Background Very preterm infants are at high risk for adverseneurodevelopmental outcomes. Magnetic resonance imaging (MRI)has been proposed as a means of predicting neurodevelopmentaloutcomes in this population.
Methods We studied 167 very preterm infants (gestational ageat birth, 30 weeks or less) to assess the associations betweenqualitatively defined white-matter and gray-matter abnormalitieson MRI at term equivalent (gestational age of 40 weeks) andthe risks of severe cognitive delay, severe psychomotor delay,cerebral palsy, and neurosensory (hearing or visual) impairmentat 2 years of age (corrected for prematurity).
Results At two years of age, 17 percent of infants had severecognitive delay, 10 percent had severe psychomotor delay, 10percent had cerebral palsy, and 11 percent had neurosensoryimpairment. Moderate-to-severe cerebral white-matter abnormalitiespresent in 21 percent of infants at term equivalent were predictiveof the following adverse outcomes at two years of age: cognitivedelay (odds ratio, 3.6; 95 percent confidence interval, 1.5to 8.7), motor delay (odds ratio, 10.3; 95 percent confidenceinterval, 3.5 to 30.8), cerebral palsy (odds ratio, 9.6; 95percent confidence interval, 3.2 to 28.3), and neurosensoryimpairment (odds ratio, 4.2; 95 percent confidence interval,1.6 to 11.3). Gray-matter abnormalities (present in 49 percentof infants) were also associated, but less strongly, with cognitivedelay, motor delay, and cerebral palsy. Moderate-to-severe white-matterabnormalities on MRI were significant predictors of severe motordelay and cerebral palsy after adjustment for other measuresduring the neonatal period, including findings on cranial ultrasonography.
Conclusions Abnormal findings on MRI at term equivalent in verypreterm infants strongly predict adverse neurodevelopmentaloutcomes at two years of age. These findings suggest a rolefor MRI at term equivalent in risk stratification for theseinfants.
Very preterm birth has profound ramifications for public healthand education worldwide. Infants born before 32 weeks of gestationnow represent more than 2 percent of all live births, and theirsurvival rates exceed 85 percent.1 Follow-up studies have revealedhigh rates of neurodevelopmental disability among very preterminfants who survive, with 5 to 15 percent having cerebral palsy,severe neurosensory impairment, or both and 25 to 50 percenthaving cognitive, behavioral, and social difficulties that impedeprogress in school and require special educational support.2,3,4
A major issue confronting clinicians who work with preterm infantsand their families is the identification of infants who aremost at risk for subsequent neurodevelopmental disability andwho may benefit from early intervention services. Several factors(including bronchopulmonary dysplasia, sepsis, surgery, thepostnatal use of corticosteroids, and evidence on ultrasonographyof intraventricular hemorrhage and periventricular leukomalacia)are recognized to increase neurodevelopmental risks. However,risk indexes for neonates that incorporate these factors haveshown limited effectiveness in identifying infants who are athigh risk for poor neurodevelopmental outcomes.5,6
One tool that may assist early prognostic evaluations of thepreterm infant is magnetic resonance imaging (MRI) during theneonatal period. Currently, the most widely used imaging techniqueis cranial ultrasonography. This method is useful for the detectionof intraventricular hemorrhage and cystic periventricular leukomalacia,but it has poor sensitivity for diffuse white-matter abnormalitiesdetected by MRI.7,8 Neonatal MRI studies have revealed thatthe majority of very preterm infants have white-matter abnormalities,including signal abnormalities, loss of volume, cystic abnormality,enlarged ventricles, thinning of the corpus callosum, and delayedmyelination.9,10,11 Gray-matter abnormalities, including decreasedcerebral gray-matter volume and delayed cortical gyration, havealso been reported in very preterm infants at term equivalent(gestational age of 40 weeks) with the use of neuroanatomicalMRI techniques.12,13 In smaller studies of preterm infants,such abnormalities have been found to be correlated with impairedworking memory14 and early neurodevelopmental delay.15,16
We performed a prospective longitudinal study of very preterminfants studied from birth to two years of age, to examine associationsbetween qualitatively defined cerebral white-matter and gray-matterabnormalities on MRI at term equivalent and neurodevelopmentaloutcomes at two years of age. We also compared the predictivevalue of MRI findings with that of findings derived from otherassessments during the neonatal period, such as cranial ultrasonography,that are currently used to predict neurodevelopmental risk.
