Survival and Factors Associated with Mortality Among Infants with Anorectal Malformation: A Population- Based Study from A Middle-Income Country

Survival and Factors Associated with Mortality Among Infants with Anorectal Malformation: A Population- Based Study from A Middle-Income Country | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Survival and Factors Associated with Mortality Among Infants with Anorectal Malformation: A Population- Based Study from A Middle-Income Country Mohd Nizam MAT BAH, Norazah ZAHARI, Aina Salwa KASIM, Noorintan Liana MOHAMED SHARIF This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2712306/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Oct, 2023 Read the published version in European Journal of Pediatrics → Version 1 posted 10 You are reading this latest preprint version Abstract Limited data on the survival of anorectal malformation (ARM) patients from lower-and-middle income countries is available. This retrospective population-based study from the State of Johor, Malaysia, determines the incidence, mortality rate, and survival of ARM patients and factors associated with mortality. Kaplan-Meier survival analysis was used to estimate the survival of ARM patients at 1-, 5- and 10- years. In addition, multivariate cox-regression analysis was used to analyze mortality-related factors. There were 175 ARM patients among 803850 live births, giving an overall ARM incidence of 2.2 (95% confidence interval [CI], 1.9 to 2.5) per 10,000 live births. The male-to-female ratio was 1.5: 1. There was 122 (69%) non-isolated ARM, of which 41 were Down syndrome and 34 had VACTERL. Seventy-three (41.7%) had CHD, with 38 severe and 35 non-severe CHD. Overall, 33 (18.9%) patients died, with a median age of death of 5.7 months (Interquartile range 25 days to 11.2 months). The overall estimated 1-, 5- and 10-year survival rate for ARM patients was 82.3% (95% CI, 76.0% – 88.6%), 77.3% (95% CI, 70.4% - 84.2%), and 77.3% (95% CI, 70.4%- 84.2%), respectively. Univariate analysis shows that non-isolated ARM, VACTREL association, and severe CHD were associated with mortality. However, only severe CHD is the independent factor associated with mortality, with a hazard ratio of 4.03 (95% CI: 1.93-8.42). Conclusion: CHD is common among ARM patients, and one in five ARM patients had a severe cardiac defect, significantly affecting their survival . Anorectal malformation Congenital heart disease Middle-income country Mortality Survival. Figures Figure 1 Figure 2 Figure 3 What Is Known VACTREL association and congenital heart disease is common in patient with anorectal malformation Low birth weight and prematurity are associated with a lower rate of survival What is new: Congenital heart disease is common in ARM patients in a middle-income country Severe congenital heart disease plays a significant role in the survival of patients with an anorectal malformation in lower- and middle-income countries. Introduction Congenital anorectal malformation (ARM) comprises a broad spectrum of abnormalities of the anus and anal cavity, with a reported prevalence of 2 to 5 per 10 000 live births ( 1 – 3 ). It is the most common gastrointestinal malformation and can occur in isolation or associated with other malformations or syndromes ( 2 ). In addition to Down syndrome and VACTERL, ARM is also known to be associated with congenital heart disease (CHD). However, the reported prevalence of CHD among ARM patients is highly variable, ranging from as low as 9% to as high as 50% ( 4 – 12 ). Furthermore, there is a conflicting report on the most common cardiac lesion in ARM patients, with ventricular septal defect ( 8 , 13 ), atrial septal defect ( 4 , 12 ), and tetralogy of Fallot ( 6 ) described as frequent lesions. In addition, the mortality and survival of ARM patients vary greatly depending on the economic status of the countries. For example, the reported mortality in high-income countries ranges from 1.7–2.9% ( 14 , 15 ). In comparison, a higher rate was observed in the lower-and-middle-income countries, with a reported rate ranging from 11.9–29% ( 14 – 16 ). Additionally, the prognosis of ARM patients was also affected by various factors such as the number of associated anomalies, prematurity, low birth weight, delayed presentation, and primary perforation ( 1 , 2 , 11 ). However, studies on the effect of CHD on the mortality and survival of ARM patients are limited ( 16 ). Furthermore, a population-based