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The Spectrum of Congenital Central Nervous System Anomalies Among Stillborn: An Autopsy Based Study

The Spectrum of Congenital Central Nervous System Anomalies Among Stillborn: An Autopsy Based Study Background: Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process. Purpose: The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings. Methods: This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail. Results: CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia. Fisher’s exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies (P < .05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. Conclusion: The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management. Keywords Congenital anomalies, central nervous system, fetal autopsy, stillborn, ultrasonography Department of Anatomy, JSS Medical College, JSS Academy of Higher Introduction Education and Research, Mysuru, Karnataka, India Department of Pediatrics, JSS Medical College, JSS Academy of Higher Congenital central nervous system (CNS) anomalies are the Education and Research, Mysuru, Karnataka, India structural or functional abnormalities of the brain and spinal Department of Pathology, JSS Medical College, JSS Academy of Higher cord that occur during the intrauterine developmental process. Education and Research, Mysuru, Karnataka, India The prevalence of congenital anomalies differs significantly Department of Obstetrics and Gynecology, JSS Medical College, JSS across the globe, which varies from 1.07% in Japan to 4.3% Academy of Higher Education and Research, Mysuru, Karnataka, India in Taiwan. This variation in prevalence may be because of the Corresponding author: complex interaction of genetic and environmental factors. S. P. Vinutha, Department of Anatomy, JSS Medical College, JSS Academy The prevalence of CNS anomalies was maximum among of Higher Education and Research, Mysuru 570015, Karnataka, India. stillborn, whereas anomalies of the musculoskeletal system E-mail: vinuthasp@jssuni.edu.in Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-Commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https:// us.sagepub.com/en-us/nam/open-access-at-sage). Vinutha et al. 225 were maximum among live births. Neural tube defects and changed the predicted probability in 18% cases. Also, (NTDs) contribute to the majority of CNS anomalies and data about demography, socioeconomic status, and maternal result from the inability of the neural tube to close between health is helpful to pinpoint the factors behind the occurrence the third and fourth weeks of intrauterine development. Spina of fetal loss. Ultrasound examination with autopsy will help bifida occulta, meningocele, myelomeningocele, and to compensate for the reduced specificity in the previous encephalocele are included in the major NTDs. investigation. Spina bifida is a common term for NTDs affecting the The present study intends to identify the prevalence of spinal region. There are two types of spina bifida: spina bifida congenital CNS anomalies among the stillborn fetuses, also occulta and spina bifida cystica. Spina bifida occulta is a an association between maternal factors and congenital defect of the vertebral arches without protrusion of the spinal anomalies, and an association between the autopsy and cord or meninges. Spina bifida cystica is also a defect of the ultrasound findings. vertebral arches, in which the neural tissue or meninges protrude and form a cyst-like sac. Methods When the meninges protrude the defect in the posterior vertebral arches, it results in meningocele. When the meninges Sampling Technique herniate along with neural tissue, it results in meningomyelocele, and the lumbosacral region is the most Nonprobability sampling (simple random) was done to recruit common location. Encephalocele is a protrusion of meninges, the stillborn fetuses. cerebral cortex, cerebellum, or portions of the brainstem, Sampling: Thirty-eight fetuses (based on the reported which affects the skull. Agenesis of the corpus callosum is incidence of congenital anomalies to be 69%, article reference also an important CNS malformation. no. 10, absolute allowable error of 15%). Anencephaly occurs as a result of the failure of closure of Sample Size = 4 PQr , where P = 69, Q = 100 – 69 = 31 the cranial neural folds. The neural tube fails to close in and r = 15 cranial and upper spinal cord regions, thus exposing the brain = 4 × 69 × 31/ (15) and the spinal cord, and this condition is called 4 = 38 craniorachischisis. For convenience, the sample size was rounded to the next Holoprosencephaly occurs as a result of incomplete higher number 50. A descriptive and cross-sectional study midline cleavage of the prosencephalon, often associated was conducted on 50 stillborn fetuses, which were obtained with neurological damage, and dysmorphism of the brain and 5 from the Department of Obstetrics and Gynecology at JSS face. Sirenomelia, also known as mermaid syndrome, is Medical College and Hospital, Mysuru. The duration of the characterized by a partial or complete fusion of lower limbs, study was two years. This study was approved by the and may include anomalies of the lumbosacral spine and 6 Institutional Ethics Committee with the approval number pelvis, genitourinary, and gastrointestinal anomalies. JSS/MC/IEC/02/660/2015-16. The World Health Organization defines stillborn as the death of a fetus when the birth weight of 500 g is attained, and Inclusion Criteria: All stillborn fetuses at or above 22 suppose if the birth weight is not known, the gestational age of weeks and fetuses whose parents gave informed consent 22 weeks or crown-to-heel length of 25 cm may be considered. were included. Congenital malformations frequently cause psychological Exclusion Criteria: Fetuses with gestational age less than disturbance to the parents, because it puts the entire life of a 22 weeks and autolyzed fetuses were excluded. child into complexities. Prenatal diagnosis of congenital Written consents were obtained from either of the parents anomalies has become an essential part of modern obstetrics. for all the stillborn fetuses before conducting the autopsy. A Antenatal ultrasonography (USG) is a very efficient study pro forma was prepared to obtain a detailed history of a detector of important congenital anomalies, but it lacks mother in terms of consanguinity, obstetric history, history of specificity, which is essential for syndrome diagnosis. It medical