Early sensitivity training for parents of preterm infants: impact on the developing brain.

After birth, preterm infants face a stressful environment, which may negatively impact early brain development and subsequent neurobehavioral outcomes. This randomized controlled trial involving 45 women with infants <30-wk gestation, assessed the effectiveness of training parents in reducing stressful experiences. Intervention consisted of 10 sessions in the Neonatal Intensive Care Unit (NICU). Postintervention, at term-equivalent (40-wk postmenstrual age), magnetic resonance imaging (MRI) was performed to evaluate brain structure and development. Quantitative volumetric techniques were used to estimate overall and regional brain volumes for different tissue types including CSF, CGM, DNGM, UWM, and MWM. DTI was used to evaluate the integrity and maturation of white matter by ADC and FA. Maturation and connectivity of white matter, characterized by diffusion MR measures of ADC and FA, were significantly enhanced in the intervention group, who displayed greater restriction in ADC and increase in FA. There were no significant effects on either brain volumes or on short-term medical outcomes. Thus, sensitivity training for parents in the NICU is associated with improved cerebral white matter micro-structural development in preterm infants.

Neurobehavior at term and white and gray matter abnormalities in very preterm infants.

OBJECTIVE: To examine the relationship between very preterm infant neurobehavior at term and concurrent magnetic resonance-defined cerebral abnormalities. STUDY DESIGN: 168 very preterm infants (birth weight <1250 g or gestation <30 weeks) were examined at term with 2 standardized neurobehavioral assessments, the Revised Hammersmith Neonatal Neurological Examination and the Neonatal Intensive Care Unit Network Neurobehavioral Scale. The relationship between composite neurobehavioral scores and qualitative white and gray matter abnormalities on magnetic resonance imaging was determined. RESULTS: Poorer neurobehavioral performance related to magnetic resonance-defined cerebral abnormalities. Composite neurobehavioral scores related to the total grade of white matter abnormality, and worse neurobehavior related most strongly to 2 components of this grade: white matter signal abnormalities and reduction in white matter volumes. Neurobehavior was not related to the total grade of gray matter abnormality. However, delayed gyral maturation, a component of the total gray matter grade, was related to poorer performance on both neurobehavioral scales. CONCLUSION: Very preterm infant neurobehavior at term is related to concurrent cerebral abnormalities in both white and gray matter defined by qualitative magnetic resonance imaging.

Parenting behavior is associated with the early neurobehavioral development of very preterm children.

OBJECTIVE: There is an increasing focus on social and environmental factors that promote and support the early development of highly vulnerable children such as those born very preterm. The aim of this study was to assess the relationship between parenting behavior, parent-child synchrony, and neurobehavioral development in very preterm children at 24 months of age. METHODS: Participants were 152 very preterm children (<30 weeks' gestation or <1250 g birth weight) and their parents/guardians. At 2 years' corrected age, parents/guardians and children completed a semistructured parent-child interaction task assessing dyad synchrony and parenting behavior (positive affect, negative affect, sensitivity, facilitation, and intrusiveness). Cognitive and motor development was assessed by using the Bayley Scales of Infant Development II, and the Infant Toddler Social and Emotional Assessment was used to assess socioemotional development (social-emotional competence and internalizing and externalizing behavior). RESULTS: fter controlling for social risk, most parenting domains were associated with cognitive development, with parent-child synchrony emerging as the most predictive. Greater parent-child synchrony was also associated with greater social-emotional competence, as was parenting that was positive, warm, and sensitive. Parents who displayed higher levels of negative affect were more likely to rate their children as withdrawn, anxious, and inhibited, but, unexpectedly, higher negative affect was also associated with more optimal psychomotor development. Parenting was not associated with externalizing behaviors at this age. CONCLUSIONS: Specific parenting behaviors, particularly parent-child synchrony, were associated with neurobehavioral development. These findings have implications for the development of targeted parent-based interventions to promote positive outcomes across different developmental domains during the first 2 years of life for very preterm children.

Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term.