study from lower-and-middle-income countries is lacking. Therefore, with a lack of resources and expertise, we postulate that the survival of ARM patients is lower than in high-income countries, and CHD plays a significant role in the survival of ARM patients. Therefore, this study aims to assess the prevalence and pattern of CHD and its effect on the overall outcome of ARM patients. Materials And Methods This retrospective cohort study included all ARM patients born between January 2006 and December 2019 in the State of Johor. There was an estimated population of 3.4 million in the State of Johor, with an annual live births of 50,000 per year. All cases of ARM and CHD were referred to Hospital Sultanah Aminah, a tertiary government hospital that provides pediatric cardiology and surgical services for the State of Johor, Malaysia ( 17 ). This study was approved by the Medical Research and Ethics Committee, Ministry of Health, Malaysia (NMRR 21-1881-61323). A waived informed consent was given due to the study's retrospective nature. All procedures performed in this study followed the institutional and national research committee's clinical standards, the 1964 Declaration of Helsinki, and its later amendments or comparable ethical standards. ARM was diagnosed based on clinical features such as imperforate anus, presence of fistula, ectopic anus, or cloacal anomaly and was classified according to the Krickenbeck classification ( 18 ). In addition, other congenital malformations were recorded and divided into four groups as described by Cuschieri et al. ( 3 ): 1) syndromes of known cause, 2) recognized syndromes and sequences of unknown etiology, 3) VACTERL association, and 4) multiple congenital anomalies. Patients with three or more defects (vertebral, anal atresia, cardiac septal defects, esophageal atresia or tracheoesophageal fistula, renal anomalies, and radial limb defects) were considered to have the VACTERL association ( 19 ). ARM was divided into two groups, those with associated other malformations or syndromes as non-isolated ARM ( 2 ) and, conversely, isolated ARM if there was no association with any syndrome or malformation. CHD was defined as a significant structural abnormality of the heart or the great intrathoracic vessel that was of actual or potential significance ( 20 ). All CHD was confirmed with two-dimensional echocardiography. Patients with patent foramen ovale, mild branch pulmonary stenosis, isolated dextrocardia, isolated bilateral superior vena cava, isolated right arch, and spontaneous closure PDA in three months (for a term infant) and six months (for premature) were not considered as CHD ( 21 ). In patients with multiple cardiac defects, the primary lesion that required the first intervention or was hemodynamic significant was regarded as the primary defect. The severity of CHD was divided into mild, moderate, and severe ( 22 ). Data were retrieved from the Pediatric Cardiology Clinical Information System, a clinical database for acquired and congenital heart disease in the State of Johor ( 21 , 23 ). Data collected included demographic data (gestational age, maternal gestational diabetes, syndrome, birth weight, sex, and ethnicity), ARM data (type and associated with other malformation), CHD data (type and severity), and finally the outcome at the last follow-up (alive or dead). All patients had a complete clinical examination by the medical and pediatric surgical team. This included a two-diemnsional echocardiogram for screening of CHD. Active screening for other congenital anomalies associated with ARM or syndrome was also conducted. Similar to CHD, further ARM management was done according to the severity of the disease. The primary outcome measured was the survival of the infant. Mortality (all causes of death) was verified with the National Registry Department, Malaysia. Cause of death was grouped into cardiac, infection, or other causes. Statistical analysis Statistical analysis was performed using Statistical Package for Social Science (SPSS) version 23 (IBM Corp., Armonk, NY, USA). Groups were compared using Student's t-test for normally distributed continuous data and a non-parametric test for non-normally distributed continuous data. Pearson's chi-square test for categorical variables. A p-value < 0.05 was considered statistically significant. The incidence of ARM was calculated as the sum of newly diagnosed ARM divided by total live births in the State of Johor and