PEDIATRICS Vol. 120 No. 4 October 2007, pp. 785-792 (doi:10.1542/10.1542/peds.2007-0211)
ARTICLE |
Neurodevelopmental Outcome in Survivors of Periventricular Hemorrhagic Infarction
a Department of Neurology, Fetal-Neonatal Neurology Research Group
b Departments of Cardiology
c Ophthalmology
d Clinical Research Program, Department of Pediatrics
e Infant Follow-up Program, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts
f Departments of Radiology
g Neonatology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVES. Periventricular hemorrhagic infarction is a serious complication of germinal matrix-intraventricular hemorrhage in premature infants. Our objective was to determine the neurodevelopmental and adaptive outcomes of periventricular hemorrhagic infarction survivors and identify early cranial ultrasound predictors of adverse outcome.
METHODS. We retrospectively evaluated all cranial ultrasounds of 30 premature infants with periventricular hemorrhagic infarction and assigned a cranial ultrasound–based periventricular hemorrhagic infarction severity score (range: 0–3) on the basis of whether periventricular hemorrhagic infarction (1) involved 
2 territories, (2) was bilateral, or (3) caused midline shift. We then performed neuromotor, visual function, and developmental evaluations (Mullen Scales of Early Learning, Vineland Adaptive Behavior Scale). Developmental scores below 2 SD from the mean were defined as abnormal.
RESULTS. Median adjusted age at evaluation was 30 months (range: 12–66 months). Eighteen subjects (60%) had abnormal muscle tone, and 7 (26%) had visual field defects. Developmental delays involved gross motor (22 [73%]), fine motor (17 [59%]), visual receptive (13 [46%]), expressive language (11 [38%]), and cognitive (14 [50%]) domains. Impairment in daily living and socialization was documented in 10 (33%) and 6 (20%) infants, respectively. Higher cranial ultrasound–based periventricular hemorrhagic infarction severity scores predicted microcephaly and abnormalities in gross motor, visual receptive, and cognitive function.
CONCLUSIONS. In the current era, two thirds of periventricular hemorrhagic infarction survivors develop significant cognitive and/or motor abnormalities, whereas adaptive skills are relatively spared. Higher cranial ultrasound–based periventricular hemorrhagic infarction severity scores predict worse outcome in several modalities and may prove to be a valuable tool for prognostication.
Key Words: ultrasonography • grade IV intraventricular hemorrhage • premature infants • outcome • score
Abbreviations: PVHI—periventricular hemorrhagic infarction • GM-IVH—germinal matrix-intraventricular hemorrhage • CUS—cranial ultrasound • PVL—periventricular leukomalacia • CI—confidence interval
Periventricular hemorrhagic infarction (PVHI), a complication of germinal matrix-intraventricular hemorrhage (GM-IVH), has been associated in earlier reports with significant adverse neurodevelopmental outcome in premature infants.1 The PVHI lesion seems to result when GM-IVH impairs venous drainage, leading to periventricular infarction with hemorrhagic transformation. The mortality of PVHI, which reached 60% in earlier reports,2 seems to be decreasing in recent years, resulting in a growing population of PVHI survivors at risk for neurodevelopmental sequelae.3,4 Two decades ago Guzzetta et al2 reported major long-term disabilities in up to 90% of PVHI survivors, including cerebral palsy, mental retardation, and seizures, findings corroborated by subsequent reports.5–9 These reports described global motor and cognitive sequelae of PVHI; to date there are no descriptions of function in specific developmental subdomains. Several studies have suggested a more favorable outcome for a subgroup of PVHI survivors2,3,8,10; however, most clinicians still consider PVHI a devastating lesion. To improve prognostic accuracy we developed a cranial ultrasound (CUS)–based PVHI severity score (Fig 1) that categorizes grades of PVHI severity.11 In the current study, our goals were threefold. We sought to delineate the impact of advances in neonatal critical care and survival on the long-term outcome of survivors of PVHI. Next, we sought to develop a more detailed understanding of the long-term neurodevelopmental sequelae of PVHI than is currently available. Finally, we aimed to test the ability of a CUS-based PVHI severity score for predicting these sequelae.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Subject Selection and Enrollment
We performed an electronic search of the Neonatal Neurology and Infant Follow-up Program databases at Children's Hospital Boston for a 6-year period (January 1997 to December 2002). The patient population of these clinical programs originates from the 3 NICUs of the Longwood Medical Area (Children's Hospital Boston, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center). Key words in our database search included periventricular hemorrhagic infarction, grade IV IVH, parenchymal hemorrhage, parenchymal echodensity, and venous infarction. All neonatal CUS studies of infants identified in this manner were reviewed simultaneously by 2 investigators (Drs Benson and Bassan), both of whom were blinded to the clinical course and outcome of these infants. In 2 cases of disparity between these 2 reviewers, a third reviewer (Dr du Plessis) was used as a tie-breaker. Inclusion criteria were all preterm infants who survived PVHI (see "Ultrasonographic Criteria") and were followed by the Neonatal Neurology or Infant Follow-up Programs. We excluded infants with a known or suspected brain malformation, dysmorphic features or congenital anomalies suggestive of a genetic syndrome, metabolic disorders, chromosomal abnormality, or confirmed central nervous system infection within the first 6 days of life. This study was approved by the institutional review boards of Children's Hospital Boston, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center. Written informed parental consent was obtained before the follow-up studies.
