ࡱ; ?@  !"#$%&'()*+,-./0123456789:;<=>ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstRoot Entry FK\M(CompObjbWordDocumentpObjectPool[M([M(  FMicrosoft Word 6.0 Document MSWordDocWord.Document.6;  Oh+'0$ H l   D h(C:\MSOFFICE\WINWORD\TEMPLATE\NORMAL.DOTAnnals Word template KFSH & RC KFSH & RC@/uNܥe3 etplTTTTTTTt:::::P:@"T6:@T;?*@TTTT^TTTT+ CONGENITAL MALFORMATIONS IN PRIMARY HEALTH CARE IN AL-QASSIM REGION Ibrahim S. Hegazy, MD; Talal H. Al-Beyari, MD; Aladin H. Al-Amri, MD; Naseem A. Qureshi, MD; Muzamil H. Abdelgadir, PhD The objective of this predesigned research was to determine the prevalence, sociodemographic correlates, and pattern of congenital malformations (CMs) in a population less than 20 years of age. From January 1991 to December 1991, the extensive examination of family health files coupled with door-to-door survey identified 1736 patients with CMs. The results showed that the prevalence of CMs was 6.9/1000 population. The male to female ratio was 1.3:1. The patient's age, sibling order, co-morbid disorders of CMs, parental age, chronic maternal diseases, and the family history of CMs were significantly associated with groups of arbitrarily classified CMs. The most frequently encountered CMs were of central nervous system (39.2%) followed by cardiovascular (22.3%), alimentary (13.1%), musculoskeletal (6.85%), urogenital (6.16%), communicative and audiovisual (5.5%), and miscellaneous (6.9%). Further one-way ANOVA found significant differences among CM categories and age of patients and parents. Unlike Western trends, our study tentatively concludes that overall the inheritance rather than socioenvironmental factors contributes significantly in the etiology of different congenital malformations. We further suggest that the basic information of this research might be useful foundation data in future analytic studies on congenital malformations. Ann Saudi Med 1995;15(1):48-53. Major congenital malformations are the leading cause not only of perinatal deaths1,2 but also of infant mortality and morbidity.3,4 They have multifactorial origin and about 40% of cases have idiopathic etiology. The major, minor, and variant features of CMs5 occur during the process of organogenesis. During the last two decades there have been several anecdotal case reports and reports of case series of different congenital malformations. Additionally, the large hospital-based studies carried out among neonates have explored the patterns of CMs and also made references to the CMs as the prime contributors to perinatal deaths.1,2,6,7 Furthermore, some studies have explored the individual specific body system's CMs.8-11 The former studies have, however, some limitations as a majority of these are hospital-based, do not reflect the prevalence of CMs in the general population, are carried out in neonates only, and moreover do not provide data regarding other age groups surviving with congenital malformations. Notably, as a result of multiple favorable factors, the perinatal and infant mortality and morbidity rates attributable to major From the Department of Community Medicine (Dr. Hegazy), University of Cairo; General Director of Health Affairs of Al-Qassim Region (Dr. Al-Beyari); Assistant General Director, Primary Health Care (Dr. Al-Amri); Psychiatric Specialist & Liaison Officer, Buraidah Mental Health Hospital (Dr. Qureshi), Buraidah; Director of Continuous Medical Education Center, Primary Health Care (Dr. Abdelgadir), Buraidah. Address reprint requests and correspondence to Dr. Al-Amri: Assistant General Director, Primary Health Care, P.O. Box 1169, Buraidah, Al Qassim, Saudi Arabia. Accepted for publication 4 June 1994. congenital malformations have considerably decreased in the developing world, though not as sharply as in developed countries. Consequently, it is expected that survival rates of neonates born with CMs would increase in underdeveloped nations, hence posing a major chronic sociomedical health problem. To our knowledge, there is no study which has explored the epidemiological parameters of CMs among different age strata in Saudi Arabia. Therefore, we piloted this study with the goals of finding out the prevalence, possible etiological correlates, and the patterns of congenital malformations in a population less than 20 years of age in the Al-Qassim Region. Material and Methods The Al-Qassim Region is geographically located in the center of Saudi Arabia. This area has been