Chapter Contents
Introduction 1227
Role of the perinatal autopsy 1227
Contribution of autopsy findings 1228
Determination of cause of death 1228
Future pregnancies and siblings 1228
Research and clinical practice development 1228
Audit, quality control and teaching 1228
Medicolegal issues/malpractice litigation 1228
Factors influencing the value of the perinatal autopsy 1228
Changes in perinatal autopsy rates 1228
Attitudes to the perinatal postmortem examination 1228
Consented versus coronial autopsies 1230
Consent 1230
The postmortem examination 1230
External and macroscopic examination 1230
Microscopic examination 1231
Ancillary investigations 1231
Retention of organs 1231
Disposal of retained tissue samples, including blocks and slides 1232
The limited/partial postmortem examination 1232
Limitations of the postmortem examination 1232
The postmortem report 1232
The minimally invasive autopsy 1232
Placental examination 1233
Specific neonatal autopsy scenarios and common associated autopsy findings 1234
Conclusion 1237
Introduction
Current guidelines in the UK ( ; ) recommend that an autopsy is offered to all parents who have experienced a perinatal death, ideally performed by specialist paediatric/perinatal pathologists. Following recent inquiries regarding organ retention, there has been a consistent decline in the number of consented perinatal autopsies performed in the UK ( ). Nevertheless, the perinatal autopsy remains an important component of perinatal and neonatal medicine, providing information for counselling, clinical governance, teaching and education, and recognition of iatrogenic complications.
This chapter will address the role of the perinatal autopsy, issues surrounding consent, the differences between consented (hospital) and coronial autopsies, the postmortem procedure itself, and recent developments such as postmortem magnetic resonance imaging (MRI) and the minimally invasive/endoscopic autopsy.
Role of the perinatal autopsy
Recent data from a systematic review of adult autopsies demonstrated that there remains substantial discrepancy between clinical diagnoses and autopsy findings. ‘Major errors’, defined as a previously unrecognised diagnosis, occur in almost one-quarter of cases, around 10% being ‘class I errors’, which may have directly affected patient management ( ). In a contemporary US institution, the estimated major error rate was 8–25%, with a class I error rate of around 4–7%. Despite rigorous investigations in life as part of current perinatal/neonatal care, similar data are available for perinatal autopsies ( Table 41.1 ). In a review of 27 studies, autopsy resulted in a ‘change in diagnosis’ or ‘additional findings’ which might have influenced management or counselling in 22–76% ( ); rates varied from 28% to 75% for stillbirths, from 22% to 49% for terminations of pregnancy and from 22% to 81% for neonatal deaths.
| STUDY | SAMPLE SIZE | SAMPLE GROUP | CONTRIBUTION OF AUTOPSY |
|---|---|---|---|
| 112 | TOPs (second trimester) | 40% additional findings ‘of clinical importance’ 11% partial discrepancy, and 4% complete discrepancy, between antenatal ultrasound and postmortem findings | |
| 328 | TOPs | 47% ‘further diagnostic findings’ In 10% this allowed syndromic diagnosis 9% discrepancy with antenatal ultrasound findings | |
| 29 | Neonatal deaths <28 weeks’ gestation | 79% new findings 28% change of diagnosis 41% iatrogenic lesions | |
| 16 | Neonatal deaths (≥37 weeks’ gestation) with HIE | 63% significant new information | |
| 132 | TOPs for structural malformations with no abnormal karyotype | 72% confirmed suspected antenatal ultrasound findings 27% changed recurrence risk (in 8% recurrence risk was increased to one in four) | |
| 61 | Perinatal and paediatric deaths | 20% major new finding 28% additional minor findings 34% information regarding treatment effects | |
| 213 | Perinatal deaths | 18% additional relevant findings 11% changed recurrence risk | |
| 47 | TOPs | 28% significant additional findings 23% minor additional findings 2% complete discrepancy with antenatal ultrasound findings | |
| 352 | TOPs | 51% autopsy findings considered ‘decisive for genetic counselling’ 9% additional major malformations | |
| 75 | Neonatal deaths | 40% additional findings 28% additional findings that may have contributed to death | |
| 209 | Neonatal deaths | 26% new information 3% new information ‘crucial for future counselling’ | |
| 197 | Neonatal deaths | 12% class I errors, likely to have affected patient outcome 27% additional major findings (class II errors, unlikely to have altered patient management) |
Contribution of autopsy findings
Determination of cause of death
In many cases a postmortem examination will establish the cause of death. However, it is noteworthy that the majority of clinically unexpected stillbirths remain unexplained even after postmortem examination, highlighting the need for further research in this area ( ). Similarly, up to half of all sudden unexpected early neonatal deaths will remain unexplained following detailed postmortem examination, a situation analogous to sudden infant death syndrome in older infants ( ). Whilst the currently available evidence suggests that additional information will be revealed in a significant proportion of perinatal and neonatal autopsies (see Table 41.1 ), it is important to recognise that even negative findings may prove reassuring to parents and clinicians.
