|Year : 2022 | Volume
| Issue : 5 | Page : 207-217
|Perinatal and Fetal Autopsies in Neuropathology: How I do it
Ram Narayan Das1, Bappa Mandal2, Mou Das3, Kaushik Sil2, Suchandra Mukherjee2, Uttara Chatterjee3
1 Department of Pathology, MJN Medical College and Hospital, Cooch Behar, West Bengal, India
2 Department of Neonatology, IPGME&R, Kolkata, West Bengal, India
3 Department of Pathology, IPGME&R, Kolkata, West Bengal, India
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|Date of Submission||30-Sep-2021|
|Date of Decision||03-Jan-2022|
|Date of Acceptance||10-Jan-2022|
|Date of Web Publication||11-May-2022|
| Abstract|| |
Fetal and perinatal autopsies are useful to identify the accurate cause of death and in the process recognize disorders which may require counselling for future pregnancies. Abnormalities of the CNS are an important cause of fetal loss and perinatal deaths. Most of these are structural abnormalities of the CNS, however a smaller portion show changes pertaining to prematurity, infections and even congenital tumors. In this review we evaluate CNS abnormalities of the fetus and the newborn as detected in autopsy series. We also describe our experience in a tertiary care hospital with a specialized neonatology unit over the last 8 years and discuss some of the newer methods like virtual autopsy.
Keywords: Congenital CNS abnormalities, fetal and perinatal autopsy, virtual autopsy
|How to cite this article:|
Das RN, Mandal B, Das M, Sil K, Mukherjee S, Chatterjee U. Perinatal and Fetal Autopsies in Neuropathology: How I do it. Indian J Pathol Microbiol 2022;65, Suppl S1:207-17
|How to cite this URL:|
Das RN, Mandal B, Das M, Sil K, Mukherjee S, Chatterjee U. Perinatal and Fetal Autopsies in Neuropathology: How I do it. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 May 24];65, Suppl S1:207-17. Available from: https://www.ijpmonline.org/text.asp?2022/65/5/207/345061
| Introduction|| |
The most important reason for doing perinatal autopsy is to determine the exact cause of death. It also provides an audit of abnormalities detected on prenatal-USG (PUSG). It provides the clinician with a feedback on the management. Most importantly for the parents it is reassuring to know if there are chances of the condition affecting their next child.
Congenital anomalies are important cause of perinatal and infant death. Globally, an estimated 303,000 newborns die within 4 weeks of birth every year due to congenital anomalies. The current perinatal mortality rate of India is 26 per 1000 births. It ranges from 16 per 1000 births in urban areas to 28 per 1000 births in rural areas. Important causes of perinatal death or early neonatal death are low birth weight (LBW), birth injury, congenital anomalies, conditions of placenta and cord etc. Of these, central nervous system (CNS) anomalies are common congenital anomalies. Antenatal radiological screening is not fully satisfactory as compared to complete postnatal fetal autopsy for accurate diagnosis of cause of perinatal death.
The prevalence of CNS abnormalities is approximately 5-10/1000 births.,,, CNS malformations are seen about 15% of infants dying due to causes associated with birth defects and 75% of fetal deaths are attributed to structural abnormalities of the CNS. There is sparse literature available from our country on prevalence of congenital CNS abnormalities.,, The abnormalities of the CNS are of diverse morphology and etiology. Genetic defects, infections, teratogens, irradiation, maternal diseases or medications have been implicated in these malformations.
A basic knowledge of embryology of the CNS is important to understand its congenital malformations. The CNS develops through a complex series of embryologic stages which starts with dorsal induction, ventral induction, neuronal proliferation, migration, organization and myelination in a stepwise and time bound fashion. Molecular and structural events controlling these events are now recognized. The formation of notochordal process from cells in the Hensen's node begins on post-ovulatory day (POD) 16. The nervous system begins on the dorsal surface of the embryo as a thickening called the neural plate around day 18 POD. It then folds into an elongated neural tube which begins to close cranially and caudally at multiple sites. The anterior neuropore closes on day 24 and the posterior neuropore on day 26 POD.,,,, The neural tube abnormalities therefore occur before this period. It can therefore be understood that all spinal malformations that arise cranial to S2 involve defects of primary neurulation. During second month the rostral part expands and forms the prosencephalon, mesencephalon and rhombencephalon. Disturbances of forebrain development lead to holoprosencephaly and associated abnormalities. Around 6 weeks post-conception, the CSF pathways develop and failure of this process can lead to hydrocephalus. During second to fourth months, neurons rapidly divide in the subependymal region, called the germinal matrix. From here, the neurons migrate to their permanent location in the cerebral cortex following radial glial scaffolding. During this process the older neurons are pushed to the deeper layers of the cortex.,, A disturbance in this course of migration gives rise to a wide range of abnormalities such as schizencephaly, lissencephaly, pachygyria and polymicrogyria. Subsequently, the neurons undergo maturation and myelination, which continue into early infancy and through childhood. Malformations of the brain are more common than other organs perhaps because of this prolonged period of development.
