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      Early Childhood Outcomes After Neonatal Encephalopathy in Uganda: A Cohort Study

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          Abstract

          Background

          Neonatal encephalopathy (NE) is a leading cause of global child mortality. Survivor outcomes in low-resource settings are poorly described. We present early childhood outcomes after NE in Uganda.

          Methods

          We conducted a prospective cohort study of term-born infants with NE (n = 210) and a comparison group of term non-encephalopathic (non-NE) infants (n = 409), assessing neurodevelopmental impairment (NDI) and growth at 27–30 months. Relationships between early clinical parameters and later outcomes were summarised using risk ratios (RR).

          Findings

          Mortality by 27–30 months was 40·3% after NE and 3·8% in non-NE infants. Impairment-free survival occurred in 41·6% after NE and 98·7% of non-NE infants. Amongst NE survivors, 29·3% had NDI including 19·0% with cerebral palsy (CP), commonly bilateral spastic CP (64%); 10·3% had global developmental delay (GDD) without CP. CP was frequently associated with childhood seizures, vision and hearing loss and mortality. NDI was commonly associated with undernutrition (44·1% Z-score < − 2) and microcephaly (32·4% Z-score < − 2). Motor function scores were reduced in NE survivors without CP/GDD compared to non-NE infants (median difference − 8·2 (95% confidence interval; − 13·0, − 3·7)). Neonatal clinical seizures (RR 4.1(2.0–8.7)), abnormalities on cranial ultrasound, (RR 7.0(3.8–16.3), nasogastric feeding at discharge (RR 3·6(2·1–6·1)), and small head circumference at one year (Z-score < − 2, RR 4·9(2·9–5·6)) increased the risk of NDI.

          Interpretation

          In this sub-Saharan African population, death and neurodevelopmental disability after NE were common. CP was associated with sensorineural impairment, malnutrition, seizures and high mortality by 2 years. Early clinical parameters predicted impairment outcomes.

          Highlights

          • This is, to our knowledge, the largest published cohort describing childhood outcomes after neonatal encephalopathy (NE) in sub-Saharan Africa

          • Children with NE are at high-risk of multidomain neurodevelopmental impairment in a setting where access to supportive services are often lacking.

          • Mortality is highest in the early neonatal period and in those with severe neurodevelopmental impairment

          • Simple early clinical predictors may support a targeted approach to follow-up of particularly high-risk children

          Outstanding Questions

          • What is the contribution of NE to cerebral palsy and other developmental disorders in low resource African settings?

          • What strategies are effective to improve childhood outcomes in NE in way of prevention and intervention?

          • What are the school-age outcomes after NE and later impacts across the life course?

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          Most cited references23

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          Every Newborn: progress, priorities, and potential beyond survival.

          In this Series paper, we review trends since the 2005 Lancet Series on Neonatal Survival to inform acceleration of progress for newborn health post-2015. On the basis of multicountry analyses and multi-stakeholder consultations, we propose national targets for 2035 of no more than 10 stillbirths per 1000 total births, and no more than 10 neonatal deaths per 1000 livebirths, compatible with the under-5 mortality targets of no more than 20 per 1000 livebirths. We also give targets for 2030. Reduction of neonatal mortality has been slower than that for maternal and child (1-59 months) mortality, slowest in the highest burden countries, especially in Africa, and reduction is even slower for stillbirth rates. Birth is the time of highest risk, when more than 40% of maternal deaths (total about 290,000) and stillbirths or neonatal deaths (5·5 million) occur every year. These deaths happen rapidly, needing a rapid response by health-care workers. The 2·9 million annual neonatal deaths worldwide are attributable to three main causes: infections (0·6 million), intrapartum conditions (0·7 million), and preterm birth complications (1·0 million). Boys have a higher biological risk of neonatal death, but girls often have a higher social risk. Small size at birth--due to preterm birth or small-for-gestational-age (SGA), or both--is the biggest risk factor for more than 80% of neonatal deaths and increases risk of post-neonatal mortality, growth failure, and adult-onset non-communicable diseases. South Asia has the highest SGA rates and sub-Saharan Africa has the highest preterm birth rates. Babies who are term SGA low birthweight (10·4 million in these regions) are at risk of stunting and adult-onset metabolic conditions. 15 million preterm births, especially of those younger than 32 weeks' gestation, are at the highest risk of neonatal death, with ongoing post-neonatal mortality risk, and important risk of long-term neurodevelopmental impairment, stunting, and non-communicable conditions. 4 million neonates annually have other life-threatening or disabling conditions including intrapartum-related brain injury, severe bacterial infections, or pathological jaundice. Half of the world's newborn babies do not get a birth certificate, and most neonatal deaths and almost all stillbirths have no death certificate. To count deaths is crucial to change them. Failure to improve birth outcomes by 2035 will result in an estimated 116 million deaths, 99 million survivors with disability or lost development potential, and millions of adults at increased risk of non-communicable diseases after low birthweight. In the post-2015 era, improvements in child survival, development, and human capital depend on ensuring a healthy start for every newborn baby--the citizens and workforce of the future. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Neonatal Encephalopathy Following Fetal Distress

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

              Summary Background Neonatal 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. Methods We 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. Findings Of 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. Interpretation Intrauterine 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. Funding The Bill & Melinda Gates Foundation, Saving Newborn Lives, and the Wellcome Trust.
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                Author and article information

                Contributors
                Journal
                EClinicalMedicine
                EClinicalMedicine
                Eclinicalmedicine
                The Lancet
                2589-5370
                1 December 2018
                December 2018
                : 6
                : 26-35
                Affiliations
                [a ]Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, UK
                [b ]Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
                [c ]Institute for Women's Health, University College London, London, UK
                [d ]MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK
                [e ]Kyaninga Child Development Centre, Fort Portal, Uganda
                [f ]Mulago National Referral and Teaching Hospital, Kampala, Uganda
                [g ]Department of Paediatrics and Child Health, Mbale Regional Referral Hospital, and Mbale Clinical Research Institute, Mbale, Uganda
                [h ]University Children Hospital of Zurich and Children's Research Center, Zurich, Switzerland
                [i ]Homerton University Hospital, London, UK
                [j ]Uganda Maternal and Newborn Hub, Knowledge for Change, UK
                [k ]National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
                [l ]Clinical Research Department, Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK
                [m ]Department of Paediatrics, Imperial College London, London, UK
                [n ]Uganda Women's Health Initiative, Kampala, Uganda
                Author notes
                [* ]Corresponding author at: MARCH Centre, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. cally.tann@ 123456lshtm.ac.uk
                Article
                S2589-5370(18)30051-8
                10.1016/j.eclinm.2018.12.001
                6358042
                30740596
                ee46c41e-d939-4f17-85f7-911775848019
                © 2018 Published by Elsevier Ltd.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 May 2018
                : 12 November 2018
                : 3 December 2018
                Categories
                Article

                neonatal encephalopathy,outcomes,neurodevelopment,impairment,cohort,study,uganda

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