Methods
Subjects
The study population included 167 very preterm infants (bornat 30 weeks of gestation or less) at either Christchurch Women'sHospital, New Zealand, between November 1998 and December 2000(81 children) or at the Royal Women's Hospital, Melbourne, Australia,between July 2001 and May 2002 (86 children). Fifty infants,all in the Christchurch cohort, received some early interventionservices. Referral for these services was based on ultrasonographicfindings, gestational age at birth, clinical history, and assessmentof physical therapy; MRI results were not used to make referraldecisions, nor were they made available to early interventionproviders.
In Christchurch, 92 percent of all eligible infants were enrolled.In Melbourne, 95 percent of eligible infants were approached,with a recruitment rate of 70 percent. Nonparticipation wasprimarily due to family circumstances or involvement in otherstudies. There were no significant (P<0.05) differences inperinatal characteristics between infants who were recruitedand those who were not recruited. At two years of age correctedfor prematurity, sample retention was high, with 95 percentof Christchurch children and 98 percent of Melbourne childrenbeing assessed. Written informed consent was obtained from allparents or guardians, and the studies were approved by hospitalor regional ethics committees, or both. Table 1 lists the characteristicsof the infants at each study center.
Table 1. Neonatal Clinical Characteristics of the Infants.
MRI
At term equivalent, all infants underwent MRI. Prior to undergoingMRI, each infant was fed, wrapped, and placed, unsedated, ina Vac Fix beanbag designed to keep the infant still and supportedin the scanner. We performed MRI using a 1.5-tesla General ElectricSigna System (GE Medical Systems) with previously documentedsequences.10 All scans were scored independently by one of theauthors and by a pediatric neuroradiologist (Christchurch) orneonatologist (Melbourne). Raters were unaware of the infants'perinatal history and ultrasonographic findings. We used a standardizedscoring system, developed in this study and consisting of eight3-point scales (Figure 1).10,17 White-matter abnormality wasgraded according to five scales, which assessed the nature andextent of white-matter signal abnormality, the loss in the volumeof periventricular white matter, and the extent of any cysticabnormalities, ventricular dilatation, or the thinning of thecorpus callosum. Gray-matter abnormality was graded accordingto three scales, which assessed the extent of gray-matter signalabnormality, the quality of gyral maturation, and the size ofthe subarachnoid space (see Supplementary Appendix 1, availablewith the full text of this article at www.nejm.org). Compositewhite-matter scores and composite gray-matter scores were createdand used to categorize infants according to the extent of theircerebral abnormalities.10,17 The categories of white-matterabnormality were none (a score of 5 to 6), mild (a score of7 to 9), moderate (a score of 10 to 12), and severe (a scoreof 13 to 15). Gray matter was categorized as normal (a scoreof 3 to 5) or abnormal (a score of 6 to 9). Interrater agreementfor the category assignments was 96 percent.
Figure 1. Representative MRI Scans of Children in the Study.
Representative coronal T2-weighted MRI (Panel A) and T1-weighted MRI (Panel B) show the four grades of white-matter abnormality (none, mild, moderate, or severe). With increasing grade of white-matter abnormality, there was increasing ventricular size, decreasing white-matter volume, increasing intensity of white-matter signal on T2-weighted imaging, and decreasing myelination in the posterior limb of the internal capsule. Also shown is axial T2-weighted MRI at the level of the deep nuclear gray matter of infants with normal gray-matter scores (Panel C) and abnormal gray-matter scores (Panel D), demonstrating the simpler gyral patterns observed among infants with gray-matter abnormalities.
Cranial Ultrasonography
We also performed cranial ultrasonography through the anteriorfontanelle, with a 7.5- or 8.5-MHz transducer (Acuson-Siemens),according to a standardized protocol.18 We acquired images withinthe first 48 hours of life, at five to seven days of age, andagain at four to six weeks of age. If an abnormality was detected,more frequent ultrasonography was performed as clinically indicated.The scans were assessed for the presence and extent of white-matterecholucency or cystic periventricular leukomalacia and the highestgrade of intraventricular hemorrhage.
