Seminars in neonatology : SN最新文献

Neonatal deaths in infants born at term are relatively rare in the USA, occurring in 0.9/1000 live births. Congenital malformations, perinatal asphyxia, infections and inborn errors of metabolism are the leading causes. Chromosomal malformation syndromes, congenital heart disease, pulmonary hypoplasia and severe neural tube defects comprise the majority of lethal malformations. Several skeletal dysplasias are lethal in the newborn infant. Group B Streptococcus still plays a major role in neonatal mortality while deaths due to other infectious agents have decreased. Hypoxic ischaemic encephalopathy is a significant cause of neonatal death. Inborn errors of metabolism have variable presentations but some, such as the fatty acid oxidation disorders, may present in neonates and cause sudden death.

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 β-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.

Iatrogenic damage from a therapeutic procedure in the neonatal period can have serious consequences. Although most side effects are minor, some may result in a major handicap or death of the infant. The development of new therapeutic strategies may result in not previously observed combinations of pathology. This review focuses on iatrogenic damage occurring in several organs and after several different therapeutic interventions. Special attention is given to pulmonary and gastrointestinal damage and iatrogenic damage as a result of systemic treatments. Valuable information and early detection of serious side effects is only possible when the pathologist is very well informed about the therapeutic interventions used, all medical devices are left in situ and a thorough autopsy is performed as completely as is permitted. However, the decline in autopsy rates could make it more difficult to determine the incidence of iatrogenic lesions.

The juxtaposition of the maternal and fetal circulations allows optimal physiological exchange between mother and fetus. Extravillous trophoblast infiltrating into the placental bed transforms the small calibre spiral arteries into large calibre uteroplacental arteries. The absence of these physiological changes, coupled with other lesions such as acute atherosis, results in a reduced uteroplacental blood flow, as seen in pre-eclampsia, intrauterine growth restriction and preterm delivery. A failure to elaborate the placental vascular tree can result in impaired flow through the fetal placental circulation. Placental vascular malformations, such as placental mesenchymal dysplasia and the commoner chorangioma, can lead to neonatal complications. Fetal thrombotic vasculopathy, commonly associated with thrombophilia, may be a cause of neurological deficit in childhood.

Non-iatrogenic anatomical findings at autopsy provide insight into preterm infant physiology. The different patterns of lipid accumulation in the adrenal may correspond to long-term differences in stress response. Cardiac papillary muscle infarction occurs with asphyxia or shock and can explain myocardial dysfunction. Underdevelopment of preterm kidneys may correlate with susceptibility to renal disease and hypertension in adult life. Immaturity of the lung or immature responses to inflammation, rather than high oxygen concentrations or high ventilation pressures, may underlie chronic lung disease in premature infants. Hepatic extramedullary haematopoiesis is normal but, if excessive or abnormally persistent, can be an indicator of fetal disease. Hypertrophic somatostatin islet cells found with intra-uterine growth retardation may correlate with low serum insulin. Thymic involution may mark the degree of stress. Small thyroglobulin stores may limit the premature neonate's initiation of thermogenesis.

An autopsy carried out by a trained perinatal pathologist can provide parents and professionals with new information about the cause of a baby's death. It is extremely stressful for parents to be asked for autopsy authorisation. The request is also very demanding for the staff. The rates of neonatal autopsy have been declining since 1990 and, almost certainly, the adverse publicity surrounding the Alder Hey enquiry precipitated a further fall in authorisation rates. Only a re-establishment of trust between parents and professionals can reverse this trend. This trust is founded on excellent perinatal communication and clinical care. The child's death must be managed in the most empathetic way, with an understanding of bereavement and the grief support required. If the parents and professionals work together as a team, the parents should sense the commitment of staff to their family. They may then be more likely to understand the importance of autopsy and to provide authorisation.

Magnetic resonance imaging (MRI) represents a non-invasive alternative to full autopsy in neonatal death if parents refuse classical full autopsy. MRI offers high resolution images of the entire neonate without disrupting the integrity of the child. Neonatal malformations or pathologies that are responsible for the death of the neonate can be identified. A major disadvantage of MR-autopsy is the lack of tissue sampling. Chromosomal, histological or microbiological analyses are consequently missing. MR-autopsy has proven to be especially helpful in the evaluation of the central nervous system but is limited in complex cardiac malformations. The limitations and possibilities of MR-autopsy are discussed.

Placental inflammatory disorders represent a diverse and important category of pathological processes leading to fetal and neonatal morbidity and mortality. These processes can be divided into two broad subcategories, those caused by micro-organisms and those caused by host immune responses to non-replicating antigens. The mechanisms by which these inflammatory processes cause death and disability are diverse and can be separated into four distinct classes: placental damage with loss of function, induction of premature labour and subsequent preterm birth, release of inflammatory mediators leading to fetal organ damage and transplacental infection of the fetus. Each specific inflammatory process can be modulated by properties of the specific organism, the route and timing of infection and variations in the host's genetic background and immune responsiveness. All of these factors combine to produce specific patterns of placental pathology that can be used to guide treatment, predict complications and explain adverse outcome.

Common causes of neonatal respiratory distress include meconium aspiration, pneumonia, persistent pulmonary hypertension of the newborn, pneumothorax and cystic adenomatoid malformation. Genomics and proteomics have enabled the recent recognition of several additional disorders that lead to neonatal death from respiratory disease. These are broadly classified as disorders of lung homeostasis and have pathological features of proteinosis, interstitial pneumonitis or lipidosis. These pathological changes result from inherited disorders of surfactant proteins or granulocyte-macrophage colony stimulating factor.

Abnormal lung vascular development is the basis for another cause of fatal neonatal respiratory distress, alveolar capillary dysplasia with or without associated misalignment of veins. Diagnosis of these genetically transmitted disorders is important because of the serious implications for future siblings. There is also a critical need for establishing an archival tissue bank to permit future molecular biological studies.