Intended for healthcare professionals


Neonatal encephalopathies

BMJ 1998; 317 doi: (Published 05 December 1998) Cite this as: BMJ 1998;317:1537

Time to reconsider the cause of encephalopathies

  1. A D Edwards, Professor of neonatal medicine,
  2. K B Nelson, Acting chief
  1. Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN
  2. Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-9130, USA

    Papers pp 1549,1544

    Neonatal encephalopathy is a significant problem. The United States collaborative perinatal project studied 39 000 infants born with birth weights greater than 2500 g and found that 70% of the infants who showed early neonatal depression and encephalopathy died or were disabled.1 For many years it was accepted that fetal asphyxia during labour was the major cause of both neonatal encephalopathy and cerebral palsy. However, the evidence for this is surprisingly thin. Diagnosis of cerebral hypoxia-ischaemia during labour is difficult and is usually inferred from non-specific signs, such as low Apgar scores or seizures observed after delivery. More precise assessment using specialist technologies like magnetic resonance is possible but not widely available,2 and a working diagnosis of hypoxic-ischaemic encephalopathy may sometimes be applied with less than irrefutable proof of its presence. Nevertheless, several large studies have been unable to show significant perinatal asphyxia in most children who develop cerebral palsy1; indeed, a growing number of other significant non-asphyxial risk factors are being recognised.

    There is thus a very real debate about how important birth asphyxia really is as a cause of either neonatal encephalopathy or cerebral palsy. The question is not whether birth asphyxia happens (of course it does) or whether it can cause brain damage (of course it can). The issues are: firstly, what proportion of neurological impairment in children is due to perinatal hypoxia-ischaemia and how much to entirely different causes; secondly, how many infants with asphyxia also have significant predisposing factors; and thirdly, what are the non-asphyxial factors which contribute to or determine unfavourable outcome.

    These are matters of tremendous practical importance. The law courts are often called on to decide whether a child's neurological impairment is due to mismanagement of labour leading to asphyxia. There is also a growing interest in “neural rescue therapies” which can be applied after birth asphyxia to ameliorate neurological injury. These therapies have generally been developed in models of hypoxic-ischaemic brain injury,3 but if hypoxia or ischaemia are only components of the pathology treatment may be less effective than the experimental work predicts.

    Researchers are reassessing the factors associated with neonatal encephalopathy and cerebral palsy, with increasing emphasis on events before the perinatal period. The two papers by Badawi et al in this issue of the BMJ report a population based case-control study which examined a large number of antepartum and intrapartum variables associated with encephalopathy in newborn infants (pp 1549, 1554). 4 5 The work is designed to test whether events before parturition may predispose to neurological abnormality in the newborn period, and the authors have chosen a particularly wide and inclusive definition of encephalopathy with the intention of investigating rather than assuming the aetiology of the illness.

    The associations they describe are interesting and often consistent with previous studies. They find a strong link between maternal thyroid disease and neonatal encephalopathy. This has been suggested before6 and may not be particularly surprising, although there is considerable interest in defining a mechanism for the effect, which may potenitally involve autoimmune, hormonal, or drug effects. They also confirm a strong link between febrile illness in the mother and neurological problems in her infant.7 This point is important, as experimental studies are now showing that inflammation has an important place in the mechanism of brain injury after hypoxia-ischaemia.8 Indeed, inflammation may be a cause or result of ischaemia, and markers of inflammation with or without evident ischaemia are strongly associated with neonatal and later neurological morbidity.9 The finding that relatively few of the infants with encepalopathy had clear evidence of birth asphyxia is interesting, but the conclusion is weakened by the non-specific clinical data used to infer presence or absence of intrapartum asphyxia, a common problem of research in this field.

    Some caution is needed in interpreting these results. The diagnosis of encephalopathy is wider than in many other studies and its long term prognosis uncertain. Until neurodevelopmental follow up data are reported is not possible to know how many encephalopathic infants develop cerebral palsy. For comparison, in a consecutive series of 56 infants at the Hammersmith Hospital diagnosed as encephalopathic on criteria similar to those used by Badawi et al, almost half were clincally normal at 18-24 months.

    These epidemiological studies provide useful controlled data on the associations of neonatal encephalopathy. The epidemiological approach in general has been successful at identifying risk factors or correlates of disease which open up new conceptual horizons. It has suggested avenues to follow—for example, into inflammation, autoimmune disease, and clotting abnormalities. A priority for clinical researchers wanting to pursue these must be to develop and use precise definitions of the brain syndromes under discussion. If it is no longer acceptable to label every neonatal encephalopathy as hypoxic-ischaemic, it must be time to define the pathophysiologies more precisely. Further use of modern technologies like magnetic resonance imaging or spectroscopy should help with this task.


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