Congenital CNS malformations are broadly divided in descriptive terms such as neural tube defects (NTDs), segmentation and cleavage abnormalities, abnormalities of sulcation, organization, migration and posterior fossa abnormalities. Of these, NTDs are the commonest in all reported series.,, In our own series of 33 cases too, NTD was the commonest abnormality. The clinicopathological profiles of our cases are listed in [Table 1].
|Table 1: Details of prenatal sonographic features and perinatal/fetal autopsy features in cases of congenital CNS abnormalities (n=33)|
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Neural tube defects
NTDs are one of the most common CNS abnormalities detected on perinatal autopsy series and comprise a wide spectrum varying in severity and location. The defects can range from anencephaly/craniorachichisis, the most severe form to spina bifida occulta with no symptoms at all. NTDs affect 0.5-2 per 1000 pregnancies, world-wide and are the second commonest group of birth defects, after congenital heart defects.,,,, The risk of recurrence is 2-5% in siblings. Most result from a complex interaction between several genes and poorly understood environmental factors., Molecular regulatory genes include BMP and sonic hedgehog pathways which have been implicated in control of neural plate bending. Preconception use of folic acid, 0.4 mg/day has been shown to reduce the prevalence, however there remains a small proportion which is resistant to folate. Associated conditions include hydrocephalus, vertebral deformities, genitourinary and gastrointestinal disorders. It can also occur as a part of syndrome associated with chromosomal abnormalities (13 and 18), Meckel-Gruber syndrome (MGS), Walker Warburg syndrome (WWS) or costo-vertebral dysplasia. Therefore it is important to do a thorough examination of other systems to rule out any syndromic association. Raised AFP in maternal serum used to be a commonly performed screening test for open NTDs, however this has largely been replaced by prenatal-USG. USG can detect anencephaly from 12 weeks and spina bifida from 16-20 weeks.,, However, small spina bifidas particularly in the lumbo-sacral region can be missed. Clinical methods have been developed and refined for the prenatal diagnosis and in-utero surgical repair of NTDs.,
We had 15 cases of NTDs in our series. There were five cases of myelomeningocele, two meningoceles, five encephaloceles and three anencephalies. There was no history of obesity, diabetes mellitus or use of anticonvulsant drugs in the mothers. Out of 15 cases of NTDs 11 cases were diagnosed by PUSG. One case of myelomeningocele was diagnosed on PUSG as polyhydramnios only. MRI is better than ultrasound to provide information about contents of meningomyelocele sac.
Anencephaly is the most severe form of NTD.,, It is due to failure of anterior neuropore closure with exposure of the brain contents to amniotic fluid. Most of these fetuses are still-born or live for only a few hours. The cranial vault and cerebral hemispheres are absent. It is 37 times more common in females., Brain stem and basal ganglia are usually recognizable. The eyes appear to be bulging because the orbits are shallow and frontal bones are absent. [Figure 1]a and [Figure 1]b The sella turcica is shallow and an angiomatous mass of neural tissue is seen to occupy the cranial cavity. Other neuro-endocrine defects are common, example pituitary and adrenal hypoplasia. Peripheral nervous system including enteric nervous system usually develop normally.