disorders, socioeconomic status, the possible cause offers an opportunity to study the abnormal fetus at an earlier of fetal death, mode of termination, and antenatal USG report. stage in development, which improves the treatment of The experts validated the study pro forma details regarding affected live-born babies. Despite antenatal diagnostic fetal and maternal factors, autopsy, and antenatal ultrasound modality, fetal autopsy still plays a vital role in the findings. The radiological examination of the fetus was done confirmation as well as identification of congenital anomalies. in suspected cases with musculoskeletal abnormalities. Fetal autopsy along with USG helps in the counseling of the parents to prevent congenital anomalies in future pregnancies. Etiological diagnosis in unexplained fetal deaths is Fetal Autopsy Procedure possible with a detailed evaluation of the fetus. The fetal autopsy is confirmed in 28.6% to 89%, diagnostic in 10% to Stillborn fetuses were fixed in 10% formalin. The formalin 38%; it provides additional information in 3.9% to 24% cases was injected into the thoracic, abdominal, and cranial cavities 226 Annals of Neurosciences 27(3-4) for the fixation of the organs. An autopsy was performed by Number Percentage the standard procedure adopted by Edith L Potter. The Fetal and Maternal Factors (n) (%) various morphometric parameters including birth weight, Consanguinity crown–rump length, and rump heel length, head, chest, and Present 10 20% abdominal circumferences were measured. The placenta and Absent 40 80% umbilical cord were also examined. The external anomalies Gravida of the stillborn fetus were noted. The cranial cavity was opened by giving coronal incision Primi 22 44% on the scalp, starting behind one ear toward the other ear Second 17 34% posterior to the vertex. The scalp was reflected and the surface Third 8 16% of the brain was inspected on each side. The brain was studied Fourth 2 4% in detail to look for any malformations present. Each fetus Fifth 1 2% was coded with the unique autopsy number for the identification of congenital anomalies. Socioeconomic Status Upper 1 2% Upper middle 15 30% Statistical Analysis Lower middle 25 50% Data collected were entered in MS Excel 2010 and analyzed Upper lower 7 14% using Statistical Package for the Social Sciences (SPSS) Lower 2 4% version 22 in (Mysuru) to obtain relevant statistics. Abbreviations: NVD, normal vaginal delivery; LSCS, lower segment Descriptive measures such as percentages, mean, and standard cesarean section; USG, ultrasonography. deviation (SD) were calculated. Fisher’s exact test was done to find out the association between hypothyroidism and Table 2. Descriptive Statistics of Fetal and Maternal Factors in congenital CNS anomalies. The results were interpreted as the Present Study (n = 50) statistically significant at P < 0.05. Birth Param- SE of Results eters Mean SD Mean Median Min Max Range Birth 1128.20 679.01 96.03 965 500 2800 2300 Out of the total 50 fetuses studied, congenital CNS anomalies weight (g) were present in 17 fetuses (34%). Among the 17 fetuses, 11 Gesta- 28.50 4.35 0.62 28 22 40 18 were males and 6 were females. The descriptive statistics of tional age (weeks) Table 1. Descriptive Statistics of Fetal and Maternal Factors in Maternal 25.82 3.62 0.51 26 19 34 15 the Present Study (n = 50) age (years) Number Percentage Abbreviations: SD, standard deviation; SE, standard error; Min, Fetal and Maternal Factors (n) (%) minimum; Max, maximum. Gender of Stillborn Fetuses fetal and maternal factors of this study are presented in Table Male 28 56% 1 and Table 2. Female 22 44% Each stillborn fetus was classified, based on birth weight, Mode of Delivery gestational age, maternal age, gravidity of the mother, and NVD 27 54% socioeconomic status of parents. Maximum fetuses 29 (58%) LSCS 23 46% were having a birth weight between 500 and 1000 g. Maximum fetuses 20 (40%) were from the gestational age Association With Ultrasound group of 22 to 26 weeks. The maximum number of fetuses 24 Autopsy confirmed USG findings 40 80% (48%) were born to mothers in the age group of 26 to 30 years Additional findings noted in the 7 14% and 22 (44%) mothers were primigravida. The socioeconomic autopsy status was calculated according to modified Kuppuswamy’s Autopsy changed the primary 3 6% socioeconomic scale. The maximum number of stillborn, diagnosis i.e., 25 (50%), belonged to the lower middle class of External Anomalies socioeconomic status. The history of consanguinity was Present 25 50% present in ten (20%) mothers. The external anomalies were present in 25 cases (50%). The distribution of various Absent 25 50% congenital CNS anomalies is presented in Table 3. Vinutha et al. 227 Table 3. The Number and Percentages of Various Types of Congenital CNS Anomalies Among Stillborn Fetuses Studied S. Type of Congenital Percent- No. CNS Anomalies Number ages (%) 1. Anencephaly 4 23 2. Anencephaly with cranio- 1 6 rachischisis 3. Meningomyelocele 5 29 4. Meningocele 1 6 5. Encephalocele 1 6 6. Meningoencephalocele 1 6 7. Agenesis of the corpus 1 6 callosum 8. Holoprosencephaly 1 6 Figure 2. Bifid Cerebellum With Hypoplastic Vermis 9. Bifi d cerebellum with 1 6 hypoplastic vermis 10. Mermaid syndrome 1 6 Total 17 100 Meningomyelocele (29%) was the most common anomaly, followed by anencephaly (23%).A small proboscis, hypotelorism, and flat nasal bridge were observed in the fetus with holoprosencephaly ( Figure 1 A ). Antenatal ultrasound showed a large monoventricle with fused thalami and thinned out at cerebral parenchyma in the same fetus ( Figure 1 B ). The other anomalies observed in stillborn fetuses were bifid cerebellum with hypoplastic vermis ( Figure 2 ), agenesis of the corpus callosum ( Figure 3 ), occipital meningoencephalocele ( Figure 4 ), meningomyelocele ( Figure 5 ), anterior view of fetus showing anencephaly with craniorachischisis ( Figure 6 Figure 3. Agenesis of Corpus Callosum A ), posterior view of fetus showing anencephaly with craniorachischisis ( Figure 6 B ), mermaid syndrome ( Figure 7 A ), and radiograph of the fetus with mermaid syndrome ( Figure 7 B ). A B A-03/16 Figure 1. (A) Holoprosencephaly With a Small Proboscis, Hypotelorism, Flat Nasal Bridge and (B) Antenatal Ultrasound Figure 4. Occipital Meningoencephalocele Image Showing Single Large Monoventricle 228 Annals of Neurosciences 27(3-4) The risk factors for NTD such as hypothyroidism in mother was observed in 11 out of 17 stillborn fetuses in the present study. Fisher’s exact test showed a significant association between hypothyroidism in mother and CNS anomaly in the stillborn fetus (Table 4). