Rod W. Hunt

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.

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. After 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.

A Systematic Review of Motor and Cognitive Outcomes After Early Surgery for Congenital Heart Disease

CONTEXT: Brain injury is the most common long-term complication of congenital heart disease requiring surgery during infancy. It is clear that the youngest patients undergoing cardiac surgery, primarily neonates and young infants, are at the greatest risk for brain injury. Developmental anomalies sustained early in life have lifelong repercussions. OBJECTIVE: We conducted a systematic review to examine longitudinal studies of cognitive and/or motor outcome after cardiac surgery during early infancy. METHODS: Electronic searches were performed in Medline, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and Embase (1998–2008). The search strategy yielded 327 articles, of which 65 were reviewed. Eight cohorts provided prospective data regarding the cognitive and/or motor outcome of infants who had undergone surgery for congenital heart disease before 6 months of age. Two authors, Ms Snookes and Dr Gunn, independently extracted data and presented results according to 3 subgroups for age of follow-up: early development (1 to <3 years); preschool age (3–5 years); and school age (>5 to 17 years). Weighted analysis was undertaken to pool the results of studies when appropriate. RESULTS: All of the identified studies reported results of the Bayley Scales of Infant Development for children younger than the age of 3. Outcome data as reported by the Bayley Scales were combined for infants assessed at 1 year of age, revealing a weighted mean Mental Development Index of 90.3 (95% confidence interval: 88.9–91.6) and Psychomotor Development Index of 78.1 (95% confidence interval: 76.4–79.7). Additional analysis was limited by a lack of data at preschool and school age. CONCLUSIONS: With this review we identified a limited number of prospective studies that systematically addressed outcome in patients at the highest risk. These studies consistently revealed cognitive and motor delay in children after cardiac surgery during early infancy. Additional investigation is required to ascertain the consequences of such impairment during later childhood and into adult life.

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.

Apparent Diffusion Coefficient in the Posterior Limb of the Internal Capsule Predicts Outcome After Perinatal Asphyxia

Objective. Predicting long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) is a difficult task. Magnetic resonance imaging, particularly diffusion imaging, holds promise in this regard as it is more sensitive to brain injury than any other available imaging modality. Previous studies have suggested that abnormal signal intensity in the posterior limb of the internal capsule (PLIC), detectable on inversion-recovery T1-weighted imaging, is a strong predictor of outcome. The aim of this study was to assess the relationship between apparent diffusion coefficient (ADC) values from the PLIC, measured by diffusion imaging, and neuromotor outcome in term infants with HIE. Methods. Twenty-eight term infants with a clinical diagnosis of HIE underwent magnetic resonance imaging as soon as practicable after birth (mean age: 5.6 days), including diffusion-weighted imaging, from which ADC values in the PLIC were measured. Motor outcome was assessed in 12 of 16 survivors. Results. The ADC value in the PLIC was significantly associated with survival in term infants with HIE. For survivors, the mean ADC value in the PLIC was 0.89 ± 0.17 μm2/ms, whereas the mean ADC value for nonsurvivors was 0.75 ± 0.17 μm2/ms (t = 2.25). Among survivors, the ADC value in the PLIC was also associated with neuromotor outcome (F = 5.60). Conclusion. The ADC value in the PLIC is an indicator of ischemic injury and may be of use as an objective prognostic marker for infants with HIE.

Abnormal White Matter Signal on MR Imaging Is Related to Abnormal Tissue Microstructure

BACKGROUND AND PURPOSE: White matter signal-intensity abnormalities (WMSA) on MR imaging are related to adverse neurodevelopmental outcome in extremely preterm infants. Diffusion tensor imaging (DTI) may detect alterations in cerebral white matter microstructure and thus may help confirm the pathologic basis of WMSA. This study aimed to relate regional DTI measures with severity of WMSA in very preterm infants. MATERIALS AND METHODS: One hundred eleven preterm infants (birth weight, <1250 g and/or gestational age, <30 weeks) were scanned at term-equivalent age (1.5T). WMSA were classified as normal, focal, or extensive. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial (λ1), and radial ([λ2 + λ3]/2) diffusivity were calculated in 12 regions of interest placed in the bilateral posterior limbs of the internal capsule, frontal (superior and inferior), sensorimotor, and occipital (superior and inferior) white matter regions. Data were compared by using 1-way analysis of variance, with a Bonferroni correction for multiple comparisons. RESULTS: Thirty-nine infants had normal, 59 infants had focal, and 13 infants had extensive WMSA. Compared with infants with normal or focal WMSA, infants with extensive WMSA had significantly lower FA in the internal capsule (P < .001), right inferior frontal regions (P < .05), and right superior occipital regions (P = .01); and higher radial diffusivity in the right internal capsule (P = .005), bilateral sensorimotor (P < .05), and right superior occipital regions (P < .05). Compared with infants with normal WMSA, infants with extensive WMSA had significantly higher ADC in bilateral sensorimotor regions (P < .01) and right superior occipital regions (P = .01), and lower axial diffusivity in the bilateral sensorimotor regions (P < .05). CONCLUSIONS: There are significant region-specific changes in ADC, FA, radial diffusivity, and axial diffusivity in preterm infants with extensive WMSA. Altered radial diffusivity was most prominent. This implies that disrupted premyelinating oligodendroglia is the major correlate with extensive WMSA rather than axonal pathology.