divided into 17 sectors with 134 primary health care centers (PHCCs), five general hospitals and one specialist hospital. In 1985, in an attempt to provide health for all at a national level, about 87.7% of family members of a total of 61,516 families were examined by a medical team and data were registered in about 96.3% (n=57,970) of family health files at PHCCs. In 1991, the total population of both genders of less than 20 years of age was 251,605 out of which 126,686 were males.12 The data about patients (n=1736) with CMs were collected on a pretested proforma by a team comprised of one doctor, a midwife, and one of the nursing staff belonging to each PHCC and assisted by the principal investigator (ISH) who periodically visited the PHCCs TABLE 1. Prevalence of congenital malformations according to age and sex in Al-Qassim, Saudi Arabia, 1991. Age GroupMale populationNo. of casesPrevalence per 1000Female populationNo. of casesPrevalence per 1000Total M & F population Cases Per 1000< 5 yrs37,9322927.7037,9842466.4875,9165387.095 - 934,2933129.1031,8852226.9666,1785348.0710 - 1429,2101635.5830,0661364.5259,2762995.0415 - 2025,2512258.9124,9841405.6050,2353657.27Total126,6869927.84124,9197445.96251,6051,7366.90 TABLE 2. Prevalence of different main groups of congenital malformations/1000 in studied population, 1991. Main Congenital MalformationsNumberPrevalence/1000Neurodevelopmental6812.71Cardiovascular3871.54Alimentary tract2270.9Musculoskeletal1190.47Urogenital1070.43Communicative and audiovisual950.38Miscellaneous1200.47 throughout the period of the study from January 1991 to December 1991. The sources of detailed data were: 1) review of all family health files which were a very good source of information as patients were repeatedly examined at PHCCs more than four times/year and had feedback clinical data about each patient referred to general and specialist hospitals; 2) direct interview of patients and their parents by a standard set of questions; 3) door-to-door survey of all families having congenital malformations registered with respective PHCCs. The proforma abstracted information about 1) characteristics of patients including age, sex, serial order among siblings, diagnoses, and associated conditions; 2) relevant parameters related to parents which included, besides sociodemographic variables, consanguinity, maternal Rh status, family history of congenital malformations, negative obstetric history such as abortion, stillbirth, neonatal death, prematurity and instrumental delivery, maternal disorders such as toxemia of pregnancy, infections, exposure to radiation, immunization, and various drugs, medical diseases such as diabetes mellitus, hypertension, heart, chest, renal, and liver diseases during pregnancy and paternal smoking habits. All the proformas were reviewed by the entire research team. In case there was any deficient information, these were referred back to concerned PHCCs for completion. Finally, the congenital malformations were operationally defined as all abnormal body structural development with adverse medical, surgical, psychological, social, and cosmetic consequences, as well as an irreversible disturbance of function associated with a recognizable internal/external structural abnormality present at birth or recognized later. Though the commonly used words such as anomalies, deformities and defects have different connotations, we have used them interchangeably with malformations occurring during organogenesis. The data were analyzed by using SPSS package and several tests including chi-square, Z, and ANOVA, which were used at appropriate places for statistical purposes. Results Table 1 showed the prevalence rate of CMs among different age categories in both genders. When male cases less than 10 years of age were pooled and analyzed against the pooled cases of females of similar age, it achieved statistical significance (Z=3.691, P<0.001). Likewise, when comparison between pooled data of two sexes above 10 years of age were made, there were highly statistically significant differences (Z=4.499, P<0.0001). It might be commented upon that significant sex divergent prevalence rates of CMs were found not only during the early developmental period but that this trend also continued with increasing age. The prevalence rates per 1000 of main CMs were demonstrated in Table 2. The important characteristics of patients and parents are summarized in Tables 3 and 