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Semin Neonatol. 2004 Aug;9(4):331-45.

The value of autopsy in determining the cause of failure to respond to resuscitation at birth.

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Department of Neuropathology, Radcliffe Infirmary, Oxford OX2 6HE, UK.


Autopsy is invaluable in identifying the causes of severe depression and very low Apgar score after birth and in assessing contributory conditions. Brain scans are increasingly used in the care of neonates who fail to respond to resuscitation at birth but their interpretation depends on the information gained from sound neuropathological studies. Asphyxia, both acute intrapartum asphyxia and chronic asphyxia, is an important cause of low Apgar scores. The gestational age and the nature of the asphyxial insult both have a profound influence on the ultimate pattern of injury. Asphyxia in the preterm brain tends to damage preferentially the white matter but some white matter damage is also seen in many infants who have an hypoxia-ischaemic insult at term though the predominant site of injury is to the central grey matter. The nature of the cellular damage and reactive change seen at autopsy is described. There is an association between low Apgar scores and intrauterine exposure to infection and maternal pyrexia. Detailed autopsy examination should include the search for infection. The placenta, cord and membranes should be examined in view of the mounting evidence of the association between intrauterine infection of the placenta and fetal membranes and prenatal brain damage. Additionally, the presence of placental thrombosis and infarction should be sought in relation to focal and global injury in the full term infant. Acquired prepartum lesions rarely cause the infant to present with a low Apgar score. The exception to this is severe damage to the brainstem and basal ganglia. Traumatic injury to the brain is now much less common than in previous decades. Subdural haemorrhage occurs more frequently than intraventricular or subarachnoid haemorrhage. Instrumental and assisted deliveries are associated with an increased incidence of subdural haemorrhage though these rarely cause significant long term damage. Careful autopsy, particularly of the neck and paravertebral tissues, spinal cord, brainstem and nerve roots is important where trauma is suspected. Tearing of nerve roots or fibre bundles in the spinal cord is readily demonstrated under the microscope using immunocytochemistry to beta-amyloid precursor protein. Disorders of the spinal cord, peripheral nerve and muscle as well as some metabolic diseases may cause a baby to be both floppy and weak. Metabolic disease, including peroxisomal disorders, non-ketotic hyperglycinaemia, lipid and glycogen storage disorders and mitochondrial diseases may cause profound hypotonia and respiratory failure at birth or shortly afterwards.

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