Ultrasonographic Features and Severity Scoring of Periventricular Hemorrhagic Infarction in Relation to Risk Factors and Outcome
OBJECTIVE. Early diagnosis of periventricular hemorrhagic infarction in premature infants is based on bedside neonatal cranial ultrasonography. Currently, evaluation of its morphology and evolution by cranial ultrasound relies largely on data predating major advances in perinatal care and lacks a consistent classification system for determining severity of injury. The objective of this study was to examine the ultrasonographic morphology and evolution of periventricular hemorrhagic infarction in the modern NICU and to determine the value of a cranial ultrasonography-based severity score for predicting outcome.
METHODS. We retrospectively evaluated all cranial ultrasounds and medical records of 58 premature infants with periventricular hemorrhagic infarction. We assigned each subject a severity score based on extent of echodensity, unilateral versus bilateral, and presence or absence of midline shift. A neurologic examination was performed after 12 months adjusted age.
RESULTS. The parenchymal echodensity of periventricular hemorrhagic infarction most often involved parietal and frontal territories and evolved into single and/or multiple cysts. One quarter of cases were bilateral, and nearly 70% were extensive. Higher severity scores were significantly associated with pulmonary hemorrhage and low bicarbonate levels and with outcomes of fatality, early neonatal seizures, and motor disability.
CONCLUSIONS. Despite advances in perinatal medicine, periventricular hemorrhagic infarction remains an important complication of prematurity. Periventricular hemorrhagic infarction can be graded using a scoring system based on sonographic characteristics. Higher severity scores predict worse outcome. Such severity scoring could improve the clinician's ability to counsel parents regarding management decisions and early intervention strategies.
- periventricular hemorrhagic infarction
- grade IV intraventricular hemorrhage
- premature infants
Periventricular hemorrhagic infarction (PVHI) is an acquired brain lesion with major impact on the neurodevelopmental outcome of infants who survive premature birth. PVHI has been considered to be the most severe (grade IV) form of germinal matrix–intraventricular hemorrhage (GM-IVH). A number of reports1–6 have suggested, however, that rather than representing simple parenchymal extension of the intraventricular blood, PVHI is a complication of GM-IVH, which results from hemorrhagic transformation of a venous infarction. For many years, neonatal cranial ultrasonography (CUS) has been the key diagnostic tool for GM-IVH and PVHI in premature infants. Detailed structural and timing characteristics of PVHI by CUS initially were described ∼25 years ago.7 Over the course of the next 2 decades, additional studies delineated a range of sonographic characteristics of PVHI.8–16 Although specific CUS diagnostic criteria for PVHI have been proposed,1, 13, 17, 18 comparison of the CUS features between various studies is limited because of the lack of a consistently used CUS scoring system for PVHI.
We therefore set out to examine the extensive CUS database at our center to describe the ultrasonographic features of PVHI in recent years. Our goals were (1) to define the extent and the topography of PVHI in the current era, (2) to delineate the typical findings on CUS with evolution of PVHI, (3) to develop a CUS-based scoring system to describe the structural severity of PVHI during the early newborn period, and (4) to determine the relationship between such a sonographic severity score and perinatal risk factors and outcome.
We performed an electronic search of the neonatal ultrasound database at Brigham and Women's Hospital for a 6-year period (January 1997–December 2002). Key words in our database search included periventricular hemorrhagic infarction, grade IV IVH, parenchymal hemorrhage, parenchymal echodensity, and venous infarction. In all cases that were identified in this manner, we reviewed the CUS studies to confirm the diagnosis of PVHI (see below). Inclusion criteria were preterm infants (<2500 g) who were admitted to the NICU during the 6-year study period and for whom we made the diagnosis of PVHI by CUS. Exclusion criteria were infants with CUS features of periventricular leukomalacia (PVL; see below); known or suspected brain malformation; dysmorphic features or congenital anomalies suggestive of a genetic syndrome, metabolic disorders, or chromosomal abnormality; or central nervous system infection in the first 6 days of life. In addition, we excluded cases with periventricular white matter cystic lesions present at birth, because these might represent antenatal injury. The Institutional Review Boards of Brigham and Women's Hospital and Children's Hospital Boston approved this study.