|Figure 1: (a and b) Anencephalic fetus with absent calvarium. (c) Stillborn fetus with occipital encephalocele. (d) Neonate with large occipital encephalocele, inset shows the MRI of the same case. (e) Photomicrograph of encephalocele with vascular malformation on surface; inset shows gross photograph with polymicrogyria (H&E X40). (f) High power view of the same (H&E X100)|
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This is fairly common condition where there is herniation of meninges and brain tissue through a defect in skull. In 80% of these cases this occurs in the occipital region. In contrast to anencephaly, which results from failure of cranial neural tube closure, encephalocele appears to be primarily a defect of cranial mesoderm development. A persistent opening in the skull, at occipital, parietal or fronto-ethmoidal locations, allows the meninges to herniate creating an extra-cranial mass., There is no increased incidence among siblings. Implicated etiological factors include maternal folate deficiency, fever and injections of toxins. Encephaloceles can be extremely large and most of these neonates are live born requiring immediate surgery at birth. We often encounter these as surgical specimens and can be as large as the head of the baby. Polymicrogyria is fairly common. Microscopically there is presence of gliotic brain tissue under the skin and meninges. Overlying vascular malformations are fairly common. These vascular malformations often resemble infantile hemangiomas. Absence of staining for GLUT-1 on immunohistochemistry can very easily distinguish these vascular malformations from hemangiomas. [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f It is important to thoroughly examine associated abnormalities. Encephaloceles are often associated with spinal dysraphism especially MMC in 7% cases. Encephaloceles are sometimes associated with syndromes such as MGS, WWS or amniotic band syndrome.
Spina bifida (meningomyelocele/myelocele)
Spina bifida (SB) is failure of closure of caudal neural tube. When there is a bony defect covered by normal skin and no neural tissue is extruded it is called SB occulta and open defects are SB aperta. Open defects are covered by a reddish membrane called medullovasculosa.
Meningomyelocele (MMC) is herniation of dura and arachnoid along with spinal cord through a vertebral defect. Vertebral arches are absent producing a widened spinal canal and lumbosacral region is the commonest site of involvement. Most of the cases of SB cystica are myelomeningoceles in which the spinal cord is a component of the cyst wall. In 5% cases there is no neural tissue and are pure meningoceles. Hydrocephalus is seen in most cases of MMC and Chiari malformation is present in 70%.,,, This is downward protrusion of cerebellum below foramen magnum overlapping the spinal cord. To demonstrate these abnormalities a posterior approach for opening the upper spine is preferable. MMC depending upon the size, can be diagnosed by PUSG and elevated levels of AFP in the amniotic fluid at 14-16 weeks of gestation. Large MMCs are difficult to distinguish from sacrococcygeal teratomas with large cystic component on USG alone. Teratoma with predominance of endodermal elements also show raised AFP levels. Distinguishing these two entities is important for management. The treatment of MMC tends to be purely surgical whereas teratomas whether mature or immature require long term follow-up in addition to surgery and often require chemotherapy. Distinguishing the two at an early stage is important in view of fetal surgery that can be offered to some cases of MMC., We have seen a case of large MMC affecting the lumbosacral region in a neonate, radiologically diagnosed to be a sacrococcygeal teratoma. This case was also associated with abnormal development of abdominal wall and gastrochisis. [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d
|Figure 2: (a) 27 weeks fetus with a large lumbosacral mass. (b and c) On opening, the mass is seen to communicate with the central canal of spinal cord, confirming the diagnosis of MMC (d) Neonate with large lumbar MMC. Inset shows MRI of the same case. (e) Sirenomelic fetus with MMC. (f) Low power of MMC showing nerve tissue and vascular malformation. Inset show that blood vessels are negative for GLUT 1 which stains the perineurium only|
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SB occulta is where there is defect of the posterior arch of one or more lumbo-sacral vertebra with intact skin. These closed NTDs unlike open ones are defects of secondary neurulation and non-disjunction. The presence of lumbar sinus, vascular nevus, dimple or a tuft of hair may be a tell-tale sign of underlying abnormality. The mildest degrees of spinal NTD include lipomeningocele or limited dorsal myelochisis. However these are rarely encountered in as autopsy specimens. Sometimes MMC can be a part of spectrum of other abnormalities. We have reported a case of meningocele associated with sirenomelia as a part of spectrum of caudal regression syndrome [Figure 2]e and [Figure 2]f.