Neonatal white matter abnormality predicts childhood motor impairment in very preterm children

Aim  Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor impairments. The aim of this study was to assess whether WMA were predictive of all levels of motor impairments in very preterm children.

Pre-operative brain injury in newborn infants with transposition of the great arteries occurs at rates similar to other complex congenital heart disease and is not related to balloon atrial septostomy.

OBJECTIVES The goal of this study was to determine the prevalence and pattern of pre-operative brain injury in infants with transposition of the great arteries (TGA) compared with other complex congenital heart disease (CHD) and to define the risk of balloon atrial septostomy (BAS) for the development of brain injury. BACKGROUND It has recently been suggested that infants with TGA are at increased risk of pre-operative brain injury, in particular, stroke, and that this is strongly associated with having a BAS. METHODS Sixty-four newborn infants with TGA (n = 44), hypoplastic left heart syndrome (n = 13), or pulmonary atresia (n = 7) had magnetic resonance imaging (MRI) scans performed before surgery. RESULTS Thirty-three (75%) of the infants with TGA had a BAS. Brain injury occurred in 19 (30%) infants: white matter injury (WMI) in 17 (27%), and stroke in 3 (5%). There was no difference in the prevalence or pattern of brain injury between diagnostic groups. There was no association between BAS and brain injury in infants with TGA. There was a trend toward increased brain injury in TGA with an intact interventricular septum compared with TGA with a ventricular septal defect (38% vs. 8%, p = 0.075). There was no association between brain injury and any clinical variables. CONCLUSIONS Pre-operative brain injury on MRI scan was present in 30% of infants with CHD. The predominant pattern was WMI. The rates and patterns of pre-operative brain injury are similar in infants with TGA compared with other complex CHD, and BAS does not increase the risk of pre-operative brain injury.

Prognostic Utility of Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy: Substudy of a Randomized Trial

OBJECTIVE To investigate the effects of hypothermia treatment on magnetic resonance imaging (MRI) patterns of brain injury in newborns with hypoxic-ischemic encephalopathy compared with normothermia, including the prognostic utility of MRI for death and/or disability at a postnatal age of 2 years. DESIGN Substudy of a randomized controlled trial. SETTING Participating centers in the Infant Cooling Evaluation trial. PARTICIPANTS Trial participants (gestational age ≥35 weeks with moderate to severe hypoxic-ischemic encephalopathy, randomized to whole-body hypothermia or normothermia) with available MRIs. MAIN EXPOSURE We performed qualitative evaluation of T1- and T2-weighted and diffusion MRIs. The posterior limb of the internal capsule was classified as normal or abnormal, whereas the basal ganglia and thalami, white matter, and cortical gray matter were classified as normal or mildly abnormal or moderately/severely abnormal. MAIN OUTCOME MEASURES Death or major disability at 2 years. RESULTS We evaluated 127 MRIs (66 patients treated with hypothermia and 61 with normothermia; mean age at scan, 6 postnatal days). The odds of having moderate/severe white matter or cortical gray matter abnormalities on T1- and T2-weighted MRI were reduced by hypothermia (white matter odds ratio, 0.28 [95% CI, 0.09-0.82]; gray matter odds ratio, 0.41 [0.17-1.00]). Abnormal MRI findings predicted adverse outcomes, with T1- and T2-weighted and diffusion MRI abnormalities in the posterior limb of the internal capsule and basal ganglia and thalami demonstrating the greatest predictive value. There was little evidence that prognostic value of the MRI was modified by therapeutic hypothermia (all interactions, P > .05). CONCLUSIONS Brain injury on T1- and T2-weighted MRI is reduced in hypothermia-treated newborns. Abnormal MRI findings are prognostic of long-term outcome in moderate to severe hypoxic-ischemic encephalopathy regardless of treatment with hypothermia.