Neurodevelopmental Outcomes at Two Years of Age
Within two weeks either before or after their second birthday(corrected for prematurity), children underwent a comprehensiveneurodevelopmental assessment conducted by examiners who wereunaware of the MRI findings and the perinatal course. The examinersassessed the cognitive and psychomotor development using theBayley Scales of Infant Development (BSID-II)19: the MentalDevelopment Index assesses environmental responsiveness andsensory and perceptual abilities, memory, learning, and earlylanguage and communication abilities; the Psychomotor DevelopmentIndex assesses both gross and fine motor skills. The six childrenwho had standard scores below 50 were assigned a score of 45,and the two children who were unable to be tested owing to impairedperceptual or cognitive ability were assigned a score of 40.A mild delay in development was defined by a score that wasmore than 1 SD below the normative mean, and a severe delaywas defined by a score that was more than 2 SD below the normativemean.
Each child also underwent a standardized pediatric neurologicevaluation to assess the quality of their motor skills, coordination,gait, and behavior.20 Cerebral palsy was diagnosed with theuse of standard criteria, including the location or body partsimpaired (e.g., hemiplegia or diplegia), the degree of impairmentof muscle tone and reflexes, and the effects of the conditionon ambulation.21 Finally, evaluations of vision and hearingwere completed by an ophthalmologist and an audiologist, respectively,or were recorded from recent hospital evaluations. A visualdefect was defined by a requirement for corrective lenses, surgery,or both for strabismus or blindness. A hearing defect was definedas a sensorineural hearing loss of more than 30 db.
Statistical Analysis
The associations between white-matter and gray-matter abnormalitieson MRI and adverse neurodevelopmental outcomes at two yearsof age were examined with the use of either one-way analysisof variance for continuously distributed variables or the Mantel–Haenszelchi-square test for dichotomous variables, with tests for lineartrend. Odds ratios (and 95 percent confidence intervals) fromchi-square analyses were reported as measures of the strengthof associations between early risk factors and subsequent neurodevelopmentaloutcomes. Logistic-regression models were then used to assessthe associations between the MRI measures and subsequent neurodevelopmentalabnormalities, after adjusting for other factors, includingabnormalities on cranial ultrasonography (grade III or IV intraventricularhemorrhage, cystic periventricular leukomalacia, or both), agestational age at birth of less than 28 weeks, intrauterinegrowth restriction, sex, the use of oxygen therapy at 36 weeks,patent ductus arteriosus, multiple birth, and postnatal useof corticosteroids. Finally, we compared the diagnostic accuracyof the MRI and ultrasonographic measures by computing the sensitivityand specificity indexes (and the 95 percent confidence intervals)from chi-square analysis tables. A P value of less than 0.05was used to indicate statistical significance.
Results
On MRI at term equivalent, 47 infants (28 percent) had no white-matterabnormalities, whereas 85 infants (51 percent) had mild white-matterabnormalities, 29 (17 percent) had moderate white-matter abnormalities,and 6 (4 percent) had severe white-matter abnormalities. Inaddition, 82 infants (49 percent) had gray-matter abnormalities.The severity of white-matter abnormalities was highly correlatedwith the presence of gray-matter abnormalities (r=0.62, P<0.001),with gray-matter abnormalities also being present in 43 of the85 children with mild white-matter abnormalities (51 percent)and 34 of the 35 children with moderate or severe white-matterabnormalities (97 percent).
At two years of age, 164 children were assessed with the BSID-II;1 child who was blind, and 2 children for whom only some datawere available, were excluded. On the Mental Development Index,87 (53 percent) had scores within 1 SD of the normalized mean(83 children) or more than 1 SD above the normalized mean (4children), signifying above-average cognitive development. Inaddition, 50 children (30 percent) had a mild cognitive delay,and 27 (17 percent) had a severe cognitive delay. On the PsychomotorDevelopment Index, 103 of the 164 children tested (63 percent)scored in the normal range (102 children) or the acceleratedrange (1 child), 44 children (27 percent) had mild psychomotordelay, and 17 (10 percent) had severe psychomotor delay. Ofall 167 children, 17 children (10 percent) met the criteriafor cerebral palsy (7 had mild, 4 moderate, and 6 severe cerebralpalsy), 9 (5 percent) had a hearing defect (3 children had hearingaids), and 12 (7 percent) had a visual defect (1 child was blind).Among those with cerebral palsy, nine children showed severepsychomotor delay.
