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Pathological and Genetic Analysis of Foetuses with Ultrasonogram Detected Congenital Anomalies: A Cross-sectional Study from Southern India |
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S Ramya Devi, Tanya Salim, Uma Thankam 1. Consultant, Department of Obstetrics and Gynaecology, Annai Velankanni Fertility Centre, Velankanni, Tamil Nadu, India. 2. Additional Professor, Department of Obstetrics and Gynaecology, Government Medical College, Trivandrum, Kerala, India. 3. Additional Professor, Department of Obstetrics and Gynaecology, Government Medical College, Trivandrum, Kerala, India. |
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Correspondence Address : Tanya Salim, Shadi Manzil, Attinkuzhi, Kazhakuttom, Trivandrum-695582, Kerala, India. E-mail: drtanyasharmad@gmail.com |
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| ABSTRACT |  | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
: Introduction: Prenatal Ultrasonogram (USG) detects the majority of congenital anomalies, but a few cases may be missed due to multiple reasons. Hence, a detailed post-mortem evaluation of foetuses following termination of pregnancy can help to arrive at a final diagnosis and aid in counselling couples about future pregnancies. Aim: To compare prenatal ultrasound findings with autopsy findings and karyotyping in medically terminated foetuses between 12 and 20 weeks of gestation. Materials and Methods: A cross-sectional hospital-based study was conducted at Department of Obstetrics and Gynaecology (OBG), Government Medical College, Trivandrum, Kerala, India, from February 2018 to January 2019. Pregnant women who underwent Medical Termination of Pregnancy (MTP) for ultrasound-detected congenital anomalies between 12 and 20 weeks were included in the study. A detailed foetal autopsy was done and karyotyping of the foetuses was carried out. Prenatal ultrasound findings were compared with the ultrasound reports. Descriptive statistics were used and results were expressed in terms of frequency and percentages. Results: The mean maternal age of the study participants was 26.32±4.9 years. Among the 50 foetuses examined, majority had Central Nervous System (CNS) anomalies, with 34 cases (46.5%). Foetal autopsy confirmed the ultrasound findings in all cases except one, resulting in 49 confirmed cases. Autopsy had full agreement with prenatal ultrasonogram in 28 cases (56%). Major additional autopsy findings were noted in 10 cases (20%), minor additional findings in 7 cases (14%) and both minor and major additional findings in 4 cases (8%). Major congenital anomalies are those that have medical, surgical, or cosmetic significance, like neural tube defects or orofacial clefting. Conclusion: Foetal autopsy plays a major role in providing additional information for counselling couples and the management of future pregnancies. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Keywords : Foetal autopsy, Karyotyping, Prenatal ultrasound | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DOI and Others :
DOI: 10.7860/IJNMR/2025/69071.2440
Date of Submission: Dec 13, 2023 Date of Peer Review: Jan 31, 2024 Date of Acceptance: Feb 24, 2025 Date of Publishing: Jun 30, 2025 AUTHOR DECLARATION: • Financial or Other Competing Interests: None • Was Ethics Committee Approval obtained for this study? Yes • Was informed consent obtained from the subjects involved in the study? Yes • For any images presented appropriate consent has been obtained from the subjects. NA PLAGIARISM CHECKING METHODS: • Plagiarism X-checker: Dec 13, 2023 • Manual Googling: Feb 17, 2025 • iThenticate Software: Feb 22, 2025 (11%) ETYMOLOGY: Author Origin EMENDATIONS: 7 |
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| INTRODUCTION |
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Foetal structural anomalies occur in 3-5% of all pregnancies (1). Progress in imaging technology has improved the antenatal detection rates of these anomalies. While 18-20 week scan remains the standard of care in most countries, first-trimester ultrasound, along with biochemical markers, has gained much importance in recent years (2). Routine prenatal ultrasound has been the most important tool for assessing foetal anatomy since 1985 (3). It provides the options of termination of pregnancy owing to serious foetal malformations, depending on personal choice as well as ethical and legal considerations. Although advancement in imaging techniques have improved the accuracy of prenatal ultrasound, some abnormalities may still be missed. This