4. Additionally in our study, the maternal literacy status, obstetric complications, maternal diseases arising during pregnancy, and Rh incompatibility were not significantly associated with congenital malformations. The results of one-way analysis of variance are shown in Table 5. Evidently, the patients with communicative and audiovisual malformations were significantly of higher age (P<0.001) than patients with all other malformations. Further, patients with central nervous system defects were significantly older than the cases with cardiovascular, urogenital, and alimentary malformations (P<0.0001) and patients with musculoskeletal malformations were significantly older than those with urogenital malformations (P<0.0001). Further, the cases with cardiovascular and musculoskeletal malformations were significantly older than those with alimentary malformations (P<0.0001). The patients with urogenital, gastrointestinal, and cardiovascular defects were not having any significant age differences among themselves (P>0.05). The maternal age at the time of conception of patients with neurodevelopmental malformations was significantly higher than the maternal age of cases with the rest of the malformations (P<0.0001). Similarly, the maternal age of cases with cardiovascular malformations was significantly higher than the maternal age of cases with communicative and audiovisual and alimentary malformations (P<0.001). The parental age at the time of conception of patients with neurodevelopmental malformations was observed to be significantly higher than the parental age of patients with all other congenital malformations (P<0.0001). Table 6 showed the detailed frequency distribution and percentages of different congenital malformations among the studied patients. Moreover, 1.61% of patients (n=28) were recognized to present with irreversible functional disturbances related to hematopoietic and reticulo-endothelial systems. Discussion The prevalence of congenital malformations as revealed in this cross-sectional study was 6.9/1000. This figure probably is an underestimation of true prevalence of congenital anomalies because about 12.3% of total family members were not traceable for examination and, TABLE 3. Characteristics of patients with congenital malformations (n=1736). CNS (n=681)CV (n=387)AT (n=227)MSK (n=119)UG (n=107)CAV (n=95)Total (n=1616)*VariablesNo.%No.%No.%No.%No.%No.%No.%PSexMale38824.0119412.0017610.89674.15684.21603.71095358.97< 0.05Female29318.1319311.940513.16523.22392.41352.17066341.03Age Groups< 5 years18111.201247.670764.70372.29422.60181.11047829.585 - 9"20012.381398.600643.96332.04271.67251.55048830.20< 0.05> 10"30018.561247.670875.38493.03382.35523.22065040.22Associated conditionsNo43426.8628517.641328.17996.13845.20815.01111569.00< 0.05Yes24715.2810206.310955.88201.24231.42140.87050131.00Sibling OrderFirst13408.3007104.400462.85362.23281.73261.6134121.102nd to 5th29818.4519011.761137.00482.97543.34432.6674646.16< 0.05above 5th24915.4212607.800684.21352.17251.55261.6152932.74F/H of Cong. malformationsYes53533.1132119.8619712.19976.00855.26664.08130180.51< 0.05No14609.0306604.0803001.86221.36221.36291.79031519.49Parental consanguinityYes36522.5922814.111027.74654.02633.90563.47087954.39> 0.05No31619.5515909.841256.31543.34442.72392.41073745.61Total68142.1438723.9522714.051196.851076.62955.51616100.00CNS=central nervous system; CV=cardiovascular; AT=alimentary tract; MSK=musculoskeletal; UG=urogenital; CAV=communicative and audiovisual; F/H=family history; *Miscellaneous (N=120). TABLE 4. Parental characteristics in relation to the indexed patients (N=1736). CNS (n=681)CV (n=387)AT (n=227)MSK (n=119)UG (n=107)CAV (n=95)Total (n=1616)*VariablesNo.%No.%No.%No.%No.%No.%No.%PPaternal Age< 25 yrs17010.52915.63613.77321.98241.49211.3039924.6925 - 34 yrs21513.301408.66734.52412.54523.22422.6056334.84< 0.05> 35 yrs29618.321569.65935.75462.85311.92321.9865440.47Maternal Age< 25 yrs1308.04654.02352.17321.98281.73281.7331819.6825 - 34 yrs1398.601066.56804.95392.41352.17221.3642126.05< 0.05> 35 yrs41225.5021613.371126.93482.97442.72452.7887554.27Medical disorders during pregnancyPresent63039.0036222.4018611.511056.50925.69855.26146090.35< 0.05Absent513.16251.55412.54140.87150.93100.621569.65CNS=central nervous system; CV=cardiovascular; AT=alimentary tract; MSK=musculoskeletal; UG=urogenital; CAV=communicative and audiovisual; F/H=family history; *Miscellaneous group (N=120). TABLE 5. Current