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Antenatal Magnesium and Cerebral Palsy in Preterm Infants.

ABSTRACT: 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.

SUBMITTER: Hirtz DG

PROVIDER: S-EPMC4587284 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Antenatal Magnesium and Cerebral Palsy in Preterm Infants.

Hirtz Deborah G DG Weiner Steven J SJ Bulas Dorothy D DiPietro Michael M Seibert Joanna J Rouse Dwight J DJ Mercer Brian M BM Varner Michael W MW Reddy Uma M UM Iams Jay D JD Wapner Ronald J RJ Sorokin Yoram Y Thorp John M JM Ramin Susan M SM Malone Fergal D FD Carpenter Marshall W MW O'Sullivan Mary J MJ Peaceman Alan M AM Hankins Gary D V GD Dudley Donald D Caritis Steve N SN

The Journal of pediatrics 20150805 4

<h4>Objective</h4>To evaluate the relationship of maternal antenatal magnesium sulfate (MgSO4) with neonatal cranial ultrasound abnormalities and cerebral palsy (CP).<h4>Study design</h4>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 hemorr ...[more]

PMID: 26254839

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Project description:Worldwide, an estimated 15 million babies are born preterm (<37 weeks' gestation) every year. Despite significant improvements in survival rates, preterm infants often face a lifetime of neurodevelopmental disability including cognitive, behavioral, and motor impairments. Indeed, prematurity remains the largest risk factor for the development of cerebral palsy. The developing brain of the preterm infant is particularly fragile; preterm babies exhibit varying severities of cerebral palsy arising from reductions in both cerebral white and gray matter volumes, as well as altered brain microstructure and connectivity. Current intensive care therapies aim to optimize cardiovascular and respiratory function to protect the brain from injury by preserving oxygenation and blood flow. If a brain injury does occur, definitive diagnosis of cerebral palsy in the first few hours and weeks of life is difficult, especially when the lesions are subtle and not apparent on cranial ultrasound. However, early diagnosis of mildly affected infants is critical, because these are the patients most likely to respond to emergent treatments inducing neuroplasticity via high-intensity motor training programs and regenerative therapies involving stem cells. A current controversy is whether to test universal treatment in all infants at risk of brain injury, accepting that some patients never required treatment, because the perceived potential benefits outweigh the risk of harm. Versus, waiting for a diagnosis before commencing targeted treatment for infants with a brain injury, and potentially missing the therapeutic window. In this review, we discuss the emerging prophylactic, reparative, and restorative brain interventions for infants born preterm, who are at high risk of developing cerebral palsy. We examine the current evidence, considering the timing of the intervention with relation to the proposed mechanism/s of action. Finally, we consider the development of novel markers of preterm brain injury, which will undoubtedly lead to improved diagnostic and prognostic capability, and more accurate instruments to assess the efficacy of emerging interventions for this most vulnerable group of infants.

Project description:Very preterm infants (born at less than 32 weeks gestational age) are at high risk for serious motor impairments, including cerebral palsy (CP). The brain network changes that antecede the early development of CP in infants are not well characterized, and a better understanding may suggest new strategies for risk-stratification at term, which could lead to earlier access to therapies. Graph theoretical methods applied to diffusion MRI-derived brain connectomes may help quantify the organization and information transfer capacity of the preterm brain with greater nuance than overt structural or regional microstructural changes. Our aim was to shed light on the pathophysiology of early CP development, before the occurrence of early intervention therapies and other environmental confounders, to help identify the best early biomarkers of CP risk in VPT infants. In a cohort of 395 very preterm infants, we extracted cortical morphometrics and brain volumes from structural MRI and also applied graph theoretical methods to diffusion MRI connectomes, both acquired at term-equivalent age. Metrics from graph network analysis, especially global efficiency, strength values of the major sensorimotor tracts, and local efficiency of the motor nodes and novel non-motor regions were strongly inversely related to early CP diagnosis. These measures remained significantly associated with CP after correction for common risk factors of motor development, suggesting that metrics of brain network efficiency at term may be sensitive biomarkers for early CP detection. We demonstrate for the first time that in VPT infants, early CP diagnosis is anteceded by decreased brain network segregation in numerous nodes, including motor regions commonly-associated with CP and also novel regions that may partially explain the high rate of cognitive impairments concomitant with CP diagnosis. These advanced MRI biomarkers may help identify the highest risk infants by term-equivalent age, facilitating earlier interventions that are informed by early pathophysiological changes.

Dataset Information

Antenatal Magnesium and Cerebral Palsy in Preterm Infants.

Publications

Antenatal Magnesium and Cerebral Palsy in Preterm Infants.

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