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PATHOMORPHOLOGICAL FEATURES OF THE ADRENAL GLANDS OF INFANTS
WHO DIED OF ASPHYXIA.
Sayfiddin Khoji Kadriddin Shuhrat ugli
Babaev Khamza Nurmatovich
Allaberganov Dilshod Shavkatovich
Khujakulov Mukhammadrizo Saminjon ugli
Nabieva Dilshodaxon Davronbekovna
Murodullayev Mironshokh Nodirbek ugli
Eshonkhodjaeva Madinakhon Otabek kizi
Ismailov Baurzhan Bakhtzhanovich
Botirkhujaeva Azizakhon Anvarkhoja kizi
Akhmedov Diyorbek Anvar ugli
Khashimova Laziza Ulugbek kizi
Master’s student in Pathological Anatomy, Tashkent State Medical University,
dr.sayfiddinkhoji@gmail.com, Orcid: https://orcid.org/0009-0000-5476-5242;
Associate professor of the Pathological anatomy department, PhD, Tashkent State Medical
University, khamzababaev@gmail.com
Orcid:https://orcid.org/0009-0009-1033-1472;
Assistent of the Pathological anatomy department, PhD, Tashkent State Medical University, The
Republican Center of Pathological Anatomy
dilshodbek9347225@mail.ru, Orcid: https://orcid.org/0009-0003-1558-5101;
Bachelor student of Tashkent State Medical University,
muhammadrizoxojaqulov29@gmail.com, Orcid: https://orcid.org/0009-0004-2050-8204;
Bachelor student of Tashkent State Medical University.
dilshodanabieva981@gmail.com, Orcid: https://orcid.org/0009-0008-3330-4867;
Bachelor student of Tashkent State Medical University.
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mironshoxmurodullayev@gmail.com Orcid: https://orcid.org/0009-0004-7474-1722;
Bachelor student of Tashkent State Medical University,
madi270105@gmail.com, Orcid: https://orcid.org/0009-0006-9714-0190;
Bachelor student of Tashkent State Medical University,
baur3355@gmail.com, Orcid: https://orcid.org/0009-0009-0426-4410;
Bachelor student of Tashkent State Medical University,
azizaxon.botirhujaeva@mail.ru, Orcid: https://orcid.org/0009-0004-9364-0396;
Bachelor student of Tashkent State Medical University,
akhmedovdiyorbek25@gmail.com, Orcid: https://orcid.org/0009-0006-6507-9604;
Bachelor student of Tashkent State Medical University,
lazikhashimova@gmail.com, Orcid: https://orcid.org/0009-0003-0971-5133
Tashkent, 100109, Uzbekistan.
Annotation:
Perinatal asphyxia remains a leading cause of neonatal mortality and morbidity
worldwide, with complex pathophysiological mechanisms affecting multiple organ systems. To
investigate the specific pathomorphological changes in adrenal glands of infants who died from
perinatal asphyxia and correlate these findings with clinical parameters and duration of hypoxic
exposure. A retrospective autopsy study was conducted on 156 infants who died from perinatal
asphyxia over a 5-year period (2019-2024). Detailed histopathological examination of adrenal
glands was performed using standard H&E staining, immunohistochemistry, and electron
microscopy. Control group consisted of 78 infants who died from non-asphyxial causes.
Significant pathomorphological changes were observed in 89.7% (140/156) of asphyxiated
infants compared to 12.8% (10/78) in controls (p<0.001). Primary findings included cortical
hemorrhage (67.3%), zona fasciculata lipid depletion (78.2%), medullary chromaffin cell
necrosis (45.5%), and capsular thickening (56.4%). Severity of changes correlated positively
with duration of asphyxia (r=0.742, p<0.001) and inversely with Apgar scores (r=-0.689,
p<0.001). These findings contribute to understanding the pathophysiology of asphyxial death and
may have implications for forensic diagnosis and therapeutic interventions.
Keywords:
Perinatal asphyxia, adrenal glands, pathomorphology, hypoxic-ischemic injury,
cortical hemorrhage, chromaffin cells, neonatal pathology, forensic pathology
Introduction
Perinatal asphyxia, defined as the failure to establish adequate gas exchange at birth, affects 2-10
per 1000 live births globally and accounts for approximately 23% of all neonatal deaths. The
condition results from various antepartum, intrapartum, or postpartum factors that compromise
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oxygen delivery to fetal or neonatal tissues, leading to progressive hypoxemia, hypercapnia, and
metabolic acidosis.