OBJECTIVES: To test the hypothesis that the impact of postnatal sepsis/necrotizing enterocolitis (NEC) on neurodevelopment may be mediated by white matter abnormality (WMA), which can be demonstrated with magnetic resonance imaging (MRI). STUDY DESIGN: A prospective cohort of 192 unselected preterm infants (gestational age <30 weeks), who were evaluated for sepsis and NEC, underwent imaging at term-equivalent age and neurodevelopmental outcome at 2 years corrected age with the Bayley Scales of Infant Development. RESULTS: Sixty-eight preterm (35%) infants had 100 episodes of confirmed sepsis, and 9 (5%) infants had confirmed NEC. Coagulase-negative staphylococci accounted for 73% (73/100) of the episodes of confirmed sepsis. Infants with sepsis/NEC had significantly more WMA on MRI at term compared with infants in the no-sepsis/NEC group. They also had poorer psychomotor development that persisted after adjusting for potential confounders but which became nonsignificant after adjusting for WMA. CONCLUSIONS: Preterm infants with sepsis/NEC are at greater risk of motor impairment at 2 years, which appears to be mediated by WMA. These findings may assist in defining a neuroprotective target in preterm infants with sepsis/NEC.

Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome.

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.

Quality of general movements is related to white matter pathology in very preterm infants.

OBJECTIVE: Preterm infants are at an increased risk for abnormalities of general movements, which predict subsequent poor neurodevelopmental outcome. The cerebral lesion that predisposes the preterm infant to abnormal general movements remains unknown. The objective of this study was to determine the association between MRI-defined cerebral abnormalities and general movements at 1 and 3 months' corrected age in infants who were born very preterm. METHODS: Eighty-six preterm infants (<30 weeks' gestation) were prospectively recruited and underwent brain MRI at term-equivalent age to investigate the relationship between qualitative white and gray matter pathology and abnormality of general movements. Standardized videotaped recordings of general movements were obtained at 1 and 3 months postterm (+/-1 week) and scored without knowledge of the MRI findings. At 1 month corrected age, general movements of a writhing character were classified as normal or abnormal (poor repertoire, cramped synchronized, or chaotic). At 3 months' corrected age, fidgety general movements were classified as present or absent. RESULTS: At 1 month, 53 (62%) infants had abnormal general movements, 46 of whom had poor repertoire general movements and 7 of whom had cramped synchronized general movements. At 3 months, 23 (25%) infants had absent fidgety movements. At both 1 and 3 months of age, consistently abnormal general movement classifications were related to increasing white matter abnormality on MRI. In contrast, there were no significant relationships between general movement classifications and gray matter abnormalities, either individually or in total. CONCLUSION: The significant relationships between general movements at 1 and 3 months and cerebral white matter abnormalities on MRI in the very preterm infant support the concept that abnormal general movements reflect white matter injury.

Perinatal risk factors altering regional brain structure in the preterm infant.

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.

Alterations in neurobehavior at term reflect differing perinatal exposures in very preterm infants.

OBJECTIVES: Preterm infants have higher rates of cognitive and behavioral difficulties at school age than their term-born peers. We hypothesized that neurobehavior at term would be different in very preterm infants compared with term infants and that perinatal exposures would be associated with these alterations in neurobehavior. PATIENTS AND METHODS: Two standardized neurobehavioral evaluations were completed on 207 infants at term equivalent, including 168 very preterm infants (<1250 g or <30 weeks' gestation) and 39 term control infants. The assessments used were the Neonatal Intensive Care Unit Network Neurobehavioral Scale and the revised Hammersmith Neonatal Neurologic Examination. The relationship of perinatal variables to preterm infant neurobehavioral scores for both evaluations was examined. RESULTS: Compared with term-born infants, preterm infant neurobehavior was significantly altered for the Hammersmith Neonatal Neurologic Examination total score and all of the subtotals. Similarly, preterm infants displayed altered neurobehavior for the majority of the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores. Complete perinatal data were available for 157 of 168 very preterm infants. The perinatal variables most strongly associated with altered preterm infant neurobehavior on multivariate regression analysis included the total number of days of assisted ventilation, intraventricular hemorrhage, and necrotizing enterocolitis. Positive perinatal influences on neurobehavioral performance at term on multivariate analysis included maternal antenatal steroids, female gender, and infants receiving breast milk at discharge home. CONCLUSIONS: Preterm infants at term equivalent showed alterations in motor behavior and higher cortically integrated functions. The pattern of abnormality in neurobehavior differed in relation to perinatal exposures. Neurobehavioral examination at term equivalent age is useful in evaluating the impact of neonatal intensive care.