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. In one stillborn fetus with holoprosencephaly, low set ears, amniotic band on the right arm, and syndactyl were the additional findings. Ultrasound showed an encephalocele in another fetus, but there were no such findings after performing the autopsy. Discussion Figure 5. Meningomyelocele Factors such as genetic, environmental, teratogenic, and infectious agents play a vital role in the etiology of congenital malformations during the most delicate period of embryogenesis, i.e., the third to eighth weeks of intrauterine life. Despite routine antenatal folic acid (5 mg) supplementation, a reduction in the incidence of congenital CNS anomalies is not regularly observed. Hence, interplay of risk factors such as hypothyroidism, diabetes, maternal infections, and genetic causes might also play a significant role. The occurrence of CNS anomalies among hypothyroid mothers was a significant observation. The details of the fetal and maternal factors observed in the present study were compared with the available literature (Table 5). Meningomyelocele (29%) was the most common anomaly, followed by anencephaly (23%) in the present study. Kapoor et al. have found that anencephaly was the most prevalent anomaly in CNS (28.5%) and it was frequently associated with meningocele or meningomyelocele. The incidence of rachischisis (spina bifida) was noted in 22.4% of cases. Figure 6. (A) Anencephaly With Craniorachischisis (Anterior Hydrocephalus was observed in 20.4% of cases, and there View) and (B) Anencephaly With Craniorachischisis (Posterior View) was an abnormal flexion of the vertebral column in 18% of fetuses. The reason may be that most of the fetuses affected with NTDs were aborted very early in the gestational period. Kale et al. have reported nine cases (15.79%), which is slightly lower as compared to the present study. Padma et al. have found 12 cases (44%) of CNS anomalies in their study. Andola et al. have found 15 cases (34.09) of CNS defects. Table 4. Association Between Maternal Hypothyroidism and Congenital CNS Anomalies Fisher's Exact Major Maternal Hypothyroidism Test System Involved Present Absent Total χ P-Value Central 11 6 17 17.962 P < .05 nervous (64.7%) (35.3%) (100.0%) system Figure 7. (A) Mermaid Syndrome and (B) Radiograph of the Fetus With Mermaid Syndrome *Significant at P < .05 Vinutha et al. 229 Table 5.Comparison of Fetal and Maternal Factors With the Available Literature No. of CNS Sex Ratio Birth Gestational Maternal Socioeco- S. Anoma- (Male: Weight in Age in Age in nomic Consan- No. Authors lies Female) Grams Weeks Years Gravida Status guinity 1. Padma et 12 (44%) 1.7:1 – 29–32 19–28 – No – al. (2011) (23.5) 2. Andola et 15 (34.09%) 1:1.5 350–1000 g 35–39 – – – – al. (2012) 3. Kapoor et 49 (33%) 1:1 – 18–20 20–25 50% primi Upper Nil al. (2013) lower 4. Kale et al. 9 (15.79%) 1.25:1 350–1000 g 20–24 20–24 50.8%primi No 4 (7.02%) (2017) 5. Present 17 (34%) 1.27:1 500–1000 g 22–26 26–30 44% primi Lower 10 (20%) study middle (2020) Taksande et al. have found 15 cases of CNS anomalies in present study. This could be because the termination of their study. The CNS defects were most commonly seen in pregnancy is immediately done after detecting congenital stillborn. Siddesh et al. have reported that 243 (31.63%) anomaly on USG. Kale et al. have found that maximum fetuses had CNS malformations in their study. NTDs fetuses were having a gestational age of 20 to 24 weeks accounted for 16.5% of all malformations and 52% of CNS (63.15%) in their study. malformations. The maternal factors considered in the present study are Gole et al. also found that CNS anomalies (36%) were the the age of the mother, gravida, socioeconomic status, most common in their study. Anencephaly associated with consanguinity, and history of medical disorders. The spina bifida was seen in two cases. Anencephaly was more maximum number of fetuses, 24 (48%), were born to mothers commonly noted in female fetuses. The results obtained in in the age group of 26 to 30 years, followed by 19 fetuses the present study are similar to that of Andola et al., Kapoor (38%) to mothers in the age group 21 to 25 years. 22 (44%) 10 17 et al., and Gole et al. Hydrocephalus and spina bifida were were born to primigravida, followed by the second gravida in the most frequent congenital CNS anomalies, and 17 fetuses (34%). The number of stillborn fetuses was hydrocephalus may be associated with spina bifida and observed maximum in the lower middle class 25 stillborn myelomeningocele. Genetic factors, low birth weight, (50%), followed by the upper middle class in 15 stillborn prematurity, both extremes of maternal age, and the deficiency (30%), according to modified Kuppuswamy’s socioeconomic of maternal folic acid intake may be linked to NTDs. scale. Kapoor et al. have found 34% of cases belonging to the On analyzing the sex ratio, the congenital malformations upper lower class. were slightly more in males (56%) than females (44%) with The history of consanguinity was observed in ten mothers the male-to-female (M:F) ratio being 1.27:1 in the present (20%) in the present study. Consanguinity was present in four study. Kale et al. have found a similar incidence to be more in mothers (7.02%) out of all congenitally malformed cases. males (52.63%) with a ratio of 1.25:1. The incidence of There was not even a single case of consanguineous marriage congenital anomalies was observed more in male fetuses than in north-west India. Consanguinity has a damaging effect on females (P < .01), and the sex ratio was 1.7:1. Andola et al. fetal growth, and it increases the risk of congenital anomalies have found the M:F ratio of 1:1.5 with female preponderance and fetal loss. A few authors have related low socioeconomic in their study. Sexual preponderance was not statistically status with consanguineous marriages, and thereby increase significant, as 83% of female fetuses had congenital anomalies in the percentage of congenital anomalies is the result of both 10 10 as compared to 75% male fetuses. The M:F ratio was 1.63:1 the abovementioned factors. The consanguinity of parents by a sex-wise distribution of 62% males and 38% females. was noted in 14 cases of congenital anomalies. Congenital anomalies were significantly observed in In the present study, there was a history of hepatitis