During the 6-year study period, CUS studies at our center were performed using the Acuson Sequoia instrument (Siemens, Mountain View, CA) equipped with a 6.5- to 8.5-MHz probe. Standardized images that were acquired for every CUS study included anterior fontanel views (6 angled coronal views, 2 midsagittal views, and 3 parasagittal views on each side), posterior fontanel views (2 parasagittal views of the occipital horns of the lateral ventricles), and posterior fossa views (angled transaxial images of the midbrain and cerebellum acquired through the mastoid [3 views] and sphenoid [2 views]) regions. Between 1997 and 1998, posterior fossa imaging was not performed routinely. The clinical CUS protocol in our NICU remained consistent during the study period, calling for a minimum of 2 CUS examinations to be performed during the first week of life and an additional CUS at 30 days of age. Additional studies were performed when clinically indicated.
CUS Classification of Lesions
Neonatal CUS scans of all study infants were evaluated by 2 of the authors (C.B.B. and H.B.), who were blinded to the infants' clinical course and outcome. In 5 cases of disparity between these 2 reviewers, a third reviewer (A.J.d.P.) was used as a tie-breaker. The time (date and hour) of each CUS study was recorded. We used the following CUS diagnostic criteria:
GM-IVH was diagnosed and categorized by previously published criteria.1, 19 Specifically, in grade I GM-IVH, echodensity is confined to the germinal matrix. In grade II GM-IVH, echodensity is present in a nondistended lateral ventricle, whereas in grade III lesions, echodensity is present in a distended lateral ventricle.
PVHI (Fig 1) was diagnosed when an echodense lesion was seen in the periventricular white matter. Lesions may be unilateral or bilateral. When bilateral, they typically are asymmetric. PVHI is always associated with an ipsilateral GM-IVH. When GM-IVH is bilateral, it usually is larger on the side ipsilateral to the PVHI.1, 12, 13
PVL appears on CUS as echodensities or echolucencies in the white matter dorsolateral to the lateral ventricles, usually bilateral and symmetric. It sometimes is associated with evolving GM-IVH.1 Cases that met these criteria were excluded from this study.
CUS Characteristics and Severity Scoring of PVHI
For each study case, we reviewed the CUS to document the following characteristics. We first identified the hemisphere(s) and then the specific territory or territories involved (anterior frontal, posterior frontal [body], parietal, temporal, or occipital). Figure 2 shows a method by which we determined territories on angled parasagittal view, using 3 imaginary lines that border the thalami. We considered a territory involved when the echodensity measured ≥5 mm in diameter on the parasagittal view. In all cases, the extent of the lesion on parasagittal view was confirmed on corresponding angled coronal views. On the basis of the number of territories involved, we categorized the extent of injury as localized (ie, limited to 1 territory) or extensive (ie, involving ≥2 territories). We assessed the mass effect of the PVHI lesion on the basis of the presence or absence of midline shift on coronal image (Fig 1b). We documented the timing of the first appearance of GM-IVH and PVHI, the temporal evolution to maximal size of PVHI, and the time of first appearance of cystic changes. We also evaluated by visual inspection the sonographic evolution for the presence of single large cyst, multiple small cysts (≤5 mm), and ventriculomegaly.
We used the CUS study that showed the largest echogenic lesion to assign a PVHI severity score to each patient. We based this score on the presence (score of 1) or absence (score of 0) of 3 factors that previously have been associated separately with severe PVHI8, 20: bilateral PVHI, midline shift, and extent of PVHI (ie, echogenicity involving ≥2 territories [based on the worse side if bilateral]). A CUS study that showed PVHI with none of these features received a score of 0, whereas a study that showed all 3 features received a score of 3.
Clinical Data Collection and Neurologic Examination
We reviewed the hospital charts of all study infants for pertinent demographic (gender, birth weight, and gestational age at birth) and clinical information, including intrapartum history, blood gas data, and postnatal information. We defined abnormal fetal heart rate as sustained fetal bradycardia <100 beats/minute, loss of variability, and/or late decelerations. Pressor support was defined as use of inotropic agents within the first 5 days of life. Patent ductus arteriosus was counted when diagnosed by echocardiogram before day of life 5 or when diagnosed clinically before day of life 5 and confirmed by subsequent echocardiogram. For all patients, we documented neonatal survival, whether life support was withdrawn, early (<5 days of age) or later neonatal seizures, and the requirement for a ventriculoperitoneal shunt.
