Antenatal Magnesium and Cerebral Palsy in Preterm Infants.

OBJECTIVE: To evaluate the relationship of maternal antenatal magnesium sulfate (MgSO4) with neonatal cranial ultrasound abnormalities and cerebral palsy (CP). STUDY DESIGN: In a randomized trial of MgSO4 or placebo in women at high risk of preterm delivery, up to 3 cranial ultrasounds were obtained in the neonatal period. Images were reviewed by at least 2 pediatric radiologists masked to treatment and other clinical conditions. Diagnoses were predefined for intraventricular hemorrhage, periventricular leukomalacia, intracerebral echolucency or echodensity, and ventriculomegaly. CP was diagnosed at 2 years of age by standardized neurologic examination. RESULTS: Intraventricular hemorrhage, periventricular leukomalacia, intracerebral echolucency or echodensity, and ventriculomegaly were all strongly associated with an increased risk of CP. MgSO4 administration did not affect the risk of cranial ultrasound abnormality observed at 35 weeks postmenstrual age or later. However, for the 82% of infants born at <32 weeks gestation, MgSO4 was associated with a reduction in risk of echolucency or echodensity. The reduction in risk for echolucency explained 21% of the effect of MgSO4 on CP (P = .04), and for echodensity explained 20% of the effect (P = .02). CONCLUSIONS: MgSO4 given prior to preterm delivery was associated with decreased risk of developing echodensities and echolucencies at <32 weeks gestation. However, this effect can only partially explain the effect of MgSO4 on CP at 2 years of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00014989.

Reader variability in the use of diagnostic terms to describe white matter lesions seen on cranial scans of severely premature infants: the ELGAN study.

PURPOSE: To evaluate reader variability of white matter lesions seen on cranial sonographic scans of extreme low gestational age neonates (ELGANs). METHODS: In 1,452 ELGANs, cranial sonographic scans were obtained in the first and second postnatal weeks, and between the third postnatal week and term. All sets of scans were read independently by two sonologists. We reviewed the use of four diagnostic labels: early periventricular leucomalacia, cystic periventricular leucomalacia, periventricular hemorrhagic infarction (PVHI), and other white matter diagnosis, by 16 sonologists at 14 institutions. We evaluated the association of these labels with location and laterality of hyperechoic and hypoechoic lesions, location of intraventricular hemorrhage, and characteristics of ventricular enlargement. RESULTS: Experienced sonologists differed substantially in their application of the diagnostic labels. Three readers applied early periventricular leucomalacia to more than one fourth of all the scans they read, whereas eight applied this label to ≤5% of scans. Five applied PVHI to ≥10% of scans, while three applied this label to ≤5% of scans. More than one third of scans labeled cystic periventricular leucomalacia had unilateral hypoechoic lesions. White matter abnormalities in PVHI were more extensive than in periventricular leucomalacia and were more anteriorly located. Hypoechoic lesions on late scans tended to be in the same locations, regardless of the diagnostic label applied. CONCLUSIONS: Experienced sonologists differ considerably in their tendency to apply diagnostic labels for white matter lesions. This is due to lack of universally agreed-upon definitions. We recommend reducing this variability to improve the validity of large multicenter studies.

Mechanisms of injury to white matter adjacent to a large intraventricular hemorrhage in the preterm brain.

The purpose of this article is to investigate the hyperechoic lesion seen adjacent to a lateral ventricle that contains blood but is not distended. The literature on ependymal barrier dysfunction was reviewed in search of mechanisms of injury to the white matter adjacent to an intraventricular hemorrhage. The clinical literature on the clinical diagnosis of periventricular hemorrhagic infarction was also reviewed to find out how frequently this diagnosis was made. Support was found for the possibility that the ventricular wall does not always function as an efficient barrier, allowing ventricular contents to gain access to the white matter where they cause damage. Hemorrhagic infarction may not be the only or the most frequent mechanism of white matter damage adjacent to a large intraventricular hemorrhage.

Bone mineral status in pediatric heart transplant recipients: a retrospective observational study of an "at risk" cohort.