may be due to factors such as oligohydramnios, maternal obesity, or foetal position. The risk of false positive diagnosis is a major concern (4). Post-mortem examination of aborted foetuses is an important tool for assessing the quality and accuracy of obstetric sonologists. It is also useful in counselling parents regarding future pregnancies. Numerous studies have compared prenatal ultrasound and autopsy findings, but they vary in inclusion criteria (5),(6),(7) and in their definition of major and minor structural anomalies. Extensive research over the last 15 years has established that the measurement of Nuchal Translucency (NT) provides effective and early screening for chromosome defects. Increased NT is also associated with cardiac defects and other foetal structural malformations (6). The risk of chromosomal abnormalities increases with both maternal age and NT thickness and in pregnancies with low foetal NT, the maternal age-related risk decreases (6),(7),(8). According to Malone FD et al., first trimester combined screening at 11 weeks is better than second trimester quadruple screening (8). A study has evaluated the efficacy of USG examination in detecting foetal anomalies and genetic defects during the first trimester and early second trimester (9). Foetal karyotyping: Cytogenetic analysis provides additional information, especially with recent advances in the diagnosis of genetic diseases. After the termination of pregnancy of a living foetus, the foetal cord, skin and placenta are reliable sources of foetal cells (10). In case of foetal demise, placental tissue is obtained to determine the karyotype. The primary goal of routine obstetric sonography at 18-20 weeks is to detect foetal anomalies and provide an option for legal termination of pregnancy. Foetal autopsy and karyotyping are important tools that help us to assess the quality and accuracy of prenatal ultrasonogram. With this background, the present study was conducted with aim to compare the prenatal ultrasound findings with autopsy findings in the medically terminated foetuses between 12 and 20 weeks of gestation. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Material and Methods |
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The present was a hospital-based cross-sectional study carried out in the Department of Obstetrics and Gynaecology at Government Medical College, Thiruvananthapuram, Kerala, India, from February 2018 to January 2019. The present study was conducted only after obtaining the clearance from the Institutional Ethics Committee (HEC No. 01/35/2018 MCT). Informed consent was obtained from all the participants. A total of 50 patients who fulfilled the inclusion criteria were included in this study. Inclusion and Exclusion criteria: Antenatal women with USG detected congenital anomalies attending antenatal Outpatient Department (OPD) and undergoing medical termination between 12 and 20 weeks of gestation were included. Patients who did not consent to undertake the study were excluded. Soft markers of aneuploidy, like choroid plexus cyst, increased nasal bone thickness and foetal pyelectasis, were not included. Study Procedure Methods of data collection study tools: Antenatal records of mothers, including ultrasonogram were reviewed. First-trimester aneuploidy screening was done by a combined risk assessment using NT, maternal age, Pregnancy-associated Plasma Protein-A (PAPP-A) and beta human Chorionic Gonadotropin (hCG). Risk was calculated using software-based risk models. Low risk is those with risk below the cut-off threshold (e.g., 1:1000 for trisomy 21), while high-risk were those with risk above cut-off threshold (1:150 for trisomy 21). Variables studied included maternal age, socioeconomic status, residence, parity, peri-conceptional folic acid intake, maternal co-morbidities, first-trimester nuchal translucency, aneuploidy screening, prenatal ultrasonogram with autopsy findings and karyotyping. After obtaining informed consent from the parents, all foetuses underwent a standard foetal autopsy that including photography, whole body X-ray, gross examination, dissection and light microscopic examination of organ tissues at the Department of Pathology, Government Medical College, Thiruvananthapuram, Kerala, India. Karyotyping results were obtained from the genetic clinic in the study Institute. Outcome measurement: Agreement with autopsy findings was expressed in the following categories (11): Category 1: Full agreement between USG and autopsy findings (100% correlation). Category 2: Minor autopsy findings not seen or recorded at USG; Category 3: Major autopsy findings not detected at USG; Category 4: Minor and major additional autopsy findings. Category 5: USG findings not confirmed at autopsy. Statistical Analysis The data was entered into excel sheet. Results were expressed in terms of frequency and percentage. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Results |