HPE is a spectrum of malformations resulting from failure of ventral induction and pattering of the prosencephalon by mesodermal floor plate rather than failure of cleavage as was earlier thought of. There is a single, incompletely divided forebrain. This heterogeneous disorder can be due to under-expression of the strong ventralizing gene Sonic hedgehog (SHH)., Depending upon the severity, a range of morphology can be seen. Alobar is the most severe form to semilobar and lobar forms. The semilobar form is most common where the hemispheres are divided by a fissure that widens posteriorly. The corpus callosum and septum pellucidum are absent. Lobar is the most differentiated form of holoprosencephaly with a well-developed dorsal but absent ventral inter-hemispheric fissure. HPE is always associated with a range of midfacial defects like cyclopia, microphthalmia, small nose, cleft lip and palate, hypotelorism and medial incisor agenesis. Interestingly, the severity of facial and brain abnormalities go hand in hand. HPE can be isolated, however 50% cases are associated with trisomy 13 or 18. Some of the HPE related genes are SHH, ZIC2, SIX3, TGIF, PTCH1, GLI2.,,, [Figure 3] illustrates a case of semilobar HPE associated with trisomy13. There was agenesis of corpus callosum with hydrocephalus. In addition to the facial features, there was polydactyly in all 4 limbs, which suggested trisomy13. The non-syndromic type shows autosomal dominant inheritance and prenatal molecular testing is now available.
|Figure 3: (a) Holoprosencephalic perinate with micro-ophthalmia and small nose. (b) Cleft lip and palate. (c and d) Polydactyly of hands and feet, characteristic of trisomy 13. (e) Dorsal surface of the brain showing incomplete fissure separating the posterior aspect of the cerebral hemispheres. Inset shows ventral aspect with no fissure at all. (f) Coronal section of the brain showing poorly formed corpus callosum|
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Agenesis of corpus callosum (ACC)
This refers to total or partial absence of corpus callosum. ACC is a common abnormality seen in congenital CNS malformation and is often a part of syndromic abnormalities., We have shown two cases of ACC here associated with HPE and WWS. [Figure 3]f and [Figure 4]a
|Figure 4: (a) Triventricular hydrocephalus with dilated third and lateral ventricles; absent corpus callosum. (b and c) Coronal section of brain in two cases of hydrocephalus affecting the lateral ventricles|
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Hydrocephalus is the end result of a process of abnormal circulation of CSF due to obstruction and rarely overproduction. The obliteration of ventricular pathways are due to ventricular pathway malformation, infection, hemorrhage or tumor. It is important to record the degree and site of hydrocephalus as it gives us a fair idea of the level of obstruction. Triventricular hydrocephalus is due to aqueduct of Sylvius stenosis whereas biventricular is due to third ventricle obstruction. There is associated thinning of the overlying cortex to a considerable degree. Post mortem examination of brain in cases of hydrocephalus detected on PUSG require adequate fixation followed by serial slicing at intervals to detect its extent and location. [Figure 4]. PUSG can detect hydrocephalus fairly early and be a tell-tale sign of other underlying abnormalities. This warrants further detailed imaging like 3D –USG or fetal MRI to categorize further.
Agyria (Lissencephaly), pachygyria and polymicrogyria
Disorders of neuronal migration produce a variety of cortical abnormalities from agyria, pachygyria, lissencephaly (smooth brain) to polymicrogyria.
Lissencephaly (LIS) refers to total or partial absence of gyri resulting from a wide range of pathological disturbances. There are two main types- the classic or LIS I and type II or cobblestone type. LIS 1 shows complete absence of gyri with thick cerebral mantle composed of 4 layered cortex. LIS I may be a part of Miller-Dieker syndrome with mutation of LIS 1 gene on chromosome 17 p13.3 or deficiency of DCX gene on Xq22.3.,,
Type II LIS is also called cobblestone lissencephaly, is the common variety. This is a migrational disorder where there is overgrowth of neuroglia beyond the pia limitans into the subarachnoid space forming an extracortical layer. This results in obliteration of subarachnoid space. The surface of brain has an opaque, cobblestone appearance. Deep white matter shows neuronal heterotopia. Corpus callosum is often absent. There is cerebellar dysplasia with absence of cerebellar vermis and brain stem disorganization. Ocular anomalies with LIS II include microphthalmia, retinal dysplasia and cataract. Gonadal dysplasia has also been reported. The most severe end of the spectrum is WWS. Less severe forms include muscle-eye-brain disease and Fukuyama congenital muscular dystrophy. These syndromes are caused by mutation of 6 or more genes including POMT1 and FKTN and belong to the spectrum of alpha-dystroglycanopathies. The mode of inheritance is autosomal recessive., Here again it is important during autopsy to take samples from eyes, muscle and gonads in order to subtype it further. [Figure 5] shows a case of cobblestone lissencephaly with WWS in which there was retinal dysplasia and muscular dystrophy. Microscopic sections of the brain showed presence of neuroglia within the arachnoid. There was associated Dandy-Walker malformation and triventricular hydrocephalus along with ACC. [Figure 5]
|Figure 5: (a) Gross photograph of lissencephaly or smooth brain (b) Fixed brain showing smooth surface and opaque meninges. (c) Cerebellum showing Dandy-Walker malformation. (d) Eyes with micro-ophthamia, posterior synechia and cataract. (e) Section of brain showing extension of neuroglial tissue beyond pia limitans into the subarachnoid space (H&E, X40). (f) Section of muscle showing hypertrophic fibres indicating muscular dystrophy (H&E X100)|
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[Figure 6] shows a case of polymicrogyria and temporal lobe dysplasia associated with thanatophoric dysplasia, which is a skeletal dysplasia associated with FGFR3 mutations. The temporal lobe shows transverse sulci on the infero-medial aspect.