With the exception of a higher rate of severe psychomotor delayfor the children in the Melbourne cohort (16 percent vs. 5 percentin the Christchurch cohort; P=0.02), no significant differenceswere found between the cohorts in the mean Mental DevelopmentIndex score, the mean Psychomotor Development Index score, orthe mean rate of severe cognitive delay, cerebral palsy, orneurosensory disorders (see Supplementary Appendix 2). Furtherexamination of the difference between cohorts in psychomotordelay revealed a tendency for more children to score just belowthe 2 SD cutoff in Melbourne than in Christchurch, despite thelack of any difference in the overall distribution of psychomotorscores across the two cohorts.
At follow-up, increasing severity of white-matter abnormalitieson MRI at term equivalent was found to be associated with poorerperformance on the cognitive and psychomotor scales of the BSID-II(P<0.001 for both scales), as well as with increased risksof severe cognitive delay (P=0.008), severe motor delay (P<0.001),cerebral palsy (P<0.001), and neurosensory impairment (P=0.003)(Table 2). Children with more severe white-matter abnormalitieshad a higher number of neurodevelopmental impairments than childrenwith less severe or no abnormalities (P<0.001).
Table 2. Neurodevelopmental Outcomes at a Corrected Age of Two Years.
Preterm infants with gray-matter abnormalities at term equivalentalso had poorer scores on the cognitive index (P=0.02) and thepsychomotor index (P=0.002) of the BSID-II and had higher risksof severe cognitive delay (P=0.02), severe motor delay (P=0.02),and cerebral palsy (P=0.02) than infants without gray-matterabnormalities. The association with neurosensory impairmentwas not significant (P=0.08) (Table 3). Children with gray-matterabnormalities also had more neurodevelopmental impairments thanchildren without gray-matter abnormalities (P=0.004).
Table 3. Cerebral Gray-Matter Abnormalities on MRI at Term Equivalent and Neurodevelopmental Outcomes at a Corrected Age of Two Years.
A number of other risk factors during the neonatal period werealso predictive of neurodevelopmental outcomes (Table 4). Inaddition to abnormalities on MRI, ultrasonographic evidenceof grade III or IV intraventricular hemorrhage was a significantunivariate predictor for severe cognitive delay, and the presenceof cystic periventricular leukomalacia on cranial ultrasonographyand postnatal use of corticosteroids predicted severe motordelay. The postnatal use of corticosteroids was also predictiveof cerebral palsy. After adjustment for perinatal factors (includinggestational age at birth of less than 28 weeks, small size forgestational age, male sex, the need for oxygen therapy at 36weeks, the presence of patent ductus arteriosus, multiple birth,postnatal use of corticosteroids, and abnormalities on cranialultrasonography), the associations between moderate-to-severewhite-matter abnormalities on MRI and subsequent risks of severemotor delay (odds ratio, 9.79; 95 percent confidence interval,2.56 to 37.47) and cerebral palsy (odds ratio, 8.39; 95 percentconfidence interval, 2.28 to 30.89) remained significant, whereasthe association with neurosensory impairment did not (odds ratio,3.27; 95 percent confidence interval, 0.97 to 11.01; P=0.06)(Table 4). In comparison, the ultrasonographic findings of gradeIII or IV intraventricular hemorrhage, periventricular leukomalacia,or both, as well as gray-matter abnormalities on MRI, were nolonger significant predictors of subsequent neurodevelopmentalrisk after adjustment for moderate-to-severe white-matter abnormalitieson MRI at term equivalent.
Table 4. Associations between Perinatal and Radiologic Factors and Neurodevelopmental Outcomes at a Corrected Age of Two Years.
