Parenting and Neurobehavioral Outcomes in Children Born Moderate-to-Late Preterm and at Term.

OBJECTIVES: To compare the parenting environment and the relationships between parenting behaviors and concurrent child neurobehavioral outcomes at 2 years of corrected age between children born moderate-to-late preterm (MLP; 32-36 weeks of gestation) and at term (≥37 weeks of gestation). STUDY DESIGN: Participants were 129 children born MLP and 110 children born at term and their mothers. Mothers' parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 2 years of corrected age using the Emotional Availability Scales. Child cognitive and language development were assessed using the Bayley Scales of Infant and Toddler Development, and social-emotional competence using the Infant Toddler Social and Emotional Assessment. RESULTS: Mothers of children born MLP and at term displayed similar parenting behaviors overall, with slightly lower nonintrusiveness in mothers of children born MLP (adjusted mean difference -0.32 [-0.60, -0.04]; P = .03). In both groups of children, greater maternal sensitivity was associated with better cognitive development (P < .001 MLP; P = .02 term), increased maternal structuring was associated with better social-emotional competence (P = .02 MLP; P = .03 term), and higher maternal nonintrusiveness was associated with better cognitive, language, and social-emotional outcomes (all P < .04). Greater maternal sensitivity and structuring were associated with better language development in children born MLP but not in children born at term. CONCLUSIONS: Parenting behaviors are important for neurobehavioral outcomes in children born MLP and at term. Language development may be more strongly influenced by select parenting behaviors in children born MLP compared with children born at term.

Nutrition, Growth, Brain Volume, and Neurodevelopment in Very Preterm Children.

OBJECTIVE: To explore the associations between nutrition in the first 28 days after birth with somatic growth from birth to term-equivalent age, brain volumes at term-equivalent age, and neurodevelopment at 24 months of corrected age. STUDY DESIGN: Prospective cohort study of 149 infants born from 2011 to 2014 at <30 weeks of gestation in a tertiary neonatal nursery in Australia. The following data were collected: average daily energy, protein, fat, and carbohydrate intakes from birth until 28 days, and the difference in weight and head circumference z scores between birth and term-equivalent. Total brain tissue volumes were calculated from brain magnetic resonance imaging at term-equivalent age. Children were assessed at 2 years of corrected age with the Bayley Scales of Infant and Toddler Development-Third Edition. Relationships of nutritional variables with growth, brain volumes, and cognitive, language, and motor development were explored using linear regression. RESULTS: Complete nutritional data were available for 116 (78%) of the cohort. A 1 g/kg/day higher mean protein intake was associated with a mean increase in weight z score per week of 0.05 (95% CI 0.05, 0.10; P = .04). There was a lack of evidence for associations of any nutritional variables with head circumference growth, with brain volumes at term-equivalent age, or with 2-year neurodevelopment. CONCLUSIONS: Only higher protein intakes in the first 28 days after birth were associated with better weight growth between birth and term-equivalent age in very preterm infants. Nutrition in the first 28 days was otherwise not substantially related to brain size or to neurodevelopmental outcomes.

Long-Term Academic Functioning Following Cogmed Working Memory Training for Children Born Extremely Preterm: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of Cogmed Working Memory Training compared with a placebo program in improving academic functioning 24 months post-training in extremely preterm/extremely low birth weight 7-year-olds. STUDY DESIGN: A multicenter double-blind, placebo-controlled randomized controlled trial was conducted across all tertiary neonatal hospitals in the state of Victoria, Australia. Participants were 91 extremely preterm/extremely low birth weight 7-year-old children born in Victoria in 2005. Children were randomly assigned to either the Cogmed or placebo arm and completed the Cogmed or placebo program (20-25 sessions of 35-40 minutes duration) at home over 5-7 weeks. Academic achievement (word reading, spelling, sentence comprehension, and mathematics) was assessed 24 months post-training, as well as at 2 weeks and 12 months post-training, via standardized testing inclusive of working memory, attention, and executive behavior assessments. Data were analyzed using an intention-to-treat approach with mixed-effects modeling. RESULTS: There was little evidence of any benefits of Cogmed on academic functioning 24 months post-training, as well as on working memory, attention, or executive behavior at any age up to 24 months post-training compared with the placebo program. CONCLUSIONS: We currently do not recommend administration of Cogmed for early school-aged children born extremely preterm/extremely low birth weight to improve academic functioning. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000124831.