The pathophysiology of perinatal asphyxia involves a complex cascade of cellular and molecular
events triggered by oxygen deprivation. During hypoxic episodes, the fetal cardiovascular
system undergoes adaptive changes, including redistribution of cardiac output to protect vital
organs such as the brain, heart, and adrenal glands. However, prolonged or severe asphyxia
overwhelms these compensatory mechanisms, resulting in multi-organ dysfunction and
potentially fatal outcomes.
The adrenal glands play a crucial role in the physiological response to stress and hypoxia through
the hypothalamic-pituitary-adrenal (HPA) axis activation and catecholamine release. These
paired endocrine organs, weighing approximately 2-4 grams in newborns, consist of two
functionally distinct regions: the outer cortex, responsible for steroid hormone production, and
the inner medulla, which synthesizes and releases catecholamines.
Previous studies have documented various pathological changes in adrenal glands following
hypoxic-ischemic injury, including hemorrhage, necrosis, and functional alterations. However,
comprehensive morphological characterization of these changes in the context of perinatal
asphyxia remains limited. Understanding the specific pathomorphological features of adrenal
involvement in asphyxiated infants is essential for several reasons: it provides insights into the
pathophysiology of asphyxial death, aids in forensic diagnosis, and may guide therapeutic
interventions in survivors.
Recent advances in histopathological techniques, including immunohistochemistry and electron
microscopy, have enabled more detailed characterization of cellular and subcellular changes in
hypoxic-ischemic injury. Additionally, correlation of morphological findings with clinical
parameters such as Apgar scores, umbilical cord blood gas analysis, and neuroimaging findings
can provide valuable information about the severity and progression of asphyxial injury.
The present study aims to systematically investigate the pathomorphological alterations in
adrenal glands of infants who died from perinatal asphyxia, utilizing a comprehensive approach
that includes gross examination, light microscopy, immunohistochemistry, and ultrastructural
analysis. By correlating these findings with clinical parameters and comparing them to controls,
we seek to establish a detailed morphological profile of adrenal involvement in perinatal
asphyxia.
Materials and Methods
Study Design and Population
This retrospective autopsy-based study was conducted at the Department of Pathology, Regional
Perinatal Center, over a 5-year period from January 2019 to December 2024. The study protocol
was approved by the Institutional Ethics Committee (Protocol No. 2019-PE-087) and conducted
in accordance with the Declaration of Helsinki principles.
Study Group:
The study population comprised 156 infants who died from perinatal asphyxia,
diagnosed based on established criteria including: (1) Apgar score ≤3 at 5 minutes, (2) umbilical
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cord arterial pH <7.00 or base deficit ≥16 mmol/L, (3) clinical evidence of acute or subacute
hypoxic-ischemic encephalopathy, and (4) exclusion of other primary causes of death.
Control Group:
A control group of 78 infants who died from non-asphyxial causes (congenital
anomalies, sepsis, sudden infant death syndrome) was included for comparison. All control cases
had normal Apgar scores (≥7 at 5 minutes) and no clinical evidence of significant hypoxic
episodes.
Inclusion and Exclusion Criteria
Inclusion Criteria:
Infants aged 0-28 days at time of death
Complete autopsy examination performed within 24 hours of death
Adequate preservation of adrenal gland tissue for histopathological analysis
Available clinical records including birth history, Apgar scores, and blood gas analysis
Exclusion Criteria:
Infants with known adrenal pathology (congenital adrenal hyperplasia, tumors)
Cases with extensive autolysis preventing adequate histopathological assessment
Incomplete clinical documentation
Parental refusal for autopsy examination
Clinical Data Collection
Comprehensive clinical data were collected from medical records, including:
Gestational age and birth weight
Mode of delivery and duration of labor
Apgar scores at 1, 5, and 10 minutes
Umbilical cord blood gas parameters (pH, pCO2, pO2, base excess)
Duration of resuscitation efforts
Neuroimaging findings (when available)
Time from birth to death
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Autopsy Procedures
All autopsies were performed by experienced pediatric pathologists using standardized protocols.
The adrenal glands were carefully dissected, weighed, and measured. Gross examination
included assessment of size, shape, color, consistency, and presence of hemorrhage or other
abnormalities.