expressed as per 10,000 live births. Kaplan–Meier analysis was used to estimate survival at 1-,5-, and 10-years. Log-rank test was used to compare the difference between the group. Univariate Cox proportional hazards regression was used to identify the unadjusted effect of age, sex, ethnicity, gestational age, birth weight, birth year, VACTERL, trisomy-21, and CHD severity on mortality. Variables with p-values < 0.1 in the univariate analyses were entered into the Cox proportional hazards regression to identify the independent risk factors associated with death. A hazard ratio was considered significant if the 95% confidence interval (CI) excluded one Results There were 175 ARM patients among 803850 live births during the study period, giving an overall ARM incidence of 2.2 (95% CI, 1.9 to 2.5) per 10,000 live births. Of 175, 105 (60.0%) were male, 136 (77.7%) were Malay ethnicity, and 60 (34.3%) had low birth weight (Table 1). The mean age of diagnosis was 1.5 days (ranging from 0 to 75 days). All patients were followed up at a median age of 5.1 years (IQR from 0.4 to 8.8 years). Of 175 ARM patients, 169 (96.6%) were detected during newborn examination, 2 (1.1%) patients presented at birth with abdominal distension, 2 (1.1%) were suspected antenatally, and 1 (0.6%) with an abnormal route of passing stools/meconium. In addition, one patient had her ARM detected at three months of life during pediatric intensive care admission for pneumonia. Of the 97 available data on the subtype of ARM, 51 (29.1%) had no fistula, 12 (6.9%) recto vestibular, 8 (4.6%) cloacal anomalies, 8 (4.6%) rectovaginal fistula, 7 (4.0%) rectourethral, 7 (4.0%) perineal and 4 (2.3%) rectal atresia. One hundred twenty-two (69.7%) ARM patients had an underlying syndrome or associated congenital malformation. Recognized syndrome with a known cause is seen in 49 (28%), with a majority (n = 41) being Down syndrome. VACTREL association was observed in 34 (19.4%) patients. In addition, one patient had Omphalocele, Exstrophy, Imperforate anus, Spinal Bifida complexes, 2 Edward syndrome, and one each for Patau syndrome, Prune-Belly, Golden-Har syndrome, Wolf-Hirschhorn syndrome, chromosomes 18 and 16 disorder. Of 175 ARM patients, 6 (3.4%) were associated with neural tube defects and 2 (1.1%) with omphalocele. There was no significant difference in the proportion of non-isolated ARM between females and males (51/70 [72.9%] vs. 71/105 [67.6%], p = .46). Seventy-three (41.7%) had CHD, of which 38 (52.1%) were severe CHD, and 35 (47.9%) were non-severe CHD (Table 2). The commonest lesions were ventricular septal defect (n = 29, 39.76%), followed by Tetralogy of Fallot (n = 10, 13.7%). Of 73 patients with CHD, 36 (49.3%) required surgery, and 11 (15.1%) patients had their cardiac defect closed spontaneously (all were small ventricular septal defects). Of 175 ARM patients, nine (5.1%) were treated with comfort care, of which three were due to lethal congenital malformation, four were due to complex congenital cardiac defects, and two were for severe persistent pulmonary hypertension of the newborn. Overall, 33 (18.9%) patients died, with a median age of death of 5.7 months (IQR 25 days to 11.2 months). Of 33 death, 8 (24.2%) were cardiac-related, 11 (33.3%) infection-related, and 14 (42.4%) of other causes. The overall 1-, 5- and 10-year survival rate for ARM patients was 82.3% (95% CI, 76.0% – 88.6%), 77.3% (95% CI, 70.4% − 84.2%), and 77.3% (95% CI, 70.4%- 84.2%), respectively. However, there was a significantly lower survival in ARM patients with non-isolated ARM, with survival at 1-, 5, and 10 years of 77.2% (95% CI 69.4% – 85.0%), 72.4% (95% CI 64.0%- 80.8%) and 72.4% (95% CI, 64.0%- 80.8%), respectively (Fig. 1 ). Further analysis revealed ARM patients with VACTERL had a lower survival rate than the non-VACTERL, with estimated survival at 1- and 5 years of VACTERL were 66.0% (95% CI, 48.8% − 83.2%) and 55.6% (95% CI, 37.6% − 77.5%), respectively (Fig. 2 ). Similarly, a lower survival was observed in ARM patients with severe CHD, with estimated survival rates at 1 and 5 years of severe CHD were 61.7% (95% CI, 45.8% − 77.6%) and 50.5% (95% CI, 34.2% − 66.8%), respectively (Fig. 3 ). In comparison, there were no significant differences in the survival of ARM patients by sex, ethnicity, or gestational age. However, corrected for sex and ethnicity, multivariable Cox regression analysis shows severe CHD as the only significant factor associated with mortality