Ultrasonographic Criteria
We defined PVHI as an echodense lesion in the periventricular white matter, which was associated with GM-IVH. Unlike periventricular leukomalacia (PVL), PVHI is unilateral or, if bilateral, it is clearly asymmetric. When GM-IVH is bilateral, it usually is larger on the side ipsilateral to the PVHI.1,12,13 We excluded infants in whom echodensities were transient leaving no CUS evidence of focal tissue loss (cyst formation), as well as those in whom the echodensities were typical of PVL alone, that is, bilateral, usually symmetric echodensities in the white matter dorsolateral to the lateral ventricles.1 In addition, we excluded cases of periventricular cysts present within the first days of life, because their etiopathogenesis and timing of onset could not be established.
We categorized the topography (ie, anterior frontal, posterior frontal [body], parietal, temporal or occipital), the extent (localized, ie, limited to 1 territory, or extensive, ie, involving 2 to 5 territories), and the presence of midline shift of all CUS echodensities, and entered these data onto a proforma sheet. We assigned a CUS-based PVHI severity score (PVHI severity score) to each patient as previously described (Fig 1).11 Briefly, the PVHI severity score is derived from the CUS study with the largest size echodensity and is based on 3 items: extensive echogenicity, that is, involvement of 2 or more territories; bilateral PVHI; and midline shift. A CUS scan with none of these findings receives a score of 0, whereas a scan with all 3 abnormalities receives a score of 3. We also documented whether the echodensities evolved into a single large cyst (>5 mm) or multiple smaller cysts.
Measures of Neurologic, Developmental, and Functional Outcome
For each child, we obtained outcome measurements by using a battery of complementary instruments. Age at evaluation was adjusted for prematurity for children <24 months of age. All testers were blinded to past medical history and imaging findings.
Neurologic Evaluations
Neurologic status was evaluated by an experienced child neurologist (Dr Bassan or du Plessis) by using a formal neurologic examination (51 items) including assessment of cranial size, cranial nerves, special senses, and motor function (ie, deep tendon reflexes, muscle tone, muscle strength, coordination, and gait). Hypertonia, when present, was scored using the Ashworth scales (grades 1–5).14 Only a score 2 was categorized as hypertonia.
Visual Evaluations
Because the optic radiations pass through areas that are susceptible to PVHI, visual function was measured by an experienced examiner (Dr Mayer) by using formal visual acuity and visual field tests. Visual acuity for gratings was tested monocularly in 22 children by using the Teller acuity cards (Vistech Consultants, Inc, Dayton, OH) and a modified acuity card procedure.15–17 The finest grating the infant was judged to detect was taken as the infant's acuity. Recognition acuity (using symbols or letters), when testable, was used as the acuity outcome in 4 children. Acuity was tested with glasses if prescribed. Acuities were compared with normal acuities for age.16,18 Visual acuity of the eye with poorer acuity was dichotomized as abnormal (below the 2.5% lower prediction limit for corrected age) or normal (at or above 2.5%).17 Visual fields were tested binocularly, using a special perimeter and method19 adapted to detect quadrantic and hemianopic field defects.20 The infant's visual orienting responses to a <1° light embedded in a hemispheric perimeter were observed using a video monitor. This light target provides a kinetic peripheral field comparable in area to fields tested with Goldmann III–V size targets.21 Confrontation testing was also performed by using small toys.