|Figure 6: (a) Gross photograph of a fetal brain at 30 weeks with agyria. (b) Gross photograph of a brain showing polymicrogyria in a case of thanatophoric dysplasia I. Inset: Infantogram showing bowing of left ulna, both femora & tibia, short ribs and platyspondyly. (c) Gross photograph of the ventral aspect of the same case showing transverse sulci in the infero-medial aspect, marked with arrows. (d) Photomicrograph of the cerebrum showing neuronal hetertopia in subependymal location. (H&E X100)|
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Dandy-walker malformation (DWM) and posterior fossa abnormalities
DWM is a common cerebellar abnormality in which there is dilation of fourth ventricle with hypoplasia and absence cerebellar vermis. It is accurately picked up on PUSG and is often associated with other CNS and extra-CNS abnormalities. DWM can be associated with CNS abnormalities like ACC, occipital encephalocele and microcephaly. Associated systemic anomalies include cleft palate, microphthalmia and cardiac anomalies. Detection of these anomalies on PUSG becomes important in cases where MTP is planned. [Figure 7]
|Figure 7: (a) Posterior approach for opening the spinal cord to look for Arnold Chiari malformation. (b and c) Dandy Walker malformation with enlarged fourth ventricle|
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Small posterior fossa cysts are picked up on PUSG which may or may not be become symptomatic. These cysts are often better demonstrated on post-mortem MRI than autopsy, as these cysts tend to collapse.,
Arnold-Chiari malformation involves displacement of medulla, 4th ventricle and cerebellar vermis into upper cervical canal leading to elongation and thinning of medulla and lower pons. Most patients have associated MMC and hydrocephalus. A posterior approach of opening the spine for is needed for visualization.
Microcephaly is a small brain, below 3 SD for age. It can be primary or secondary to cranial-synostosis due to premature closure of cranial sutures. The causes of microcephaly can be genetic, environmental or infectious. Autosomal recessive microcephaly (microcephaly vera) is caused by mutations in MCPH 1, CDK5RAP2, CENPJ, STIL genes and several more which appear to affect centrosomes. [Figure 8] shows a case of trisomy 18 with characteristic rocker-bottom feet, clenched fists and central cyanosis due to cyanotic congenital heart disease. There was cranial-synostosis with microcephaly and hydrocephalus in this case.
|Figure 8: (a) Neonate with severe central cyanosis, microcephaly and clenched fists. (b) Rocker bottom feet, characteristic of trisomy 18. (c) Craniosynostosis affecting coronal, sagittal and lamboid sutures. (d) Microcephalic brain weighing 150 g. (e) Ventral surface of the same. (f) Section of the cerebrum showing calcification. (H&E X40)|
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Brain tumors in neonates are infrequent. Unlike older children where posterior fossa tumors are the commonest, in fetuses and the neonate the commonest location is supratentorial.,, The most common neonatal brain tumor is teratoma followed by choroid plexus papilloma (CPP). Other reported neonatal tumors are embryonal tumors, medulloblastoma, ATRT and glial tumors sometimes in a setting of NF1. Coexistence of a brain tumor and an intracardiac mass, such as a rhabdomyoma, may suggest tuberous sclerosis complex. This association itself should lead to screening and counselling for future pregnancies.