Future pregnancies and siblings
As outlined in Table 41.1 , in around 20% of cases, additional information will become available following autopsy which may directly affect siblings or the recurrence risk and counselling of future pregnancies. Placental examination may reveal potentially recurrent disorders, including massive perivillous fibrin deposition and chronic histiocytic intervillositis, both of which are associated with an adverse pregnancy outcome and carry a high risk of recurrence ( ).
Research and clinical practice development
Postmortem studies have led to a better understanding of a variety of neonatal diseases, including pulmonary hypoplasia, bronchopulmonary dysplasia and patterns of hypoxic–ischaemic brain injury. Moreover, autopsy-based research contributes to the assessment of new diagnostic procedures and the effects of new treatment modalities and therapeutic interventions, including complications and side-effects ( ), as well as providing important epidemiological information regarding the pathological spectrum of rare or emerging new infectious diseases, such as viral epidemics ( ; ).
Audit, quality control and teaching
Autopsy plays an important role in audit: comparisons between postmortem findings and imaging during life, including antenatal ultrasonography, are imperative in order to improve diagnostic accuracy ( ; ; ), and regular discussion and feedback at multidisciplinary meetings will improve patient care and service provision. Furthermore, the postmortem examination remains an invaluable resource for teaching medical staff, including surgeons, pathologists and undergraduates ( ).
Medicolegal issues/malpractice litigation
Increasingly, the perinatal pathologist is requested to perform a coronial autopsy if there is risk of litigation relating to an intrapartum or neonatal death. In such instances, questions usually relate to the timing of events, such as hypoxic–ischaemic brain injury or iatrogenic injury, such as that related to placement of long lines or other therapeutic interventions. If litigation is thought likely, the case should be referred to HM Coroner (see below).
Factors influencing the value of the perinatal autopsy
Sophisticated antemortem imaging and clinical expertise may decrease the likelihood of identifying additional findings at postmortem, although tertiary care centres are likely to be referred more complex cases, which tend to yield more additional information ( ). Similarly, the results of the postmortem examination are affected by the expertise of the pathologist, with autopsies performed by specialist perinatal/paediatric pathologists being more likely to reveal significantly useful information ( ).
Unsurprisingly, technical factors (such as the extent of maceration) may limit the pathologist’s ability to identify subtle abnormalities. In one study, almost 8% of antenatally detected brain abnormalities could not be confirmed at autopsy owing to maceration and/or postmortem autolysis ( ). Significant findings may also remain undetected if the autopsy is limited to a specific body region, or ancillary investigations are not performed; for example, microbiological investigations or tandem mass spectrometric analysis of postmortem blood and bile in sudden unexpected early neonatal deaths ( ).