The presence of any white-matter abnormalities and the presenceof moderate-to-severe white-matter abnormalities on MRI weremore sensitive than were ultrasonographic findings of intraventricularhemorrhage or periventricular leukomalacia in identifying childrenwho had subsequent severe neurodevelopmental impairments (Table 5).Although the findings on MRI were less specific than the abnormalitieson ultrasonography, the use of moderate-to-severe abnormalityto define "abnormal" resulted in reasonable specificity (82to 89 percent): most children with a normal or mildly abnormalresult on MRI were free of severe impairments at two years ofage.
Table 5. Sensitivity and Specificity of Findings on MRI and Cranial Ultrasonography in Predicting Severe Neurodevelopmental Impairment at a Corrected Age of Two Years.
Discussion
We found significant associations between the qualitative measuresof cerebral white-matter and gray-matter abnormalities on MRIat term equivalent and the subsequent risks of adverse neurodevelopmentaloutcomes at two years of age among very preterm infants. Thepresence of moderate-to-severe white-matter abnormalities waspredictive of severe psychomotor delay and cerebral palsy, independentlyof abnormalities on cranial ultrasonography and of other perinatalfactors.
As in previous studies,22,23,24 neurodevelopmental impairmentwas common among preterm infants in this cohort by two yearsof age. The most common impairment was severe cognitive delay;nearly one in five children scored six months or more belowtheir corrected age level. In addition, approximately 10 percentof children had severe psychomotor delay and a similar percentagereceived a diagnosis of cerebral palsy. Finally, 11 percenthad neurosensory impairment (visual, hearing, or both). Thesehigh rates of neurodevelopmental impairment underscore the importanceof the early identification of infants who are at greatest neurodevelopmentalrisk.
As in our study, prior studies have demonstrated associationsbetween the presence of white-matter and gray-matter abnormalitieson MRI at term equivalent and subsequent risks of neurobehavioralabnormalities,17,25 cerebral palsy,26,27,28 impaired workingmemory,14 and global developmental delay.15,29 However, thesestudies have been limited by the use of small or selected samplesor both, the assessment of a narrow range of outcomes, and thecombination of different outcomes that are likely to have differentcauses and correlates on MRI. Furthermore, it has been unclearto what extent information yielded by MRI during the neonatalperiod improves on other available clinical information forrisk prediction.
We found that white-matter abnormalities, especially those thatare moderate and severe, were useful markers for the elevatedrisk of severe cognitive delay, severe psychomotor delay, cerebralpalsy, and neurosensory impairment. Gray-matter abnormalities,assessed qualitatively, were also associated with an increasedrisk of severe cognitive delay, psychomotor delay, and cerebralpalsy, but to a lesser extent than white-matter abnormalities.These findings confirm the relevance of early structural neurologicabnormalities for subsequent neurodevelopmental risk acrossmultiple domains spanning neurologic, cognitive, and motor functioning.
A number of other factors during the neonatal period that arerecognized to predict subsequent neurodevelopmental outcomeswere also predictive of subsequent severe impairment in ourcohort. These factors included the postnatal use of dexamethasoneand the ultrasonographic findings of grade III or IV intraventricularhemorrhage and cystic periventricular leukomalacia.30,31,32However, these factors were infrequent in our cohort, accountingfor only a small proportion of the children with severe impairmentat two years of age. Furthermore, when MRI and other measureswere taken into account, postnatal exposure to corticosteroidsremained a significant predictor of subsequent motor impairment(psychomotor delay or cerebral palsy), but the presence of gradeIII or IV intraventricular hemorrhage or cystic periventricularleukomalacia was no longer a significant predictor of outcome(data not shown). In contrast, abnormalities on qualitativeMRI at term equivalent were more strongly associated with neurodevelopmentalimpairment than were findings on cranial ultrasonography andother measurements performed during the neonatal period. TheMRI findings also predicted impairment independently of thosemeasures.
The potential for MRI performed during the neonatal period toimprove the prediction of adverse neurodevelopmental outcomesin preterm infants was further supported by analyses showinga high sensitivity of moderate-to-severe abnormalities on MRIfor these outcomes. However, it is important to note that asubstantial proportion of children with moderate-to-severe white-matterabnormalities were free of severe impairment at two years ofage. Although a longer-term follow-up of these children is needed,this finding underscores the fact that worrisome MRI findingsmay not necessarily result in severe neurodevelopmental problems.It also highlights the potential importance of other factors,both genetic and environmental, in influencing neurodevelopmentaloutcomes.