In our series we have reported two cases each of immature teratomas and choroid plexus papillomas. There was one case of subependymal giant cell astrocytoma associated with cardiac rhabdomyoma, which strongly indicates tuberous sclerosis complex. Hydrocephalus was detected in prenatal USG in all the cases.
The incidence of birth trauma has dropped significantly and account for less than 2% of neonatal death. Knowledge of the spectrum of birth injuries and their sequelae is important for distinguishing these from post-mortem changes. Important risk factors that predispose infants to birth injury include hydrocephalus, macrosomia, malpresentation, cephalopelvic disproportion and forceps/vacuum delivery. These range from scalp hematoma to caput succedaneum, subgaleal hemorrhage and cephalhematoma Skull fractures were typically reported with forceps delivery., Epidural hemorrhage, subdural hematoma and subarachnoid hemorrhage can be associated with birth trauma., Subdural hematoma is the most common type intracranial bleeding and this is our experience too.
Lesions associated with prematurity
With improved obstetric and neonatal facilities the mortality rate associated with prematurity has gone down considerably. However mortality due to prematurity is the commonest cause of death in NICU. The classic lesions associated with prematurity are germinal matrix (GMH)/intraventicular hemorrhage and peri-ventricular leucomalacia (PVM). In our setting, prematurity associated with multiple pregnancy is quite common. GMH is the most common brain lesion in preterms. This layer is vascular and the vessels are poorly supported. The hemorrhage may spread to the ventricular system leading to intraventricular hemorrhage, obstruction to CSF outflow causing post-hemorrhagic hydrocephalus. Despite advancement in the care of preterm infants, germinal matrix-intraventricular hemorrhage remains a dreaded complication. The incidence is 20-25% among very LBW infants and is one of the main causes of neurodevelopmental disability in these infants. PVM is hypoxic-ischemic necrosis of the white matter in superior and lateral angles of lateral ventricles and is typical of the immature brain of the preterm infants. PVM has been found in up to 75% of preterm infants and up to 20% in term infants during autopsy.
Congenital infections of the brain can occur antepartum, intrapartum or in immediate postpartum period. The commonest causes of infections are by the gram positive cocci like Group B Streptococci manifesting as neutrophilic inflammation of the meninges, ependyma, causing vasculitis, thrombosis and infarction. TORCH infections by toxoplasma, rubella, cytomegalovirus and herpes in utero can result in severe necrosis, periventricular calcification, microcephaly and hydrocephalus. Toxoplasma specially causes multifocal necrosis and calcification in the periventricular, cortical and subcortical areas. CMV too causes similar calcifications as well as polymicrogyria. Therefore thorough external examination and appropriate sampling is important if TORCH antibodies are positive in the mother.
Prenatal USG, fetal MRI and postmortem MRI: Where we stand today
Though there have been considerable advances in prenatal imaging and genetic diagnosis, conventional autopsy is the gold standard till date because it can provide additional information in up to 40% of cases., Ultrasonography is the primary screening modality in evaluating fetal well-being and detecting fetal structural anomalies. It is devoid of side effects to mother and fetus and provides real time imaging. However it has several short comings. Lomax, et al. showed the sensitivity of ultrasound with regard to malformation in the brain and spine was 100% and specificity was 87%. With regard to malformations in other organs (urogenital, GIT, abdominal wall and diaphragm) the sensitivity was 91% and specificity was 89%.,
Fetal MRI is now being used to increasingly by obstetricians for better and accurate diagnosis of abnormalities picked up on PUSG, e.g., complete or partial agenesis of ACC, posterior fossa malformations, renal abnormalities, lung cysts and congenital diaphragmatic hernia. This is especially important in the light of fetal surgery which is now available for some of these conditions and taking decision concerning termination of pregnancy.,
Recently, use of MRI has become an important ancillary investigation to the conventional autopsy. The successful introduction of MRI as an adjunct investigation in the fetal, and perinatal autopsy is gradually replacing the conventional post mortem examination., The main drawback of conventional autopsy is its long reporting time, body disfigurement and associated superstitions. MRI has been shown to be more sensitive for picking up CNS abnormalities compared to cardiac anomalies. Postmortem MRI or virtual autopsy is more sensitive than conventional autopsies for picking up posterior fossa abnormalities and neuronal migration disorders. In cases of macerated fetuses, MRI provides more detailed information about brain lesions than conventional autopsy., Virtual autopsy uses USG, MRI and CT-scan. MR imaging using 1.5-Tesla offers an overall diagnostic accuracy of 77%-94%. It is the best choice for virtual autopsy for fetuses >20 weeks' gestation. Postmortem ultrasound with a high-frequency probe also provides sufficient information with overall sensitivity and specificity of 67%-77% and 74%-90%, respectively. For fetuses ≤20 weeks' gestation, micro-focus CT achieves close to 100% agreement with autopsy and is likely to be the technique of the future in this subgroup. Though image techniques may offer sufficiently accurate anatomical abnormalities, they cannot provide histopathological changes of tissue, which is main drawback. Image-guided core needle biopsy, however, is a good alternative. MRI is useful in differentiating stillbirth from infanticide.
