Does aetiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy influence the outcome of treatment?

Abstract

HIE Hypoxic-ischaemic encephalopathyNeonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates.Neonatal encephalopathy is a clinical syndrome of disordered neurological function occurring in the first days of life in term-born and late preterm neonates and is characterized by difficulty initiating and maintaining respiration, an abnormal level of consciousness, depression of tone and reflex responses, and often seizures. This symptom complex affects about 3 in every 1000 births, and is an important predictor of perinatal death and a major contributor to long-term adverse neurological outcomes, particularly cerebral palsy (CP). 1,2 Evidence from clinical and experimental studies agrees that some instances of neonatal encephalopathy are related to hypoxic-ischaemic injury, but the proportions of neonatal encephalopathy attributed to recent asphyxial events vary with the definitions used and the methodology of the investigations. Studies of infants in representative populations indicate that asphyxial complications at birth account for only a minority of neonatal encephalopathy. These population-based studies also identify other factors that contribute to increased risk of neonatal encephalopathy, such as intrauterine exposure to inflammation or fetal growth restriction, and note that some non-asphyxial factors can produce a clinical picture that closely mimics hypoxia-ischaemia. [3][4][5] In contrast, studies of neonatal cooling have approached this topic from the ...

Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders

“…Oesophageal atresia is the most frequent congenital anomaly of the oesophagus. Oesophageal atresia per se can lead to hypoxic ischemic encephalopathy early after birth (Volpe 2012, McIntyre et al 2015.…”

Report of a workshop on research gaps in the treatment of cerebral palsy

“…For example, the differential response to therapeutic cooling in the neonate may well be related to differences in the etiology of an initial encephalopathic event. 4 It is therefore difficult for the family and the treating physician to determine which treatment fits best to an individual child, given each child's unique developmental goals and trajectories. There is a critical need for greater precision in diagnosis and treatment at the level of the individual with CP in order to develop best-practice approaches for providing comprehensive, optimal care from infancy through adulthood.…”

Asphyxia in the Newborn: Evaluating the Accuracy of ICD Coding, Clinical Diagnosis and Reimbursement: Observational Study at a Swiss Tertiary Care Center on Routinely Collected Health Data from 2012-2015

“…According to the Committee on Fetus and Newborn, the AAP, and the Committee on Obstetrics Practice, ACOG [39]: “An infant who has had “asphyxia” proximate to delivery that is severe enough to result in acute neurologic injury should have demonstrated all of the following criteria: (a) profound metabolic or mixed acidemia (pH < 7.00) on an umbilical arterial blood sample, if obtained, (b) an Apgar score of 0 to 3 for longer than 5 minutes, (c) neurologic manifestation, e.g, seizure, coma, or hypotonia, and (d) evidence of multiorgan dysfunction”. The 1- minute Apgar score appears to be less useful in the sense of predictability, prognosis and diagnostic accuracy than the 5- minute or 10- minute score [36, 39–49]. …”