E virus stillbirths (P < .01) when compared to live births, with a Immunoglobulin M antibodies positive in the mother in a frequency of 4.68% and 1.84%, respectively. fetus with holoprosencephaly. There was a history of The birth weight of stillborn fetuses ranged from 500 to chickenpox in the mother in a fetus with bifid cerebellum and 2800 g. Similar to the other studies, maximum fetuses 29 hypoplastic vermis. There was a history of hypertension in (58%) were having a birth weight between 500 and 1000 g. the mother in one fetus with anencephaly. There was a history The association between congenital anomalies and low birth of diabetes in the mother in a fetus with mermaid syndrome. weight is well known. The gestational age of most of the The risk factors for congenital malformations are the stillborn fetuses ranged from 22 to 26 weeks (40%) in the presence of hydramnios, first-trimester febrile illness, 230 Annals of Neurosciences 27(3-4) Table 6. Association Between the Autopsy Findings and Ultrasound Findings Autopsy Confirmed USG Findings No Change in Diag- Additional Findings Noted in Autopsy Changed the Pri- S. No. Authors Year nosis the Autopsy mary Diagnosis 1. Yeo et al.21 2002 27/88 30/88 31/88 (30.68%) (34.09%) (35.22%) 2. Shankar et al.19 2006 55/134 77/134 2/134 (41.04%) (57.46%) (1.49%) 3. Pradhan et al.20 2013 44/70 18/70 8/70 (62.86%) (25.71%) (11.43%) 4 Kale et al.11 2017 27/57 27/57 3/57 (47.37 %) (47.37 %) (5.26%) 5. Present study 2020 40/50 7/50 3/50 (80%) (14%) (6%) previous abortions, eclampsia, and history of congenital heart Future Implications of Experimental disease or malformed babies. Maternal diabetes, hypertension, Research in Animal Models and hypothyroidism show a positive correlation with congenital anomalies. A significant association between Neural stem cells are originated from the embryonic ectoderm, maternal hypothyroidism and CNS anomaly in the stillborn which produces the neuroepithelial cells. A large number of fetus was observed in this study. neural stem cells are required for the basic research as well as The association between the autopsy and ultrasound for the development of novel approaches, needed for the findings is compared with that of previous studies in Table 6. treatment of various neurological disorders. Human With the current advanced ultrasound techniques, the embryonic stem cell that is derived from retinal pigment false-positive diagnosis is very rare. However, poor visibility epithelium is known to protect the visual function in an because of oligohydramnios or obesity is an important cause animal model of retinal disease. When fetal neurons were of errors in ultrasound diagnosis. Sometimes USG may fail to evaluated, they are known to survive the transplantation detect associated malformations, which may lead to alteration surgery much better than adult neurons, which reflects the in etiological diagnosis. Fetal autopsy provided significant value of fetal-derived neural stem cells. additional information in 38% of cases and the change in Hematopoietic, mesenchymal, embryonic, neural, and recurrence risk in 18% of cases. retinal stem cells are known to differentiate into neuronal When postmortem examinations were compared with lineages, and they may be able to regenerate neural USG findings, in eight cases (11.43%) the USG findings were retinal tissue. incorrect. In 18 cases (25.71%), additional information was Neural stem cells are localized in the highly vascularized obtained on autopsy. Only a few studies have shown a regions of the CNS, instead of being distributed throughout comparison of antenatal ultrasonographic findings and the brain. autopsy findings. Autopsy diagnosis confirmed USG findings Anand et al. have stated that the potential use of traditional in 54 cases (94.74%), it provided additional information in 27 herbs such as Brahmi (Bacopa monniera) needs deeper cases (47.37%), whereas the primary diagnosis provided by investigation. Brahmi appears to perform very important USG was changed in three cases (5.26%). functions in the CNS. A better understanding of the When a major anomaly has already been detected, the physiopathological nature of different neurological diseases at various levels (systemic, organ, tissue, and cell) is of error in prenatal diagnosis is a failure to conduct a complete paramount importance for further progress, and the examination of the fetus. It is avoided by using a systematic mechanisms underlying the effects of Brahmi need to be approach to perform a comprehensive anatomic evaluation elucidated in animal models. of the fetus. Accurate prenatal diagnosis of all associated anomalies is not possible every time, even in the ideal situation. There is an alarming decrease of autopsy Conclusion procedures, because of the centralization of pathology facilities or changes in clinician’s perception of autopsy Congenital CNS anomalies are the most commonly observed importance or improvements in ultrasound diagnostics, or anomalies in the present study. Meningomyelocele was the most poor counseling provided by inexperienced personnel. As common CNS anomaly, followed by anencephaly. There was a a result, parents are refusing to give consent to a fetal significant association between maternal hypothyroidism and CNS anomalies. It is mandatory to have an autopsy study for all the autopsy procedure. Vinutha et al. 231 stillborn fetuses to predict and counsel for safe future pregnancy 9. Pushpa, B Subitha, S Lokesh Kumar, V. Study on various con- outcomes. Hence, this study focuses on the importance of genital anomalies in fetal autopsy. Int J Med Res Rev 2016; concomitant fetal autopsy and antenatal USG in providing accurate 4(9): 1667–1674. genetic counseling. Future studies are required to evaluate the cause 10. Kapoor, K Singh, K Sharma, A Congenital anomalies in North of fetal loss as a multidisciplinary holistic approach. Western Indian population: A fetal autopsy study. Eur J Anat 2013; 17(3): 166–175. 