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      Cerebral Palsy—Trends in Epidemiology and Recent Development in Prenatal Mechanisms of Disease, Treatment, and Prevention

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          Abstract

          Cerebral palsy (CP) is the most common motor disability in childhood. This syndrome is the manifestation of intrauterine pathologies, intrapartum complications, and the postnatal sequel, especially among preterm neonates. A double hit model theory is proposed suggesting that an intrauterine condition along with intrapartum or postnatal insult lead to the development of CP. Recent reports demonstrated that treatment during the process of preterm birth such as magnesium sulfate and postnatal modalities such as cooling may prevent or reduce the prevalence of this syndrome. Moreover, animal models demonstrated that postnatal treatment with anti-inflammatory drugs coupled with nanoparticles may affect the course of the disease in pups with neuroinflammation. This review will describe the changes in the epidemiology of this disease, the underlying prenatal mechanisms, and possible treatments that may reduce the prevalence of CP and alter the course of the disease.

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          Most cited references74

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          A report: the definition and classification of cerebral palsy April 2006.

          For a variety of reasons, the definition and the classification of cerebral palsy (CP) need to be reconsidered. Modern brain imaging techniques have shed new light on the nature of the underlying brain injury and studies on the neurobiology of and pathology associated with brain development have further explored etiologic mechanisms. It is now recognized that assessing the extent of activity restriction is part of CP evaluation and that people without activity restriction should not be included in the CP rubric. Also, previous definitions have not given sufficient prominence to the non-motor neurodevelopmental disabilities of performance and behaviour that commonly accompany CP, nor to the progression of musculoskeletal difficulties that often occurs with advancing age. In order to explore this information, pertinent material was reviewed on July 11-13, 2004 at an international workshop in Bethesda, MD (USA) organized by an Executive Committee and participated in by selected leaders in the preclinical and clinical sciences. At the workshop, it was agreed that the concept 'cerebral palsy' should be retained. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, health officials, families and the public and would provide a common language for improved communication. Panels organized by the Executive Committee used this information and additional comments from the international community to generate a report on the Definition and Classification of Cerebral Palsy, April 2006. The Executive Committee presents this report with the intent of providing a common conceptualization of CP for use by a broad international audience.
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            An update on the prevalence of cerebral palsy: a systematic review and meta-analysis.

            The aim of this study was to provide a comprehensive update on (1) the overall prevalence of cerebral palsy (CP); (2) the prevalence of CP in relation to birthweight; and (3) the prevalence of CP in relation to gestational age. A systematic review and meta-analysis was conducted and reported, based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement. Population-based studies on the prevalence of CP in children born in 1985 or after were selected. Statistical analysis was carried out using computer package R, version 2.14. A total of 49 studies were selected for this review. The pooled overall prevalence of CP was 2.11 per 1000 live births (95% confidence interval [CI] 1.98-2.25). The prevalence of CP stratified by gestational age group showed the highest pooled prevalence to be in children weighing 1000 to 1499g at birth (59.18 per 1000 live births; 95% CI 53.06-66.01), although there was no significant difference on pairwise meta-regression with children weighing less than 1000g. The prevalence of CP expressed by gestational age was highest in children born before 28 weeks' gestation (111.80 per 1000 live births; 95% CI 69.53-179.78; p<0.0327). The overall prevalence of CP has remained constant in recent years despite increased survival of at-risk preterm infants. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.
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              Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis.

              To estimate the effect of low-dose aspirin started in early pregnancy on the incidence of preeclampsia and intrauterine growth restriction (IUGR). A systematic review and meta-analysis were performed through electronic database searches (PubMed, Cochrane, Embase). Randomized controlled trials of pregnant women at risk of preeclampsia who were assigned to receive aspirin or placebo (or no treatment) were reviewed. Secondary outcomes included IUGR, severe preeclampsia and preterm birth. The effect of aspirin was analyzed as a function of gestational age at initiation of the intervention (16 weeks of gestation or less, 16 weeks of gestation or more). Thirty-four randomized controlled trials met the inclusion criteria, including 27 studies (11,348 women) with follow-up for the outcome of preeclampsia. Low-dose aspirin started at 16 weeks or earlier was associated with a significant reduction in preeclampsia (relative risk [RR] 0.47, 95% confidence interval [CI] 0.34-0.65, prevalence in 9.3% treated compared with 21.3% control) and IUGR (RR 0.44, 95% CI 0.30-0.65, 7% treated compared with 16.3% control), whereas aspirin started after 16 weeks was not (preeclampsia: RR 0.81, 95% CI 0.63-1.03, prevalence in 7.3% treated compared with 8.1% control; IUGR: RR 0.98, 95% CI 0.87-1.10, 10.3% treated compared with 10.5% control). Low-dose aspirin started at 16 weeks or earlier also was associated with a reduction in severe preeclampsia (RR 0.09, 95% CI 0.02-0.37, 0.7% treated compared with 15.0% control), gestational hypertension (RR 0.62, 95% CI 0.45-0.84, 16.7% treated compared with 29.7% control), and preterm birth (RR 0.22, 95% CI 0.10-0.49, 3.5% treated compared with 16.9% control). Of note, all studies for which aspirin had been started at 16 weeks or earlier included women identified to be at moderate or high risk for preeclampsia. Low-dose aspirin initiated in early pregnancy is an efficient method of reducing the incidence of preeclampsia and IUGR.
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                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                13 February 2017
                2017
                : 5
                : 21
                Affiliations
                [1] 1Faculty of Health Sciences, School of Medicine, Ben Gurion University of the Negev , Beer Sheva, Israel
                [2] 2Department of Obstetrics and Gynecology, University of Bari Aldo Moro , Bari, Italy
                [3] 3Faculty of Health Sciences, Department of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Ben Gurion University of the Negev , Beer Sheva, Israel
                [4] 4Systems Biology of Reproduction Lendulet Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences Budapest , Budapest, Hungary
                [5] 5Maternity Private Department, Kutvolgyi Clinical Block, Semmelweis University , Budapest, Hungary
                [6] 6First Department of Pathology and Experimental Cancer Research, Semmelweis University , Budapest, Hungary
                [7] 7Faculty of Health Sciences, Maternity Department “D”, Division of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Ben Gurion University of the Negev , Beer Sheva, Israel
                Author notes

                Edited by: Giuseppe Buonocore, University of Siena, Italy

                Reviewed by: Giovanni Vento, Catholic University of the Sacred Heart, Italy; Nathalie Linda Maitre, Vanderbilt University, USA

                *Correspondence: Offer Erez, erezof@ 123456bgu.ac.il

                Specialty section: This article was submitted to Neonatology, a section of the journal Frontiers in Pediatrics

                Article
                10.3389/fped.2017.00021
                5304407
                28243583
                5b2ff77b-2119-43d5-8bbd-3b55affbb101
                Copyright © 2017 Stavsky, Mor, Mastrolia, Greenbaum, Than and Erez.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 July 2016
                : 25 January 2017
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 105, Pages: 10, Words: 8991
                Categories
                Pediatrics
                Review

                cerebral palsy,neuroinflammation,progesterone,n-acetyl cysteine,nanoparticles,magnesium sulfate,birth asphyxia,intrauterine infection

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