A pediatric neurologist (H.B. or A.J.d.P.) examined all survivors at or above 12 months' adjusted age for prematurity using a predefined, formal neurologic examination that included assessment of motor function (deep tendon reflexes, muscle tone, muscle strength, coordination, and gait), cranial nerves, and special senses. Neuromotor findings were categorized as normal or abnormal. Abnormal neuromotor examination was defined as any abnormality in tone, posture, or strength. Abnormalities then were subclassified according to type (hemiplegia, diplegia, quadriplegia, and dystonia). Cranial size (>12 months' adjusted age) was considered abnormal when measured below the 2nd or above the 98th percentile. Age on follow-up examination was adjusted for prematurity for infants who were younger than 24 months' chronological age.
We categorized our data according to birth weight groups (<750, 750–1500, and 1500–2500 g). We additionally categorized the PVHI scores into low scores (0–1) and high scores (2–3). Simple comparisons between fatal and nonfatal PVHI and between low or high PVHI scores were made for continuous variables by Student's 2-tail t test and for dichotomous variables by the Fisher's exact test. Multiple logistic regression was used on the strongest risk factors detected by the univariant analysis. Comparisons among the 4 ordered score categories (0–3) and all outcome factors were made by the exact Cochrane-Armitage trend test and by logistic-regression analysis. SAS (SAS Institute, Cary, NC) and SPSS (SPSS, Inc, Chicago, IL) were used for all computations.
Characteristics of the Study Population
A total of 5774 premature infants who weighed <2500 g were born at the study site between 1997 and 2002. Our initial electronic database search identified a total of 68 infants with possible PVHI. By our selection criteria described above, 10 infants were excluded for the following reasons: criteria met for PVL (n = 2), meningitis (n = 1), congenital periventricular cysts (n = 2), and transient echodensities without evolution to cystic residua (n = 5). We identified 58 infants with PVHI (mean: 1%; range: 0.4%–1.6%, over each of the 6 years). These patients had a median gestational age at birth of 25.6 weeks (range: 23–33 weeks) and median birth weight of 733 g (range: 450–2375 g). Twenty-one (36%) infants were female. Twenty-three (40%) infants died in the neonatal period. Additional incidence data as well as the associated risk factors of this population are described elsewhere (unpublished observations).
The first, second, and third CUS studies in the study infants were performed at mean (±SD) postnatal ages of 1.3 days (±1.2), 3.6 days (±2.3), and 5.9 days (±2.6), respectively. By the seventh day of life, infants with PVHI had a median of 2 (range: 1–4) CUS studies performed. Throughout their NICU stay, study neonates had a median total of 10 (range: 1–54) CUS studies performed.
The sonographic findings in our 58 neonates with PVHI are presented in Table 1. PVHI was more often unilateral than bilateral (43 vs 15 cases). The unilateral lesions occurred equally often on the right and the left (20 vs 23 respectively; P = .66). In the bilateral cases, PVHI was more often extensive (93%; 14 of 15), involving ≥2 territories, as compared with cases of unilateral PVHI, for which 58% (25 of 43) were extensive (P = .01). The extensiveness of PVHI was similar for the following birth weight categories: <750 g, 21 (68%) of 31; 750 to 1500 g, 16 (70%) of 23; and 1500 to 2500 g 2 (50%) of 4 (P = not significant). In addition, no significant association was found between gestational age at birth and the extensiveness of PVHI (P = not significant). The topographic distribution of PVHI in our patients is presented in Fig 2; the parietal territory was most commonly involved, followed by the frontal, occipital, and temporal territories.
Timing of Appearance and Evolution of PVHI on CUS
The initial CUS scan was normal in 34% (20 of 58) of the infants. In 47 (81%) of 58 cases (mean birth weight ± SD: 830 ± 292 g), PVHI was diagnosed in the first 4 days of life. Specifically, 17% (n = 10) received a diagnosis of PVHI on the first day of life. By the second and third days, the number of infants who had received a diagnosis of PVHI increased to 41% (n = 24) and 62% (n = 36), respectively. In 11 (19%) cases (mean birth weight ± SD: 987 ± 518 g), PVHI was diagnosed after day of life 4. These 11 infants had a median of 1 scan (range: 0–2) in the first 4 days of life.