Histopathological Examination
Tissue Processing:
Adrenal gland specimens were fixed in 10% neutral buffered formalin for
24-48 hours, processed through graded alcohols and xylene, and embedded in paraffin wax.
Serial sections of 4-5 μm thickness were cut and mounted on glass slides.
Routine Staining:
Hematoxylin and eosin (H&E) staining was performed on all cases for
routine histopathological examination. Additional special stains included:
Periodic acid-Schiff (PAS) for glycogen demonstration
Oil Red O for lipid visualization (on frozen sections)
Masson's trichrome for collagen assessment
Reticulin stain for architectural evaluation
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Immunohistochemistry:
Selected cases underwent immunohistochemical analysis using the
following antibodies:
Chromogranin A (1:500, Dako) for chromaffin cells
Synaptophysin (1:200, Dako) for neuroendocrine cells
CD68 (1:100, Dako) for macrophages
Ki-67 (1:400, Dako) for proliferation assessment
Cleaved caspase-3 (1:200, Cell Signaling) for apoptosis detection
Electron Microscopy
Ultrastructural examination was performed on 45 selected cases using transmission electron
microscopy. Small tissue blocks (1mm³) were fixed in 2.5% glutaraldehyde in phosphate buffer,
post-fixed in 1% osmium tetroxide, dehydrated, and embedded in epoxy resin. Ultrathin sections
were stained with uranyl acetate and lead citrate and examined using a JEOL JEM-1400
transmission electron microscope.
Morphological Assessment
Pathomorphological changes were systematically evaluated and scored according to predefined
criteria:
Cortical Changes:
Hemorrhage: absent (0), focal (1), multifocal (2), diffuse (3)
Lipid depletion: absent (0), mild (1), moderate (2), severe (3)
Necrosis: absent (0), focal (1), multifocal (2), extensive (3)
Inflammatory infiltrate: absent (0), mild (1), moderate (2), marked (3)
Medullary Changes:
Chromaffin cell necrosis: absent (0), focal (1), multifocal (2), extensive (3)
Vascular congestion: absent (0), mild (1), moderate (2), severe (3)
Hemorrhage: absent (0), focal (1), multifocal (2), diffuse (3)
Capsular and Stromal Changes:
Capsular thickening: absent (0), mild (1), moderate (2), marked (3)
Fibrosis: absent (0), minimal (1), moderate (2), extensive (3)
Statistical Analysis
Statistical analysis was performed using SPSS version 28.0 (IBM Corporation, Armonk, NY).
Categorical variables were expressed as frequencies and percentages, while continuous variables
were presented as mean ± standard deviation or median with interquartile range, depending on
distribution normality assessed by the Shapiro-Wilk test.
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Group comparisons were performed using chi-square test or Fisher's exact test for categorical
variables and Student's t-test or Mann-Whitney U test for continuous variables. Correlation
analysis was conducted using Pearson's or Spearman's correlation coefficients as appropriate.
Multiple logistic regression analysis was performed to identify independent predictors of specific
pathomorphological changes. Statistical significance was set at p<0.05 for all analyses.
Results
Clinical Characteristics
The study population consisted of 156 infants who died from perinatal asphyxia (study group)
and 78 controls who died from non-asphyxial causes. The demographic and clinical
characteristics are summarized in Table 1.
Table 1: Clinical Characteristics of Study Population
Parameter
Asphyxia Group (n=156) Control Group (n=78) p-value
Gestational age (weeks) 37.2 ± 3.1
36.8 ± 2.9
0.342
Birth weight (grams)
2847 ± 612
2793 ± 598
0.518
Male sex, n (%)
89 (57.1)
42 (53.8)
0.649
Cesarean delivery, n (%) 78 (50.0)
31 (39.7)
0.148
Apgar score at 5 min
2.1 ± 1.2
8.2 ± 0.9
<0.001
Umbilical artery pH
6.89 ± 0.15
7.28 ± 0.08
<0.001
Base excess (mmol/L)
-18.7 ± 4.3
-2.1 ± 1.8
<0.001
Age at death (hours)
28.4 ± 16.7
72.3 ± 48.2
<0.001
Adrenal Gland Morphometry
Adrenal glands from asphyxiated infants showed significant alterations in weight and dimensions
compared to controls. The combined adrenal weight was significantly increased in the asphyxia
group (8.7 ± 2.1 g vs. 6.2 ± 1.4 g, p<0.001), primarily due to congestion and hemorrhage. The
cortex-to-medulla ratio was preserved in most cases (2.8 ± 0.6 vs. 2.9 ± 0.5, p=0.234).
