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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 61  |  Issue : 4  |  Page : 495-499
An autopsy based descriptive study of the spectrum of pulmonary lesions encountered in fetal deaths at a tertiary care center


Department of Pathology, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, India

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Date of Web Publication10-Oct-2018
 

   Abstract 


Background: Fetal autopsy has been an indispensable tool in evaluating the cause of death. The most common cause for fetal deaths is associated with respiratory disorders accounting for around 60%. This study was undertaken to evaluate the gross and microscopic features of lungs in fetal autopsies and estimate the incidence of deaths attributable to pulmonary causes. Materials and Methods: All fetuses received for autopsy at our institute were included in the study with prior consent. Gross and microscopic findings along with relevant clinical data were recorded. Results: A total of 426 autopsies were conducted from January 2011 to August 2016. Of those, 184 had abnormal pulmonary findings constituting 43.19%. Aspiration pneumonia was the most common finding with 67 cases (36.4%), followed by atelectasis 54 cases (29.3%), congenital cystic adenomatoid malformation in 13 cases (7.1%), lung hypoplasia 12 cases (6.5%), pulmonary hemorrhage 21 (11.4%), 15 cases (8.15%) of hyaline membrane disease, one case (0.5%) of heterotaxy, and one case of extralobar pulmonary sequestration (0.5%). Congenital malformations of lungs were seen in 27 (14.67%) cases and 38 cases (20.65%) had other associated anomalies. Conclusion: Pulmonary pathology is the most common finding in fetal deaths with aspiration pneumonitis being the most common avoidable cause. Accurate fetal autopsy along with clinical data are important in evaluating fetal deaths and can help in reduction of unexplained stillbirths.

Keywords: Congenital lung malformation, fetal autopsy, pulmonary lesions

How to cite this article:
Neeha S, Kattimani SR, Mahanta AA, Patil AG. An autopsy based descriptive study of the spectrum of pulmonary lesions encountered in fetal deaths at a tertiary care center. Indian J Pathol Microbiol 2018;61:495-9

How to cite this URL:
Neeha S, Kattimani SR, Mahanta AA, Patil AG. An autopsy based descriptive study of the spectrum of pulmonary lesions encountered in fetal deaths at a tertiary care center. Indian J Pathol Microbiol [serial online] 2018 [cited 2018 Dec 19];61:495-9. Available from: http://www.ijpmonline.org/text.asp?2018/61/4/495/242983





   Introduction Top


Fetal death is defined as death occurring prior to the complete expulsion or extraction of the products of conception, independent of the duration of pregnancy, and is indicated by absent breathing, heartbeat, pulsating umbilical cord, or muscular movement and includes intrauterine and intrapartum deaths.[1] The fetal mortality rate is the number of fetal deaths × 1000, divided by the sum of live births and fetal deaths in a population.[1] More than a quarter of global deaths among neonates occur in India, being the highest in the world, accounting for 0.76 million deaths each year.[2] Perinatal mortality is the cause of socioeconomic loss and used as an indicator of health-care status, nevertheless, there is a paucity of framework for estimating the stillbirth burden and epidemiologic correlates.[3] About three-fourths of all neonatal deaths occur in the 1st week of life. The first 24 h account for more than one-third (36.9%) of the deaths that occur in the entire neonatal period.[2]

A systematic analysis of causes of perinatal mortality identified prematurity and infections to be the major causes of neonatal deaths in India. Perinatal asphyxia and malformations were found to be the other two significant causes of neonatal mortality.[2]

Fetal death is an unfortunate event for the family and they expect answers regarding the cause of death. Information from autopsy aids emotional and psychological recovery, provides diagnosis for proper counseling and future planning of pregnancy. Perinatal autopsy is the ideal investigation into the cause of perinatal death.[3] Immense progress has been made in the understanding of perinatal mortality over the past 50 years. Collection, compilation, analysis, and dissemination of reliable and standardized perinatal data are considered pillars of developing optimal quality perinatal care.[3] Autopsy remains a focal point for the integration of medical knowledge and provides critical data for medical quality assurance and ultimately, quality improvement.[4] Hence, knowledge of the gamut of common neonatal disorders in the Indian context is important, as it helps to ensure appropriate facilities and management protocol to improve survival of the fetus.

Since respiratory disorders remain a major cause of neonatal mortality and morbidity and respiratory pathology is the most common autopsy finding among early neonatal deaths, and also because studies exclusively on lung lesions in fetuses are less common, neonatal pulmonary pathology merits study.[5]


   Materials and Methods Top


All autopsies conducted during January 2011 to December 2016 were included in the study. Ethical clearance was obtained from the Institutional Ethics Committee. Data was collected from medical records. Autopsies were carried out according to the standard protocol. Anthropometric data were recorded for each fetus, and after thorough external examination, “I” shaped incision was taken and en bloc dissection done. Internal examination for gross organ anomaly was followed by sectioning of each organ for histopathological examination. Tissue was processed in an automated tissue processor, slides prepared from paraffin blocks, and stained with hematoxylin and eosin and examined for the microscopic features.