Forty-seven patients who received a diagnosis of PVHI within the first 4 days of life had a median of 2 CUS scans (range: 1–3) during this early period. Among these 47 patients, the median age at CUS diagnosis of PVHI was 46 hours (range: 4–96 hours) from time of birth. PVHI was diagnosed either concurrently with GM-IVH (n = 41, 87%) or after the diagnosis of GM-IVH (13% [n = 6]). In these 47 cases, the PVHI lesion size increased on sequential CUS studies in 22 (47%; mean ± SD lag time: 54 ± 38 hours), whereas in the remaining 25 (53%) cases the size of the PVHI was at its maximum at the time of the first diagnosis on CUS. In no case did the GM-IVH appear after the PVHI.
Among the 35 infants who survived the neonatal period, the echodense PVHI lesion most often evolved into 1 of 3 distinct CUS patterns: a single large cyst (66% [n = 23]), multiple small cysts (9% [n = 3]), or a combination of large and small cysts (23% [n = 8]). In 1 infant, follow-up CUS images were not available. Median time until the first appearance of cystic changes was 7 days (range: 1–15 days) after the initial diagnosis of PVHI.
Thirty-four (97%) of the 35 surviving infants developed ventriculomegaly after day of life 7. By the time of discharge, ventriculomegaly was present in 80% (n = 28) of surviving infants, with 27 (77%) having asymmetric and only 1 (3%) having symmetric ventricular dilatation. Three of the surviving infants (9%; mean ± SD gestational age: 27.2 ± 0.2 weeks; birth weight: 1065 ± 332 g) developed CUS findings of concomitant contralateral PVL.
Clinical Course and Outcome of PVHI
Eleven (19%) infants experienced clinical seizures during their NICU stay (5 of them before day of life 5), and 13 infants required ventriculoperitoneal shunts. The mortality rate in our infants with PVHI was 40% (n = 23). Twenty-two of 23 deaths followed a decision to withdraw life support, thus limiting our ability to associate some clinical factors and neonatal death. Nevertheless, fatal cases had a significantly lower mean (± SD) gestational age (25 ± 2 weeks) and birth weight (705 ± 162 g) than survivors (27 ± 2 weeks and 962 ± 396 g; P < .004), as well as an earlier PVHI diagnosis than survivors (45 ± 32 vs 69 ± 44 hours; P = .03). Finally, among the 45 infants who had a posterior fossa view by CUS, the presence of blood in the fourth ventricle was significantly more common in those who died (14 [93%] of 15 vs 17 [56%] of 30; P = .016). Of the 35 survivors, 31 (89%) underwent long-term follow-up neurologic examinations after 12 months' adjusted age. These were performed at a mean ± SD adjusted age of 36.7 ± 20 months. Of these 31 infants, 12 (39%) had a normal neurologic examination. Neuromotor abnormalities were found in 19, including 11 (35%) with spastic hemiplegia, 4 (13%) with spastic diplegia and hemiplegia, and 4 (13%) with spastic quadriplegia (of these, 2 also exhibited dystonia). Also among these 31 survivors, abnormal head circumference was documented in 10 cases (32% [6 microcephalic and 4 macrocephalic]).
Relationship of PVHI Severity Score to Perinatal Factors and Outcome
Univariate analysis of risk factors revealed that high PVHI scores were associated with low bicarbonate levels during the first 2 days of life and with pulmonary hemorrhage (P < .02; Table 2). Multiple logistic regression of 3 predictors (pulmonary hemorrhage, low Apgar score at 5 minutes, and low bicarbonate) showed that pulmonary hemorrhage is an independent predictor for higher PVHI severity scores (P = .014), whereas low Apgar score at 5 minutes was borderline significant (P = .049) and low bicarbonate was not statistically significant (P = .11).
