ArticlesLong-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review
Introduction
Nearly 140 million children per year are born worldwide, with 3·6 million neonatal deaths and 2·6 million stillbirths.1, 2, 3 More than 90% of neonatal deaths occur in resource-poor countries, mostly in rural areas.4 Worldwide, an increasing proportion (currently more than 40%) of mortality in children younger than 5 years occurs in the neonatal period (aged 0–28 days), which has led to increased attention to neonatal mortality. The common causes of neonatal mortality include preterm birth complications, intrapartum-related factors such as hypoxic ischaemic encephalopathy, infections (notably sepsis, meningitis, and neonatal tetanus), and other conditions such as jaundice and congenital infections (cytomegalovirus, toxoplasma, syphilis, and rubella).4, 5, 6 However, the prevalences of these insults and the long-term consequences for neonates who survive, particularly in resource-poor regions, are unclear.4
Many neonates survive major insults without any evidence of impairment because of the plasticity of the developing brain and improvements in medical care. However, in some newborn babies, insults can cause varying degrees of long-term neurodevelopmental impairment.5, 6, 7, 8 These impairments cause a major socioeconomic burden, especially in resource-poor countries. Intrauterine and neonatal insults substantially affect the global burden of disease, measured in disability-adjusted life-years, because they contribute to both premature mortality and long-term disability.9 However, little is known about the severity and distribution of long-term impairments after intrauterine or neonatal insults. As a result, sequelae from intrauterine and neonatal insults have not been adequately captured in estimates of the global burden of disease.10
We reviewed published data for the long-term consequences of intrauterine and neonatal insults. The questions addressed were: what are the long-term outcomes after intrauterine and neonatal insults (neonatal sepsis, neonatal meningitis, hypoxic ischaemic neonatal encephalopathy, neonatal jaundice, preterm birth, neonatal tetanus, congenital infections [cytomegalovirus, toxoplasma, syphilis, rubella], and HIV)? What is the risk and severity of at least one sequela and of multiple sequelae reported after these insults? And what is the risk and severity of sequelae after multiple insults for one infant?
Section snippets
Search strategy and selection criteria
We included studies that reported neurological outcomes after an identifiable and well defined neonatal insult (webappendix). 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. For unpublished studies and grey literature, we searched Dissertation Abstracts International and WHO library. The initial search strategy used the words “neonate” and “outcome”, and each of the
Results
Our search identified 28 212 publications. From the titles we selected 1330 (5%) for review of the abstract and finally selected 949 studies for detailed review (figure 1). We excluded 796 (84%) after assessment of full text because they did not meet the inclusion criteria. The main reasons for exclusion were that numbers of survivors with sequelae could not be extracted; no clear description or diagnosis of the neonatal insult was provided; less than 80% of survivors were followed up after
Discussion
In our study, the median overall risk of sequelae in survivors of intrauterine and neonatal insults was very high. Our Article provides supportive evidence that intrauterine and neonatal insults result in significant long-term neurological morbidity and that these insults have a high risk of affecting more than one domain (eg, cognitive impairment, motor impairment and hearing and vision loss). Despite the fact that we initially identified many studies, few had data that were suitable for
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