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Congenital anomalies were more common in the maternal age group of 21-25 years, accounting for 24 cases (48%) (Table/Fig 1). The mean maternal age was 26.32±4.9 years. The maximum anomalies were noticed in the paternal age group of 26-30 years, with a mean paternal age of 32.32±4.4 years. Socioeconomic status was determined according to World Health Organisation (WHO)-modified Kuppuswamy’s classification. About 18 participants (36%) belonged to the upper lower class and 17 participants (34%) belonged to the lower middle class (Table/Fig 2). A total of 32 participants (64%) were from rural areas. A total of 42 (84%) were of non consanguineous marriage. Only eight participants gave H/o consanguineous marriage (16%). In the present study, 32 cases (64%) were primigravidas, 7 (14%) were second gravida with one normal delivery, 7 (14%) were second gravida with one abortion, 3 (6%) were third gravida and one candidate had H/o recurrent pregnancy loss. Paternal smoking history was elicited in 31 participants (62%). Among the participants, 36 had no family history of congenital anomaly, while 5 had a previous child with a congenital anomaly (10%). There was a history of congenital anomalies in first-degree relatives in nine participants. A total of 37 cases (74%) were conceived spontaneously, 9 (18%) by ovulation induction and 4 (8%) via In-vitro Fertilisation (IVF). A total of 37 of the women did not take periconceptional folic acid (74%). Considering maternal co-morbidity, 27 participants had no associated co-morbidities (54%), eight had H/o diabetes mellitus, six had epilepsy, three had thyroid disorder and two each had heart diseases, hypertension and autoimmune disease. Regarding exposure to infections and drugs in first trimester, 31 (62%) had no exposure. Eight had H/o infections and 11 had H/o drug intake in the first trimester. Considering first-trimester exposure to drugs and infection, 8 (16%) had acute febrile illness: five cases of varicella, two cases of TORCH (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex and one case of influenza-like illness. Among five varicella cases, three had neural tube defects, one had non immune hydrops and one had holoprosencephaly. Of the two TORCH-positive cases, one had cystic hygroma and the other had acrania. In the 50 samples studied, first trimester nuchal translucency measurements were >2.5 mm in 42% and <2.5 mm in 58% (Table/Fig 3). First trimester nuchal translucency. First trimester Aneuploidy screening using NT and biochemical markers was not done in 28 participants (56%). Among those who had done screening, 10 were classified as low-risk and 12 as high-risks (24%) (Table/Fig 4). Of the foetuses, 20 were male and 19 were female. On gross examination, sex was not identified in 11 foetuses. examination. In the present study, 56% of cases had prenatal USG correlating with foetal autopsy, with additional autopsy findings in 42%. Major additional findings were seen in 20%, minor additional findings in 14% and both minor and major additional autopsy findings in 8%. 2% of prenatal USG findings did not correlate with autopsy findings; one case of cerebellar vermis agenesis present in ultrasonogram could not be found in autopsy (Table/Fig 5). Isolated malformations accounted for 52% of cases, while multiple malformations accounted for 48% (Table/Fig 6). Central nervous system was the most common system affected accounting for 34 cases (Table/Fig 7). In this study, all 50 foetuses underwent karyotyping, out of which aneuploidy was detected in 17 cases (34%). Trisomy 18 was the most common abnormality detected, appearing in eight samples (Table/Fig 8). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Discussion |
