 |
|
 |
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ARTICLE |
a Departments of Paediatrics
b Imaging Sciences, Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Campus, London, United Kingdom
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
|---|
METHODS. Between January 1997 and November 2000, consecutive infants born at <30 weeks’ gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment.
RESULTS. A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage.
CONCLUSIONS. Diffuse white matter abnormalities and post–hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes.
Key Words: premature infants • brain imaging • magnetic resonance imaging • neurodevelopment
Abbreviations: GA—gestational age • HPI—hemorrhagic parenchymal infarction • GLH—germinal layer hemorrhage • IVH—intraventricular hemorrhage • DEHSI—diffuse excessive high signal intensity • DQ—developmental quotient • IUGR—intrauterine growth restriction • CP—cerebral palsy • SDS—SD score • ECS—extracerebral space
Premature birth is associated with significant neurologic, cognitive, and behavioral problems.1–4 Outcomes after major destructive lesions such as hemorrhagic parenchymal infarction (HPI) or cystic periventricular leukomalacia are well documented.5,6 However, most infants with neurocognitive deficits do not exhibit these patterns of injury, which suggests that more subtle changes occur, perhaps altering cerebral maturation or causing more diffuse injury.
MRI can indicate the normal development of the preterm brain and can identify diffuse damage.7–12 Most studies evaluated preterm infants at term-equivalent ages or acquired single images at earlier gestational ages (GAs).10,12–15 Outcome studies concentrated on specific lesions and did not consider the full range or natural history of abnormalities.13,15
Previously, we reported serial imaging findings for a small number of consecutively recruited infants born at GA of <30 weeks.16 The recruitment of this cohort continued, and we now report our findings from birth to term for a larger consecutive population of infants recruited over 3 years, the majority of whom have undergone neurodevelopmental follow-up monitoring after 18 months of age, corrected for prematurity. This allowed us to perform the first comprehensive MRI survey of the natural history of cerebral abnormalities in an unselected cohort of extremely preterm infants, together with preliminary correlation between imaging and developmental outcomes.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Birth weight and mode of delivery were recorded, and fetal membranes were examined for chorioamnionitis.17 Intrauterine growth restriction (IUGR), defined as weight of <10th percentile for GA and gender, calculated with Child Growth Foundation software,18 was recorded. Postnatal steroid use was documented.
MRI
A dedicated, neonatal, 1.0-T, MRI scanner (Phillips Medical Systems, Best, Netherlands) installed within the NICU was used for the majority of imaging; Phillips 1.5-T Eclipse and 1.0-T HPQ scanners were used for 9 and 3 infants at term, respectively. Infants were sedated with orally administered chloral hydrate (20–50 mg/kg), and ear protection was applied. A neonatologist trained in MRI supervised all imaging, with monitoring described previously.19 The MRI scans acquired included T1-weighted conventional spin echo (repetition time: 600 milliseconds; echo time: 20 milliseconds) and T2-weighted fast spin echo (repetition time: 3500 milliseconds; echo time: 208 milliseconds) scans in transverse and coronal planes.
The first MRI scan was obtained as soon as possible after birth. Infants underwent serial MRI scanning during admission to the NICU. Scan timing was dependent on clinical stability, but images were not acquired or used for clinical purposes. An image obtained at or soon after postmenstrual age of 36 weeks was defined as a term MRI scan.
Image Analysis
Qualitative image analysis was performed by 2 experienced observers; both observers assessed all scans, and any discrepancies were resolved through consensus. Scans were categorized as shown in Table 1 (Figs 1–3). 16,20,21 Images were reported as normal if they had age-appropriate white matter details and myelination, normal-sized ventricles, and no diffuse or focal pathologic findings.
|
|
|
Statistical Analyses
Data were analyzed with StatsDirect statistical software (StatsDirect, Sale, United Kingdom). Statistical results are reported for groups that were large enough to analyze, and the results were significant at a level of P 
.05. Exploratory analyses of outcomes were undertaken, and the quoted statistics are univariate. Where appropriate, infants with significant focal lesions were excluded from analysis, so that the effect of an abnormality on outcome could be examined in isolation. Parametric and nonparametric tests were used as appropriate.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
The median time after delivery for the first brain MRI scan was 2 days (interquartile range: 1–5 days). Infants underwent a median of 2 scans (range: 1–8 scans), and 24 had >3 scans. A total of 327 scans were performed. Eighty-seven surviving infants (82%) had a term MRI scan, at a median postmenstrual age of 40 weeks 6 days (range: 36 weeks to 53 weeks 2 days).