Changes in perinatal autopsy rates
Despite the potential benefits of the autopsy outlined above, postmortem rates have decreased over recent years. According to data released by the , perinatal autopsy rates fell from 48% in 2000 to 39% in 2003. Current data reveal a plateau in the proportion of neonatal deaths referred for consented postmortem examination: 28% in 2000, 22% in 2003 and 21% in 2007 ( ). However, the proportion of neonatal autopsies not offered by clinicians, and that declined by parents, has changed dramatically: from 29% in 2002 to 18% in 2007 (option of autopsy not offered to parents), and from 40% in 2002 to 52% in 2007 (autopsy declined by parents). Whilst it is reassuring that the proportion of postmortem examinations not offered to parents has fallen, it remains unclear why the proportion of parents declining an autopsy has increased to over 50%; possible reasons are discussed below.
Attitudes to the perinatal postmortem examination
Bereaved parents
Parents’ opinions are undoubtedly influenced by the organ retention issues that surrounded Bristol and Alder Hey hospitals: parents are concerned about the unauthorised and/or undisclosed retention and use of tissues and organs ( ; ). In addition, identified two main reasons for parents declining the autopsy: first, the ‘dread of the child being mutilated’, often coupled with the notion that, in deaths where the child was in the intensive care unit, the infant had been ‘through enough’ already; and second, the feeling by parents that there were ‘no unanswered questions’, an attitude that may be more likely to reflect the opinion of the consenting clinician (see later).
Parents’ decision not to consent to a postmortem examination may also be influenced by cultural and religious considerations, although most major religions do not explicitly prohibit the autopsy ( ). Recent data from the UK show that the proportion of parents declining an autopsy following a neonatal death is similar among most ethnic groups – 52% of white parents, 55% of Asian parents and 56% of Chinese and black parents ( ). It is also noteworthy that 30% of women who refused an autopsy subsequently regretted this choice ( ).
Clinicians’ attitudes
There is little doubt that neonatologists may find discussing the option of a postmortem examination with bereaved parents difficult, ‘distasteful and distressing’ ( ). Clinicians’ attitudes may be further exacerbated by the lengthy consent forms now required in the UK, which are very detailed, time-consuming and possibly confusing. It has been reported that younger clinicians regard the autopsy as less useful compared with their senior colleagues ( ). Clinicians’ perceptions are probably also influenced by pathologists’ attitudes, with delays in issuing a final postmortem report, lack of clinicopathological correlation and paucity of appropriate multidisciplinary team meetings undoubtedly contributing to the notion that the autopsy is of limited value in the immediate and subsequent management of the patient and/or parents ( ).
Consented versus coronial autopsies
The majority of neonatal postmortem examinations will require consent by one or both parents since the likely cause of death will be known. Occasionally, intrapartum and neonatal deaths may be referred to HM Coroner, who may decide to instruct a perinatal/paediatric pathologist to perform a (coroner’s) autopsy on his/her behalf; in these circumstances, parental consent is not required and the coroner’s decision overrides that of the parents. Neonatal deaths that should be referred to the coroner include cases in which ( ):
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cause of death is unknown, or sudden and unexpected
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death occurred during an operation or before recovery from the effects of an anaesthetic
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deceased infant was not seen by the certifying medical practitioner, either after death or within 14 days of death
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death may have been caused by violence or neglect
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death may have been due to an accident
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death may have been in any other way unnatural or there are suspicious circumstances.
Once the coroner has completed the investigation, samples taken as part of the autopsy fall under the Human Tissue Act (see below) and should be handled according to parents’ wishes. If there is a potential issue of litigation owing to neglect by hospital staff, the case should always be discussed with HM Coroner.
Consent
The came into force on 1 September 2006; its implementation was overseen by the Human Tissue Authority (HTA). In addition, the HTA oversees the licensing of organisations and establishments that deal with human tissue ( http://www.hta.gov.uk ). The Act requires consent for the removal, storage and use of human tissue for any ‘scheduled purpose’, including determination of the cause of death and tissue for research, clinical audit, education and quality assurance. This applies to all tissue removed at postmortem, including small samples such as blocks and slides (see below), and samples that might be kept as part of the infant’s medical record. The Act applies to all stillbirths and neonatal deaths.