   Results Top


A total of 426 fetal autopsies were conducted from January 2011 to December 2016, out of which 184 cases showed pulmonary pathology as the primary or secondary cause of death accounting to 43.19% of cases. [Figure 1] describes the distribution of various lesions encountered. The age of fetuses ranged from 16 gestational weeks to postnatal day one, with most of cases in the age group of 28–32 weeks, followed by 32–36 weeks. Out of 184 cases, 86 were male and 91 were female accounting for 46.7% and 49.4%, respectively, with a male: female ratio of 0.9:1, showing slight female preponderance. In 7 cases, the sex could not be determined as the gestational age was less or fetus too small. The weight of the fetuses was in the range of 200 g to 3.5 kg with majority weighing 1 to 2 kg [Table 1], [Table 2], [Table 3].
Figure 1: Diagramatic representation of spectrum of various lesions encountered

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Table 1: Age-wise distribution of pulmonary lesion

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Table 2: Sex wise distribution of pulmonary lesions

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Table 3: Weight and age wise distribution of pulmonary lesions

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Among the various causes attributable to fetal deaths, Aspiration pneumonitis was found in 67 cases (36.4%). Majority of the cases showing aspiration pneumonia were in the age group of 28–36 weeks. Nine cases of aspiration pneumonia were associated with other anomalies such as hydrocephalus (2), ventricular septal defect (VSD) with an accessory lobe in liver and lung (1), meningocele (1), encephalocele (3), sacrococcygeal teratoma (1), Renal dysplasia and Single umbilical artery (1).

The second common finding was that of atelectasis accounting for 29.3% (54) of cases. Most common age group was 18–32 weeks. Thirty-eight cases were involved primarily and 16 cases were associated with other anomalies/syndromes, namely anencephaly (1), Anencephaly with holoacrania and rachischisis (1), hydrocephalus (3), biliary atresia (1), spina bifida (1), Potter's syndrome (1) with polycystic kidney disease (PKD) (1), Edwards syndrome (1), achondroplasia (1), atrial septal defect (ASD)-VSD (1), patent ductus arteriosus (1), hydrops (1), renal dysplasia (1), meningocele with hydrocephalus (1).

Congenital malformations of lung constituted the third group accounting to 14.67% (27 cases), with congenital cystic adenomatoid malformation (CCAM) in 13 (7.1%) cases and lung hypoplasia in 12 (6.5%) cases. There were four cases of CCAM Type 1, 3 cases of CCAM Type 2 and six cases of CCAM Type 3. One case was found in association with anencephaly, omphalocele, cleft palate and one more with hernia, left renal agenesis, and single umbilical artery. Renal dysplasia was seen in one case. Lung hypoplasia was bilateral in four cases, involved the left lobe in seven cases (where it was associated with diaphragmatic hernia), whereas one case showed extralobar pulmonary sequestration with left lung and left kidney hypoplasia and renal cystic dysplasia.

The next common finding was pulmonary hemorrhage with a total of 21 cases accounting for 11.4%, and in the age group of 24–28 weeks. There was one case each associated with ASD and hydrocephalus, spina bifida. There were 15 cases of hyaline membrane disease (HMD) (8.2%). One case of heterotaxy (0.5%) and a single case of extralobar pulmonary sequestration (0.5%).

Thirty-eight (24%) cases were associated with other congenital anomalies/syndromes including anencephaly, hydrocephalus, encephalocele, VSD, ASD, Ebstein's anomaly, Edwards' syndrome, and Potter's syndrome.


   Discussion Top


The study included 426 fetuses that were autopsied during the period of January 2011 to December 2016, in which lung lesions were found in 184 cases, accounting to 43.19%, of which majority of deaths occurred in 28–32 weeks fetuses and the common finding was aspiration pneumonia, seen in 36.4% of cases, comparable to Kamakeri et al. (25%).[6] Aspiration occurs during gasping in cases with intrauterine distress as with cesarean section, advanced gestational age, hypoxia and few cases have shown aspiration in preterm and premature babies.[1],[7],[8] Microscopically, it is characterized by the presence of anucleated squames in the alveolar spaces, and stained with meconium [Figure 2]a. The high incidence of aspiration indicates the need for better antenatal and intra-natal monitoring of the mother and fetus to avoid fetal distress and deaths.
Figure 2: Photomicrographs of (a) Aspiration pneumonia showing squames and meconium staining in the air spaces (H and E ×40). (b) Atelectasis showing collapsed alveolar spaces. (H and E ×10)