MRI Analysis
Fifty-one infants (44%) had normal initial MRI scans, with the exclusion of 2 infants who first underwent scanning near term-equivalent age (69 and 89 days). Infants with abnormal initial imaging results had lower GAs (P = .02). The abnormalities found on initial scans are summarized in Fig 4. Seven (8%) of the term MRI scans were reported as normal, and 5 of those infants had normal imaging results throughout the neonatal period. The remaining 2 infants both had widened extracerebral spaces (ECSs), with unilateral germinal layer hemorrhage (GLH) or unilateral intraventricular hemorrhage (IVH), on their initial scans. These abnormalities were no longer seen at term. There were no significant differences in GA or birth weight between infants with and without normal imaging results at term. None of the infants with normal term imaging results received postnatal steroid treatment. The abnormalities found on the term scans are shown in Fig 5. The majority of infants in the cohort had several abnormalities on each of their scans, with a median of 2 abnormalities per scan (range: 0–6 abnormalities).
|
|
|
IVH
IVH occurred for 29 infants (24%) and was bilateral for 24. Twenty-four infants also had GLH. Infants with IVH had significantly lower GAs at birth, compared with infants with GLH or no hemorrhage (P = .0035). IVH was more common after vaginal delivery (P = .006), with a risk ratio of 2.54 (95% confidence interval: 1.37–4.57). Twenty-two infants with IVH underwent term imaging, and the hemorrhage had resolved in all cases. Eleven infants (50%) developed ventricular dilation.
Extracerebral Hemorrhage
Six infants (5%) had extracerebral hemorrhage present on their first scans. Hemorrhage occurred only in the posterior fossa for 4 infants, was hemispheric for 1 infant, and was found in both locations for 1 infant. Five of 6 infants also had evidence of GLH or IVH. There was no difference in mode of delivery between infants with extracerebral hemorrhage and the rest of the cohort. One infant developed hemispheric extracerebral hemorrhage later in the neonatal period, after an episode of cardiovascular collapse. Hemorrhage resolved by term in all cases.
Punctate White Matter Abnormalities
Twenty-six infants (22%) had punctate white matter abnormalities, and these were identified on the first MRI scans for 13 infants. The lesions were first noted on the term scans for 3 infants. The number of lesions identified per infant ranged from 1 to 9, with a median of 2. Five infants with punctate lesions on early scans still had lesions noted at term, although the lesions were less obvious and less numerous. There were no significant differences in GA or birth weight for infants with and without punctate white matter abnormalities. There were also no associations with mode of delivery, chorioamnionitis, or IUGR.
Diffuse Cerebral Abnormalities
Diffuse White Matter Abnormalities
Two infants with term MRI scans had severe ventricular dilation and had insufficient white matter volume to assess diffuse excessive high signal intensity (DEHSI) within the white matter on T2-weighted imaging scans. Sixty-eight infants (80%) had DEHSI present within their white matter; this was classified as severe in 10 cases. There was a lower incidence of DEHSI among infants with IUGR (risk ratio: 0.74; 95% confidence interval: 0.5–0.94; P = .018). There were no significant differences in GA, birth weight, mode of delivery, chorioamnionitis, or postnatal steroid exposure between infants with and without DEHSI. There was also no relationship with earlier lesions, such as hemorrhage or punctate white matter abnormalities, or with ventricular dilation or an enlarged ECS. There were no significant differences in the proportions of infants with each abnormality between the whole cohort and the subgroup of infants with DEHSI.