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In the present study, congenital anomalies were most commonly observed in the maternal age group of 21-25 years, with a mean age of 26.32 years. According to a study by Hollier LM et al., maternal age beyond 25 years is associated with an increased risk of congenital malformation not caused by aneuploidy (12). The authors observed that anomalies were more frequent in primigravida accounting for 64%. The result is similar to several previous studies (13),(14),(15). Duong HT et al., found that primigravida were more likely to have infants with conditions such as amniotic band syndrome, hydrocephaly, oesophageal atresia (13). In the present study, anomalies were more common in patients who conceived spontaneously (74%). However, according to literature suggests that congenital anomalies are more common among IVF-conceived patients (12),(13). Paternal smoking was noticed in 62% of cases. According to a study by Deng K et al., Congenital Heart Defects (CHD) are more common in cases involving paternal smoking (16). Considering first trimester exposure to drugs and infection, 8 (16%) had acute febrile illness-five had varicella, two had TORCH infections and one had an influenza-like illness. Among five varicella cases, three had neural tube defects, one had non immune hydrops and one had holoprosencephaly. Of the two TORCH-positive cases, one had cystic hygroma and other acrania. According to Golatipour MJ et al., there is association between TORCH infections in first trimester and congenital anomalies (17). A total of 11 participants had a history of drug intake, of which five had taken antiepileptics, two had taken azathioprine, one took prednisolone and another took metformin and olanzapine and three cases took valproate usage. All three cases of valproate intake were associated with neural tube defects. According to Turget U et al., high-dose valproate led to neural tube defects (18). Perinatal USG with autopsy correlation: In the present study, autopsy confirmed the presence of USG findings in 98% (49 cases), except for one case of cerebellar vermis agenesis, which was not found in autopsy. This finding coincides with the study conducted by Sankar VH and Phadke SR (19). In their study, Foetal autopsy was able to provide a definitive final diagnosis in 59%. Autopsy failed to confirm USG findings in 2% of 206 samples. Additional findings were seen in 77 cases. In another study by Amini H et al., Ultrasound (USG) findings were confirmed in 53.4% of cases and additional findings were noted in 37.8% (20). A retrospective study by Kaasen A et al., showed full agreement between USG and autopsy in 58.4% of cases, with additional autopsy findings in 31.4% (5). In 2010, Phadke SR and Gupta A, in a 7-year retrospective study, demonstrated complete concordance between prenatal scan and autopsy findings in 72.5% and major concordance in 23% (11). In the present study, Nuchal Translucency (NT) and aneuploidy screening in the first trimester were also examined. A total of 42% of the participants had an NT measurement greater than 2.5 mm. According to Bahado-Singh RO et al., elevated NT in first trimester is associated with congenital heart disease (21). Among the study participants, 24% were classified as high-risk for aneuploidy and 20% were classified as low-risk. All cases classified as low-risk had normal karyotyping. According to a study by Vogt C et al., 30% of foetuses that were terminated had abnormal karyotyping, with trisomy 18 being the most common abnormality detected (22). A similar study by Rossi AC and Prefumo F confirmed prenatal ultrasound findings in 68% of cases, provided additional information in 22.5% and found unconfirmed prenatal ultrasound in 9.2%. Additionally, 3.2% of cases were false positive and 2.5% were false negative (23). A study on the association between selected structural defects and chromosomal abnormalities by Acavado-Gallegos S et al., showed that association of two or more structural defects increased the probability of a foetus having a positive karyotyping result. The most important association was among heart defect facial clefts and trisomy 13 (24). Congenital anomalies remain a common cause of perinatal deaths (19). The recurrence of anomalies in subsequent pregnancy varies depending on the oetiology of diagnosis. The present study tries to bring out the importance foetal autopsy in confirming ultrasound findings and detecting additional findings. With the advent of new genetic testing tools, like whole gene sequencing and exome sequencing, the detection rate of genetic abnormalities has improved highly (25). Further studies using these techniques will go a long way in the prenatal detection of genetic diseases, This will allow the clinician and parents to make an informed decision regarding the management of the pregnancy. Limitation(s) The small sample size may affect the accuracy of the diagnostic yield of karyotyping. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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