Gross Pathological Findings
Macroscopic examination revealed abnormalities in 134 of 156 (85.9%) adrenal glands from
asphyxiated infants compared to 8 of 78 (10.3%) controls (p<0.001). The most common gross
findings included:
Hemorrhage:
Present in 105/156 (67.3%) asphyxia cases vs. 3/78 (3.8%) controls
(Image 1.)
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Image 1.
Congestion:
Observed in 118/156 (75.6%) asphyxia cases vs. 12/78 (15.4%) controls
Swelling:
Noted in 92/156 (59.0%) asphyxia cases vs. 6/78 (7.7%) controls(Image 2)
Image 2.
Color changes:
Documented in 87/156 (55.8%) asphyxia cases vs. 4/78 (5.1%) controls
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Histopathological Findings
Microscopic examination revealed significant pathomorphological changes in adrenal glands of
asphyxiated infants across all anatomical zones.
Cortical Changes
Zona Glomerulosa:
Cellular swelling was observed in 89/156 (57.1%) cases
Nuclear pyknosis and karyorrhexis in 67/156 (42.9%) cases
Lipid accumulation in 45/156 (28.8%) cases
Vascular congestion in 112/156 (71.8%) cases
Zona Fasciculata:
Lipid depletion was the most consistent finding, present in 122/156 (78.2%) cases
Cellular vacuolization in 98/156 (62.8%) cases
Eosinophilic change in 76/156 (48.7%) cases
Focal necrosis in 58/156 (37.2%) cases
Zona Reticularis:
Eosinophilia and cellular shrinkage in 71/156 (45.5%) cases
Nuclear condensation in 63/156 (40.4%) cases
Lipofuscin accumulation in 34/156 (21.8%) cases
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Medullary Changes
Significant alterations were observed in the adrenal medulla:
Chromaffin cell necrosis:
71/156 (45.5%) cases showed focal to extensive necrosis
Vascular congestion:
Present in 89/156 (57.1%) cases
Hemorrhage:
Observed in 52/156 (33.3%) cases
Inflammatory infiltrate:
Mild to moderate infiltration in 43/156 (27.6%) cases
Vascular and Stromal Changes
Capsular thickening:
Documented in 88/156 (56.4%) cases
Sinusoidal congestion:
Present in 127/156 (81.4%) cases
Endothelial swelling:
Observed in 94/156 (60.3%) cases
Microthrombi formation:
Noted in 23/156 (14.7%) cases
Immunohistochemical Findings
Immunohistochemical analysis revealed important functional alterations:
Chromogranin A:
Decreased expression in medullary chromaffin cells was observed in 68/89
(76.4%) tested cases, indicating impaired neuroendocrine function.
Synaptophysin:
Reduced staining intensity in 61/89 (68.5%) cases, correlating with chromaffin
cell damage.
CD68:
Increased macrophage infiltration was noted in 34/89 (38.2%) cases, particularly in areas
of necrosis and hemorrhage.
Ki-67:
Proliferation index was generally low (<2%) in both cortical and medullary regions.
Cleaved caspase-3:
Positive staining indicating apoptosis was present in 45/89 (50.6%) cases,
predominantly in the zona fasciculata and medulla.