Dilation of the Lateral Ventricles
Thirty-six infants (30%) had ventricular dilation identified on their first scans, and these infants were born at significantly lower GAs (P < .001), with lower birth weights (P = .013). Sixteen of these infants also had IVH identified. The dilation was no longer present at term for 4 infants. Forty-seven infants (39%) had ventricular dilation on their final scans; for 25, it was associated with GLH or IVH. Two infants had marked post–hemorrhagic hydrocephalus and required ventriculoperitoneal shunts (Fig 7). No other infants required treatment for ventricular dilation. There was no difference in the development of ventricular dilation after isolated GLH, compared with IVH.
|
Other Lesions
Cerebellar Hemorrhagic Lesions
Cerebellar hemorrhagic lesions were present on the first scans for 8 infants (7%), who were born earlier (P = .007) and with lower birth weights (P = .03) than the rest of the cohort. Infants with cerebellar hemorrhagic lesions were more likely to have been born vaginally (risk ratio: 4.53; 95% confidence interval: 1.25–16.3; P = .037). Six of 8 hemorrhagic lesions were unilateral, and 4 were associated with IVH. Cerebellar atrophy developed for 4 of 6 infants with term scans.
Basal Ganglia and Thalamic Abnormalities
Seventeen infants (14%) had basal ganglia or thalamic abnormalities. These findings are summarized in Table 3. The caudate nucleus was affected most frequently. Hemorrhage within the caudate was usually associated with either GLH or IVH. All hemorrhagic and cystic lesions had resolved by term for infants who underwent subsequent imaging. Five infants had bilateral atrophy of the thalamus identified at term. None of these infants had previous abnormalities within the thalamus, and all of them had associated white matter atrophy, with marked ventricular dilation. There were no infants with basal ganglia or thalamic injuries consistent with an acute hypoxic ischemic injury.
|
Neurodevelopmental Examination Results
Sixteen infants (13.4%) died before follow-up assessment, having had 
1 MRI brain scan. These infants were born at lower GAs (P = .0001), had lower birth weights (P = .002), and had a higher incidence of chorioamnionitis (P = .05). Cerebellar hemorrhagic lesions also were more prevalent in these infants (P = .012) (Table 4). Sixty-eight surviving infants (66%) underwent neurodevelopmental follow-up assessment, at a median age of 23.93 months (range: 19.5–34.43 months) (Fig 8).
|
|
|
Correlation of MRI and Follow-up Findings
To assess the effects of specific abnormalities on outcomes, the analyses were performed before and after exclusion of infants with other significant focal lesions. Eleven infants with HPI, basal ganglia and thalamic lesions, cerebellar hemorrhage, and congenital abnormalities were excluded. The overall DQ of the cohort after exclusion of these infants was 100 ± 16.2 and was not significantly different from that of the whole cohort.
Thirty-two infants (68%) with normal initial MRI scans and 35 infants (51%) with abnormal initial MRI scans underwent follow-up monitoring. There was no difference in the number of infants who died before follow-up evaluation between the 2 groups. Infants with abnormal initial imaging results had a higher DQ (normal initial scan: 93.5 ± 15.27; abnormal initial scan: 101.8 ± 18; P = .048). There was no relationship between overall DQs and numbers of abnormalities per scan. There were no significant differences in SDSs for weight or head circumference at follow-up evaluation between the 2 groups. Six infants with normal term scans underwent developmental follow-up assessment. These infants had a higher DQ than did infants with abnormal imaging results at term (112 ± 15 vs 96 ± 16.8; P = .034).
Major Destructive Parenchymal Lesions
One infant with cystic periventricular leukomalacia died, and the other was not evaluated between 18 and 36 months of age but is known to have diplegia. One infant with bilateral HPI died at 2 weeks of age, as a result of necrotizing enterocolitis. The infant with a small unilateral HPI had a DQ of 92 and no motor deficit, as would be predicted from the symmetrical myelination within the posterior limb of the internal capsule at term.5
Hemorrhagic Lesions
GLH and IVH
Two infants with GLH and 6 infants with IVH died before follow-up evaluation. There were no significant differences in DQs or SDSs for weight or head circumference at follow-up assessment between groups of infants without hemorrhage, with GLH, or with IVH. This did not change when infants with other significant lesions were excluded from analysis.
Extracerebral Hemorrhage
One infant with extracerebral hemorrhage died as a result of necrotizing enterocolitis, and another had a low DQ of 59. This infant had cerebellar hemorrhage and had DEHSI at term. The remaining 4 infants all had DQs above 90. There were no differences in SDSs for weight or head circumference at follow-up evaluation between infants with and without extracerebral hemorrhage.
Punctate White Matter Lesions
Seventeen infants with punctate white matter abnormalities were assessed. There were no significant differences in DQs or SDSs for weight or head circumference at follow-up evaluation between infants with and without punctate white matter lesions, and this was not altered by removal of infants with significant focal lesions from analysis. There was also no relationship between the number of lesions or the resolution of lesions by term and developmental outcomes.