Developmental Assessments
A certified psychologist (Dr Visconti or Avery) performed the Mullen Scales of Early Learning22 to evaluate gross motor, fine motor, visual reception (visual perceptual ability), receptive language, and expressive language. For each of these scales, a t score (mean: 50; SD: 10) was obtained. A summary measure of general cognitive function (Early Learning Composite) was derived from the visual receptive, fine motor, receptive language, and expressive language scales, and was expressed as a standard score (mean: 100; SD: 15). The Peabody Developmental Motor Scales23 was administered by a certified occupational therapist (Dr Limperopoulos) to evaluate the gross motor abilities in 5 children who were older than 33 months in age (ie, above the upper limit for gross motor assessment in the Mullen scale). Developmental Motor Quotients were derived for each of these subjects with a mean of 100 and SD of 15. The Vineland Adaptive Behavior Scale was administered to the parents as a semistructured interview, to measure the child's functional status in communication, daily living skills, socialization, and motor skills. Standard scores were generated with a mean of 100 and SD of 15.24 We defined an abnormal score of the Mullen, Peabody-motor, and Vineland as a score below 2 SDs of the mean.
Socioeconomic Status and Medical History
We used the modified, 2-factor index Hollingshead Scale and averaged the maternal and paternal scores for socioeconomic status.25 We also administered a medical history questionnaire to review the child's services and medical problems. We defined epilepsy as 2 convulsive episodes after discharge from the NICU.
Statistical Analysis
Outcome data were compared across subgroups of documented injury patterns, such as location and side of injury and PVHI severity score. Fisher's exact test for binomial proportions was used for any dichotomous outcome variables. Comparisons between the 4 ordered score categories (0–3) and all outcome factors were made by logistic regression analysis, adjusted for gender, gestational age, and socioeconomic status. SAS (SAS institute, Cary, NC) and SPSS (SPSS, Inc, Chicago, IL) were used for all computations.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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We identified 44 potential subjects meeting our definition of PVHI. Five infants with transient echodensities were excluded. Four families declined enrollment, 3 moved out of state, and 2 could not be located. Therefore, 30 infants underwent neurodevelopmental outcome testing. Demographic and sonographic characteristics of the study subjects are presented in Table 1. The demographic characteristics of the 9 children who were not enrolled were similar to those of the enrolled infants (median gestational age: 27 weeks [range: 24.9–30.9 weeks]; P = .6 and median birth weight: 937.5 g [range: 653–1335 g]; P = .5). The PVHI lesions in the infants unavailable for study were graded as extensive11 in 4 (44%) of 9 cases, compared with the 21 (70%) of 30 extensive cases available for follow-up.
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Clinical Course and Neurodevelopmental Outcome of PVHI
The median age at follow-up (adjusted for prematurity if <24 months) was 30 months (range: 12–66 months). The neuromotor outcome characteristics of the PVHI survivors are presented in Table 2. Visual function abnormalities are presented in Table 3. Visual field evaluations were not performed in 3 children (1 was blind because of severe retinopathy of prematurity), and visual acuity tests were not performed in an additional infant.
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Twelve infants (44.4%) had abnormal acuity in at least 1 eye, and 9 (33.3%) had abnormal visual fields. It is notable that 15 PVHI survivors (55%) showed either visual acuity or visual field abnormalities.
Developmental evaluation (Table 4) revealed that delay in gross motor function was most common, occurring in 73% of survivors. Cognitive skills (based on the Early Learning Composite) were significantly diminished in 50% of children. Impairment in daily living skills was documented in 10 subjects (33%) (Table 4). Of all 29 survivors with complete follow-up data, 21 (72%) had either abnormal neurologic examination or low (<2 SD) cognition scores (based on the Early Learning Composite). Epilepsy occurred in 7 children (23.3%). Eleven children (36.7%) required ventriculoperitoneal shunt placement, 6 of whom (55%) had shunt revisions with a median number of revisions of 3.5 (range: 1–8). Twenty-seven (90%) and 26 (86.7%) children required physical and occupational therapy, respectively. Thirteen (43%) required speech therapy and 7 (23.3%) were receiving specialized vision education. Ten children (33.3%) had previously received botulinum toxin injections for spasticity. Finally, socioeconomic status by the Hollingshead Scale was not statistically associated with any of the outcome measures.