Univariate analysis of outcome factors revealed a significant association between PVHI severity scores and fatality (decision to withdraw life support), early neonatal seizures, and abnormal neuromotor examination after 12 months' adjusted age (P < .05; Table 3). Logistic regression of abnormal neuromotor examination on the continuous PVHI score showed a statistically significant relationship (P = .011) with an odds ratio of 4.1 for abnormal examination per unit increase in the PVHI score (95% confidence interval: 1.4–11.9). The area under the receiver operating characteristic curve was 0.80 (95% confidence interval: 0.62–0.97), indicating strong predictive ability. As a predictor of abnormal neuromotor examination, higher PVHI severity scores (score 2–3) versus lower PVHI severity scores (score 0–1) had specificity of 92% and sensitivity of 58%. Thus, positive predictive value and negative predictive value were 92% and 58%, respectively. We also studied separately all 3 components of the PVHI score and found that the extent of echodensity and midline shift were significantly associated with abnormal neuromotor examination (P = .022 and .046, respectively), whereas bilateral PVHI, which also was more common in infants with abnormal neuromotor outcome, did not reach statistical significance.
Anterior frontal PVHI was significantly more common in infants with abnormal versus normal neuromotor examination (11 [58%] of 19 vs 2 [17%] of 12; P = .032). In addition, occipital involvement was significantly more common in infants with microcephaly than in those without (3 [75%] of 4 vs 3 [11%] of 26; P = .029). PVHI involving the posterior frontal, parietal, and temporal territories had no significant association with any of the outcome factors studied. Finally, evolution to multiple microcysts was more common in infants with abnormal versus normal neuromotor examination (9 [47%] of 19 vs 1 [9%] of 11), but this association was only of marginal statistical significance (P = .049).
CUS remains the most commonly used method for diagnosing neonatal intracranial hemorrhage, and its accuracy and reliability have been proved in a variety of studies.8–10, 12, 14, 21, 22 In this study, we describe the ultrasonographic features of PVHI in the current era of perinatal care and sonographic technology. We then show that PVHI can be graded using a scoring system that is based on sonographic characteristics. Such a scoring system correlates with perinatal risk factors and outcome. Finally, we show that abnormal neuromotor outcome and microcephaly are associated with anterior frontal and occipital involvement, respectively.
Structural Characteristics of PVHI by CUS
Our findings show that the appearance of PVHI by CUS in our NICU is severe in the majority of infants: two thirds had extensive distribution, one quarter were bilateral, and almost half had midline shift. In addition, we found a predilection of PVHI for the parietal and frontal territories. Our observations corroborate previous reports8–11, 20, 23 and confirm that in the current era, PVHI remains a serious and important complication of premature infants. Unlike previous studies,8, 20 there was no left-sided predominance of PVHI in our study, the incidence of right- and left-sided lesions being equal.
Timing of CUS Diagnosis of PVHI
Our results show that in most infants, PVHI is diagnosed in the first 4 days of life. Even in our late cases (diagnosed after day of life 4), an earlier presentation may have been masked by low scanning frequency, presumably as a result of the milder clinical presentation of these infants. It is interesting that a diagnosis of PVHI on the first day of life, as seen in one fifth of our infants, raises the possibility of an intrapartum or antepartum onset for these cases. The early neonatal presentation of PVHI in our study, also previously recognized,10, 14 underscores how critical the first days of life (including the antenatal or intrapartum period in some cases) are for the development and the prevention of this severe lesion.
Evolution of PVHI by CUS
Our data suggest that the parenchymal echodensity of PVHI may evolve in 3 broad ways. The most common end result is a single large cyst, with or without communication with the lateral ventricles. The second most common pattern is that of multiple small cysts combined with a large cyst, a combination previously described in infants with PVHI.8, 9, 11, 12, 24 Third and least common, PVHI results in multiple small cysts.
The presence of multiple small cysts in 9% of our survivors with PVHI is a morphology that is seen more commonly in the arterial end zone lesion of PVL. Possible mechanisms for these multicystic evolutions are as follows. First, they may represent a transitional phase of the venous infarct toward confluence into a single, larger cyst. Conversely, they may represent arterial ischemic lesions that occur in combination with the larger venous infarct.
