Fetal Pathology

Role of the Perinatal Autopsy

The role of the autopsy is multi-faceted and includes:

• 1.

  Determination of the cause of death.

• 2.

  Recognition of unsuspected or associated findings.

• 3.

  Provision of additional information for clinicians and parents for future pregnancies and current siblings.

• 4.

  Audit and assessment of current clinical practice including confirmation of findings from ultrasound.

• 5.

  Identification of potential pathologies with public health implications.

• 6.

  Findings regarding possible associations and outcomes guiding new technologies and treatment modalities.

Data from a review of 27 studies examining discrepancy between clinical diagnosis and autopsy findings demonstrated that the perinatal postmortem examination resulted in a ‘change in diagnosis’ or ‘additional findings’ which might have influenced management or counselling in 22–76% of cases, the rate varying from 28–75% for stillbirths, 22–49% for terminations of pregnancy, and 22–81% for neonatal deaths. Importantly, up to 35% of antenatal ultrasound diagnoses were modified by additional findings at autopsy. Furthermore, a study of 309 terminations of pregnancy for prenatally diagnosed abnormalities reported that, of the 132 cases (which were chromosomally normal but found to have a structural defect on antenatal ultrasound examination) undergoing postmortem examination, the autopsy revealed additional findings which modified the recurrence risk in almost one third of cases.

Consent

There are two major categories of perinatal postmortem examination in the UK, consented autopsies and those performed on behalf of HM Coroner.

Cases referred to the coroner include those in which:

• The cause of death is unknown, or sudden and unexpected.

• The death occurred during an operation or before recovery from the effects of an anaesthetic.

• The deceased infant was not seen by the certifying medical practitioner, either after death or within 14 days of death.

• The death may have been caused by violence or neglect.

• The death may have been due to an accident.

• The death may have been in any other way unnatural or there are suspicious circumstances.

Clearly, in relation to perinatal autopsies, the major cases referable to the coroner are neonatal deaths in which there is suspicion of neglect or accident. If there is a potential issue of litigation due to neglect by hospital staff, the case should also always be discussed with HM Coroner. If a coroner's postmortem examination is performed, parental consent is not required and the coroner's decision overrides that of the parents. Once the coroner has completed the investigation, all tissue samples taken as part of the postmortem examination will then fall under the Human Tissue Act (see below) and should be handled according to parents' wishes.

However, the vast majority of perinatal postmortem examinations will not be on behalf of the coroner and will therefore require consent by one or both parents. The Human Tissue Act (2004), overseen by the Human Tissue Authority (HTA) in the UK, is responsible for defining standards, published as codes of practice, and licenses organizations and establishments that deal with human tissue (The Human Tissue Authority, 2008).

The HTA specifies that informed consent is required for the removal, storage and use of human tissues, including small samples such as blocks and slides which might be kept as part of the medical record, and therefore includes consent to perform a postmortem examination. However, the details of the Act only strictly apply to stillbirths and neonatal deaths. Fetuses born dead at <24 weeks' gestation are not regarded as having independent life and under the Act are subject to consent requirements for tissue from the mother. However, for ease of application and sensitivity regarding autopsy practice, it is recommended that consent be obtained for postmortem examination of all fetal tissue regardless of the gestational age.

Consent for autopsy must be given voluntarily by an appropriately informed person who has the capacity to agree to the activity, which for perinatal postmortem examinations will usually be one or both parents. It is recommended that, where possible, consent is obtained from the mother, and that, where appropriate, both parents are involved. Consent from one parent is sufficient. Parents may of course withdraw consent at a later stage. It is the clinician's (who should be sufficiently senior and well informed, with knowledge of the postmortem procedure) responsibility to seek consent. 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 usually required by the local hospital policy.

As can be seen from the above section, since the introduction of the HTA, the requirements and criteria for gaining consent for postmortem examination are somewhat complicated in order to fulfil the stipulated conditions. In our experience, the most common practical problem affecting the process of perinatal autopsy examination is incorrectly completed consent forms, which may then delay the performance of the examination. It is highly recommended that a member or members of the clinical team lead on this process and establish systems for reliable and accurate consenting. The pathologist undertaking the examination should also be available to provide advice and guidance as required. Parents should be informed that samples obtained (blocks and slides; Figure 22-1 ) will be kept as part of the medical record, as in life, and that if these are destroyed according to parents, wishes, it will not be possible to review the case or perform additional tests at a later date if new information becomes available.