Diffuse Cerebral Abnormalities
DEHSI
Fifty-seven infants with term MRI scans underwent follow-up evaluation; when all of these infants were included in the analysis, there were no significant differences in DQs or SDSs for weight or head circumference at follow-up evaluation between infants with no DEHSI, DEHSI, or severe DEHSI. After exclusion of the 11 infants with focal lesions, there were 34 infants (74%) with DEHSI, with 6 cases being classified as severe. A significant relationship was found between DEHSI and overall DQs (no DEHSI: 111 ± 20; DEHSI: 94 ± 11.6; severe DEHSI: 92 ± 7.5; P = .027). When the analysis was repeated by comparing infants with normal scans with infants whose only abnormality was DEHSI, the number of infants included was very small. Despite this, there remained a significant difference in DQs between the 2 groups (mean DQ with normal scan: 105; mean DQ with DEHSI: 91; P = .023). There were no significant differences between these groups with respect to GA, birth weight, gender, or age at term scan.
Dilation of Lateral Ventricles
There were no differences in DQs or SDSs for weight or head circumference at follow-up evaluation between infants with and without ventricular dilation on their first scans or on their term scans. There were no differences in DQs between posthemorrhagic and nonhemorrhagic causes; however, infants with ventricular dilation after IVH had a significantly smaller SDS for head circumference at follow-up evaluation (–2.06 ± 1.57 vs –0.3 ± 0.85; P = .01). When only infants with IVH were considered, those who developed ventricular dilation subsequently had a significantly lower DQ (88 ± 14 vs 102 ± 14.4; P = .044), compared with infants who did not develop ventricular dilation.
ECS
There were no differences in overall DQs between infants with a widened ECS at term and those with a normal ECS. There was also no difference in SDSs for head circumference at follow-up evaluation between the 2 groups.
Other Lesions
Cerebellar Hemorrhagic Lesions
Three infants with cerebellar hemorrhagic lesions died. Two of the remaining infants had significant developmental delay, with DQs of 59 and 60. Neither infant had associated focal cerebral lesions, but both developed cerebellar atrophy. A third infant also had very severe developmental delay, with a DQ of <50 and CP when evaluated at 1 year of age; however, this infant also experienced postnatal cardiovascular collapse and developed severe ventricular dilation, with white matter, basal ganglia, and thalamic atrophy. The remaining 2 infants had DQs of 92, with cerebellar atrophy on subsequent scans, and 114, without cerebellar atrophy. Infants with cerebellar hemorrhagic lesions had a significantly smaller SDS for head circumference at follow-up evaluation (–2.68 ± 1.95 vs –1.28 ± 1.42; P = .045) but no difference in SDS for weight.
Basal Ganglia and Thalamic Abnormalities
Four infants with basal ganglia or thalamic abnormalities died, and only 7 underwent follow-up evaluation, which made it inappropriate to draw conclusions because the infants had heterogeneous pathologic conditions. The mean overall DQ for those evaluated was 89 ± 20, and their mean SDS for head circumference was –1.48 ± 0.9. Only infants with thalamic atrophy on term scans had motor impairments at follow-up assessments.
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
This study was designed without previous hypotheses, and imaging was performed at varying times according to clinical stability. The timing of lesions and developmental processes was therefore approximate, because not all infants underwent imaging at each time point. The definition of the term scan was broad and encompassed infants between 36 and 53 weeks' postmenstrual age. The statistics quoted were univariate and were not adjusted for GA or multiple comparisons. There is multicolinearity among many of the exposure and confounder variables, which makes statistical modeling difficult. Ascertainment of neurodevelopmental outcome data were not complete; therefore, conclusions concerning the relationship of imaging findings to neurologic function remain preliminary and require additional validation.
Neurologic outcomes were reported for 66% of infants. Infants without follow-up data were not significantly different except for being less likely to have received postnatal steroid therapy, but potential bias caused by incomplete follow-up data is well recognized.27 We reviewed 93% of the total cohort, although we evaluated many subjects outside the age range included in this study. Therefore, we know that the infants included in this report are representative of the cohort as a whole. We will publish more-comprehensive results after completion of the 6-year follow-up monitoring.