In our study, a high proportion of involved infants developed ventriculomegaly, which may have been attributable to periventricular tissue loss, impaired cerebrospinal fluid dynamics with increased ventricular pressure, or both. A recent study25 also found ventricular dilatation in >70% of survivors with PVHI. Concomitant contralateral cystic PVL was found in 9% of our patients. Our data probably underestimate the frequency of associated PVL given the lack of CUS sensitivity for diagnosis of the diffuse form of PVL.26
Associations of Ultrasonographic Features With Risk Factors and Outcome
We developed a CUS-based PVHI severity scoring system and correlated it with the presence of clinical risk factors and outcomes. Previous studies27–29 have suggested that birth weight, gestational age, and hemodynamic disturbances are important antecedents of PVHI. Our data do not support an association between these known risk factors and PVHI severity. Our multivariate modeling suggests that pulmonary hemorrhage is an independent predictor of PVHI severity. Potential mechanisms to explain this association include intrinsic coagulation disturbance and consumption of clotting factors. It also has been suggested that hemorrhage into the lung and brain could occur during reperfusion of vulnerable areas that previously were affected by ischemia.10
To examine the validity and the predictive ability of our PVHI severity scoring system, we tested our score against short- and long-term outcome factors. We found a strikingly significant relationship between PVHI score and the likelihood to withdraw care, the development of early neonatal seizures, and abnormal neuromotor examination beyond 12 months' adjusted age. The grouping of 3 structural sonographic severity items into a single scoring system therefore may allow improved severity assessment and prognostication of PVHI as opposed to relying on separate factors.
In contrast to a previous study that associated poor neuromotor outcome with posterior PVHI,11 we found that anterior frontal involvement was associated with abnormal neuromotor examination. We did not find a significant relationship between fatality and topography of PVHI. It is interesting that posterior lesions were associated with smaller head size in survivors of PVHI; however, the mechanism of this association is unclear.
As a retrospective analysis, our study has several potential limitations. Although our data provide some insights into the timing of PVHI diagnosis by CUS, our reliance on a routine clinical CUS protocol with a limited number of studies precludes the precise timing of PVHI onset. We also cannot retrospectively assign causality to the risk factors that are associated with the complex PVHI severity scores that were assigned via our system. Finally, the potential of our PVHI severity scoring to predict long-term cognitive outcome is not addressed by this study and should be evaluated further.
Despite major advances in perinatal care, PVHI as diagnosed by ultrasound in our center is extensive in the majority of cases and remains an important neurologic complication of prematurity. Detailed assessment of PVHI topography by CUS and the development of a severity score for PVHI may improve the power of early prognostication for early seizures and long-term neuromotor disability in these infants. This severity scoring tool could improve the clinician's ability to counsel parents regarding life support decisions and early intervention strategies.
Dr Bassan is supported by the LifeBridge Fund. This project was funded in part by grant MO1-RR02172 from the National Center for Research Resources, National Institutes of Health, to the Children's Hospital Boston General Clinical Research Center.
We thank Shaye Moore for assistance with manuscript preparation and Amy Kroeplin and Gene Walter for data management.
- Accepted November 17, 2005.
- Address correspondence to Adré J. du Plessis, MD, Department of Neurology, Fegan 11, Children's Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
- ↵Volpe JJ. Neurology of the Newborn. 4th ed. Philadelphia, PA: WB Saunders; 2001
- ↵Pape KE, Blackwell RJ, Cusick G, et al. Ultrasound detection of brain damage in preterm infants. Lancet.1979;1(8129) :1261– 1264
- ↵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
- ↵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
- ↵Maalouf EF, Duggan PJ, Counsell SJ, et al. Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants. Pediatrics.2001;107 :719– 727
- ↵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
- ↵Murphy BP, Inder TE, Rooks V, et al. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed.2002;87 :F37– F41
- ↵Inder TE, Anderson NJ, Spencer C, Wells S, Volpe JJ. White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. AJNR Am J Neuroradiol.2003;24 :805– 809
- ↵Weintraub Z, Solovechick M, Reichman B, et al. Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed.2001;85 :F13– F17
- ↵Linder N, Haskin O, Levit O, et al. Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study. Pediatrics.2003;111(5) . Available at: www.pediatrics.org/cgi/content/full/111/5/e590
- Copyright © 2006 by the American Academy of Pediatrics