Associations of Newborn Brain Magnetic Resonance Imaging with Long-Term Neurodevelopmental Impairments in Very Preterm Children.

OBJECTIVE: To determine the relationship between brain abnormalities on newborn magnetic resonance imaging (MRI) and neurodevelopmental impairment at 7 years of age in very preterm children. STUDY DESIGN: A total of 223 very preterm infants (<30 weeks of gestation or <1250 g) born at Melbourne's Royal Women's Hospital had a brain MRI scan at term equivalent age. Scans were scored using a standardized system that assessed structural abnormality of cerebral white matter, cortical gray matter, deep gray matter, and cerebellum. Children were assessed at 7 years on measures of general intelligence, motor functioning, academic achievement, and behavior. RESULTS: One hundred eighty-six very preterm children (83%) had both an MRI at term equivalent age and a 7-year follow-up assessment. Higher global brain, cerebral white matter, and deep gray matter abnormality scores were related to poorer intelligence quotient (IQ) (Ps < .01), spelling (Ps < .05), math computation (Ps < .01), and motor function (Ps < .001). Higher cerebellum abnormality scores were related to poorer IQ (P = .001), math computation (P = .018), and motor outcomes (P = .001). Perinatal, neonatal, and social confounders had little effect on the relationships between the MRI abnormality scores and outcomes. Moderate-severe global abnormality on newborn MRI was associated with a reduction in IQ (-6.9 points), math computation (-7.1 points), and motor (-1.9 points) scores independent of the other potential confounders. CONCLUSIONS: Structured evaluation of brain MRI at term equivalent is predictive of outcome at 7 years of age, independent of clinical and social factors.

Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks' Gestation.

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 at <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 7 years of age. We adjusted for age, sex, social risk, and neonatal illness in linear regression. RESULTS: A greater number of days on which infants received >50% breast milk was associated with greater deep nuclear gray matter volume at term equivalent age (0.15 cc/d; 95% CI, 0.05-0.25); and with better performance at age 7 years of age on IQ (0.5 points/d; 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 of age in relation to breast milk intake were observed. CONCLUSION: Predominant breast milk feeding in the first 28 days of life was associated with a greater 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.

Brain Volumes at Term-Equivalent Age Are Associated with 2-Year Neurodevelopment in Moderate and Late Preterm Children.

OBJECTIVE: To explore the association between brain maturation, injury, and volumes at term-equivalent age with 2-year development in moderate and late preterm children. STUDY DESIGN: Moderate and late preterm infants were recruited at birth and assessed at age 2 years using the Bayley Scales of Infant and Toddler Development, Third Edition. Brain magnetic resonance imaging (MRI) was performed at term-equivalent age and qualitatively assessed for brain maturation (myelination of the posterior limb of the internal capsule and gyral folding) and injury. Brain volumes were measured using advanced segmentation techniques. The associations between brain MRI measures with developmental outcomes were explored using linear regression analyses. RESULTS: A total of 197 children underwent MRI and assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Larger total brain tissue volumes were associated with higher cognitive and language scores (adjusted coefficients per 10% increase in brain size; 95% CI of 3.2 [0.4, 5.6] and 5.6 [2.4, 8.8], respectively). Similar relationships were documented for white matter volumes with cognitive and language scores, multiple cerebral structures with language scores, and cerebellar volumes with motor scores. Larger cerebellar volumes were independently associated with better language and motor scores, after adjustment for other perinatal factors. There was little evidence of relationships between myelination of the posterior limb of the internal capsule, gyral folding, or injury with 2-year development. CONCLUSIONS: Larger total brain tissue, white matter, and cerebellar volumes at term-equivalent age are associated with better neurodevelopment in moderate and late preterm children. Brain volumes may be an important marker for neurodevelopmental deficits described in moderate and late preterm children.

Association between postnatal dexamethasone for treatment of bronchopulmonary dysplasia and brain volumes at adolescence in infants born very preterm.

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.

Very preterm birth influences parental mental health and family outcomes seven years after birth.