Diffuse white matter injury was the most common finding for the cohort, and its presence and severity at term were related to adverse neurodevelopmental outcomes. Isolated hemorrhage (GLH, IVH or extracerebral hemorrhage) was not associated with poor outcomes but, if IVH was associated with ventricular dilation, then there was a relationship with reduced DQ. Focal, punctate, white matter lesions were common on initial scans and did not affect outcomes adversely. Infants with basal ganglia and thalamic lesions represented a heterogeneous group for which conclusions could not be drawn; however, later thalamic atrophy was associated with marked ventricular dilation and white matter atrophy and thus with poor outcomes. Destructive parenchymal brain lesions and cerebellar hemorrhage occurred for small numbers of infants, but both were associated with poor outcomes.
Infants with abnormal initial scans or normal term scans had higher DQs than did those with normal initial scans or abnormal term scans, although the number of infants with normal scans at term was very small. This suggests that the period spent in the NICU might have a significant effect on the brain.
DEHSI was present within the white matter on the T2-weighted term scans for 80% of infants. After exclusion of infants with significant focal lesions from analysis, the presence and severity of DEHSI were shown to be related to lower overall DQs. The classification of DEHSI in this study was qualitative, but Counsell et al28 showed that infants with DEHSI on T2-weighted scans had increased apparent diffusion coefficients within their white matter on diffusion-weighted imaging. These values were significantly greater than apparent diffusion coefficients for infants with normal white matter but were similar to those for infants with overt, white matter, pathologic lesions. This suggests that DEHSI represents an abnormality of white matter, although it is still unclear whether this is a maturational delay or is secondary to injury. Postmortem studies of DEHSI are not available, because these infants have survived the neonatal period and are unlikely to die as they reach term. Animal models have been established to explore the effect of preterm birth on cerebral white matter,29 although there are no published findings at term equivalent.
The cause of the white matter abnormality is unclear. A reduction in white matter injury was associated previously with IUGR.12,30 Such infants are often exposed to differing prenatal and perinatal environments, compared with preterm infants with appropriate growth. They have undergone stress responses and are less likely to be delivered vaginally or exposed to chorioamnionitis. No relationship between chorioamnionitis and DEHSI was identified in this study, which suggests either that the etiology of DEHSI is not primarily infective or that a histologic definition of chorioamnionitis does not reflect adequately the fetal inflammatory state. Our previous work showed that fetal immune activation and the generation of CD45RO+ memory T lymphocytes were associated with cerebral injury31 and also that bacterial colonization is a complex process that is not always associated with inflammation.32 It would be premature to exclude a role for fetal inflammation, although alternative hypotheses need to be considered. DEHSI may represent delayed or aberrant maturation of the white matter. An injurious process could result in a decreased DQ, but delayed maturation could also be a marker for later suboptimal neurodevelopment. No relationship between DEHSI and ventricular dilation or SDS for head circumference at follow-up evaluation was identified, which suggests that the pathologic process does not necessarily involve white matter atrophy. Preliminary volumetric studies have confirmed that at term there is no reduction in total cerebral volume for preterm infants with DEHSI,33 although quantification at later ages is still required. The etiology of DEHSI therefore remains unclear; diffusion-weighted imaging studies should provide additional information, but appropriate animal models or postmortem studies may be required for a full understanding of its histopathologic features.
Punctate white matter abnormalities were also a common finding. These lesions may represent petechial hemorrhage, although their relative signal intensities on MRI scans do not provide good evidence for this; they are much more prominent on T1-weighted MRI scans than on T2-weighted MRI scans. Lack of resolution by term suggests that gliosis or mineralization may occur in some cases. Consistent with previously published work,13 punctate lesions did not predict adverse developmental outcomes.
Posthemorrhagic ventricular dilation was related to poorer neurodevelopmental outcome, with lower DQs, as described previously.34 Infants with ventricular dilation after IVH had lower SDSs for head circumference at follow-up evaluation. A relationship between IVH and white matter injury has been suggested to be related to cellular injury from iron.35
Cerebellar hemorrhagic lesions were related to low GA, low birth weight, and vaginal delivery. They were more common among infants who died before follow-up evaluation, and survivors tended to have lower DQs, especially if there was subsequent cerebellar atrophy. Children with CP who are born extremely preterm often show cerebellar lesions,36 although whether the lesions are the primary cause of adverse outcomes is not clear. In one study, cerebellar abnormalities were associated with adverse outcomes only when supratentorial lesions were also seen.37 Advances in cranial ultrasonography and greater use of the posterior fontanelle as an acoustic window may identify these lesions more readily without MRI.38 A larger prospective study would therefore be possible.