Future progress in imaging techniques, possibly towards the development of better quality 3- dimensional imaging may eventually result in less invasive autopsy particularly in cases of structural abnormalities.
Techniques of autopsy and brain removal in suspected malformations
After checking the consent forms and identification of the body, it is important to go through the entire clinical history including the obstetric history of the mother in details before starting the autopsy. Review the serial PUSG findings before starting. Where body is for the hospital disposal we immerse the body in 10% formalin, similar to surgical specimens. At this point, for better preservation of the brain we inject full strength formalin through the anterior fontanel into the ventricles. It is our practice to do postmortem radiography. In addition to dating, it is important for spinal abnormalities associated with NTDs. Other skeletal abnormalities are also documented in the process, e.g., thanatophoric dysplasia and achondroplasia both of which bear mutations of FGFR3.
A thorough external examination is important, paying special attention to shape of the head, cleft lip and palate, position of the ears, central cyanosis, syndactyly/polydactyly, webbing of toes, rocker bottom feet, omphalocele etc. These findings are especially important as they may be suggestive of chromosomal disorder. These are important if karyotyping facility is not there or sample has not been collected soon after death. Photographic documentation before dissection is valuable.
The technique of brain removal is easier than in the case of adults as the sutures are not fused. Bulging fontanel and widening of sutures indicate underlying hydrocephalus. Although rare at present, birth trauma in the form of cephalhematoma, subgaleal and subdural hemorrhages should be looked for. An inter-mastoid incision followed by the reflection of scalp anteriorly and posteriorly is done. After exposure of the calvarium, the anterior and posterior fontanelles and all sutures are carefully examined. The 4 bone-plates are cut parallel to the sutures and reflected to expose the brain. After removal the brain is fixed in 20% formalin by suspending the brain in a gauze sling or surgical cap. Usually a week to 10 days fixation is sufficient. The degree of development of cerebral convolutions is compared with values normal for the gestational age and the maturity of the gyral pattern is identified. Serial coronal sections are made at 1 cm interval.
Although the spine is easier to remove anteriorly, in cases of posterior fossa abnormalities and MMC posterior approach is important for demonstration of Chiari malformation. A midline incision from occiput to upper back is made and dorsal laminectomy exposes the spinal canal. In some cases it may be useful to take samples of skeletal muscle, eyes and gonads for example in case of WWS. Autopsy done in cases of MTP for congenital anomalies must be done meticulously from a legal point of view. It is a good practice to invite the radiologists also to the subsequent CPC of these cases.
Lastly, the placenta is like a black box of pregnancy. It is good to be able to examine the placenta using standard protocol in all cases of fetal and perinatal deaths and look for changes of fetal vascular malperfusion in the form of thrombosis of fetal vessels. There is an increased risk of neurologic injury associated with fetal vascular malperfusion. In fact there is very little available in literature on placental pathology associated with CNS malformation.
| Conclusion|| |
Fetal and perinatal autopsy are important to find out the cause of death and is an audit for anomalies picked up or missed on PUSG. It helps in investigation of parents for subtle expression of a disease or a carrier status. Meticulous dissection followed by histology goes a long way in establishing the diagnosis in the absence of cytogenetic, molecular and metabolic workup. Postmortem MRI is a new emerging tool which is particularly relevant for CNS abnormalities.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Department of Pathology, IPGME and R, 244 AJC Bose Road, Kolkata - 700020, West Bengal
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
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