European Journal of Cardiovascular Medicine

Congenital malformations are a major cause of fetal death, emphasizing the critical role of autopsy in determining the cause of intrauterine fetal demise. Identifying the underlying etiology not only aids in understanding the event but also enables the prediction of recurrence risk, allowing for informed counseling and preventive strategies in future pregnancies. A comprehensive diagnostic approach involving prenatal investigations such as ultrasonography, chromosomal analysis, fetal autopsy, and placental examination is essential, as it significantly lowers the recurrence risk, which could otherwise be as high as 25%. In developing countries like India, congenital anomalies contribute to 10–15% of perinatal mortality and account for 13–16% of neonatal deaths. Globally, these malformations also represent a significant proportion of fetal and neonatal mortality and disability. They reflect defects in early fetal development, which may be physical, metabolic, or anatomical, often detectable before birth or within the first year of life. Although ultrasonography remains a vital tool for identifying developmental abnormalities, certain anomalies may evade detection during routine scans. In such instances, fetal autopsy plays a pivotal role in confirming or refining the clinical diagnosis and contributes substantially to understanding the phenotype of various genetic disorders, especially in the molecular era. It also serves as a vital audit of clinical care, offering insights into adverse pregnancy outcomes and guiding improvements in maternal and neonatal healthcare. The perinatal autopsy, typically performed from 28 weeks of gestation to the first week of life, is indicated in cases of spontaneous or missed miscarriage, intrauterine fetal death, or termination of pregnancy. It often provides partial or complete explanations for pregnancy loss and enhances diagnostic accuracy in nearly half of all cases. This study aims to investigate and correlate clinical, radiological, and pathological findings in cases of fetal death, thereby evaluating the utility of fetal autopsy in establishing a definitive diagnosis.

AIM & OBJECTIVES

Aim:
To evaluate the diagnostic accuracy and clinical utility of fetal autopsies in determining the cause of fetal deaths and congenital malformations in a tertiary care institute.

Objectives:

1. To assess the role of fetal autopsy in confirming or refining the clinical and radiological diagnosis of fetal demise and congenital abnormalities.
2. To explore parental perspectives and the factors influencing their decision to consent to fetal autopsies.
3. To identify ways to improve communication, counseling, and support for families experiencing fetal loss or congenital anomalies.

This retrospective study was conducted over a period of 24 months, from 2022 to 2024, in the Department of Pathology of our tertiary care institute. Fetal autopsy specimens received during this period were fixed in 10% buffered formalin, followed by routine tissue processing, paraffin embedding, sectioning, and staining with hematoxylin and eosin (H&E). A systematic review of all fetal autopsies referred to the department during the study duration was undertaken with the objective of evaluating the causes of fetal deaths and congenital malformations.

Inclusion Criteria

1. All fetal autopsies referred to the department for examination within the specified study period were included.
2. Parental or guardian consent was obtained prior to conducting each autopsy.
3. The study encompassed a broad range of gestational ages. Clinical data including maternal history, prenatal ultrasound findings, biochemical markers, and genetic study reports (where available) were reviewed.
4. This inclusive approach aimed to facilitate a comprehensive understanding of fetal deaths and malformations across gestational ages, thereby offering deeper clinical insights for improved patient management.

Exclusion Criteria

• Autopsies exhibiting significant autolytic changes were excluded to avoid compromised diagnostic interpretation.
• Cases lacking adequate clinical or diagnostic data were also excluded from the analysis.

Macroscopic Examination

External examination included detailed anthropometric measurements such as crown-rump length, crown-to-heel length, foot length, and head, abdominal, and chest circumferences. These assessments were crucial for evaluating fetal development and identifying visible anomalies. A midline longitudinal incision was made to access thoracic and abdominal cavities, where the presence of any fluid collections in pleural and peritoneal spaces was recorded. Visceral organs were carefully examined in situ to assess positioning and detect abnormalities such as organ hypoplasia or agenesis. Organs were then excised en bloc and subjected to detailed gross examination. The placenta and umbilical cord were thoroughly examined, and representative sections were obtained for histological evaluation to identify additional contributing factors to fetal demise. This meticulous macroscopic assessment was designed to ensure diagnostic accuracy and to enrich understanding of fetal pathology.

Histopathological Analysis

Tissue sections from all major organs were examined microscopically to detect structural abnormalities, inflammatory changes, or other underlying pathologies that may not have been apparent on gross inspection. The histopathological examination played a critical role in identifying etiologies of fetal deaths and congenital anomalies, contributing significantly to diagnostic clarity and enhancing clinical decision-making.