Ultrastructural Findings
Electron microscopy examination of 45 selected cases revealed detailed subcellular changes:
Cortical Cells:
Mitochondrial swelling and cristae disruption in 38/45 (84.4%) cases
Lipid droplet depletion in zona fasciculata cells: 35/45 (77.8%) cases
Nuclear chromatin condensation: 28/45 (62.2%) cases
Endoplasmic reticulum dilatation: 31/45 (68.9%) cases
Chromaffin Cells:
Dense-core vesicle depletion: 26/45 (57.8%) cases
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Cytoplasmic vacuolization: 22/45 (48.9%) cases
Nuclear pyknosis: 19/45 (42.2%) cases
Mitochondrial damage: 33/45 (73.3%) cases
Correlation with Clinical Parameters
Strong correlations were observed between pathomorphological findings and clinical parameters:
Apgar Scores:
Inverse correlation with cortical hemorrhage (r = -0.689, p<0.001)
Inverse correlation with lipid depletion severity (r = -0.634, p<0.001)
Inverse correlation with medullary necrosis (r = -0.578, p<0.001)
Umbilical Cord pH:
Inverse correlation with overall pathological score (r = -0.723, p<0.001)
Stronger correlation with cortical changes (r = -0.698) than medullary changes (r = -0.542)
Duration of Asphyxia:
Positive correlation with severity of changes (r = 0.742, p<0.001)
Particularly strong correlation with chromaffin cell necrosis (r = 0.687, p<0.001)
Severity Scoring System
Based on the observed changes, a comprehensive pathomorphological severity score was
developed:
Mild (Score 1-4):
Focal cortical changes, minimal medullary involvement
Present in 23/156 (14.7%) cases
Associated with shorter asphyxia duration (<30 minutes)
Moderate (Score 5-8):
Multifocal cortical and medullary changes
Present in 67/156 (42.9%) cases
Intermediate clinical parameters
Severe (Score 9-12):
Extensive cortical and medullary necrosis with hemorrhage
Present in 66/156 (42.3%) cases
Associated with prolonged asphyxia and lowest Apgar scores
Age-Related Changes
Analysis of changes relative to postnatal age revealed:
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0-24 hours:
Predominantly acute changes (hemorrhage, congestion)
24-72 hours:
Mixed acute and subacute changes (early necrosis, inflammatory infiltrate)
>72 hours:
Predominantly subacute changes (established necrosis, early repair)
Discussion
The present study provides comprehensive morphological characterization of adrenal gland
pathology in perinatal asphyxia, demonstrating consistent and severe alterations that reflect both
the acute stress response and hypoxic-ischemic damage. The high prevalence of
pathomorphological changes (89.7%) in our asphyxiated cohort, compared to minimal changes
in controls (12.8%), underscores the particular vulnerability of adrenal tissue to hypoxic injury.
Pathophysiological Mechanisms
The observed pathomorphological changes can be understood within the context of the complex
pathophysiology of perinatal asphyxia. During hypoxic episodes, the fetal stress response leads
to massive activation of the hypothalamic-pituitary-adrenal axis, resulting in increased cortisol
and catecholamine production. This hyperactivity, while initially adaptive, becomes detrimental
during prolonged asphyxia.
The predominant finding of lipid depletion in the zona fasciculata (78.2% of cases) reflects the
rapid mobilization of cholesterol esters for steroid hormone synthesis during stress. This finding
is consistent with previous experimental studies demonstrating increased steroidogenesis during
hypoxic stress. The correlation between lipid depletion severity and clinical markers of asphyxia
(Apgar scores, umbilical cord pH) suggests that this morphological change serves as a reliable
indicator of stress response magnitude.
Cortical hemorrhage, observed in 67.3% of cases, likely results from multiple factors including
increased vascular permeability due to hypoxia, elevated catecholamine levels causing
vasoconstriction and subsequent reperfusion injury, and direct endothelial damage from acidosis.
The adrenal glands' rich vascular supply, while normally advantageous for hormone transport,
predisposes them to hemorrhagic complications during hypoxic-ischemic episodes.
Chromaffin Cell Pathology
The significant medullary changes, particularly chromaffin cell necrosis (45.5% of cases), reflect
the dual vulnerability of these cells to hypoxic damage and catecholamine depletion. Chromaffin
cells are metabolically active and highly dependent on adequate oxygen supply for
catecholamine synthesis and vesicle transport. The observed ultrastructural changes, including
dense-core vesicle depletion and mitochondrial damage, support the concept of functional
exhaustion followed by cellular death.
The immunohistochemical findings of decreased chromogranin A and synaptophysin expression
provide additional evidence of functional impairment. These proteins are essential for
catecholamine storage and release, and their reduction indicates compromised neuroendocrine
function. This may have important implications for surviving infants, as adrenal insufficiency
could contribute to hemodynamic instability and poor outcomes.
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Temporal Evolution of Changes
Our findings suggest a temporal progression of pathomorphological changes. Early changes (0-
24 hours) are predominantly vascular and include congestion, hemorrhage, and acute cellular
swelling. These reflect the immediate response to hypoxic injury and hemodynamic alterations.
Intermediate changes (24-72 hours) involve the development of cellular necrosis and early
inflammatory response, while late changes (>72 hours) show established necrosis with beginning
repair processes.
This temporal pattern has important forensic implications, as the morphological findings may
help estimate the timing and duration of asphyxial episodes. The strong correlation between
pathological severity and clinical parameters supports the use of adrenal morphology as an
adjunct in forensic diagnosis of perinatal asphyxia.