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Relationship of CUS Findings to Outcome
Of all unilateral cases, left-sided PVHI was significantly associated with abnormal tone (10 of 14 vs 2 of 10; P = .036) and with ventriculoperitoneal shunt insertion (8 of 14 vs 1 of 10; P = .033). There was a tendency for more left-sided PVHI to be extensive (11 of 14 vs 5 of 10), but this association was not statistically significant (P = .2). No other outcome parameters were significantly associated with the side of injury.
Cerebellar hemorrhage (as identified by posterior fossa views using a mastoid CUS approach) was present in 5 PVHI cases (17%). There were no significant differences in any outcome parameter between PVHI survivors with or without cerebellar hemorrhage.
Logistic regression demonstrated a statistically significant relationship (P < .05; Table 5) between the PVHI severity score and epilepsy, microcephaly, abnormal tone, and delays in gross motor, visual receptive, receptive language, and cognitive function. As a predictor of abnormal gross motor outcome, higher PVHI severity scores (scores 2 and 3) versus lower PVHI severity scores (scores 0 and 1), had specificity of 87.5% and sensitivity of 54.6%. Thus, positive predictive value and negative predictive value were 92.3% and 41.18%, respectively. As a predictor of abnormal cognitive outcome (Early Learning Composite < 2 SD), higher PVHI severity scores (scores 2 and 3) versus lower PVHI severity scores (scores 0 and 1) had specificity of 64.3% and sensitivity of 71.4%. Thus, positive predictive value and negative predictive value were 69.2% and 66.7%, respectively. The areas under the receiver operating characteristic curve for abnormal gross motor and cognitive outcomes were 0.77 (95% confidence interval [CI]: 0.56–0.98) and 0.79 (95% CI: 0.62–0.96) respectively, indicating strong predictive ability.
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We also studied separately all 3 components of the PVHI severity score and found that the extent of echodensity and midline shift were associated with gross motor development, visual-receptive scores, abnormal neuromotor examination, and hypertonia (extent of echodensity: P = .032, .038, .001, and .002, respectively; midline shift: P = .014, .006, .018, and .007, respectively). We additionally found that extent of echogenicity was significantly associated with fine motor development (P = .014), and there was a trend for bilateral PVHI to predict hypertonia (6 of 6 [bilateral] vs 11 of 24 [unilateral]; P = .057). No other outcome parameters were significantly associated with bilaterality of PVHI. Receptive and expressive language, cognition (Early Learning Composite), and microcephaly were not significantly associated with the 3 components of the PVHI severity score when analyzed separately. The relationship between PVHI size (extent of echogenicity) and outcome is presented in Table 6.
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PVHI involving the anterior frontal and posterior frontal territories was significantly associated with abnormal scores of visual-receptive domain (P = .002 and .038, respectively) and fine motor domain (P = .008 and .014, respectively), with abnormal neurologic examination (P < .0001 and .001, respectively), and with hypertonia (P = .003 and .002, respectively). In addition, posterior frontal PVHI was significantly associated with abnormal gross motor scores (P = .032). PVHI involving the parietal, occipital and temporal territories had no significant association with any of the outcome factors studied.
Finally, evolution of the echogenicity to multiple microcysts (versus single cyst) was significantly associated with abnormal fine motor skills (8 of 8 vs 8 of 20; P = .008), adaptive motor skills (6 of 8 vs 4 of 21; P = .009), and with hypertonia (7 of 8 vs 9 of 21; P = .04).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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In this study, we found that PVHI in premature infants remains a major risk factor for adverse neurodevelopmental outcome in survivors, despite the advances in neonatal critical care over the past 2 decades.1 We speculate that this is due in large part to the increased survival of extremely sick premature infants, those at greatest risk for PVHI.26 Overall, two thirds of survivors had motor delays, and half had cognitive impairment. Visual field abnormalities were detected in one third of subjects and late seizures were reported in one quarter. However, we found that the adaptive and communication skills were relatively preserved in over two thirds of our subjects. Of importance, approximately one third of PVHI survivors in this study showed no significant long-term neuromotor or cognitive sequelae.