patients' age, maternal age, and paternal age in relation to different congenital malformations. Patients' AgeMaternal Age*Paternal Age*Different groups of CMsMean+SDMean+SDMean+SDCentral Nervous System (n=681) 9.45 6.22 28.56 9.03 42.34 11.58Cardiovascular (n=387)8.105.6826.797.5538.1610.11Alimentary tract (n=227)7.576.4024.997.5338.1510.73Musculoskeletal (n=119)8.866.9526.157.1337.8810.62Urogenital (n=107)7.205.9926.187.6139.3610.92Comm & Audiovisual (n=95) 11.15 6.48 24.46 7.21 38.47 8.70*Age at the time of conception of patients; SD=standard deviation. moreover, 3.7% of family health files were not registered at primary health centers. The different sociodemographic correlates of congenital anomalies are under constant reappraisal; therefore, their etiological significance should be taken cautiously. In this survey, we found that the different congenital malformations were significantly related to male sex (P<0.05), thus corroborating the results of other researchers.13-15 This finding raised some speculations; for instance, either females were afflicted relatively more by fatal congenital anomalies or alternatively, they survived with more minor anomalies as found by some investigators,13 which is possibly overlooked in our study. Similarly, the young age (<10 years) was significantly associated with congenital malformations, which attests to the fact that morbidity from congenital malformations is more common among young children. Further, there were significant associated multiple conditions (P<0.05) among studied population, hence reflecting the polymorphous nature of congenital anomalies. This finding, inter alia, might have been utilized in reaching the syndromal diagnoses of congenital malformations, a limitation of our research work. However, the preliminary nature of this research precluded a venture on this perspective. Furthermore, patients having increasing sibling orders (>5th) tend to have a significantly high distribution of congenital malformations (P<0.05), thus reflecting the paramount role of multiparity in the production of congenital deformities.15,16 Regarding the maternal sociodemographic correlates, this study found that maternal age (>25 years) and chronic medical diseases, most importantly diabetes, were significantly correlated (P<0.05) with congenital malformation, thus partially substantiating the results of other studies.13,17 In a study, about 12% of diabetic mothers had congenital malformations; in particular, cardiac defects were twice the rate in controls.17 The effects of untreated hypertension on the developing fetus are equally serious, especially causing intrauterine fetal growth retardation. Our study did not substantiate this finding, which could be explained by very close antenatal checkup and early treatment of hypertension for Saudi TABLE 6. Frequency distribution and percentages of different congenital malformations among the studied patients (n=1736). Congenital MalformationFrequencyTotal %Central Nervous System68139.23Mental Retardation30617.63Down syndrome17710.20Cerebral palsy955.47Hydrocephalus362.07Epilepsy311.79Microcephaly181.04Other conditions181.04Cardiovascular39722.29VSD29416.94ASD301.73Valvular Disease271.56Hemangiomas170.98PDA150.86Dextrocardia60.35Fallot tetralogy50.29Coarctation of aorta30.17Alimentary tract22713.08Cleft lip543.11Cleft palate150.86Combined form of 1 & 2593.40Imperforate anus191.09Umbilical hernia160.92Inguinal hernia140.81Diaphragmatic hernia110.63Supernumerary teeth100.58Hirschsprung disease70.40Ectopic anus50.29Pyloric stenosis50.29Tracheoesophageal fistula50.29Esophageal atresia40.23Biliary atresia30.17Musculoskeletal1196.85Joint deformities311.79Talipes equinovarus301.73Dislocation of hip271.56Muscle/bone disorders130.75Finger deformities120.69Phocomelia & others60.35Urogenital1076.17Hypospadias341.96Undescended testes261.50Polycystic kidney160.92Hydrocele100.58Absent right/left kidney80.46Varicocele80.46Others50.29Communicative & Audiovisual955.47Deaf-mutism382.19Strabismus261.50Blindness70.40Ptosis70.40Cataract60.35Exophthalmos50.29Glaucoma30.17Dysarthria20.12Microphthalmos10.06Miscellaneous Group1206.91Skin Diseases321.84Respiratory Diseases311.79Endocrinological diseases291.67Blood & reticuloendothelial diseases281.61pregnant women, as also reported by several other researchers.18 Further, in relation to age, the corroboration seems hazardous because in developed nations, the relatively advanced