Comparison with Literature
Our findings are consistent with previous studies but provide more detailed morphological
characterization. Hankins et al. reported adrenal hemorrhage in 45% of asphyxiated newborns,
lower than our 67.3%, possibly due to differences in diagnostic criteria and population
characteristics. The high prevalence of lipid depletion in our study (78.2%) exceeds previous
reports, likely due to our comprehensive histochemical analysis including Oil Red O staining.
The correlation coefficients we observed between morphological changes and clinical
parameters (r = 0.689-0.742) are stronger than previously reported, possibly reflecting our
systematic scoring approach and larger sample size. These strong correlations support the
concept that adrenal morphology accurately reflects the severity of asphyxial injury.
Clinical and Forensic Implications
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From a clinical perspective, our findings suggest that adrenal dysfunction may be an
underrecognized component of perinatal asphyxia. The extensive cortical damage observed
could result in transient or permanent adrenal insufficiency, contributing to hemodynamic
instability, hypoglycemia, and electrolyte imbalances in survivors. This supports the
consideration of cortisol supplementation in severely asphyxiated infants, although this remains
controversial and requires further clinical investigation.
The forensic implications are significant, as adrenal pathology may serve as valuable evidence in
cases where perinatal asphyxia is suspected but clinical documentation is incomplete. The
consistency of findings and strong correlations with objective clinical parameters support the
reliability of adrenal examination in forensic settings.
Methodology Considerations
Our study benefited from several methodological strengths, including a large sample size,
comprehensive pathological examination using multiple techniques, and systematic correlation
with clinical parameters. The use of electron microscopy in selected cases provided valuable
ultrastructural information that enhanced understanding of cellular pathology.
However, certain limitations should be acknowledged. The retrospective design limited our
ability to control for all confounding variables, and the autopsy population may not fully
represent the spectrum of perinatal asphyxia. Additionally, the lack of functional studies
(hormone measurements) prevented correlation of morphological changes with endocrine
dysfunction.
Future Research Directions
Several areas warrant further investigation. Prospective studies correlating morphological
findings with hormonal measurements in both fatal and non-fatal cases would provide valuable
functional correlation. Investigation of potential therapeutic interventions to protect adrenal
function during asphyxia could have important clinical applications.
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The development of non-invasive imaging techniques to assess adrenal pathology in living
infants could enable early diagnosis and intervention. Additionally, molecular studies
investigating the cellular and genetic mechanisms underlying adrenal vulnerability to hypoxic
injury could provide insights for targeted therapies.
Long-term follow-up studies of survivors with significant adrenal pathology would help
determine the clinical significance of these changes and the need for endocrine monitoring and
intervention.
Conclusion
This comprehensive study demonstrates that adrenal glands undergo consistent and severe
pathomorphological alterations in perinatal asphyxia, with changes affecting both cortical and
medullary regions. The high prevalence of abnormalities (89.7%) and strong correlations with
clinical parameters establish adrenal pathology as a reliable marker of asphyxial injury severity.
The most significant findings include cortical hemorrhage (67.3%), zona fasciculata lipid
depletion (78.2%), and medullary chromaffin cell necrosis (45.5%). These changes reflect both
the physiological stress response and direct hypoxic-ischemic damage, with severity correlating
strongly with clinical markers of asphyxia including Apgar scores (r = -0.689) and umbilical
cord pH (r = -0.723).
The temporal evolution of changes, from acute vascular alterations to established necrosis,
provides insights into the pathophysiology of asphyxial death and has important forensic
applications. The detailed morphological characterization presented here contributes to our
understanding of perinatal asphyxia pathophysiology and may guide future therapeutic
interventions.
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From a clinical perspective, these findings suggest that adrenal dysfunction may be an
underrecognized component of perinatal asphyxia, with potential implications for the
management of survivors. The consistency and severity of adrenal pathology support the
inclusion of detailed adrenal examination in all cases of suspected perinatal asphyxia.
Future research should focus on correlating morphological findings with functional outcomes,
developing non-invasive diagnostic methods, and investigating therapeutic strategies to protect
adrenal function during hypoxic episodes. Such studies may ultimately improve outcomes for
infants affected by perinatal asphyxia, one of the leading causes of neonatal mortality and
morbidity worldwide.
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ISSN: 3030-3931, Impact factor: 7,241
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