The strengths of our study include its prospective design, thehigh rate of retention of subjects, and the assessment of adiverse range of outcomes by observers who were unaware of theMRI findings. However, the limitations of this study shouldalso be noted. First, despite a relatively large sample size,the low rate of hearing impairment precluded a separate analysisof hearing and visual problems. Second, the low rates of somefactors during the neonatal period may have limited the statisticalpower of the study to assess their contributions to the outcomes.Third, given that early delays in development may not correspondwith subsequent impairment,33 further follow-up including neuropsychological,motor, educational, and behavioral assessments will be importantto better understand the clinical implications of our MRI findings.
Nonetheless, our findings suggest that the identification ofearly cerebral abnormalities with the use of MRI should offera valuable complement to other neonatal and psychosocial riskfactors in improving the identification of preterm infants athigh risk for subsequent neurodevelopmental impairment.
Supported by grants from the Neurological Foundation of NewZealand, the Lottery Grants Board of New Zealand, the CanterburyMedical Research Foundation, the Health Research Council ofNew Zealand, the Murdoch Children's Research Institute, andthe National Health and Medical Research Council of Australia.
No potential conflict of interest relevant to this article wasreported.
We are indebted to John Horwood for biostatistical advice, toNigel Anderson for ultrasonographic analysis, to Dr. Scott Wellsand the Canterbury Radiology Group, to Michael Kean and theMedical Imaging Department of the Royal Children's Hospital,to our research team (Merilyn Bear, Michelle VanDyk, MichelleDavey, Carole Spencer, Rod Hunt, and Karli Treyvaud) for itsdedicated efforts, and most importantly, to the families inthe study for their willingness to share their children's liveswith us.
Source Information
From the University of Canterbury and the Van der Veer Institute for Parkinson's and Brain Research (L.J.W.) and Christchurch Women's Hospital (N.C.A.) — all in Christchurch, New Zealand; the Murdoch Childrens Research Institute (P.J.A., T.E.I.) and the Department of Psychology (K.H.), University of Melbourne, Melbourne, Australia; and the Department of Pediatrics, Neurology, and Radiology, St. Louis Children's Hospital, Washington University, St. Louis (T.E.I.).
Address reprint requests to Dr. Woodward at the Canterbury Child Development Research Group, Department of Psychology, University of Canterbury, Private Bag 4800, Christchurch, New Zealand, or at lianne.woodward{at}canterbury.ac.nz.
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Berman, J.I., Glass, H.C., Miller, S.P., Mukherjee, P., Ferriero, D.M., Barkovich, A.J., Vigneron, D.B., Henry, R.G.
(2009). Quantitative Fiber Tracking Analysis of the Optic Radiation Correlated with Visual Performance in Premature Newborns. Am. J. Neuroradiol.
30: 120-124
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Tich, S. N. T., Anderson, P.J., Shimony, J.S., Hunt, R.W., Doyle, L.W., Inder, T.E.
(2009). A Novel Quantitative Simple Brain Metric Using MR Imaging for Preterm Infants. Am. J. Neuroradiol.
30: 125-131
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Kuban, K. C. K., Allred, E. N., O'Shea, T. M., Paneth, N., Pagano, M., Dammann, O., Leviton, A., Du Plessis, A., Westra, S. J., Miller, C. R., Bassan, H., Krishnamoorthy, K., Junewick, J., Olomu, N., Romano, E., Seibert, J., Engelke, S., Karna, P., Batton, D., O'Connor, S. E., Keller, C. E.
(2009). Cranial Ultrasound Lesions in the NICU Predict Cerebral Palsy at Age 2 Years in Children Born at Extremely Low Gestational Age. J Child Neurol
24: 63-72
[Abstract]
Heep, A., Scheef, L., Jankowski, J., Born, M., Zimmermann, N., Sival, D., Bos, A., Gieseke, J., Bartmann, P., Schild, H., Boecker, H.
(2009). Functional Magnetic Resonance Imaging of the Sensorimotor System in Preterm Infants. Pediatrics
123: 294-300
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Chau, V., Poskitt, K. J., Sargent, M. A., Lupton, B. A., Hill, A., Roland, E., Miller, S. P.