There is a paucity of literature assessing the burden of bone loss in PHT recipients. We sought to describe the bone mineral status in PHT recipients by doing a retrospective medical record review of those who underwent evaluation of BMD when clinically indicated. Data collected included patient demographics, BMD evaluations, serum calcium, phosphorus, alkaline phosphatase, cumulative steroid dose, osseous complications and their management. Of 149 PHT recipients, 26 underwent BMD evaluation. This evaluation was done at a median of 3.4 yrs after PHT. There total serum calcium, phosphorus and alkaline phosphatase were similar at transplant and BMD study. The median BMD Z-scores were: whole body -0.09 (1.5 to -5.13) and lumbar spine -1.1 (1.5 to -5.16). Bone loss (Z-score <-1) was present in 14 (53.8%). Three patients had spinal fractures and/or avascular necrosis of various bones. Treatment included calcitrol and bisphosphonates; and vertebroplasty for spinal fracture. Bone loss was present in a significant proportion of PHT recipients and may be associated with fractures and avascular necrosis. More than half of our "at risk" cohort had bone loss. Careful surveillance of these patients should be performed to prevent morbidity.

Cranial ultrasound lesions in the NICU predict cerebral palsy at age 2 years in children born at extremely low gestational age.

Our prospective cohort study of extremely low gestational age newborns evaluated the association of neonatal head ultrasound abnormalities with cerebral palsy at age 2 years. Cranial ultrasounds in 1053 infants were read with respect to intraventricular hemorrhage, ventriculomegaly, and echolucency, by multiple sonologists. Standardized neurological examinations classified cerebral palsy, and functional impairment was assessed. Forty-four percent with ventriculomegaly and 52% with echolucency developed cerebral palsy. Compared with no ultrasound abnormalities, children with echolucency were 24 times more likely to have quadriparesis and 29 times more likely to have hemiparesis. Children with ventriculomegaly were 17 times more likely to have quadriparesis or hemiparesis. Forty-three percent of children with cerebral palsy had normal head ultrasound. Focal white matter damage (echolucency) and diffuse damage (late ventriculomegaly) are associated with a high probability of cerebral palsy, especially quadriparesis. Nearly half the cerebral palsy identified at 2 years is not preceded by a neonatal brain ultrasound abnormality.

Observer variability assessing US scans of the preterm brain: the ELGAN study.

BACKGROUND: Neurosonography can assist clinicians and can provide researchers with documentation of brain lesions. Unfortunately, we know little about the reliability of sonographically derived diagnoses. OBJECTIVE: We sought to evaluate observer variability among experienced neurosonologists. MATERIALS AND METHODS: We collected all protocol US scans of 1,450 infants born before the 28th postmenstrual week. Each set of scans was read by two independent sonologists for the presence of intraventricular hemorrhage (IVH) and moderate/severe ventriculomegaly, as well as hyperechoic and hypoechoic lesions in the cerebral white matter. Scans read discordantly for any of these four characteristics were sent to a tie-breaking third sonologist. RESULTS: Ventriculomegaly, hypoechoic lesions and IVH had similar rates of positive agreement (68-76%), negative agreement (92-97%), and kappa values (0.62 to 0.68). Hyperechoic lesions, however, had considerably lower values of positive agreement (48%), negative agreement (84%), and kappa (0.32). No sonologist identified all abnormalities more or less often than his/her peers. Approximately 40% of the time, the tie-breaking reader agreed with the reader who identified IVH, ventriculomegaly, or a hypoechoic lesion in the white matter. Only about 25% of the time did the third party agree with the reader who reported a white matter hyperechoic lesion. CONCLUSION: Obtaining concordance seems to be an acceptable way to assure reasonably high-quality of images needed for clinical research.

Spine bone densitometry in asthmatic children treated with high dose corticosteroids: correcting for racial discrepancies.

PURPOSE: Our hypothesis is that the use of standards based on Caucasian children will under-estimate the incidence of abnormal bone density in African American children. MATERIALS AND METHODS: Eighty-two African American and 80 Caucasian asthmatic children classified as high-dose inhaled corticosteroid users comprised the study population. Bone mineral density measurements were compared to reference standards, based on Caucasians, to calculate Z-values. Regression analysis was used to compare Z-values derived from the race-specific and Caucasian standards for 32 African American children. The derived regression analysis equation was then applied to the entire African American population to determine the incidence of abnormal bone density. RESULTS: The asthmatic Caucasian mean spine bone density was significantly less than the normal standards (p < .001), but the African American mean spine bone density was not, despite the high-dose steroid use. Using the Caucasian standards, Caucasians were significantly more likely to have abnormal bone density detected (p < 0.015). Regression analysis of the 32 children with available race specific standards resulted in the following equation: Z African American= Z Caucasian-0.86. The number of African Americans with abnormal bone density detected using the regression equation was not significantly different than the Caucasian children (p > 0.12). CONCLUSIONS: Asthmatic African Americans treated with high-dose inhaled corticosteroids had denser bones than Caucasians. Caucasian standards can be adjusted using a regression equation.