Data Analysis

All findings were analyzed descriptively to determine the frequency and distribution of congenital anomalies, identify potential causes of fetal death, and assess the diagnostic yield of fetal autopsy in comparison with clinical and prenatal findings.

A total of 28 fetal autopsies were evaluated over the study period. A probable diagnosis was established in 42.85% (12 out of 28) of the cases, demonstrating the clinical utility of fetal autopsy in confirming or refining the cause of fetal demise and congenital malformations.

The majority of cases (82.14%) were less than 37 weeks of gestation, indicating a predominance of preterm fetal losses, mainly stillbirths. Of the total, 14.85% were induced abortions due to detected anomalies or maternal complications, while 2% accounted for spontaneous intrauterine fetal demise.

A notable observation was the high degree of agreement between prenatal ultrasound findings and autopsy results (83.1%), which underscores the reliability of ultrasonography as a diagnostic tool, while also highlighting the value of autopsy in confirming or adding crucial pathological details in certain cases.

Table 4: Gestational Age wise distribution N = 28 cases

A male preponderance (67.85%) was noted among the cases, which could suggest gender-related vulnerability in fetal loss, though further research with larger cohorts is required to confirm this trend. A small number (7.14%) of cases remained inconclusive due to factors such as advanced maceration or inadequate clinical data. The data also reveals that a significant proportion of losses occurred in the stillbirth category (71.42%), most commonly below 37 weeks gestation.

Table 5. Cause of death and related frequency:

While numerical data for this table wasn't provided, notable cases included the following pathological conditions:

• Cystic Hygroma: Characterized by dilated lymphatic spaces embedded within adipose tissue, with focal areas of fibrosis and scattered lymphocytes. This condition is commonly associated with chromosomal anomalies like Turner syndrome and may lead to hydrops fetalis, contributing to fetal demise.
• Anencephaly: Histopathology revealed primitive neural elements interspersed with dilated blood vessels. Anencephaly, a type of neural tube defect, is a lethal malformation and a common cause for termination of pregnancy during the second trimester when diagnosed via ultrasound.
• Sirenomelia (Mermaid Syndrome): A rare and fatal congenital disorder, observed in one case, characterized by the fusion of the lower limbs and associated with severe urogenital, gastrointestinal, and vascular anomalies. This condition often results in incompatible-with-life outcomes and is typically diagnosed prenatally.

Fig.01 and Fig.02  -composed of dilated lymphatic spaces involving adipose tissue &focal areas of fibrosis with scattered lymphocytes

Fig.a and Fig.b (H&E40x) primitive neural elements interspersed with enlarged, dilated blood vessels

Sirenomelia, commonly known as mermaid syndrome, is a rare congenital condition characterized by the fusion of the lower limbs

The present study highlights the significant diagnostic utility of fetal autopsy in cases of intrauterine fetal demise and congenital malformations. A probable diagnosis was reached in 42.85% of cases, affirming the value of autopsy in circumstances where clinical evaluations, imaging, and other diagnostic methods fail to provide definitive answers. This is particularly relevant in low- and middle-income settings, where advanced prenatal testing may not always be accessible or routinely performed.

In our cohort, a large majority of fetal deaths (82.14%) occurred before 37 weeks of gestation, indicating that most cases were preterm stillbirths. This observation is in line with findings by Bhale et al., who noted a high prevalence of fetal losses between 15–19 weeks, emphasizing the need for improved surveillance during the mid-trimester. In our study, spontaneous intrauterine fetal demise (IUFD) was rare, accounting for only 2%, while 14.85% were medically terminated pregnancies, primarily due to prenatally suspected anomalies. This underscores the importance of early and accurate prenatal imaging, which enables timely decision-making for parents and clinicians alike.

A key finding was the strong correlation (83.1%) between ultrasound and autopsy findings, indicating that modern prenatal imaging is largely accurate in identifying major structural anomalies. However, this correlation does not negate the role of fetal autopsy; rather, it complements and enhances the diagnostic picture. For instance, Fatima et al. reported a lower concordance rate of 34%, yet found that autopsy revealed additional findings in 47.5% of cases, many of which were clinically significant. Similarly, Shankar and Phadke emphasized that autopsy can confirm or correct misidentified anomalies seen on ultrasound—especially internal or subtle anomalies such as renal hypoplasia, minor cardiac defects, or CNS abnormalities that may not be fully visualized on imaging alone.