age (>40 years) is implicated in the etiology of congenital chromosomal syndromes. Contrasting the early marriages, overemphasis on large families and lack of an adequate amount of time between subsequent pregnancies in this culture probably give rise to multiparity at a young age, 25 years or so, which relates significantly to the congenital malformations. Some studies with nearly complete ascertainment have found a higher incidence of trisomy-21 in babies born to mothers less than 20 years of age when compared with mothers having an age of 20 to 29 years.19 As regards paternal age (>25 years), it was also significantly associated with a group of congenital malformations (P<0.05). Though the adverse effects of paternal age on fetal development is fraught with controversies, some experts have highlighted the significant contributions of paternal age20 and joint effect of parental age21 to the development of congenital chromosomal syndromes. It is evident from the literature that there are large reported variations in the pattern of congenital malformations involving different body systems. This survey found that the CNS was the most commonly affected by congenital malformations, as also reported in the literature.3,13,22 Among specific CNS malformations, mental retardation of clinically moderate grade (45%) was the most common disorder followed by trisomy-21 and cerebral palsy. In a community survey carried out in the Eastern Province, Al-Rajeh and associates23 also found the syndromes of mental retardation (6.27/1000) and cerebral palsy (5.30/1000) as the second and third most common neurological impairments. In the USA, 16% of neurologic handicaps are due to T-21; however, in our study, the percentage of T-21 among the neurologically impaired is 25.99%. With special reference to T-21, its incidence worldwide is between 0.12% and 0.33%. In cultures where prenatal detection of T-21 among late age pregnancies is customary, it is about 0.1% to 0.2%. In Saudi Arabia, its incidence is about 0.33% as prenatal screening for T-21 is not practiced and pregnancies after 35 years of age are a common occurrence. It is known that the median life expectancy of T-21 was about 40 years before cardiac surgery. About 25% of T-21 can have a severe congenital heart disease (CHD) that warrants surgery. Given all these considerations, our findings are most interesting. Since our survey is for an age group of <20 years, the prevalence of T-21 should have been about 0.6%, while we found only 177 T-21 in a population of 251,605, only 0.07%. This figure is five to 10 times less than expected. Attrition due to death of a T-21 patient from CHD is highly unlikely in Saudi Arabia since there is a great awareness of CHD and most medical centers engage in its correction. Also, it is highly unlikely to miss the clinical diagnosis of T-21 since the health care system is sophisticated and it is a disease that is hard to miss. Phenotypically less apparent T-21 is usually encountered in mosaic T-21, which is not more than 1% to 2% of this syndrome. Not enough numbers of T-21 encountered in our surveyed population support the results of other researchers from Saudi Arabia.23 In the Western literature, the falling rate of Down syndrome has been attributed largely to decline in fertility among older mothers. Interestingly, it is evident from our study that the consanguinity in the families involved is 54%, an important correlate of congenital malformation,24 while the familial occurrence of congenital malformations is 80%. Although in Western cultures most multigenic diseases are congenital and are caused by environmental factors, in our surveyed population, the pattern suggests inheritance. Although these conditions could have an inheritance basis,15 the congenital malformations in Saudi Arabia are due to inherited defects rather than socioenvironmental factors. The clinical implications of these findings are that the public at large need educational programs which should include genetic counseling, significant utilization of optimal antenatal care and prenatal diagnostic screening. The prevalence of congenital cardiovascular malformations varies due to multiple factors. However, in agreement with others,13 our survey found that the acyanotic cardiac defects (96.14%) as compared to the cyanotic malformations (3.86%) were more frequent. The distribution of cyanotic cardiac malformations among neonates is comparatively