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Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review

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      BackgroundNeonatal interventions are largely focused on reduction of mortality and progression towards Millennium Development Goal 4 (child survival). However, little is known about the global burden of long-term consequences of intrauterine and neonatal insults. We did a systematic review to estimate risks of long-term neurocognitive and other sequelae after intrauterine and neonatal insults, especially in low-income and middle-income countries.MethodsWe searched Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase for studies published between Jan 1, 1966, and June 30, 2011, that reported neurodevelopmental sequelae after preterm or neonatal insult. For unpublished studies and grey literature, we searched Dissertation Abstracts International and the WHO library. We reviewed publications that had data for long-term outcome after defined neonatal insults. We summarised the results with medians and IQRs, and calculated the risk of at least one sequela after insult.FindingsOf 28 212 studies identified by our search, 153 studies were suitable for inclusion, documenting 22 161 survivors of intrauterine or neonatal insults. The overall median risk of at least one sequela in any domain was 39·4% (IQR 20·0–54·8), with a risk of at least one severe impairment in any insult domain of 18·5% (7·7–33·3), of at least one moderate impairment of 5·0% (0·0–13·3%), and of at least one mild impairment of 10·0% (1·4–17·9%). The pooled risk estimate of at least one sequela (weighted mean) associated with one or more of the insults studied (excluding HIV) was 37·0% (95% CI 27·0–48·0%) and this risk was not significantly affected by region, duration of the follow-up, study design, or period of data collection. The most common sequelae were learning difficulties, cognition, or developmental delay (n=4032; 59%); cerebral palsy (n=1472; 21%); hearing impairment (n=1340; 20%); and visual impairment (n=1228; 18%). Only 40 (26%) studies included data for multidomain impairments. These studies included 2815 individuals, of whom 1048 (37%) had impairments, with 334 (32%) having multiple impairments.InterpretationIntrauterine and neonatal insults have a high risk of causing substantial long-term neurological morbidity. Comparable cohort studies in resource-poor regions should be done to properly assess the burden of these conditions, and long-term outcomes, such as chronic disease, and to inform policy and programme investments.FundingThe Bill & Melinda Gates Foundation, Saving Newborn Lives, and the Wellcome Trust.

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      Measuring inconsistency in meta-analyses.

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        Global, regional, and national causes of child mortality in 2008: a systematic analysis.

        Up-to-date information on the causes of child deaths is crucial to guide global efforts to improve child survival. We report new estimates for 2008 of the major causes of death in children younger than 5 years. We used multicause proportionate mortality models to estimate deaths in neonates aged 0-27 days and children aged 1-59 months, and selected single-cause disease models and analysis of vital registration data when available to estimate causes of child deaths. New data from China and India permitted national data to be used for these countries instead of predictions based on global statistical models, as was done previously. We estimated proportional causes of death for 193 countries, and by application of these proportions to the country-specific mortality rates in children younger than 5 years and birth rates, the numbers of deaths by cause were calculated for countries, regions, and the world. Of the estimated 8.795 million deaths in children younger than 5 years worldwide in 2008, infectious diseases caused 68% (5.970 million), with the largest percentages due to pneumonia (18%, 1.575 million, uncertainty range [UR] 1.046 million-1.874 million), diarrhoea (15%, 1.336 million, 0.822 million-2.004 million), and malaria (8%, 0.732 million, 0.601 million-0.851 million). 41% (3.575 million) of deaths occurred in neonates, and the most important single causes were preterm birth complications (12%, 1.033 million, UR 0.717 million-1.216 million), birth asphyxia (9%, 0.814 million, 0.563 million-0.997 million), sepsis (6%, 0.521 million, 0.356 million-0.735 million), and pneumonia (4%, 0.386 million, 0.264 million-0.545 million). 49% (4.294 million) of child deaths occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan, and China. These country-specific estimates of the major causes of child deaths should help to focus national programmes and donor assistance. Achievement of Millennium Development Goal 4, to reduce child mortality by two-thirds, is only possible if the high numbers of deaths are addressed by maternal, newborn, and child health interventions. WHO, UNICEF, and Bill & Melinda Gates Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.
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          4 million neonatal deaths: when? Where? Why?

          The proportion of child deaths that occurs in the neonatal period (38% in 2000) is increasing, and the Millennium Development Goal for child survival cannot be met without substantial reductions in neonatal mortality. Every year an estimated 4 million babies die in the first 4 weeks of life (the neonatal period). A similar number are stillborn, and 0.5 million mothers die from pregnancy-related causes. Three-quarters of neonatal deaths happen in the first week--the highest risk of death is on the first day of life. Almost all (99%) neonatal deaths arise in low-income and middle-income countries, yet most epidemiological and other research focuses on the 1% of deaths in rich countries. The highest numbers of neonatal deaths are in south-central Asian countries and the highest rates are generally in sub-Saharan Africa. The countries in these regions (with some exceptions) have made little progress in reducing such deaths in the past 10-15 years. Globally, the main direct causes of neonatal death are estimated to be preterm birth (28%), severe infections (26%), and asphyxia (23%). Neonatal tetanus accounts for a smaller proportion of deaths (7%), but is easily preventable. Low birthweight is an important indirect cause of death. Maternal complications in labour carry a high risk of neonatal death, and poverty is strongly associated with an increased risk. Preventing deaths in newborn babies has not been a focus of child survival or safe motherhood programmes. While we neglect these challenges, 450 newborn children die every hour, mainly from preventable causes, which is unconscionable in the 21st century.
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            Author and article information

            Affiliations
            [a ]Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Kilifi, Kenya
            [b ]Saving Newborn Lives/Save the Children, Cape Town, South Africa
            [c ]Neurosciences Unit, Institute of Child Health, University College London, London, UK
            [d ]Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
            Author notes
            [* ]Correspondence to: Dr Michael K Mwaniki, Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, PO Box 230, Kilifi, Kenya michael.kivkiv@ 123456gmail.com
            Contributors
            Journal
            Lancet
            Lancet
            Lancet
            Lancet Publishing Group
            0140-6736
            1474-547X
            04 February 2012
            04 February 2012
            : 379
            : 9814
            : 445-452
            3273721
            22244654
            LANCET61577
            10.1016/S0140-6736(11)61577-8
            © 2012 Elsevier Ltd. All rights reserved.

            This document may be redistributed and reused, subject to certain conditions.

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