11. Kale, PP Kanetkar, SR Shukla, DB Study of congenital malfor- Acknowledgment mations in fetal and early neonatal autopsies. Ann Pathol Lab I would like to thank Dr Pushpalatha K., Professor and HOD of Med 2017; 4(4): 433–441. Anatomy, and Dr Shama Sundar N. M., Professor of Anatomy, JSS 12. Bairwa, M Rajput, M Kuppuswamy’s, Sachdeva S. Modified Medical College for providing the help and constant support during socioeconomic scale: Social researcher should include updated the study. income criteria, 2012. Indian J Community Med 2013; 38(3): 185–186. Ethical Statement 13. Padma, S Ramakrishna, D Jijiya, BP Pattern of distribution of congenital anomalies in stillborn: A hospital based prospective This study was approved by the Institutional Ethics Committee of study. Int J Pharm Bio Sci 2011; 2(2): 604–610. JSS Medical College, Mysuru with the approval number JSS/MC/ 14. Andola, US Anita, AM Ahuja, M Congenital malformations IEC/02/660/2015-16. The written informed consent was obtained in perinatal autopsies: A study of 100 cases. J Clin Diagn Res from the participants in the study. 2012; 6(10): 1726–1730. 15. Taksande, A Vilhekar, K Chaturvedi, P Congenital malforma- Declaration of Conflicting Interests tions at birth in Central India: A rural medical college hospital based data. Indian J Hum Genet 2010; 16(3): 159–163. The authors declared no potential conflicts of interest with respect 16. 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The Spectrum of Congenital Central Nervous System Anomalies Among Stillborn: An Autopsy Based Study

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Abstract

Background: Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process. Purpose: The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings. Methods: This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail. Results: CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia. Fisher’s exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies (P < .05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. Conclusion: The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management. Keywords Congenital anomalies, central nervous system, fetal autopsy, stillborn, ultrasonography Department of Anatomy, JSS Medical College, JSS Academy of Higher Introduction Education and Research, Mysuru, Karnataka, India Department of Pediatrics, JSS Medical College, JSS Academy of Higher Congenital central nervous system (CNS) anomalies are the Education and Research, Mysuru, Karnataka, India structural or functional abnormalities of the brain and spinal Department of Pathology, JSS Medical College, JSS Academy of Higher cord that occur during the intrauterine developmental process. Education and Research, Mysuru, Karnataka, India The prevalence of congenital anomalies differs significantly Department of Obstetrics and Gynecology, JSS Medical College, JSS across the globe, which varies from 1.07% in Japan to 4.3% Academy of Higher Education and Research, Mysuru, Karnataka, India in Taiwan. This variation in prevalence may be because of the Corresponding author: complex interaction of genetic and environmental factors. S. P. Vinutha, Department of Anatomy, JSS Medical College, JSS Academy The prevalence of CNS anomalies was maximum among of Higher Education and Research, Mysuru 570015, Karnataka, India. stillborn, whereas anomalies of the musculoskeletal system E-mail: vinuthasp@jssuni.edu.in Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-Commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https:// us.sagepub.com/en-us/nam/open-access-at-sage). Vinutha et al. 225 were maximum among live births. Neural tube defects and changed the predicted probability in 18% cases. Also, (NTDs) contribute to the majority of CNS anomalies and data about demography, socioeconomic status, and maternal result from the inability of the neural tube to close between health is helpful to pinpoint the factors behind the occurrence the third and fourth weeks of intrauterine development. Spina of fetal loss. Ultrasound examination with autopsy will help bifida occulta, meningocele, myelomeningocele, and to compensate for the reduced specificity in the previous encephalocele are included in the major NTDs. investigation. Spina bifida is a common term for NTDs affecting the The present study intends to identify the prevalence of spinal region. There are two types of spina bifida: spina bifida congenital CNS anomalies among the stillborn fetuses, also occulta and spina bifida cystica. Spina bifida occulta is a an association between maternal factors and congenital defect of the vertebral arches without protrusion of the spinal anomalies, and an association between the autopsy and cord or meninges. Spina bifida cystica is also a defect of the ultrasound findings. vertebral arches, in which the neural tissue or meninges protrude and form a cyst-like sac. Methods When the meninges protrude the defect in the posterior vertebral arches, it results in meningocele. When the meninges Sampling Technique herniate along with neural tissue, it results in meningomyelocele, and the lumbosacral region is the most Nonprobability sampling (simple random) was done to recruit common location. Encephalocele is a protrusion of meninges, the stillborn fetuses. cerebral cortex, cerebellum, or portions of the brainstem, Sampling: Thirty-eight fetuses (based on the reported which affects the skull. Agenesis of the corpus callosum is incidence of congenital anomalies to be 69%, article reference also an important CNS malformation. no. 10, absolute allowable error of 15%). Anencephaly occurs as a result of the failure of closure of Sample Size = 4 PQr , where P = 69, Q = 100 – 69 = 31 the cranial neural folds. The neural tube fails to close in and r = 15 cranial and upper spinal cord regions, thus exposing the brain = 4 × 69 × 31/ (15) and the spinal cord, and this condition is called 4 = 38 craniorachischisis. For convenience, the sample size was rounded to the next Holoprosencephaly occurs as a result of incomplete higher number 50. A descriptive and cross-sectional study midline cleavage of the prosencephalon, often associated was conducted on 50 stillborn fetuses, which were obtained with neurological damage, and dysmorphism of the brain and 5 from the Department of Obstetrics and Gynecology at JSS face. Sirenomelia, also known as mermaid syndrome, is Medical College and Hospital, Mysuru. The duration of the characterized by a partial or complete fusion of lower limbs, study was two years. This study was approved by the and may include anomalies of the lumbosacral spine and 6 Institutional Ethics Committee with the approval number pelvis, genitourinary, and gastrointestinal anomalies. JSS/MC/IEC/02/660/2015-16. The World Health Organization defines stillborn as the death of a fetus when the birth weight of 500 g is attained, and Inclusion Criteria: All stillborn fetuses at or above 22 suppose if the birth weight is not known, the gestational age of weeks and fetuses whose parents gave informed consent 22 