The majority of basal ganglia abnormalities had resolved by term. Five infants developed thalamic atrophy despite no previous thalamic abnormalities, and all had significant white matter atrophy and ventricular dilation at term. Atrophy of the thalamus has been described previously for infants with moderate or severe periventricular leucomalacia,39 and thalamic and basal ganglia volume reduction has been identified with image segmentation and tissue classification approaches for infants with milder white matter injury.40 No infants had basal ganglia or thalamic lesions typical of acute hypoxic-ischemic injury, and it is possible that these gray matter lesions might be at least in part attributable to white matter damage and loss of normal developmental cues.
Abnormalities on the initial scans, unlike those detected at term, did not predict a lower DQ, which suggests that perinatal and intrauterine insults may be less significant for brain function than abnormalities that develop later during neonatal intensive care. Although functionally important early damage might not be detectable with earlier MRI, this study cannot confirm the hypothesis that intrauterine and perinatal insults such as chorioamnionitis are significant causes of brain damage. However, the data do suggest that additional examination of the effects of extrauterine exposures on brain structure or growth may be useful.
|
|
ACKNOWLEDGMENTS |
|---|
We are grateful to the families who consented to take part in the study and to the nursing and medical staff members who participated in caring for the infants.
|
FOOTNOTES |
|---|
Address correspondence to A. David Edwards, FMedSci, Department of Paediatrics, Hammersmith Hospital, Du Cane Road, London, W12 0NN, United Kingdom. E-mail: david.edwards{at}imperial.ac.uk
This work was presented in part at meetings of the Paediatric Academic Society; May 4, 2004; San Francisco, CA; the Neonatal Society; July 2, 2004; Cambridge, United Kingdom; and the European Society for Paediatric Research; September 1, 2005; Siena, Italy.
The authors have indicated they have no financial relationships relevant to this article to disclose.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
 |
|
 |
|
  M. V. Johnston Diffusion Tensor Imaging of White Matter and Developmental Outcome Pediatrics, September 1, 2008; 122(3): 656 - 657. [Full Text] [PDF]
|
|
|
|
|
|
H. C. Glass, S. L. Bonifacio, V. Chau, D. Glidden, K. Poskitt, A. J. Barkovich, D. M. Ferriero, and S. P. Miller Recurrent Postnatal Infections Are Associated With Progressive White Matter Injury in Premature Infants Pediatrics, August 1, 2008; 122(2): 299 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Atkinson, O Braddick, S Anker, M Nardini, D Birtles, M A Rutherford, E Mercuri, L E Dyet, A D Edwards, and F M Cowan Cortical vision, MRI and developmental outcome in preterm infants Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2008; 93(4): F292 - F297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Spittle, N. C. Brown, L. W. Doyle, R. N. Boyd, R. W. Hunt, M. Bear, and T. E. Inder Quality of General Movements Is Related to White Matter Pathology in Very Preterm Infants Pediatrics, May 1, 2008; 121(5): e1184 - e1189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O Khwaja and J J Volpe Pathogenesis of cerebral white matter injury of prematurity Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2008; 93(2): F153 - F161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Constable, L. R. Ment, B. R. Vohr, S. R. Kesler, R. K. Fulbright, C. Lacadie, S. Delancy, K. H. Katz, K. C. Schneider, R. J. Schafer, et al. Prematurely Born Children Demonstrate White Matter Microstructural Differences at 12 Years of Age, Relative to Term Control Subjects: An Investigation of Group and Gender Effects Pediatrics, February 1, 2008; 121(2): 306 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Krishnan, L. E. Dyet, J. P. Boardman, O. Kapellou, J. M. Allsop, F. Cowan, A. D. Edwards, M. A. Rutherford, and S. J. Counsell Relationship Between White Matter Apparent Diffusion Coefficients in Preterm Infants at Term-Equivalent Age and Developmental Outcome at 2 Years Pediatrics, September 1, 2007; 120(3): e604 - e609. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||