with a hazard ratio of 4.03 (95% CI: 1.93–8.42) (Table 3). Discussion This first population-based study from lower-and-middle income countries examined the prevalence of CHD among ARM patients over a 14-year duration. In addition, it analyzed its effect on the overall survival of ARM patients. In this cohort, almost one in two ARM patients had CHD, and severe CHD was associated with poor outcomes. Previous studies showed wide variation in the prevalence of CHD among ARM patients, ranging from 9% to % 50% ( 4 – 12 ). The broad difference in the prevalence of CHD among ARM patients is due to the nature of the study, which involved a single center, a small sample size, and patient selection. The prevalence of CHD among ARM patients in this study (41.7%) is slightly higher than the population-based studies in Italy and the United Kingdom, with a rate of 36% ( 1 , 2 ). There are several possible explanations for this result. Firstly, due to the active screening for CHD with 2d-echocardiogram in all neonates with congenital anomalies. Secondly, it could be due to the inclusion of a small ventricular septal defect, which closed spontaneously. Nevertheless, our study shows that one in five ARM patients had a severe cardiac defect. Similarly, there were contradicting reports of the most common CHD in ARM patients, with ventricular septal defect, atrial septal defect, and Tetralogy of Fallot as the commonest lesion ( 4 , 8 , 12 , 13 ). In this study, a ventricular septal defect is the commonest cardiac defect among ARM patients and represents one-third of CHD. This result is similar to our general population, where a ventricular septal defect is the most common type of CHD ( 21 ). The incidence of ARM in this study is within the lower range of the published population-based studies, ranging from 2 to 4 per 10,000 live births ( 1 ). A lower incidence of ARM in this study could be due to underreporting, as some infants have died before reaching a diagnosis or were referred to other surgical centers in a nearby state. The overall mortality of ARM varied, with a higher rate in the lower-and-middle income countries than in higher-income countries ( 14 , 15 ). A slightly higher rate of mortality was observed in this study compared to the 12.5% reported by Wright et al.( 14 ). A higher rate of mortality could be due to the inclusion of those who were treated with comfort care secondary to lethal congenital malformation as well as hypoplastic left heart syndrome in our cohort. Another reason was that notable death was related to infection in this study, which is still a common scenario in other lower-and-middle income countries ( 24 ). The overall estimated survival rate of ARM patients at one year was 82% and reached a plateau at three years with a rate of 77%, with a lower survival rate in non-isolated ARM. Our survival rate is lower than a recent study from high-income countries by Ford et al.( 1 ) from the United Kingdom and Cassina et al. ( 2 ) from Italy. In these two high-income countries, the survival rate of non-isolated ARM patients ranged from 87–89% compared to 72% in our cohort. There were many contributing factors associated with poor survival. Previous studies have shown that low birth weight, prematurity, late presentation, and a higher number of congenital anomalies as significant factors associated with mortality ( 1 , 2 , 11 ). However, this study shows that severe CHD plays a significant role in ARM survival. Almost half of the ARM patients with severe CHD did not survive by five years of age and were five times more likely to die than non-severe CHD or non-CHD. This result is not surprising, being a lower-and-middle income country lacking resources and expertise, especially in dealing with a non-isolated ARM with severe CHD. Therefore, in relation to Sustainable Development Goal 3.2, "end preventable deaths in neonates and children under five by 2030, overall infection control and prompt access to congenital cardiac surgery are much needed to improve the survival of ARM patients. Early detection and surgical intervention of severe CHD are pivotal to achieving this goal. Strength Of The Study The major strength of this study includes a population study over 14 years with an early cardiac evaluation with a 2d-echocardiogram. This allows early diagnosis of severe CHD, allowing a preoperative plan and subsequent management. Limitations There were a few limitations of the study. Firstly, as in other studies