weeks or crown-to-heel length of 25 cm may be considered. were included. Congenital malformations frequently cause psychological Exclusion Criteria: Fetuses with gestational age less than disturbance to the parents, because it puts the entire life of a 22 weeks and autolyzed fetuses were excluded. child into complexities. Prenatal diagnosis of congenital Written consents were obtained from either of the parents anomalies has become an essential part of modern obstetrics. for all the stillborn fetuses before conducting the autopsy. A Antenatal ultrasonography (USG) is a very efficient study pro forma was prepared to obtain a detailed history of a detector of important congenital anomalies, but it lacks mother in terms of consanguinity, obstetric history, history of specificity, which is essential for syndrome diagnosis. It medical disorders, socioeconomic status, the possible cause offers an opportunity to study the abnormal fetus at an earlier of fetal death, mode of termination, and antenatal USG report. stage in development, which improves the treatment of The experts validated the study pro forma details regarding affected live-born babies. Despite antenatal diagnostic fetal and maternal factors, autopsy, and antenatal ultrasound modality, fetal autopsy still plays a vital role in the findings. The radiological examination of the fetus was done confirmation as well as identification of congenital anomalies. in suspected cases with musculoskeletal abnormalities. Fetal autopsy along with USG helps in the counseling of the parents to prevent congenital anomalies in future pregnancies. Etiological diagnosis in unexplained fetal deaths is Fetal Autopsy Procedure possible with a detailed evaluation of the fetus. The fetal autopsy is confirmed in 28.6% to 89%, diagnostic in 10% to Stillborn fetuses were fixed in 10% formalin. The formalin 38%; it provides additional information in 3.9% to 24% cases was injected into the thoracic, abdominal, and cranial cavities 226 Annals of Neurosciences 27(3-4) for the fixation of the organs. An autopsy was performed by Number Percentage the standard procedure adopted by Edith L Potter. The Fetal and Maternal Factors (n) (%) various morphometric parameters including birth weight, Consanguinity crown–rump length, and rump heel length, head, chest, and Present 10 20% abdominal circumferences were measured. The placenta and Absent 40 80% umbilical cord were also examined. The external anomalies Gravida of the stillborn fetus were noted. The cranial cavity was opened by giving coronal incision Primi 22 44% on the scalp, starting behind one ear toward the other ear Second 17 34% posterior to the vertex. The scalp was reflected and the surface Third 8 16% of the brain was inspected on each side. The brain was studied Fourth 2 4% in detail to look for any malformations present. Each fetus Fifth 1 2% was coded with the unique autopsy number for the identification of congenital anomalies. Socioeconomic Status Upper 1 2% Upper middle 15 30% Statistical Analysis Lower middle 25 50% Data collected were entered in MS Excel 2010 and analyzed Upper lower 7 14% using Statistical Package for the Social Sciences (SPSS) Lower 2 4% version 22 in (Mysuru) to obtain relevant statistics. Abbreviations: NVD, normal vaginal delivery; LSCS, lower segment Descriptive measures such as percentages, mean, and standard cesarean section; USG, ultrasonography. deviation (SD) were calculated. Fisher’s exact test was done to find out the association between hypothyroidism and Table 2. Descriptive Statistics of Fetal and Maternal Factors in congenital CNS anomalies. The results were interpreted as the Present Study (n = 50) statistically significant at P < 0.05. Birth Param- SE of Results eters Mean SD Mean Median Min Max Range Birth 1128.20 679.01 96.03 965 500 2800 2300 Out of the total 50 fetuses studied, congenital CNS anomalies weight (g) were present in 17 fetuses (34%). Among the 17 fetuses, 11 Gesta- 28.50 4.35 0.62 28 22 40 18 were males and 6 were females. The descriptive statistics of tional age (weeks) Table 1. Descriptive Statistics of Fetal and Maternal Factors in Maternal 25.82 3.62 0.51 26 19 34 15 the Present Study (n = 50) age (years) Number Percentage Abbreviations: SD, standard deviation; SE, standard error; Min, Fetal and Maternal Factors (n) (%) minimum; Max, maximum. Gender of Stillborn Fetuses fetal and maternal factors of this study are presented in Table Male 28 56% 1 and Table 2. Female 22 44% Each stillborn fetus was classified, based on birth weight, Mode of Delivery gestational age, maternal age, gravidity of the mother, and NVD 27 54% socioeconomic status of parents. Maximum fetuses 29 (58%) LSCS 23 46% were having a birth weight between 500 and 1000 g. Maximum fetuses 20 (40%) were from the gestational age Association With Ultrasound group of 22 to 26 weeks. The maximum number of fetuses 24 Autopsy confirmed USG findings 40 80% (48%) were born to mothers in the age group of 26 to 30 years Additional findings noted in the 7 14% and 22 (44%) mothers were primigravida. The socioeconomic autopsy status was calculated according to modified Kuppuswamy’s Autopsy changed the primary 3 6% socioeconomic scale. The maximum number of stillborn, diagnosis i.e., 25 (50%), belonged to the lower middle class of External Anomalies socioeconomic status. The history of consanguinity was Present 25 50% present in ten (20%) mothers. The external anomalies were present in 25 cases (50%). The distribution of various Absent 25 50% congenital CNS anomalies is presented in Table 3. Vinutha et al. 227 Table 3. The Number and Percentages of Various Types of Congenital CNS Anomalies Among Stillborn Fetuses Studied S. Type of Congenital Percent- No. CNS Anomalies Number ages (%) 1. Anencephaly 4 23 2. Anencephaly with cranio- 1 6 rachischisis 3. Meningomyelocele 5 29 4. Meningocele 1 6 5. Encephalocele 1 6 6. Meningoencephalocele 1 6 7. Agenesis of the corpus 1 6 callosum 8. Holoprosencephaly 1 6 Figure 2. Bifid Cerebellum With Hypoplastic Vermis 9. Bifi d cerebellum with 1 6 hypoplastic vermis 10. Mermaid syndrome 1 6 Total 17 100 Meningomyelocele (29%) was the most common anomaly, followed by anencephaly (23%).A small proboscis, hypotelorism, and flat nasal bridge were observed in the fetus with holoprosencephaly ( Figure 1 A ). Antenatal ultrasound showed a large monoventricle with fused thalami and thinned out at cerebral parenchyma in the same fetus ( Figure 1 B ). The other anomalies observed in stillborn fetuses were bifid