The role of the perinatal autopsy in the new millennium.

The perinatal death rate in Australia ranges between 8.4 and 10.6 deaths per 1000 total births, while the fetal death rate is 5.5 to 7.0 deaths per 1000 total births.¹ Across the world, it has been estimated that at least 2.65 million babies are stillborn each year.² In Australia, one in every 140 babies are stillborn, a figure that represented a loss to 2188 families in 2008.³ Such a loss can be very difficult for parents, their families and the healthcare professionals caring for them to understand and accept.

The autopsy still remains the ‘gold standard’ in diagnostic evaluation of the causes of perinatal death.^4,5 Information gained from an autopsy provides an independent assessment of events surrounding the death of a baby for both the family and health professionals, often relieving the woman and her physician of blame. The autopsy can assist future pregnancy and delivery options by determining the magnitude of any recurrence risk, and helping point to different management strategies.^4-7

Studies show new information, unsuspected prior to birth, is gained from perinatal autopsies in between a quarter and a half of all cases.^4-7 Identification of the exact pathology and cause of death can advance medical knowledge by allowing clinicians to monitor and validate therapies, providing information that can eventually improve clinical practice through research. Studies continue to validate the autopsy as an important source of clinically relevant information, a teaching tool and a quality assurance measure.⁸

The classical complete perinatal autopsy involves a comprehensive assessment of the baby (external examination including standard measurements, internal examination with dissection, photographic documentation of external and internal features, histologic evaluation of tissue biopsies, radiology, DNA storage, cytogenetics +/- microbiology and metabolic screens), placenta (macroscopic, microscopic +/- cytogenetics and microbiology) and mother (history, examination, haematological, biochemical and microbiological tests). Between one-third and a half of the time, the cause of death will be placental⁹ and in the remainder of cases, either a maternal and/or baby pathology will be to blame. Currently, about ten per cent of the time no cause of death will be found despite a classical complete autopsy examination⁴, and this rises to 28–41.5 per cent in the stillbirth group, depending on whether an autopsy is performed.³

The classical complete autopsy examination needs to begin with a review of the clinical history, prenatal laboratory studies, any radiologic images and a discussion of the clinical questions with the clinical provider and/or genetic counsellor.¹⁰ Guidelines have been developed by a multidisciplinary team within the Perinatal Society of Australia and New Zealand (PSANZ) with ‘the purpose of providing a systematic approach to the investigation and audit of perinatal deaths across Australia and New Zealand and to enhance the provision of appropriate care for parents.’ The guidelines are available on the website: www.psanz.com.au/special-interest/perinatal-mortality-group/psanzcpg [link expired; search www.psanz.com.au]. These guidelines have recently been updated and still consider the classical complete autopsy to be the gold standard.

There is increasing interest in noninvasive postmortem imaging studies, such as conventional radiography (X-rays), computed tomography (CT), and magnetic resonance imaging (MRI) as valuable alternatives and/or addition to the classical conventional autopsy.^10-13 The main value of these imaging techniques is they are non-invasive and the digitally stored data can be reviewed at any time. The main disadvantages are that, like a pathologist performing the dissection and histological assessment of tissues, these imaging techniques require special expertise for interpretation and there is limited access to MRI, and to a lesser extent CT, for live patients let alone postmortem ones.

X-rays are considered a standard part of the classical complete autopsy examination and are an essential tool in confirming or rejecting an antenatal diagnosis of a skeletal dysplasia, for example.¹⁰ Plain X-rays also assist the pathologist in determining the gestational age of a baby and can provide important information in the advent of trauma. Identification of fractures, in the absence of trauma, can direct additional molecular diagnostic and/or biochemical studies toward disorders of collagen synthesis, such as osteogenesis imperfecta.¹⁰

Postmortem MRI has been used for nearly two decades, and its use and evaluation have expanded in recent years. MRI provides excellent visualisation of soft tissues and most organs, but has poor delineation of bony structures and in the detection of cardiac abnormalities.^10,12 MRI is particularly helpful in the evaluation of structural abnormalities of the brain and spinal cord¹², because of the difficulties of assessing perinatal brains owing to the rapid onset of softening and the difficulties in detecting small and subtle abnormalities.^11-12 Most studies have shown, apart from examination of the brain and spinal cord, MR imaging rarely provides more information than a classical complete autopsy.¹²

The UK Department of Health, in 2004, commissioned research into postmortem MRI. The results of those studies were published this year and have revealed that the cause of death, or major pathological lesion, detected by MRI alone was concordant with conventional autopsy in 79 of 185 fetuses born at less than 24 weeks (42.7 per cent, CI 35.8–49.9), in 58 of 92 fetuses born at more than 24 weeks gestation (63.0 per cent, CI 52.8–72.2) and 85 of 123 children (69.1 per cent, CI 60.5–76.6). Overall, MRI was concordant with conventional autopsy in 222 of 400 cases
(55.5 per cent, CI 50.6–60.3), was non-diagnostic in 72 cases (18 per cent), discordant in 106 cases (27 per cent) and apparently false positive in six cases (two per cent), despite all radiographers and radiologists having extensive experience with postmortem MRI.

This group also evaluated the use of a minimally invasive autopsy [defined as a postmortem investigation with no incisions or dissection, but with postmortem blood sampling via needle puncture]. The procedure included a review of the cases’ clinical history and a summary of the relevant antemortem information, external examination, postmortem MRI, and other postmortem imaging, genetic and metabolic tests (antemortem or postmortem blood sampling), and examination of the placenta or placental tissue. Cause of death or major pathological lesion detected by minimally invasive autopsy was much more acceptable, being concordant with conventional autopsy in 357 (89.3 per cent, 95 per cent CI 85.8–91.9) cases: 175 (94.6 per cent, CI 90.3–97.0) of 185 fetuses at 24 weeks gestation or less; 88 (95.7 per cent, CI 89.3–98.3) of 92 fetuses at more than 24 weeks gestation; and 34 (81.0 per cent, CI 67.7–90.0) of 42 newborns aged one month or younger. The results of these studies may well influence how we study the dead for many years to come.¹³

Postmortem CT imaging can be used to evaluate skeletal abnormalities in a baby. Postmortem visualisation of soft-tissue structures is, however, poor, precluding the use of postmortem CT scanning as a replacement for conventional internal autopsy examination.¹⁰

In the forensic setting, the use of Virtopsy has been evaluated over the past 15 years in Switzerland. Virtopsy consists of body volume documentation and analysis using CT, MRI and microradiology; and 3D body surface documentation using forensic photogrammetry and 3D optical scanning. These studies have included a small number of babies although the combination of techniques is not currently in routine use in perinatal pathology.¹⁴

There has been a significant change in public opinion about autopsy in general, and specifically about perinatal autopsy, over the past few years because of a series of high-profile cases in the UK.¹² Education of parents and health professionals about the value of autopsy assessment is thus vital. While the classical complete autopsy assessment is essential in the context of a stillbirth, a more targeted autopsy can be considered if being performed to confirm or refute antenatal diagnoses, and the family is reluctant to give consent owing to social, religious or psychological reasons. These more targeted autopsies require particularly careful review of antenatal history, examination and investigations but, by their limited nature, can only report on the parts of the body that they access.

In summary, while there has been significant development in our understanding and management of diseases during the perinatal period, at this time, the classical complete autopsy remains the best investigation for a stillbirth or death of a baby in the perinatal period.