Motor Neurodevelopmental and Adaptive Outcomes
Our findings corroborate those of previous reports that suggested a 50% to 85% incidence of cerebral palsy in survivors of PVHI.2,6,8,10,27,28 Motor abnormalities were significantly associated with anterior frontal and posterior frontal PVHI, presumably secondary to pyramidal fiber injury. This finding is in contrast to a previous study that associated poor motor outcome with PVHI located posterior to the trigone.8 Explanation of this disagreement, which could result from methodologic differences in topography and outcome definitions, must await additional study. Additional predictors of tone abnormalities were left-sided PVHI and microcystic evolution of the original PVHI echogenicity. Whether microcystic evolution is dictated by a specific pathophysiologic mechanism or merely represents a morphologic finding must also await additional study.
In contrast to the hemiplegia seen in middle cerebral artery stroke survivors, which shows significant sparing of leg function, the hemiplegia seen in ex-premature infants with PVHI tends to involve the arms and legs more or less equally.1 This latter pattern of hemiplegia was present in half of our subjects. However, the fact that gross motor development was more affected than fine motor development suggests a relative sparing of the more laterally positioned pyramidal supply to the hands. Motor delays were common in our population, and essentially 90% of patients required physical and occupational therapies. Interestingly, associated cerebellar hemorrhagic injury did not increase the degree of gross or fine motor dysfunction. Importantly, adaptive motor behavior (Vineland scale) was relatively spared in 70% of subjects. This important finding indicates a higher level of motor function in daily activities despite the significant delays detected by the formal developmental tests. We speculate that this may be the result of more intensive and widespread early habilitation practices in recent years.
Cognition, Language, and Behavioral Outcome
Significant cognitive dysfunction was present in half of PVHI survivors, which corroborates the findings of previous studies.2,6 Others have described an even higher prevalence of cognitive dysfunction in this population.29,30 Visual receptive delays were significantly associated with anterior frontal and posterior frontal PVHI, whereas dysfunction in language and cognition did not correlate significantly with the topography of PVHI. Language development has been relatively unexplored in previous studies. In our population of PVHI survivors, expressive language development was relatively spared, whereas receptive language and visual receptive skills tended to correlate with cognitive function. Adaptive social, communication and daily living skills were relatively spared in over two thirds of our children.
Visual Function Outcome
Visual abnormalities in PVHI survivors that could be attributed to retinopathy of prematurity and/or central visual impairments have been previously reported.6,9,10 However, these studies used ophthalmologic examination and not formal visual field assessment. To the best of our knowledge, the current study is the first report that specifically addresses visual field abnormalities in survivors of PVHI. In addition to oculomotor abnormalities affecting 43% and abnormal acuities affecting 44% of survivors, visual field abnormalities were diagnosed in approximately one third. Visual field abnormalities likely result from injury to visual pathways passing through the periventricular regions en route the calcarine cortex.17
Neurologic Sequelae of PVHI
Approximately 40% of PVHI survivors required ventriculoperitoneal shunt, and half of these had shunt revisions. Nevertheless, the need for shunt did not increase the risk for neurodevelopmental disabilities in our population.
Periventricular white matter injury has been associated with impaired development of the overlying cortical gray matter,31,32 a process that may underlie the 20% prevalence of epilepsy in our PVHI survivors.
Association of PVHI Severity Score With Neurodevelopmental Outcome
We tested the CUS-based PVHI severity score previously shown by us to correlate with neonatal risk factors and with long-term neuromotor outcome.11 We found a significant relationship between PVHI severity score and epilepsy, microcephaly, and motor, language and cognitive impairments. According to our analysis, the grouping of 3 sonographic severity items into a single scoring system allows improved severity assessment and prognostication of PVHI as opposed to relying on separate factors.
The strength of our study, compared with previous reports, is its detailed neurologic, visual, and subdomain standardized developmental battery in a relatively large sample of PVHI survivors. Conversely, our study has the potential limitations inherent to any retrospective study. Some of the children who could not be enrolled may represent cases with better outcome, which would potentially have reduced the overall incidence of disability in our PVHI survivors. In addition, the outcome measures in our study were performed at a median age of 30 months, and therefore minor delays and late-onset learning and attention disabilities may be underestimated.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Our study shows that despite the advances in neonatal intensive care over the past few decades, PVHI remains a major risk factor for significant cognitive delays and/or motor abnormalities among the increasing numbers of infants that survive premature birth. However, despite the high prevalence of abnormal test scores for individual domains of neurodevelopmental outcome, the broad range of outcomes as well as the relatively preserved overall adaptive skills among our subjects need to be considered carefully when prognosticating during the early periods of critical illness. The CUS-based severity score for PVHI used in this study may enhance prognostic accuracy during the early neonatal period.