cerebellum with hypoplastic vermis ( Figure 2 ), agenesis of the corpus callosum ( Figure 3 ), occipital meningoencephalocele ( Figure 4 ), meningomyelocele ( Figure 5 ), anterior view of fetus showing anencephaly with craniorachischisis ( Figure 6 Figure 3. Agenesis of Corpus Callosum A ), posterior view of fetus showing anencephaly with craniorachischisis ( Figure 6 B ), mermaid syndrome ( Figure 7 A ), and radiograph of the fetus with mermaid syndrome ( Figure 7 B ). A B A-03/16 Figure 1. (A) Holoprosencephaly With a Small Proboscis, Hypotelorism, Flat Nasal Bridge and (B) Antenatal Ultrasound Figure 4. Occipital Meningoencephalocele Image Showing Single Large Monoventricle 228 Annals of Neurosciences 27(3-4) The risk factors for NTD such as hypothyroidism in mother was observed in 11 out of 17 stillborn fetuses in the present study. Fisher’s exact test showed a significant association between hypothyroidism in mother and CNS anomaly in the stillborn fetus (Table 4). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. In one stillborn fetus with holoprosencephaly, low set ears, amniotic band on the right arm, and syndactyl were the additional findings. Ultrasound showed an encephalocele in another fetus, but there were no such findings after performing the autopsy. Discussion Figure 5. Meningomyelocele Factors such as genetic, environmental, teratogenic, and infectious agents play a vital role in the etiology of congenital malformations during the most delicate period of embryogenesis, i.e., the third to eighth weeks of intrauterine life. Despite routine antenatal folic acid (5 mg) supplementation, a reduction in the incidence of congenital CNS anomalies is not regularly observed. Hence, interplay of risk factors such as hypothyroidism, diabetes, maternal infections, and genetic causes might also play a significant role. The occurrence of CNS anomalies among hypothyroid mothers was a significant observation. The details of the fetal and maternal factors observed in the present study were compared with the available literature (Table 5). Meningomyelocele (29%) was the most common anomaly, followed by anencephaly (23%) in the present study. Kapoor et al. have found that anencephaly was the most prevalent anomaly in CNS (28.5%) and it was frequently associated with meningocele or meningomyelocele. The incidence of rachischisis (spina bifida) was noted in 22.4% of cases. Figure 6. (A) Anencephaly With Craniorachischisis (Anterior Hydrocephalus was observed in 20.4% of cases, and there View) and (B) Anencephaly With Craniorachischisis (Posterior View) was an abnormal flexion of the vertebral column in 18% of fetuses. The reason may be that most of the fetuses affected with NTDs were aborted very early in the gestational period. Kale et al. have reported nine cases (15.79%), which is slightly lower as compared to the present study. Padma et al. have found 12 cases (44%) of CNS anomalies in their study. Andola et al. have found 15 cases (34.09) of CNS defects. Table 4. Association Between Maternal Hypothyroidism and Congenital CNS Anomalies Fisher's Exact Major Maternal Hypothyroidism Test System Involved Present Absent Total χ P-Value Central 11 6 17 17.962 P < .05 nervous (64.7%) (35.3%) (100.0%) system Figure 7. (A) Mermaid Syndrome and (B) Radiograph of the Fetus With Mermaid Syndrome *Significant at P < .05 Vinutha et al. 229 Table 5.Comparison of Fetal and Maternal Factors With the Available Literature No. of CNS Sex Ratio Birth Gestational Maternal Socioeco- S. Anoma- (Male: Weight in Age in Age in nomic Consan- No. Authors lies Female) Grams Weeks Years Gravida Status guinity 1. Padma et 12 (44%) 1.7:1 – 29–32 19–28 – No – al. (2011) (23.5) 2. Andola et 15 (34.09%) 1:1.5 350–1000 g 35–39 – – – – al. (2012) 3. Kapoor et 49 (33%) 1:1 – 18–20 20–25 50% primi Upper Nil al. (2013) lower 4. Kale et al. 9 (15.79%) 1.25:1 350–1000 g 20–24 20–24 50.8%primi No 4 (7.02%) (2017) 5. Present 17 (34%) 1.27:1 500–1000 g 22–26 26–30 44% primi Lower 10 (20%) study middle (2020) Taksande et al. have found 15 cases of CNS anomalies in present study. This could be because the termination of their study. The CNS defects were most commonly seen in pregnancy is immediately done after detecting congenital stillborn. Siddesh et al. have reported that 243 (31.63%) anomaly on USG. Kale et al. have found that maximum fetuses had CNS malformations in their study. NTDs fetuses were having a gestational age of 20 to 24 weeks accounted for 16.5% of all malformations and 52% of CNS (63.15%) in their study. malformations. The maternal factors considered in the present study are Gole et al. also found that CNS anomalies (36%) were the the age of the mother, gravida, socioeconomic status, most common in their study. Anencephaly associated with consanguinity, and history of medical disorders. The spina bifida was seen in two cases. Anencephaly was more maximum number of fetuses, 24 (48%), were born to mothers commonly noted in female fetuses. The results obtained in in the age group of 26 to 30 years, followed by 19 fetuses the present study are similar to that of Andola et al., Kapoor (38%) to mothers in the age group 21 to 25 years. 22 (44%) 10 17 et al., and Gole et al. Hydrocephalus and spina bifida were were born to primigravida, followed by the second gravida in the most frequent congenital CNS anomalies, and 17 fetuses (34%). The number of stillborn fetuses was hydrocephalus may be associated with spina bifida and observed maximum in the lower middle class 25 stillborn myelomeningocele. Genetic factors, low birth weight, (50%), followed by the upper middle class in 15 stillborn prematurity, both extremes of maternal age, and the deficiency (30%), according to modified Kuppuswamy’s socioeconomic of maternal folic acid intake may be linked to NTDs. scale. Kapoor et al. have found 34% of cases belonging to the On analyzing the sex ratio, the congenital malformations upper lower class. were slightly more in males (56%) than females (44%) with The history of consanguinity was observed in ten mothers the male-to-female (M:F) ratio being 1.27:1 in the present (20%) in the present study. Consanguinity was present in four study. Kale et al. have found a similar incidence to be more in mothers (7.02%) out of all congenitally malformed cases. males (52.63%) with a ratio of 1.25:1. The incidence of There was not even a single case of consanguineous marriage congenital anomalies was observed more in male fetuses than in north-west India. Consanguinity has a