Jeanie L.Y. Cheong

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.

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.

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.

Gastrointestinal manifestations of postnatal cytomegalovirus infection in infants admitted to a neonatal intensive care unit over a five year period

Sixteen cases of postnatal cytomegalovirus (CMV) infection were identified in a neonatal intensive care unit population over a five year period. Eleven of these infants had gastrointestinal signs at the time of presentation. These ranged from minor and transient (abdominal distension and enteral feed intolerance) to severe and life threatening (protein losing enteropathy, diarrhoea, and hypernatraemic dehydration). An initial diagnosis of necrotising enterocolitis was common, but no infant showed intestinal or hepatic portal pneumatosis. The gestational age of the infants was 24–38 weeks. All had received fresh maternal breast milk. It is suggested that CMV enteritis is added to the spectrum of clinical manifestations of postnatal CMV infection. Signs suggestive of necrotising enterocolitis with atypical features should prompt investigations for CMV infection.

Caffeine and brain development in very preterm infants

Caffeine improves neurological outcome in very preterm infants, but the mechanisms responsible for this neurological benefit are unknown. The objective of this study was to assess whether caffeine influenced brain macro‐ or microstructural development in preterm infants.

Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

General Movements in Very Preterm Children and Neurodevelopment at 2 and 4 Years

OBJECTIVE: Although ∼50% of very preterm (VP) children have neurodevelopmental impairments, early prediction of infants who will experience problems later in life remains a challenge. This study evaluated the predictive value of general movements (GM; spontaneous and endogenous movements) at 1 and 3 months’ corrected age for neurodevelopment at 2 and 4 years of age in VP children. METHODS: At 1 and 3 months’ corrected age, infants born <30 weeks’ gestation had GM assessed as normal or abnormal. Motor, cognitive, and language development at 2 years was assessed by using the Bayley Scales of Infant and Toddler Development, Third Edition. At 4 years, cognitive and language outcomes were assessed by using the Differential Ability Scale–Second Edition and motor outcomes with the Movement Assessment Battery for Children–Second Edition; a diagnosis of cerebral palsy was documented. RESULTS: Ninety-nine VP infants were recruited, with 97% and 88% of survivors followed up at age 2 and 4 years, respectively. Abnormal GM at 1 month were associated with worse motor outcomes at 2 and 4 years but not language or cognitive outcomes. Abnormal GM at 3 months were associated with worse motor, cognitive, and language outcomes at both 2 and 4 years. Overall, GM at 1 month demonstrated better sensitivity to impairments at 2 and 4 years, whereas GM at 3 months had better specificity and were more accurate overall at distinguishing between children with and without impairment. CONCLUSIONS: Abnormal GM in VP infants, particularly at 3 months postterm, are predictive of worse neurodevelopment at ages 2 and 4 years.

Family functioning, burden and parenting stress 2 years after very preterm birth☆

BACKGROUND Examining rates of difficulties in family functioning following very preterm birth has been a relatively neglected area of research. AIMS To examine family functioning, burden and parenting stress in families with very preterm compared with term born children, and investigate influences of parental mental health problems and child neurodevelopmental disability on family outcomes in families with preterm children. STUDY DESIGN Participants were 184 very preterm and 71 term children and their parents. Parents completed the Family Assessment Device, Parenting Stress Index and Impact on Family questionnaires when their children were 2 years old (corrected for prematurity). Parental mental health and social risk information were also collected. Children were assessed for neurodevelopmental disability. RESULTS Families with very preterm children reported poorer family functioning (p=.03) compared with families with term born children, with less evidence for differences between families with very preterm and term born children in parenting stress and family burden. Within very preterm families, parental mental health problems were associated with higher levels of parenting stress (p=.001), and parents of children with a neurodevelopmental disability were more likely to report higher family burden (p=.04). CONCLUSIONS For families with very preterm children, parental mental health symptoms and child neurodevelopmental disability may identify families at risk of greater stress and burden who may benefit from additional support.

Moderate and Late Preterm Birth: Effect on Brain Size and Maturation at Term-Equivalent Age

PURPOSE To compare the size of multiple brain structures, maturation in terms of both brain myelination and gyral development, and evidence of brain injury between moderate and late preterm (MLPT) and term-born infants at term-equivalent age. MATERIALS AND METHODS The study was approved by the human research ethics committees of the participating hospitals, and informed parental consent was obtained for all infants. One hundred ninety-nine MLPT and 50 term-born infants underwent 3-T magnetic resonance (MR) imaging brain examinations at 38-44 weeks of corrected gestational age. T1- and T2-weighted MR images were compared between groups for size of multiple cerebral structures, degree of myelination in the posterior limb of the internal capsule, gyral maturation, signal intensity abnormalities, and presence of cysts by a single assessor who was blinded to the gestational group and perinatal course of the infants. Group differences were compared by using linear regression for continuous variables and logistic regression for categorical variables, and interrater and intrarater reliability was assessed by using intraclass correlation coefficients. RESULTS Compared with those in the term-born control group, measurements of brain biparietal diameter, corpus callosum, basal ganglia and thalami, and cerebellum were smaller in infants in the MLPT group (all P ≤ .01), while extracerebral space was larger (P < .0001). Myelination of the posterior limb of the internal capsule was less developed, and gyral maturation was delayed in the MLPT group (both P < .001). Signal intensity abnormalities and cysts were uncommon in both groups, with 13 (6.5%) MLPT infants and one (2%) term infant having abnormalities. Inter- and intrarater reliability was good for most measures, with intraclass correlation coefficients generally greater than 0.68. CONCLUSION MLPT birth is associated with smaller brain size, less-developed myelination of the posterior limb of the internal capsule, and more immature gyral folding than those associated with full-term birth. These brain changes may form the basis of some of the long-term neurodevelopmental deficits observed in MLPT children. Online supplemental material is available for this article.