(2009). Comparison of Computer Tomography and Magnetic Resonance Imaging Scans on the Third Day of Life in Term Newborns With Neonatal Encephalopathy. Pediatrics
123: 319-326
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Sherlock, R. L., McQuillen, P. S., Miller, S. P., on behalf of aCCENT,
(2009). Preventing Brain Injury in Newborns With Congenital Heart Disease: Brain Imaging and Innovative Trial Designs. Stroke
40: 327-332
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Ludeman, N. A., Berman, J. I., Wu, Y. W., Jeremy, R. J., Kornak, J., Bartha, A. I., Barkovich, A. J., Ferriero, D. M., Henry, R. G., Glenn, O. A.
(2008). Diffusion tensor imaging of the pyramidal tracts in infants with motor dysfunction. Neurology
71: 1676-1682
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Beauchamp, M. H., Thompson, D. K., Howard, K., Doyle, L. W., Egan, G. F., Inder, T. E., Anderson, P. J.
(2008). Preterm infant hippocampal volumes correlate with later working memory deficits. Brain
131: 2986-2994
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Bodeau-Livinec, F., Marlow, N., Ancel, P.-Y., Kurinczuk, J. J., Costeloe, K., Kaminski, M.
(2008). Impact of Intensive Care Practices on Short-Term and Long-term Outcomes for Extremely Preterm Infants: Comparison Between the British Isles and France. Pediatrics
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Vermeulen, R. J., van Schie, P. E. M., Hendrikx, L., Barkhof, F., van Weissenbruch, M., Knol, D. L., Pouwels, P. J. W.
(2008). Diffusion-weighted and Conventional MR Imaging in Neonatal Hypoxic Ischemia: Two-year Follow-up Study. Radiology
249: 631-639
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Limperopoulos, C., Gauvreau, K. K., O'Leary, H., Moore, M., Bassan, H., Eichenwald, E. C., Soul, J. S., Ringer, S. A., Di Salvo, D. N., du Plessis, A. J.
(2008). Cerebral Hemodynamic Changes During Intensive Care of Preterm Infants. Pediatrics
122: e1006-e1013
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O'Shea, T. M., Kuban, K. C. K., Allred, E. N., Paneth, N., Pagano, M., Dammann, O., Bostic, L., Brooklier, K., Butler, S., Goldstein, D. J., Hounshell, G., Keller, C., McQuiston, S., Miller, A., Pasternak, S., Plesha-Troyke, S., Price, J., Romano, E., Solomon, K. M., Jacobson, A., Westra, S., Leviton, A., for the Extremely Low Gestational Age Newborns Stu,
(2008). Neonatal Cranial Ultrasound Lesions and Developmental Delays at 2 Years of Age Among Extremely Low Gestational Age Children. Pediatrics
122: e662-e669
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Glass, H. C., Bonifacio, S. L., Chau, V., Glidden, D., Poskitt, K., Barkovich, A. J., Ferriero, D. M., Miller, S. P.
(2008). Recurrent Postnatal Infections Are Associated With Progressive White Matter Injury in Premature Infants. Pediatrics
122: 299-305
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Atkinson, J, Braddick, O, Anker, S, Nardini, M, Birtles, D, Rutherford, M A, Mercuri, E, Dyet, L E, Edwards, A D, Cowan, F M
(2008). Cortical vision, MRI and developmental outcome in preterm infants. Arch. Dis. Child. Fetal Neonatal Ed.
93: F292-F297
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Dubois, J, Benders, M, Cachia, A, Lazeyras, F, Ha-Vinh Leuchter, R, Sizonenko, S. V., Borradori-Tolsa, C, Mangin, J. F., Huppi, P. S.
(2008). Mapping the Early Cortical Folding Process in the Preterm Newborn Brain. Cereb Cortex
18: 1444-1454
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Cheong, J. L. Y., Hunt, R. W., Anderson, P. J., Howard, K., Thompson, D. K., Wang, H. X., Bear, M. J., Inder, T. E., Doyle, L. W.
