Best Practice Guideline article
Epidemiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy

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Abstract

Neonatal encephalopathy (NE) is the clinical manifestation of disordered neonatal brain function. Lack of universal agreed definitions of NE and the sub-group with hypoxic-ischaemia (HIE) makes the estimation of incidence and the identification of risk factors problematic. NE incidence is estimated as 3.0 per 1000 live births (95%CI 2.7 to 3.3) and for HIE is 1.5 (95%CI 1.3 to 1.7). The risk factors for NE vary between developed and developing countries with growth restriction the strongest in the former and twin pregnancy in the latter. Potentially modifiable risk factors include maternal thyroid disease, receipt of antenatal care, infection and aspects of the management of labour and delivery, although indications for some interventions were not reported and may represent a response to fetal compromise rather than the cause. It is estimated that 30% of cases of NE in developed populations and 60% in developing populations have some evidence of intrapartum hypoxic-ischaemia.

Introduction

Neonatal encephalopathy (NE) is the clinical manifestation of disordered neonatal brain function. It is a relatively common clinical condition which results in serious consequences for many of the infants including death, cerebral palsy, epilepsy and other significant cognitive, developmental and behavioural problems. The financial and human costs to infants affected, their parents, professionals and wider society are enormous. Some, but by no means all, of these costs are reflected in awards following medical litigation. In the UK about half of the cases dealt with by the National Health Service Litigation Authority (NHSLA) concern birth related adverse events; cases of NE and cerebral palsy feature heavily. In 2008 the outstanding liability of the NHSLA stood at £11.9 billion [1]. An expert group led by the Chief Medical Officer for England reported in 2000 estimating that preventing 10% of birth related adverse events would save about £20 million per year [2].

Important initial considerations in trying to describe the epidemiology of NE and hypoxic ischaemic encephalopathy (HIE) are the lack of a universally agreed definition of both these terms [3] and the need for a clear consensus in understanding of the relationship between the two that is reflected in common medical parlance. In this article we aim to provide an epidemiological background to the related papers in this edition and start by considering issues surrounding the definition of NE and HIE, how these affect incidence estimates and the identification of risk factors. Finally we consider current research needs to further our understanding of the aetiology of NE and HIE.

Section snippets

Definitions

Nelson and Leviton described NE as a “clinically defined syndrome of disturbed neurologic function in the earliest days of life in the term infant, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, subnormal level of consciousness, and often by seizures” [4].

Volpe defines hypoxaemia as the “diminished amount of oxygen in the blood supply” and cerebral ischaemia as the “diminished amount of blood perfusing the brain” with the latter being the

Incidence

The reported incidence of NE from different studies ranges from about 2.0 to 6.0 per 1000 live births (Table 1) [8], [9], [10], [11]. The incidence of HIE ranges from about 1.0 to 8.0, excluding the estimate from Nigeria [16] based on a single hospital series which was 26.2 per 1000 live births (Table 2) [12], [13], [14], [15], [16], [17], [18], [19], [20]. There are, however, several difficulties in interpreting these figures. With the exception of the data from Derby, UK where three

Risk factors

As with any condition, identifying the risk factors for NE and HIE is key to understanding the causal pathways and developing preventive strategies [24]. Progress has been hindered by the absence of a universally accepted case definition and a paucity of appropriately designed unbiased studies. Although clinically NE is a relatively common condition, in population terms it is relatively rare. As a consequence the case–control study design is the only realistic approach to aetiological

Future directions

The causal chain of events resulting in NE is complex, multifactorial and far from completely understood. Several promising lines of enquiry and hypotheses relating to potentially modifiable risk factors were generated by previous epidemiological studies although these studies are now well over a decade old and there have been substantial changes in clinical practice and clinical governance since their publication. Even the most recent population-based studies were carried out before improved

Acknowledgements

This paper reports on independent work which is part-funded by the Policy Research Programme in the Department of Health, England. The views expressed are not necessarily those of the Department.

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