OBJECTIVE: To evaluate the long-term influence of very preterm birth on parental mental health, family functioning, and parenting stress at age 2 and 7 years. STUDY DESIGN: Participants were 183 children born very preterm (<30 weeks gestation; n = 148 families) and 69 term-born children (n = 66 families). When children were age 7 years, parents were assessed based on the Hospital Anxiety and Depression Scale, the Family Assessment Device, the Parenting Stress Index, and the Social Support Questionnaire. Similar measures were evaluated at age 2 years. RESULTS: When the children were age 7 years, parents of the very preterm-born children were more likely to report moderate to severe anxiety symptoms (P = .03), higher levels of depression symptoms (P = .03), poorer family functioning (P < .05), and higher levels of parenting stress (P < .001) compared with parents of the children born at term. Group differences in parenting stress and family functioning persisted after adjustment for social risk and child neurodevelopmental disability. There was strong evidence of a relationship between family functioning and parent-related stress at age 2 and 7 years (P < .001), but little evidence that parental mental health problems at 2 years were predictive of anxiety (P = .15) or depression (P = .28) at 7 years for parents of very preterm children. CONCLUSION: These findings demonstrate that very preterm birth has a negative influence on parent and family functioning at 7 years after birth, which for some families is consistent with their functioning at 2 years. These results have implications for the support required by parents of very preterm children.

Quality of life at age 18 years after extremely preterm birth in the post-surfactant era.

OBJECTIVES: To assess the self-reported quality of life, health status, self-esteem, and functional outcomes at age 18 years of extremely preterm (EP; <28 weeks gestation) or extremely low birth weight (ELBW; birth weight <1000 g) adolescents born in 1991-1992 compared with normal birth weight (birth weight >2499 g) controls, and, within the EP/ELBW cohort, to assess whether these outcomes are related to gestational age or birth weight. STUDY DESIGN: Self-reported measures of quality of life, health status, self-esteem, and functional outcomes were obtained at age 18 years from a geographic cohort of all survivors born EP/ELBW in 1991-1992 in the state of Victoria, Australia, along with matched normal birth weight controls. RESULTS: Data were available from 194 EP/ELBW and 148 control adolescents. EP/ELBW adolescents reported similar overall quality of life, health status, and self-esteem as controls (P > .05). Birth at younger gestational age or lower birth weight were not related to poorer quality of life within the EP/ELBW cohort (P > .05). EP/ELBW adolescents reported less physical activity (OR, 0.5; 95% CI, 0.3-0.8; P < .01), sexual activity (OR, 0.6; 95% CI, 0.4-0.9; P = .01), and alcohol intake (OR, 0.5; 95% CI, 0.3-0.8; P = .01) compared with controls. Other aspects of risk-taking behavior were similar in the 2 groups (P > .05). CONCLUSION: EP/ELBW individuals born after the introduction of exogenous surfactant are transitioning well into young adulthood, despite the fact that more of the tiniest and most immature infants survive than ever before. They report similar quality of life, self-esteem, and social and risk-taking behaviors as controls.

Arterial ischemic stroke risk factors: the International Pediatric Stroke Study.

OBJECTIVE: To describe presumptive risk factors (RFs) for childhood arterial ischemic stroke (AIS) and explore their relationship with presentation, age, geography, and infarct characteristics. METHODS: Children (29 days-18 years) were prospectively enrolled in the International Pediatric Stroke Study. Risk factors, defined conditions thought to be associated with childhood AIS, were divided into 10 categories. Chi-square tests were used to compare RFs prevalence across regions and age; logistic regression was used to determine whether RFs were associated with particular features at presentation or infarct characteristics. RESULTS: A total of 676 children were included. No identifiable RFs was present in 54 (9%). RFs in others included arteriopathies (53%), cardiac disorders (CDs) (31%), infection (24%), acute head and neck disorders (AHNDs) (23%), acute systemic conditions (ASCs) (22%), chronic systemic conditions (CSCs) (19%), prothrombotic states (PTSs) (13%), chronic head and neck disorders (CHNDs) (10%), atherosclerosis-related RFs (2%), and other (22%). Fifty-two percent had multiple RFs. There was lower prevalence of arteriopathy in Asia, lower prevalence of CSCs in Europe and Australia, higher prevalence of PTSs in Europe, and higher prevalence of ASCs in Asia and South America. Prevalence of CDs and ASCs was highest in preschoolers, arteriopathies in children 5 to 9 years old, and CHNDs were highest in children aged 10 to 14 years. Arteriopathies were associated with focal signs and ASCs, CHNDs, and AHNDs with diffuse signs. Arteriopathies, CSCs, and ASCs were associated with multiple infarcts and CDs with hemorrhagic conversion. INTERPRETATION: RFs, especially arteriopathy, are common in childhood AIS. Variations in RFs by age or geography may inform prioritization of investigations and targeted preventative strategies.