Across literature, diagnostic success rates vary depending on expertise and investigative approach. Faye Petersen et al. reported an impressive 94% diagnostic yield when fetal autopsies were performed by experienced pathologists in collaboration with clinicians. Pasztor et al. observed that combining autopsy with placental examination improved the ability to determine exact causes of death in 57.9% of stillbirths, reinforcing the value of a multidisciplinary approach to fetal demise.

In our study, the most frequent causes of death were of fetal origin, particularly congenital anomalies involving the central nervous system (CNS) and cardiovascular system (CVS), and in a few cases, infections. These findings are consistent with previous studies: Rasheed Fatima and Uroos Fatima reported that fetal causes accounted for 37.5% and 35.72% of perinatal deaths, respectively. CNS anomalies such as anencephaly, Arnold-Chiari malformation, and hydrocephalus, along with congenital heart diseases, continue to be leading contributors to fetal mortality, especially in regions with limited access to prenatal screening and folic acid supplementation.

While placental causes were less frequently identified in our study, their diagnostic utility is well supported in literature. Reggiani Bonetti et al. demonstrated that placental pathology could reduce the proportion of unexplained stillbirths from 20.16% to 15%. Similarly, Pekkola et al. and Uroos Fatima identified placental lesions—including infarction, chorioamnionitis, and vascular malformations—in 40–60% of cases. These lesions can significantly contribute to fetal hypoxia, growth restriction, and eventually demise, and their identification is crucial for guiding care in future pregnancies.

Maternal factors, though less prominent in our study, cannot be overlooked. Conditions like preeclampsia, hypothyroidism, and gestational diabetes are well-documented contributors to poor perinatal outcomes. Our findings are in agreement with those of Bhatia et al. and Thakur et al., who also noted these factors in a minority of cases. However, the clinical relevance lies in the fact that many maternal conditions are preventable or manageable, and failure to address them can result in recurrence in subsequent pregnancies.

Despite thorough autopsy evaluations, 20% of cases remained unexplained, echoing trends reported in broader literature. This residual unexplained group may reflect limitations in current diagnostic tools or may require molecular and genetic investigations, which are not yet routinely available in many Indian centers. Pekkola et al. emphasized that adoption of standardized postmortem protocols, along with genetic and metabolic work-ups, could further reduce the percentage of unexplained deaths.

An important barrier to comprehensive fetal evaluation is the declining rate of consent for autopsy, driven by cultural, religious, and financial factors. These limitations hamper our ability to uncover the causes of fetal death and provide closure to grieving families. Nevertheless, fetal autopsy remains invaluable—not only for determining the cause of death but also for guiding future pregnancies, improving the accuracy of prenatal imaging, and offering medicolegal clarity in cases of suspected negligence or malpractice.

Comparative Summary of Fetal Autopsy Studies with Specified Data

Fetal autopsy continues to be a cornerstone in the postmortem evaluation of intrauterine fetal demise and congenital anomalies, offering diagnostic clarity in a significant proportion of cases where clinical and radiological findings may be inconclusive or incomplete. In our study, a probable diagnosis was established in 42.85% of cases, underscoring its crucial role in enhancing diagnostic yield and supporting informed clinical decisions.

The high concordance rate between prenatal ultrasound and autopsy findings (83.1%) reaffirms the reliability of antenatal imaging, while also highlighting the autopsy’s unique value in confirming, refining, or identifying additional pathologies—particularly internal and subtle anomalies not evident on imaging alone. Congenital anomalies of fetal origin, especially involving the central nervous and cardiovascular systems, emerged as the predominant cause of fetal demise, aligning with existing literature and emphasizing the need for improved prenatal screening and early intervention strategies.

While placental and maternal factors contributed to a smaller proportion of cases, their identification remains critical, particularly for predicting and preventing recurrence in future pregnancies. The persistence of unexplained fetal deaths, despite comprehensive autopsy, calls for the integration of genetic, molecular, and placental evaluations into standard protocols.

Despite sociocultural and logistical challenges, fetal autopsy remains an indispensable diagnostic tool. It not only provides closure for grieving families but also serves as an essential guide for clinicians in managing subsequent pregnancies. Increasing awareness, promoting consent, and adopting a multidisciplinary approach—including clinicians, pathologists, radiologists, and geneticists—are vital steps toward improving perinatal outcomes and reducing preventable fetal loss.

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