damaging effect on females (P < .01), and the sex ratio was 1.7:1. Andola et al. fetal growth, and it increases the risk of congenital anomalies have found the M:F ratio of 1:1.5 with female preponderance and fetal loss. A few authors have related low socioeconomic in their study. Sexual preponderance was not statistically status with consanguineous marriages, and thereby increase significant, as 83% of female fetuses had congenital anomalies in the percentage of congenital anomalies is the result of both 10 10 as compared to 75% male fetuses. The M:F ratio was 1.63:1 the abovementioned factors. The consanguinity of parents by a sex-wise distribution of 62% males and 38% females. was noted in 14 cases of congenital anomalies. Congenital anomalies were significantly observed in In the present study, there was a history of hepatitis E virus stillbirths (P < .01) when compared to live births, with a Immunoglobulin M antibodies positive in the mother in a frequency of 4.68% and 1.84%, respectively. fetus with holoprosencephaly. There was a history of The birth weight of stillborn fetuses ranged from 500 to chickenpox in the mother in a fetus with bifid cerebellum and 2800 g. Similar to the other studies, maximum fetuses 29 hypoplastic vermis. There was a history of hypertension in (58%) were having a birth weight between 500 and 1000 g. the mother in one fetus with anencephaly. There was a history The association between congenital anomalies and low birth of diabetes in the mother in a fetus with mermaid syndrome. weight is well known. The gestational age of most of the The risk factors for congenital malformations are the stillborn fetuses ranged from 22 to 26 weeks (40%) in the presence of hydramnios, first-trimester febrile illness, 230 Annals of Neurosciences 27(3-4) Table 6. Association Between the Autopsy Findings and Ultrasound Findings Autopsy Confirmed USG Findings No Change in Diag- Additional Findings Noted in Autopsy Changed the Pri- S. No. Authors Year nosis the Autopsy mary Diagnosis 1. Yeo et al.21 2002 27/88 30/88 31/88 (30.68%) (34.09%) (35.22%) 2. Shankar et al.19 2006 55/134 77/134 2/134 (41.04%) (57.46%) (1.49%) 3. Pradhan et al.20 2013 44/70 18/70 8/70 (62.86%) (25.71%) (11.43%) 4 Kale et al.11 2017 27/57 27/57 3/57 (47.37 %) (47.37 %) (5.26%) 5. Present study 2020 40/50 7/50 3/50 (80%) (14%) (6%) previous abortions, eclampsia, and history of congenital heart Future Implications of Experimental disease or malformed babies. Maternal diabetes, hypertension, Research in Animal Models and hypothyroidism show a positive correlation with congenital anomalies. A significant association between Neural stem cells are originated from the embryonic ectoderm, maternal hypothyroidism and CNS anomaly in the stillborn which produces the neuroepithelial cells. A large number of fetus was observed in this study. neural stem cells are required for the basic research as well as The association between the autopsy and ultrasound for the development of novel approaches, needed for the findings is compared with that of previous studies in Table 6. treatment of various neurological disorders. Human With the current advanced ultrasound techniques, the embryonic stem cell that is derived from retinal pigment false-positive diagnosis is very rare. However, poor visibility epithelium is known to protect the visual function in an because of oligohydramnios or obesity is an important cause animal model of retinal disease. When fetal neurons were of errors in ultrasound diagnosis. Sometimes USG may fail to evaluated, they are known to survive the transplantation detect associated malformations, which may lead to alteration surgery much better than adult neurons, which reflects the in etiological diagnosis. Fetal autopsy provided significant value of fetal-derived neural stem cells. additional information in 38% of cases and the change in Hematopoietic, mesenchymal, embryonic, neural, and recurrence risk in 18% of cases. retinal stem cells are known to differentiate into neuronal When postmortem examinations were compared with lineages, and they may be able to regenerate neural USG findings, in eight cases (11.43%) the USG findings were retinal tissue. incorrect. In 18 cases (25.71%), additional information was Neural stem cells are localized in the highly vascularized obtained on autopsy. Only a few studies have shown a regions of the CNS, instead of being distributed throughout comparison of antenatal ultrasonographic findings and the brain. autopsy findings. Autopsy diagnosis confirmed USG findings Anand et al. have stated that the potential use of traditional in 54 cases (94.74%), it provided additional information in 27 herbs such as Brahmi (Bacopa monniera) needs deeper cases (47.37%), whereas the primary diagnosis provided by investigation. Brahmi appears to perform very important USG was changed in three cases (5.26%). functions in the CNS. A better understanding of the When a major anomaly has already been detected, the physiopathological nature of different neurological diseases at various levels (systemic, organ, tissue, and cell) is of error in prenatal diagnosis is a failure to conduct a complete paramount importance for further progress, and the examination of the fetus. It is avoided by using a systematic mechanisms underlying the effects of Brahmi need to be approach to perform a comprehensive anatomic evaluation elucidated in animal models. of the fetus. Accurate prenatal diagnosis of all associated anomalies is not possible every time, even in the ideal situation. There is an alarming decrease of autopsy Conclusion procedures, because of the centralization of pathology facilities or changes in clinician’s perception of autopsy Congenital CNS anomalies are the most commonly observed importance or improvements in ultrasound diagnostics, or anomalies in the present study. Meningomyelocele was the most poor counseling provided by inexperienced personnel. As common CNS anomaly, followed by anencephaly. There was a a result, parents are refusing to give consent to a fetal significant association between maternal hypothyroidism and CNS anomalies. It is mandatory to have an autopsy study for all the autopsy procedure. Vinutha et al. 231 stillborn fetuses to predict and counsel for safe future pregnancy 9. Pushpa, B Subitha, S Lokesh Kumar, V. Study on various con- outcomes. 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Annals of NeurosciencesSAGE

Published: Jul 1, 2020

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