(2008). Head Growth in Preterm Infants: Correlation With Magnetic Resonance Imaging and Neurodevelopmental Outcome. Pediatrics
121: e1534-e1540
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Spittle, A. J., Brown, N. C., Doyle, L. W., Boyd, R. N., Hunt, R. W., Bear, M., Inder, T. E.
(2008). Quality of General Movements Is Related to White Matter Pathology in Very Preterm Infants. Pediatrics
121: e1184-e1189
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Miller, S. P., McQuillen, P. S., Hamrick, S., Xu, D., Glidden, D. V., Charlton, N., Karl, T., Azakie, A., Ferriero, D. M., Barkovich, A. J., Vigneron, D. B.
(2007). Abnormal Brain Development in Newborns with Congenital Heart Disease. NEJM
357: 1928-1938
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Gianni, M. L., Picciolini, O., Vegni, C., Gardon, L., Fumagalli, M., Mosca, F.
(2007). Twelve-Month Neurofunctional Assessment and Cognitive Performance at 36 Months of Age in Extremely Low Birth Weight Infants. Pediatrics
120: 1012-1019
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Miller, S. P, McQuillen, P. S
(2007). Neurology of congenital heart disease: insight from brain imaging. Arch. Dis. Child. Fetal Neonatal Ed.
92: F435-F437
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Back, S. A., Miller, S. P.
(2007). Cerebral White Matter Injury: The Changing Spectrum in Survivors of Preterm Birth. NeoReviews
8: e418-e424
[Abstract][Full Text]
Limperopoulos, C., Bassan, H., Gauvreau, K., Robertson, R. L. Jr, Sullivan, N. R., Benson, C. B., Avery, L., Stewart, J., MD, J. S. S., Ringer, S. A., Volpe, J. J., duPlessis, A. J.
(2007). Does Cerebellar Injury in Premature Infants Contribute to the High Prevalence of Long-term Cognitive, Learning, and Behavioral Disability in Survivors?. Pediatrics
120: 584-593
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Krishnan, M. L., Dyet, L. E., Boardman, J. P., Kapellou, O., Allsop, J. M., Cowan, F., Edwards, A. D., Rutherford, M. A., Counsell, S. J.
(2007). Relationship Between White Matter Apparent Diffusion Coefficients in Preterm Infants at Term-Equivalent Age and Developmental Outcome at 2 Years. Pediatrics
120: e604-e609
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Waddington, J. L.
(2007). Neuroimaging and other neurobiological indices in schizophrenia: relationship to measurement of functional outcome. Br. J. Psychiatry
191: s52-s57
[Abstract][Full Text]
Srinivasan, L., Dutta, R., Counsell, S. J., Allsop, J. M., Boardman, J. P., Rutherford, M. A., Edwards, A. D.
(2007). Quantification of Deep Gray Matter in Preterm Infants at Term-Equivalent Age Using Manual Volumetry of 3-Tesla Magnetic Resonance Images. Pediatrics
119: 759-765
[Abstract][Full Text]
Skranes, J., Vangberg, T. R., Kulseng, S., Indredavik, M. S., Evensen, K. A. I., Martinussen, M., Dale, A. M., Haraldseth, O., Brubakk, A.-M.
(2007). Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. Brain
130: 654-666
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Fraser, M., Bennet, L., Helliwell, R., Wells, S., Williams, C., Gluckman, P., Gunn, A. J., Inder, T.
(2007). Regional Specificity of Magnetic Resonance Imaging and Histopathology Following Cerebral Ischemia in Preterm Fetal Sheep. Reproductive Sciences
14: 182-191
[Abstract]
Derrick, M., Drobyshevsky, A., Ji, X., Tan, S.
(2007). A Model of Cerebral Palsy From Fetal Hypoxia-Ischemia. Stroke
38: 731-735
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Suresh, G. K., Teachey, D. T., Inder, T. E., Woodward, L. J., Anderson, P. J.
(2006). Neonatal MRI and Neurodevelopmental Outcomes. NEJM
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(2006). Neonatal Predictions of Neurodevelopmental Outcomes in Premature Infants. JWatch Neurology
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Romantseva, L., Msall, M. E
(2006). Advances in Understanding Cerebral Palsy Syndromes After Prematurity. NeoReviews
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