The initial steps in the process of perinatal nervous system evaluation, namely the planning of the optimal approach and choice of samples to be obtained, are driven by the clinical context. Of key importance are the following data:

1. 
   

   a. Gestational age at the time of demise (if stillborn) or gestational age and postnatal age (if liveborn), for comparison with normative standards of development (see the Appendix)

   
   
2. 
   

   b. State of maternal health (age, parity, preexisting medical conditions or ones appearing during gestation or around the time of delivery, exposure to medications/toxins/infections) and health of siblings or other family members

   
   
   
   
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     – Concerns for inherited (i.e., genetic) conditions, metabolic disorders, congenital infections, and so forth, may indicate the need for special testing.

   
   
   
   
3. 
   

   c. Details of prenatal course, including any imaging, amniocentesis, or monitoring

   
   
   
   
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     – Prenatal imaging modalities most commonly consist of transabdominal ultrasonography, typically done at the time of the first prenatal visit (to confirm pregnancy) or more typically in the mid–second trimester for the detection of fetal or placental anomalies. If further detailed imaging is needed, maternal/fetal magnetic resonance imaging (MRI) may be undertaken (see Chapter 2).

     
     
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     – Amniocentesis, with or without chorionic villus sampling (CVS), may be offered in specific circumstances (maternal age >35; abnormal maternal serum screening for alpha-fetoprotein [AFP], human chorionic gonadotropin [hCG], estriol [“triple screen”], and sometimes inhibin-A [“quadruple screen”]; prior history of fetal loss or abnormality; suspicion of anomalies on ultrasound), and karyotypes or more advanced genetic analyses (see Chapter 6) may be performed to aid the parents and practitioners in planning or decision-making.

     
     
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     – Biophysical profiling (BPP) of the fetus in utero may be performed in high-risk cases (prior pregnancy loss, maternal vascular or other disease, twin or multiple pregnancy, abnormal amniotic fluid volume, Rh factor incompatibility, maternal report of decreased fetal movements). BPP includes electronic fetal heart rate monitoring, as well as an examination of breathing, movements, muscle tone, and volume of amniotic fluid, usually in the last trimester. Each factor is assigned a value, summing to a score, which the practitioner may use to advise regarding whether to proceed with initiating delivery. This information assists in determining the nature of the likely causes of fetal demise and may help focus the overall autopsy.

   
   
   
   
4. 
   

   d. Details of labor and delivery, including intrapartum fetal monitoring data

   
   
5. 
   

   e. Findings in the placenta, even if only available as macroscopic observations from the delivering obstetrician or midwife (as discussed in more detail later in this chapter)

Depending on these data points, the prosector may choose to set aside tissue samples for confirmatory or ancillary support of otherwise standard autopsy examination (see Chapters 5–8).

As mentioned previously, review of any prenatal imaging (transabdominal ultrasonography, or maternal/fetal MR imaging) of fetal cases, or antemortem studies of liveborns, will assist greatly in the planning of the prosection. In addition, postmortem imaging (whether of the whole infant or of the isolated brain specimen) may be desirable in certain circumstances, assuming the consent for examination includes this as a diagnostic technique, and has the obvious advantage of lack of movement artifact:

1. 
   

   a. Plain X-rays (“babygram”; performed within many pathology departments using stand-alone imaging devices, or in collaboration with Radiology colleagues in “off hours”) may reveal evidence of:

   
   
   
   
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     – Skull, vertebral, rib, and/or long bone fractures (Figure 2.1);

     
     
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     – Skeletal dysplasias, which can secondarily affect the nervous system;

     
     
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     – Congenital skull or vertebral defects related to dysraphism or patterning abnormalities;

     
     
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     – Calcification within the brain in congenital infections, vascular malformations or ischemia, or other injuries.

   
   
   
   
2. 
   

   b. CT of the deceased fetus or infant (performed with collaboration of radiology colleagues) may disclose:

   
   
   
   
   • 
     

     – Fractures of skull, vertebrae, and/or long bones;

     
     
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     – Presence of blood products associated with scalp soft tissues, periosteum and cranium (e.g., cephalhematoma; skull fracture), meninges, brain parenchyma, and/or cerebral ventricles;

     
     
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     – Mineralization of brain parenchyma or vasculature;

     
     
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     – Occult spinal dysraphism;

     
     
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     – Unsuspected cerebral malformations, masses, or tissue disruptions.

   
   
   
   

   Of note, the correlation of postmortem CT and autopsy findings is best for bony abnormalities, and for subarachnoid and intraventricular hemorrhage; it is less reliable for subdural and epidural hemorrhages [1]. Postmortem CT is somewhat more sensitive than autopsy to the presence of cerebral edema and to abnormalities in sites that are challenging to dissect [1].

   
   
3. 
   

   c. MRI of the deceased fetus or infant (also performed with Radiology oversight) requires some expertise in proper sequences and technique [2] (Figure 2.2.).

   
   

   In general, the degree of contrast among imaging signals is less in postmortem than in vivo scans, in part because of temperature differences [3]. Specifically, postmortem T1 values tend to be shorter than those obtained in vivo, while T2 values tend to be longer [4]. Protein cross-linking by formalin-fixation introduces extracellular matrix changes to underlie these observations [3]. Recognition of postmortem artifacts is important to avoid errors in interpretation [2].

   
   
4. 
   

   d. MRI of fixed brain specimens (performed by special arrangement with imaging facility, due to concern for blood-borne pathogen and fixative exposure to personnel and equipment) affords even greater anatomical detail for eventual clinicopathologic correlation, particularly if surface coils are available. In addition, special techniques, such as tractography, are possible on isolated post-mortem specimens [5] (Figure 2.3).

(a) Lateral view demonstrating evidence of medical intervention (nasogastric tube, intravascular lines, as well as diastasis of cranial sutures (indicating brain swelling) and acute non-displaced linear parietal bone fractures.

(b) Anteroposterior view further identifying healing rib and displaced clavicular fractures.

Figure 2.1 Plain radiograph of infant at postmortem (“babygram”).

(a) Conventional T1-weighted image;

(b, c) Short and long dual-echo short tau inversion recovery images, respectively;

(d) susceptibility-weighted image;

(e) diffusion-weighted image.

(Reprinted with permission from [2])

Figure 2.2 Normal images obtained from post-mortem MRI of a 3-month-old sudden unexpected death in infancy.

(a) The red tract signals indicate differences, presumably white matter loss, in the splenium and thalamus.

(b) More widespread differences in another preterm cohort.

(c, d) Probabilistic tractography of the posterior thalamic radiation in a control child, compared to loss of red signal in a preterm child with periventricular leukomalacia.

(Reprinted with permission from [5])

Figure 2.3 Tractography and use of tract-based spatial statistics allow comparison of fractional anisotropy (directional water diffusion, as along coherent bundles of axonal tracts) of preterm infants with perinatal injury to age-matched controls.