The Act ( ) defines the giving of consent as a positive action; the absence of refusal is not evidence of adequate consent. In order for consent to be valid, it must be given voluntarily by an appropriately informed person with the capacity to agree. The Act defines who may give consent, which for perinatal postmortem examinations will usually be parents. For stillbirths and neonatal deaths, it is recommended that, if possible, consent is obtained from the mother, and that, where appropriate, both parents are involved. It is usually the treating clinician’s responsibility to seek consent; the clinician should be sufficiently senior and with knowledge of the postmortem procedure. It is recommended that he or she be trained in the management of bereavement and should have witnessed a postmortem examination.
As valid consent can only be given if appropriate communication has taken place, information leaflets and consent forms should be available in the main local community languages for patients whose first language is not English, and interpreters should be used. Written consent is not required by law, although it is usually required by the local hospital policy.
The postmortem examination
External and macroscopic examination
Once the clinical details have been reviewed by the pathologist, and, ideally, the case discussed with the requesting clinician, the consent status verified and the body correctly identified, a careful external examination is performed. The infant is weighed and basic measurements taken, which are compared with standard reference tables. Assessment of fetal biometry allows identification of intrauterine growth restriction/small-for-gestational-age infants and macrosomic/large-for-gestational-age infants.
The degree of postmortem change is assessed, which includes documenting the extent of skin discoloration, blistering and skin slippage, allowing the pathologist to make an approximate estimate of the duration of time since death, although it must be emphasised that such estimates are not precise and may be affected by various factors, including duration of the interval between delivery and postmortem examination, the size of the fetus, storage of the body and the presence of (ascending amniotic fluid) infection or maternal pyrexia ( ; ).
Particular emphasis is placed on identifying possible dysmorphic features, although the external appearances should be interpreted in the context of the gestational age and subtle syndromic abnormalities may not be readily discernible in mid-trimester fetuses.
The fetus or infant is assessed for other general features such as pallor, oedema and traumatic or iatrogenic lesions. Routine photographs are usually taken and stored as part of the infant’s medical record, with more detailed photographs to document specific abnormalities; these may prove invaluable, not only for multidisciplinary team meetings and as teaching aids but also for review by clinical geneticists to enable direct assessment of possible dysmorphic features.
External examination is followed by a detailed macroscopic investigation of the body. Access to the thoracic and abdominal viscera is traditionally gained via a midline incision through the anterior thorax and abdomen. Careful inspection and dissection of the internal organs are performed, and the organs are then removed, weighed and further dissected. If the brain is to be examined, the scalp is incised posteriorly, and the skull opened by following the non-fused cranial suture lines, although in older infants cranial bones may have to be cut. The brain can either be examined immediately (‘fresh’) or following a period of formalin fixation, which may require several weeks for complex brain anomalies.
Abnormalities are described and documented, after which small samples are routinely taken for histological examination. The organs are then returned to the body, which is reconstructed prior to release. All organs are routinely weighed, and the weights compared with reference tables against the gestational age; more helpful are weight ratios, such as the brain : liver weight ratio and combined lung : body weight ratio ( ; ).
Microscopic examination
The standard postmortem examination involves taking small tissue samples of organs for microscopic examination to confirm or exclude the presence of disease. It is well recognised that many conditions will only be apparent on histological examination, and that in a significant proportion of cases an organ may be normal on macroscopic examination despite significant pathology on histological examination, for example the heart in myocarditis ( ).
The tissue samples taken for microscopic examination are processed into small paraffin wax blocks and glass microscope slides ( Fig. 41.1 ). The average size of these tissue samples is that of a standard postage stamp and measures around 3–5 mm in thickness; in small fetuses, the samples are considerably smaller. The tissue section on the glass slide, which measures around 3–5 µm in thickness, is stained with haematoxylin and eosin ( Fig. 41.2 ), as well as a range of histochemical and immunohistochemical stains in selected cases to allow for detailed characterisation of the underlying disease process; other options include in situ hybridisation techniques and occasionally electron microscopy.