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Atelectasis was the second most common finding in our study, both as the primary and secondary cause of death, primary as in cases of prematurity (lack of surfactant), impaired breathing, cord compression and secondary in cases of lung infection or following aspiration. Microscopic findings in atelectasis are that of compressed alveolar walls [Figure 2]b. This could be kept in check by appropriate management of premature deliveries and monitoring lung infections. The study of D'costa et al.[5] found the incidence of atelectasis to be 52%, which was higher than the findings in our study [Table 4].
Table 4: Comparison of pulmonary lesions observed with other studies

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Congenital malformations involving the respiratory system namely lung hypoplasia and CCAM account for 14.67%, slightly higher than reported by Naik et al.[9] at 8.33%. Hakverdı et al.[10] reported an incidence of 2.5% and it was more common in females. Lung hypoplasia is one of the most common anomalies in neonates, defined as defective or incomplete development of lungs that are immature for gestational age. This could be primary with pathology in the lungs or secondary due to abnormality outside the respiratory tract like chest hypoplasia and diaphragmatic defect (other causes being renal agenesis and dysplastic cystic kidneys). The ultrasonographic finding of lung hypoplasia includes reduced thoracic diameter with cardiac shift [Figure 3]a. Microscopically, decreased radial alveolar counts is used as a tool to assess pulmonary hypoplasia [Figure 3]e and [Figure 3]f.[1] In case of a diaphragmatic hernia intestinal loops could be identified in the thoracic cavity [Figure 3]b and [Figure 3]c. We found 6.5% incidence of lung hypoplasia and 3.8% of cases associated with diaphragmatic hernia which correlated with 11.3% in a study of 850 cases done by Aghabiklooei et al.[11] which showed a higher incidence of diaphragmatic hernia [Table 4]. We found one case of heterotaxy in our study in a 30-week female fetus weighing 1.3 kg with right isomerism (dextrocardia and trilobed lungs) [Figure 3]d. We also found one case of extralobar pulmonary sequestration with left lung and left kidney hypoplasia and renal cystic dysplasia. Microscopically, it showed cystically dilated alveolar spaces and alveolar ducts with lymphoid hyperplasia. Kidneys showed glomeruli and tubules with multiple cystically dilated spaces lined by flattened epithelium.
Figure 3: (a) Ultrasonographic image of lung hypoplasia. (b) Ultrasonographic image of diaphragmatic hernia showing loop of intestine in the thoracic cavity. Gross photograph at autopsy showing (c) Diaphragmatic hernia. (d) Right-sided isomerism showing three lobes of lung. Photomicrograph of hypoplastic lung. The radial alveolar count is found to be decreased, (e) low power (f) high power

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CCAM is a rare congenital malformation of the lung representing 25% of congenital lung malformations and 95% of congenital lung lesions. Grossly, the greater part of the affected lobe is involved; the lobe is increased in size and weight and is devoid of its normal lobular pattern [Figure 4]a and [Figure 4]b. On cut section, the mass may consist of a single large cyst with multiple smaller ones about its periphery or more often, many large cavities with smaller cysts interspersed between them. Microscopy differs depending on the type of CCAM lesion, ranging from large multilocular cysts to small, uniform cysts lined by ciliated pseudostratified tall columnar epithelium to plump cuboidal or flattened cells.[1] [Figure 4]c and [Figure 4]d. We found the incidence to be 9.3% of lung lesion and 57% of congenital lung malformation which was higher compared to 0.8% as found by Kamakeri et al.[6] CCAM occurs more often in males (1.8:1), and is primarily unilateral, but may occur bilaterally. Associated anomalies are rare. In this study, it was associated with anencephaly, diaphragmatic hernia and Ebstein's anomaly.
Figure 4: Findings in a case of congenital cystic adenomatoid malformation (a) Ultrasonographic image of congenital cystic adenomatoid malformation of lung, demonstrating unilateral echogenic lung. (b) Gross picture of congenital cystic adenomatoid malformation lung at autopsy. Note the cysts at the base of the lung.(c) Photomicrograph of congenital cystic adenomatoid malformation type II showing cystic spaces lined by ciliated cuboidal to columnar cells. (d) Congenital cystic adenomatoid malformation type III showing air spaces lined by plump cuboidal epithelium. (e) Photomicrograph of pulmonary hemorrhage, showing extensive hemorrhage in the air spaces (×10). (f) High power view depicting red blood cells in the alveolar spaces (×40)

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Pulmonary hemorrhage is common in very low birth weight babies who suffer asphyxia or perinatal stress. It can be found in stillborn and live-born babies.[12] Grossly, the lungs appear heavy and dark-red and microscopically shows confluent areas of hemorrhage with blood-filled alveoli.[1] Microscopically, extensive hemorrhage was found in and around the air spaces. [Figure 4]e and [Figure 4]f. D'costa et al. reported the incidence of pulmonary hemorrhage to be 37.3%, which is high compared to 11.4% found in our study.[5]