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ACKNOWLEDGMENTS |
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Dr Bassan is supported by the LifeBridge Fund. This work was supported by the LifeBridge Fund, the Caroline Levine Foundation, and the Trust Family Foundation. Statistical analysis and outcome evaluations for this study were supported by the General Clinical Research Center of Children's Hospital Boston, which is funded by National Center for Research Resources (National Institutes of Health) grant MO1-RR02172.
We thank Elaine Veracruz for data management, Shaye Moore for assistance with manuscript preparation, and the children and their families for participating in this study.
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FOOTNOTES |
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Accepted Apr 30, 2007.
Address correspondence to Adré J. du Plessis, MBChB, MPH, Department of Neurology, Fegan 11, Children's Hospital, 300 Longwood Ave, Boston MA 02115. E-mail: adre.duplessis{at}childrens.harvard.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
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REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
- Volpe JJ. Neurology of the Newborn . 4th ed. Philadelphia, PA: WB Saunders; 2001
- Guzzetta F, Shackelford G, Volpe S, Perlman JM, Volpe JJ. Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome.
Pediatrics. 1986;78
:995
–1006
[Abstract/Free Full Text] - de Vries LS, Van Haastert IL, Rademaker KJ, Koopman C, Groenendaal F. Ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. J Pediatr. 2004;144 :815 –820[Web of Science][Medline]
- Bassan H, Feldman HA, Limperopoulos C, et al. Periventricular hemorrhagic infarction: risk factors and neonatal outcome. Pediatr Neurol. 2006;35 :85 –92[Web of Science][Medline]
- Bernert G, Gottling A, Rosenkranz A, Zoder G. Hemorrhagic and hypoxic-ischemic intracranial lesions in neonates diagnosed by realtime sonography: incidence and short-term outcome. Padiatr Padol. 1988;23 :25 –37[Medline]
- Blackman JA, McGuinness GA, Bale JF Jr, Smith WL Jr. Large postnatally acquired porencephalic cysts: unexpected developmental outcomes.
J Child Neurol. 1991;6
:58
–64
[Abstract/Free Full Text] - Perlman JM, Rollins N, Burns D, Risser R. Relationship between periventricular intraparenchymal echodensities and germinal matrix-intraventricular hemorrhage in the very low birth weight neonate.
Pediatrics. 1993;91
:474
–480
[Abstract/Free Full Text] - Rademaker KJ, Groenendaal F, Jansen GH, Eken P, Devries LS. Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Paediatr. 1994;83 :602 –608[Web of Science][Medline]
- Gibson JY, Masingale TW, Graves GR, LeBlanc MH, Meydrech EF. Relationship of cranial midline shift to outcome of very-low-birth-weight infants with periventricular hemorrhagic infarction. J Neuroimag. 1994;4 :212 –217[Medline]
- Bass WT, Jones MA, White LE, Montgomery TR, Aiello F 3rd, Karlowicz MG. Ultrasonographic differential diagnosis and neurodevelopmental outcome of cerebral white matter lesions in premature infants. J Perinatol. 1999;19 :330 –336[CrossRef][Medline]
- Bassan H, Benson CB, Limperopoulos C, et al. Ultrasonographic features and severity scoring of periventricular hemorrhagic infarction in relation to risk factors and outcome.
Pediatrics. 2006;117
:2111
–2118
[Abstract/Free Full Text] - de Vries LS, Roelants-van Rijn AM, Rademaker KJ, Van Haastert IC, Beek FJ, Groenendaal F. Unilateral parenchymal haemorrhagic infarction in the preterm infant. Eur J Paediatr Neurol. 2001;5 :139 –49[CrossRef][Medline]
- de Vries LS, Groenendaal F. Neuroimaging in the preterm infant. Ment Retard Dev Disabil Res Rev. 2002;8 :273 –280[CrossRef][Web of Science][Medline]
- Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity.