Perinatal Autopsy Procedure

Whilst consent is being discussed, the body of the fetus or infant should be stored in a secure refrigerated unit (in order to delay postmortem autolysis and increase or improve of success for other investigations), ideally in the hospital mortuary. If skin or placental sampling is required for fibroblast culture for genetic studies, this should ideally be performed as soon as practical following delivery rather than waiting for the autopsy in order to optimize the sample for culture, especially if there may be delay due to the requirement to transfer the body to a specialist unit.

The body should be labelled with at least two identification markers, including maternal details, date of delivery and hospital number, and documentation must include the completed consent form and relevant clinical details, with particular regard to any specific questions that the parents or clinicians would like the postmortem examination to address. Prior to commencement of evisceration, it is routine to obtain full-body X-ray imaging, including anterior–posterior and lateral views to identify any skeletal abnormalities, although the benefit of this routine investigation remains undetermined. In some cases unexpected skeletal findings may be detected and skeletal bio­metry provides further indication of gestational age in cases where this is not known such as unbooked pregnancies.

Biometric measurements and body weight are then obtained, followed by an external examination for abnormalities and photographic documentation of such if required. It should be noted that there may be significant differences between birth weight and body weight at autopsy due to postmortem changes, primarily fluid loss. Such changes vary with duration of intrauterine retention and the postmortem interval, and should be accounted for when interpreting body weights for gestation.

Examination for dysmorphic features is performed and common findings which may not be detected antenatally are described in Table 22-1 .

Subsequent examination proceeds with evisceration of the internal organs and detailed organ dissection. There are numerous protocols for this procedure, which vary according to the specific indication for autopsy, gestational age and pathologist preference. However, parents should be aware that a standard perinatal autopsy will involve a large midline incision from neck to pelvis, and if histological brain examination is required, an additional incision across the scalp. Following the procedure the organs are returned to the body, and the incisions are sutured or closed by other means.

Maceration

Maceration (meaning to soften by soaking in liquid) is the process of post-fetal death change which occurs with retention in utero after death. The degree of mac­eration change increases with the duration of intra­uterine retention, which allows some estimation to be made regarding the timing of an intrauterine death before delivery ( Table 22-2 ; Figure 22-2A and B ). Changes include skin slippage, ‘blistering’, discolouration and joint laxity.

Autolysis

Autolysis is the process of cellular degeneration which occurs following death of an organism and loss of normal control of cellular metabolic and enzyme activity. This may coexist with putrification, the process of tissue degeneration due to bacterial activity, and maceration (see above). These processes are related to the temperature at which the body is stored following death/delivery, with any significant retention of the fetus in a warm environment (i.e. room temperature) hastening the rate of tissue degeneration. Extensive autolysis makes adequate macroscopic, and especially microscopic, examination difficult ( Figure 22-3A and B ).

Feticide

According to current guidelines it is recommended that feticide is performed for termination of pregnancy beyond 21 weeks of gestation , which is usually performed by intracardiac injection of potassium chloride. Following feticide, it appears that the rate of autolytic change is increased, resulting in greater chance of non-diagnostic autopsy findings, especially when feticide is accompanied by prolonged intrauterine retention post intrauterine death and a long postmortem interval (cases where potassium administration was given were twice as likely to have discordant findings between ultrasound and postmortem findings ). This is especially important for terminations of pregnancy for cardiac and brain abnormalities, when autopsy findings are likely to be important for providing a specific diagnosis; in such cases the fetus should be stored in a refrigerated unit as soon as possible after the delivery and the autopsy should be performed within the shortest reasonable time period to minimize the risk of non-diagnostic findings. The mechanism is uncertain but may be due to combination of direct cytotoxic damage and autolysis, and development of tissue salt crystals.

Autopsy Samples for Genetic Analysis

If samples are required for karyotyping or fibroblast culture it is recommended that these are obtained as soon as possible following delivery (or prenatally) rather than at the time of autopsy, to maximize the chance of successful culture and analysis. Samples may therefore include fetal/cord blood, fetal skin biopsy or placental tissue biopsy, all of which may be used for karyotyping and subsequent molecular genetic examination. If there is a prolonged postmortem interval, samples obtained at the time of autopsy may be suboptimal for use. It should be noted that if a sample, either fetal or placental, is fixed in formalin/formaldehyde, it will not be suitable for fibroblast culture or standard karyotyping, although some specific molecular genetic testing with other techniques such as polymerase chain reaction may be possible.