HMD or respiratory distress syndrome (RDS) occurs due to surfactant deficiency leading to alveolar collapse and hypoxemia, resulting in diffuse alveolar damage. Microscopically, they appear as smooth, homogeneous, eosinophilic membranes lining the terminal bronchioles, and alveolar ducts and are composed of necrotic alveolar cells, plasma transudate, aspirated squamous cells, and fibrin. Polymorphonuclear cells may infiltrate and can be seen if infection supervenes RDS.[13] In this study, the incidence of HMD is 8.2%, comparable to D'costa et al. (10.6%).[5] Microscopically, the small airways containing the hyaline membranes are surrounded by collapsed acini of the surfactant-deficient lungs. Extra lobar pulmonary sequestration was seen in 24-week male fetus weighing 750 g.


   Conclusion Top


Improving perinatal mortality in India is the need of the hour. Accurate fetal autopsy along with clinical data is important in evaluating fetal deaths and can help in reduction of unexplained stillbirths. Majority of the lesions responsible for fetal deaths are modifiable and such studies can help in further categorizing fetal death.

We found pulmonary lesions to be the most common and modifiable cause of death. Improvement in socioeconomic condition, maternal nutrition, health education, antenatal care, intrapartum management, and neonatal intensive care along with referral system can be helpful in reducing the incidence of aspiration pneumonia, atelectasis and HMD as they constitute the major cause of death and thus reducing perinatal mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Askin FB, Gilbert-Barness E. Respiratory system. In: Gilbert-Barness E, editor. Potter's Pathology of the Fetus, Infant and Child. 2nd ed. St. Louis: Mosby, Elsevier; 2007. p. 1096-133.  Back to cited text no. 1
    
2.
Zodpey S, Paul VK. PHFI, AIIMS, and SC- State of India's Newborns (SOIN) 2014 – A report. New Delhi, India: Public Health Foundation of India, All India Institute of Medical Sciences and Save the Children; 2014.  Back to cited text no. 2
    
3.
Pradhan R, Mondal S, Adhya S, Raychaudhuri G. Perinatal autopsy: A study from India. J Indian Acad Forensic Med 2013;35:10-3.  Back to cited text no. 3
    
4.
Finkbeiner WE, Ursell PC, Davis RL. Autopsy Pathology: A Manual and Atlas. 2nd ed. Philadelphia: Saunders, Elsevier; 2009. p. 9-11.  Back to cited text no. 4
    
5.
D'costa GF, Chincholikar M, Patil Y. Trends in neonatal lung pathology. Bombay Hospital J 2006; 48:547-60.  Back to cited text no. 5
    
6.
Kamakeri NS, Ramalingappa CA, Vinayraju D. Study of perinatal autopsies in tertiary care hospital 20-year experience. Int J Reprod Contracept Obstet Gynecol 2017; 6:2914-8.  Back to cited text no. 6
    
7.
Dargaville PA, Copnell B; Australian and New Zealand Neonatal Network. The epidemiology of meconium aspiration syndrome: Incidence, risk factors, therapies, and outcome. Pediatrics 2006; 117:1712-21.  Back to cited text no. 7
    
8.
Liu WF, Harrington T. Delivery room risk factors for meconium aspiration syndrome. Am J Perinatol 2002; 19:367-78.  Back to cited text no. 8
    
9.
Naik V, Babu P, Reddy ES, Prasad BV, Radha BA, Myreddy N, et al. Study of various congenital anomalies in fetal and neonatal autopsy. Int J Res Med Sci 2015; 3:1114-21.  Back to cited text no. 9
    
10.
Hakverdı S, Güzelmansur I, Güngören A, Toprak S, Yaldiz M, Hakverdı AU, et al. Evaluation of fetal autopsy findings in the Hatay region: 274 cases. Turk Patoloji Derg 2012; 28:154-61.  Back to cited text no. 10
    
11.
Aghabiklooei A, Goodarzi P, Kariminejad MH. Lung hypoplasia and its associated major congenital abnormalities in perinatal death: An autopsy study of 850 cases. Indian J Pediatr 2009; 76:1137-40.  Back to cited text no. 11
    
12.
Becroft DM, Thompson JM, Mitchell EA. Pulmonary interstitial hemosiderin in infancy: A common consequence of normal labor. Pediatr Dev Pathol 2005; 8:448-52.  Back to cited text no. 12
    
13.
Agrons GA, Courtney SE, Stocker JT, Markowitz RI. From the archives of the AFIP: Lung disease in premature neonates: Radiologic-pathologic correlation. Radiographics 2005; 25:1047-73.  Back to cited text no. 13
    

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Correspondence Address:
Saara Neeha
#5-739, Roza Khurd, Kalaburagi, Karnataka - 585 104
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_461_17

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