). This suggests that support vector regression may provide a means for predicting neurodevelopmental outcome in individual infants., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To examine the association of difficult feeding behaviors in very preterm infants at age 2 years with growth and neurodevelopmental outcomes and family factors and functioning., Study Design: Eighty children born ≤30 weeks gestation were studied from birth until age 2 years. Feeding difficulties were assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment at age 2 years, along with growth measurement and developmental testing. Maternal mental health and family factors were assessed using standardized questionnaires. ANOVA and χ(2) analyses were performed to determine associations between feeding difficulties and growth, neurodevelopmental outcomes, and family characteristics., Results: Twenty-one children (26%) were at risk for feeding difficulties, and an additional 18 (23%) had definite feeding difficulties at age 2 years. Those with feeding difficulties were more likely to be subject to a range of neurodevelopmental problems, including impaired cognition (P = .02), language (P = .04), motor (P = .01), and socioemotional (P < .007) skills. Compared with the parents of children with fewer feeding difficulties, parents of the children with feeding difficulties had higher parenting stress (P = .02) and reported more difficulty managing their child's behavior (P = .002) and more frequent parent-child interaction problems (P = .002). No associations were found between difficult feeding behaviors and growth, maternal mental health, or family factors., Conclusion: Difficult feeding behaviors in children born very preterm appear to be highly comorbid with other developmental and family challenges, including neurodevelopmental impairment and parent-child interaction difficulties. Focusing on improving feeding skills, in conjunction with supporting positive parent-child interactions, may be beneficial for improving outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To determine if late preterm (LP) children differ from full term (FT) children in volumes of the cortex, hippocampus, corpus callosum, or amygdala and whether these differences are associated with anxiety symptoms at school-age., Study Design: LP children born between 34 and 36 weeks gestation and FT children born between 39 and 41 weeks gestation from a larger longitudinal cohort had magnetic resonance imaging scans at school-age. Brain volumes, cortical surface area, and thickness measures were obtained. Anxiety symptoms were assessed using a structured diagnostic interview annually beginning at preschool-age and following the magnetic resonance imaging., Results: LP children (n = 21) had a smaller percentage of total, right parietal, and right temporal lobe gray matter volume than FT children (n = 87). There were no differences in hippocampal, callosal, or amygdala volumes or cortical thickness. LP children also had a relative decrease in right parietal lobe cortical surface area. LP children had greater anxiety symptoms over all assessments. The relationship between late prematurity and school-age anxiety symptoms was mediated by the relative decrease in right temporal lobe volume., Conclusions: LP children, comprising 70% of preterm children, are also at increased risk for altered brain development particularly in the right temporal and parietal cortices. Alterations in the right temporal lobe cortical volume may underlie the increased rate of anxiety symptoms among these LP children. These findings suggest that LP delivery may disrupt temporal and parietal cortical development that persists until school-age with the right temporal lobe conferring risk for elevated anxiety symptoms., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years., Study Design: Maternal/infant dyads (n=62) born ⩽30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment., Result: Maternal obesity was associated with positive screen for autism (odds ratio=9.88, P=0.002) and lower composite language scores (β=-9.36, (confidence interval=-15.11, -3.61), P=0.002)., Conclusion: Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity.

Aim: To investigate early medical and family factors associated with later feeding risk in preterm infants., Methods: For this longitudinal study, 136 infants born ≤30 weeks gestation were enrolled. Medical and social background factors were assessed at term equivalent age. Infants underwent magnetic resonance imaging, neurobehavioral evaluation and feeding assessment. Parent involvement in the neonatal intensive care unit was tracked, and maternal mental health was assessed at neonatal intensive care unit discharge. At age 2 years, feeding outcome was assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment (n = 80). Associations between feeding problems at age 2 years and (i) early medical factors, (ii) neurobehavioral functioning and feeding at term equivalent age, (iii) cerebral structure and (iv) maternal mental health were investigated using regression., Results: Eighteen (23%) children had feeding problems at age 2 years. Feeding problems were associated with early hypotonia (p = 0.03; β = 0.29) and lower socio-economic status (p = 0.046; β = -0.22). No associations were observed between early medical factors, early feeding performance, cerebral structure alterations or maternal well-being and feeding outcome., Conclusion: Early hypotonia may disrupt the development of oral-motor skills. Hypotonia and poor feeding also may share a common aetiology. Associations with lower socio-economic status highlight the potential influence of family background factors in feeding problems in the preterm infant., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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: We investigated whether particular demographics, maternal psychosocial and infant factors identified mothers of very preterm infants at risk for postpartum depression or anxiety at the time of discharge from a level III urban Neonatal Intensive Care Unit (NICU)., Study Design: A racially diverse cohort of mothers (N=73) of preterm infants (gestational age <30 weeks) completed a comprehensive questionnaire at discharge from the NICU assessing postpartum depression, anxiety and psychosocial and demographic factors. Additionally, infants underwent brain magnetic resonance imaging before discharge., Result: Twenty percent of mothers had clinically significant levels of depression whereas 43% had moderate to severe anxiety. Being married (P<0.01), parental role alteration (P<0.01) and prolonged ventilation (P<0.05) were associated with increased depressive symptoms. No psychosocial, demographics or infant factors, including severity of brain injury, were associated with state anxiety levels., Conclusion: Maternal factors, such as marital status, stress from parental role alteration and infant factors, such as prolonged ventilation, are associated with increased depression. However, clinically significant levels of anxiety are common in mothers of very preterm infants with few identifiable risk factors. These findings support the need for universal screening within the NICU.