high.1,2,13 As such defects are associated with high mortality, our study also found considerable reduction in cyanotic malformations among young adolescents. With special reference to alimentary tract malformations, we found the similar patterns of cleft lip with or without cleft palate as reported in a study from Kuwait.9 Despite some caveats already highlighted, we suggest that data of this preliminary research might be utilized as a data base for future analytical research involving several other etiological factors15,22,25 related to congenital malformations in Saudi Arabia. Acknowledgment We express our thanks to the staff of Online Search Division of King Abdulaziz City for Science and Technology, Riyadh; also to Dr. Laila El-Ghorury for entering the data into the computer and all other workers of Continuous Medical Education Center, Primary Health Care, Qassim General Health Affairs. References 1. Sayeed MA, Sanousi AA. Major congenital anomalies: two years' experience in Prince Salman Hospital, Riyadh (Abstract). Ann Saudi Med 1990;10:488. 2. Meshlah RA. Perinatal mortality at the Riyadh Armed Forces Hospital, Riyadh. Saudi Med J 1985;6:135-44. 3. Vaughan VC, III. The field of pediatrics. In: Nelson Textbook of Pediatrics, Behrman RE, Vaughan VC, III, eds. Nelson WE. XIII edition. WB Saunders Co. 1987:1-5. 4. Ohlsson A. Range of diseases at a public pediatric clinic in Saudi Arabia. Lakartidningen 1981;78:3149-52. 5. Ekelund H, Kullander S, Kallen B. Major and minor malformations in newborns and infants up to one year of age. Acta Paediatr Scand 1970;59:297-302. 6. Ahmad GS, Khan S, Abu-Taleb A, et al. Perinatal mortality at King Fahad National Guard Hospital, Riyadh (Abstract). Ann Saudi Med 1990;10:487. 7. Ohlsson A, Serenius F. Neonatal septicemia in Riyadh, Saudi Arabia. Acta Paediatr Scand 1981;70:825-9. 8. Al-Naquib N. Neurodevelopmental problems in children in Riyadh, Saudi Arabia: 1-year's experience in a family practice centre. J Trop Pediatr 1988;34:294-300. 9. Naguib KK, Al-Awidi AS, Moussa MA, et al. Syndromal and nonsyndromal cleft lip with or without cleft palate in Kuwait. Ann Saudi Med;1989;9:388-92. 10. Khawaja S, Al-Breiki H, Grant C, et al. Congenital diaphragmatic hernia. Saudi Med J 1985;6:229-35. 11. Jaiesimi F, Ruberu DK, Misra VK. Pattern of congenital heart disease in King Fahad Specialist Hospital, Buraidah. Ann Saudi Med 1993;13:407-12. 12. Annual Health Report. Al-Qassim General Health Affairs, Kingdom of Saudi Arabia, 1440 (1991), Al-Jisir Printing, Publication and Distribution House; 24, 76. 13. Mir NA, Galczek WC, Soni A. Easily identifiable congenital malformations in children: survey of incidence and pattern in 32,332 live born neonates. Ann Saudi Med 1992;12:366-71. 14. Khan SMD, Ahmed GS, Abu-Talib A, et al. Are congenital anomalies more frequent in Saudi Arabia [Abstract]? Ann Saudi Med 1990;10:488-9. 15. Peckham CS, Ross EM, Farmer RDT. Congenital malformations. In: Epidemiology of diseases. Miller DL, Farmer RDT, eds. Blackwell Scientific Publications 1982;452-65. 16. Mir NA, Soni A, Kishan J, et al. Facial clefting in Arab infants. Ann Saudi Med 1988;8:206-8. 17. Day RE, Insley J. Maternal diabetes and congenital malformations. Archives Dis Childhood 1976;51:935-8. 18. Ounsted MK, Moar VA, Good FJ, Redman CWG. Hypertension during pregnancy with and without specific treatment: the children at the age of 4 years. Br J Obstet & Gynaecol 1980;87:19-24. 19. Mikkelsen M, Ficher G, Stene E, Stene J, Petersen E. Incidence study of Down syndrome in Copenhagen, 1960-1971: with chromosome investigation. Ann Hum Genet 1976;40:177-82. 20. Matsunaga E, Tonomura A, Oishi H, Kikuchi T. Re-examination of paternal age effect in Down syndrome. Hum Genet 1978;40:259-68. 21. Stene J, Stene E, Stengel-Rutkowski S, Murken JD. Paternal age and Down syndrome: data from prenatal diagnoses (DFG). Hum Genet 1981;59:119-24. 22. Johnstone FD, Forfar JO. Prenatal paediatrics. In: Textbook of Paediatrics, Vol 1. Forfar JO, Arneil GC, eds. 3rd ed. Churchill Livingstone 1984;81-116. 23. Al-Rajeh S, Bademosi O, Ismail H, et al. A community survey of neurological disorders in Saudi Arabia: the Thugbah study. Neuroepidemiol 1993;1:164-78. 24. Baird PA, Sadovnick AD, Yee ML. Maternal age and birth defects: a population study. Lancet 1991;37:527-30. 25. Czeizel AE, Dudas I. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-5.  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