Phys Ther. 1987;67
:206
–207
[Abstract/Free Full Text] - Teller DY, McDonald MA, Preston K, Sebris SL, Dobson V. Assessment of visual acuity in infants and children: the acuity card procedure. Dev Med Child Neurol. 1986;28 :779 –789[Web of Science][Medline]
- Mayer DL, Beiser AS, Warner AF, Pratt EM, Raye KN, Lang JM. Monocular acuity norms for the Teller Acuity Cards between ages one month and four years.
Invest Ophthalmol Vis Sci. 1995;36
:671
–685
[Abstract/Free Full Text] - SanGiovanni JP, Allred EN, Mayer DL, Stewart JE, Herrera MG, Leviton A. Reduced visual resolution acuity and cerebral white matter damage in very-low-birthweight infants. Dev Med Child Neurol. 2000;42 :809 –815[CrossRef][Web of Science][Medline]
- Manny RE, Hussein M, Gwiazda J, Marsh-Tootle W. Repeatability of ETDRS visual acuity in children.
Invest Ophthalmol Vis Sci. 2003;44
:3294
–300
[Abstract/Free Full Text] - Mayer DL, Fulton AB, Cummings MF. Visual fields of infants assessed with a new perimetric technique.
Invest Ophthalmol Vis Sci. 1988;29
:452
–459
[Abstract/Free Full Text] - Mayer DL, Fulton AN. Development of the human visual field. In: Simons K, ed. Early Visual Development, Normal and Abnormal . New York, NY: Oxford University Press; 1993:117–129
- Cummings MF, van Hof-van Duin J, Mayer DL, Hansen RM, Fulton AB. Visual fields of young children. Behav Brain Res. 1988;29 :7 –16[CrossRef][Web of Science][Medline]
- Mullen EM. Mullen Scales of Early Learning (AGS Edition) . Circle Pines, MN: American Guidance Service; 1995
- Hinderer KA, Richardson PK, Atwater SW. Clinical implication of the Peabody developmental motor scales: a constructive review. Phys Occup Ther Pediatr. 1989;9 :81 –106[Medline]
- Rosenbaum P, Saigal S, Szatmari P, Hoult L. Vineland Adaptive Behavior Scales as a summary of functional outcome of extremely low-birthweight children. Dev Med Child Neurol. 1995;37 :577 –586[Web of Science][Medline]
- Freedman LZ, Hollingshead AB. Neurosis and social class. I. Social interaction.
Am J Psychiatry. 1957;113
:769
–775
[Abstract/Free Full Text] - Meadow W, Lee G, Lin K, Lantos J. Changes in mortality for extremely low birth weight infants in the 1990s: implications for treatment decisions and resource use.
Pediatrics. 2004;113
:1223
–1229
[Abstract/Free Full Text] - Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr. 1983;103 :273 –277[CrossRef][Web of Science][Medline]
- Futagi Y, Toribe Y, Ogawa K, Suzuki Y. Neurodevelopmental outcome in children with intraventricular hemorrhage. Pediatr Neurol. 2006;34 :219 –224[CrossRef][Web of Science][Medline]
- Pikus H, Levy M, Gans W, Mendel E, McComb J. Outcome, cost analysis, and long-term follow-up in preterm infants with massive grade IV germinal matrix hemorrhage and progressive hydrocephalus. Neurosurgery. 1997;40 :983 –989[CrossRef][Web of Science][Medline]
- Hamrick SE, Miller SP, Leonard C, et al. Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia. J Pediatr. 2004;145 :593 –599[CrossRef][Web of Science][Medline]
- Inder TE, Huppi PS, Warfield S, et al. Periventricular white matter injury in the premature infant is followed by reduced cerebral cortical gray matter volume at term. Ann Neurol. 1999;46 :755 –760[CrossRef][Web of Science][Medline]
- Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr. 2003;143 :171 –179[CrossRef][Web of Science][Medline]
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T. Sawyer Withdrawing Support for Withdrawing Support From Premature Infants With Severe Intracranial Hemorrhage Pediatrics, May 1, 2008; 121(5): 1071 - 1072. [Full Text] [PDF]
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H. Bassan and A. J. du Plessis Withdrawing Support for Withdrawing Support From Premature Infants With Severe Intracranial Hemorrhage: In Reply Pediatrics, May 1, 2008; 121(5): 1072 - 1073. [Full Text] [PDF]
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