Pathology

The majority of perinatal losses never have a definitive cause of death identified. However, this may be due to a lack of evaluation, or incomplete evaluation, in many cases. Clinical evaluation has been shown to identify a cause of death in roughly 24% of cases. Adding placental examination improves this to 61%, and autopsy increases it again to 74%. Information learned from the placental examination alone will alter clinical management in more than one third of cases.

Even in situations where a definitive answer is not determined, much can be learned from ruling out potential causes. This information will often inform future pregnancies and can reassure families about things that were not a concern. Some families find it healing to know that what is learned could help scientists learn more about these deaths to influence future studies and help future families. Barriers to a complete pathology evaluation include myths and misconceptions about what autopsy is and how the body is handled, lack of knowledge by health professionals who are guiding families through the decision, shortage of perinatal/placental pathologists, financial implications, and cultural or religious practices.

Families should be offered a full menu of options for evaluating their losses. At minimum, each family should have a comprehensive review of the medical, social, family, and pregnancy history including the parents’ perception of the pregnancy loss, symptoms, and events surrounding the loss. A variety of blood tests, genetic testing, and imaging can also be helpful and are usually acceptable to families. Placenta and umbilical cord pathologic examination is one of the most impactful evaluation options, followed by a complete autopsy. If a complete autopsy is not possible, a partial autopsy may be performed.

Families should be reassured that their baby will be treated with respect throughout the process and the baby’s body will be returned to the family or appropriate facility as soon as possible. A meeting should be scheduled with the family when results are expected to be available to review the findings and any implications.
Multidisciplinary collaboration can be beneficial when interpreting the results and developing a plan with the family. If the cause of death is determined to be something other than what was initially indicated on the death report, this report should be revised to improve the accuracy of this data.

Recommendations

• Cytogenic analysis of tissue should be offered after early perinatal losses. Instructions should be provided on how to collect samples at home if individuals opt for expectant management or medication management of their loss. Single nucleotide polymorphism (SNP) array and next generation sequencing (NGS) are preferred.
• Antepartum deaths should receive an ultrasound for fetal biometry, AFI,
  and any fetal/placental/cord abnormalities as soon as possible after the diagnosis of fetal death
• Examination of cord, placenta, and baby at birth
• Full medical history, including family, maternal health, current pregnancy and obstetric histories
• Prepare placenta and cord for examination by pathologist by keeping them refrigerated and unfixed
• Autopsy (limited or complete) or equivalent offered to every family
• Placenta and cord examination (including histopathology) offered to every family
• If an autopsy is not possible or acceptable to the family, the family should be offered a partial autopsy, gross examination by a pathologist, or imaging (MRI, ultrasound, and/or XRay)
• CBC, syphilis screen, Kleihauer-Betke (before delivery if possible), parvovirus B-19 serology, TSH, Lupus anticoagulant, Anticardiolipin antibodies, beta 2 glycoprotein AB
• Microarray is preferred over karyotype due to a lower failure rate. In case of prolonged demise-to-delivery period, consider performing microarray on placental tissues.
• Thrombophilia testing should be done if there is evidence of placental complications, including FGR
• CMV, toxoplasmosis, parvo, listeria serology should be done if indicated by history, placental pathology, signs of infection, or if the baby is SGA.
• HbA1C if baby is LGA, FGR, or SGA
• LFTs and non-fasting bile acid testing if there is a maternal history of pruritus
• Substance use testing unless cause of death is already known
• RPR and antibody screening if not completed previously
• Provide information to parents about where their baby’s body will be, that it will be treated with respect, when they can see their baby again, and what time frame to expect for testing and results
• Schedule a meeting with parents to discuss results
• If test results are not conclusive, it is appropriate to share with the family what is and is not known and how that may impact future decisions.
• Revise the cause of death on the Fetal Death Report if the evaluation identified a different cause than initially suspected