using clinical registry ( 2 ), missing data in the subtype of ARM and a small number of other congenital anomalies in this cohort prevent us from analyzing the effect of these variables on the overall survival of ARM patients. Secondly, we may miss some early and undiagnosed neonatal deaths, which may have underestimated the prevalence of CHD among ARM patients. Finally, the lack of surgical ARM data in the registry prohibits us from analyzing the roles of the surgical variable on the overall survival of the ARM in our cohort Conclusion This study explored the prevalence of CHD and its effect on the overall survival of ARM patients in lower-and-middle income countries. The present study shows that CHD is common among ARM patients, and severe CHD is associated with a lower survival rate. Hence, improved overall medical care, particularly for those with severe CHD in lower-and-middle income countries, is needed for better ARM survival. Abbreviations ARM-anorectal malformation CHD-congenital heart disease CI-confidence interval IQR-interquartile range Declarations Acknowledgments: We thank the Director-General of Health Malaysia for permission to publish this article. Additionally, we would like to thank the Biostatistics & Data Repository Sector, National Institute of Health, Setia Alam - for the data linkage service, and the National Registration Department (JPN) for their willingness to share their mortality records for research purposes. Funding source: No funding was received for conducting this study Conflict of interest/Competing interests: All the authors declare that they have no conflict of interest. This work is original and has not been published or presented elsewhere, nor is it currently under consideration for publication elsewhere Availability of data and material: The data that support the findings of this study are available from the corresponding author upon reasonable request Code availability: Not applicable Authors' contribution: All authors contributed to the study conception and design. AS, and NLMS performed material preparation, and data collection. MNMB performed the analysis. MNMB and NZ wrote the first draft of the manuscript, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethical approval: All procedures performed in studies involving human participants followed the clinical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Medical Research and Ethics Committee, Ministry of Health, Malaysia (National Medical Research Register (NMMR-21-1881-81323) Consent to participate: Medical Research and Ethics Committee, Ministry of Health, Malaysia waived the written informed consent. Consent for publication: Not applicable References Ford K, Peppa M, Zylbersztejn A, Curry JI, Gilbert R. Birth prevalence of anorectal malformations in England and 5-year survival: a national birth cohort study. Arch Dis Child. 2022;107(8):758–66. 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The birth prevalence, severity, and temporal trends of congenital heart disease in the middle-income country: A population-based study. Congenit Heart Dis. 2018;13(6):1012–27. Hoffman JIE, Kaplan S. The incidence of congenital heart disease. Vol. 39, Journal of the American College of Cardiology. 2002. p. 1890–900. Mat Bah MN, Alias EY, Razak H, Sapian MH, Foo FH. Epidemiology, clinical characteristics, and immediate outcome of Kawasaki disease : a population-based study from a tropical country. Eur J Pediatr. 2021;180(8):2599–606. Umar Nisar M, Iqbal A, Javed N, Sikander S, Burki SA, Chaudhry MA. Factors affecting the outcome of neonates with anorectal malformation in a developing country. J Pediatr Adolesc Surg. 2021;1(2):66–9. Tables Table I. The characteristic and immediate outcome of an infant with an anorectal malformation Variable Total (n = 175) Final Outcome P-value Survivor (n = 142) Non-survivor (n = 33) Sex Male 105 (60.0) 89 (62.7) 16 (48.5) .13 Female 70 (40.0) 53 (37.3) 17 (51.5) Gestational age Premature 34 (19.4) 30 (21.1) 4 (12.1) .33 Term 141 (80.6) 112 (78.9) 29 (87.9) Race Malay 136 (77.7) 108 (76.1) 28 (84.8) .36 Non-Malay 39 (22.3) 34 (23.9) 5 (15.2) Birth weight < 2.5kg 60 (34.3) 48 (33.8) 12 (36.4) .78 2.5kg and more 115 (65.7) 94 (66.2) 21 (63.6) Birth Year 2006–2010 42 (24.0) 32 (22.5) 10 (30.3) .59 2011–2015 75 (42.9) 63 (44.4) 12 (36.4) 2016–2019 58 (33.1) 47 (33.1) 11 (33.3) Maternal Diabetic No 148 (84.6) 122 (85.9) 26 (78.8) .30 Yes 27 (15.4) 20 (14.1) 7 (21.2) Non-isolated ARM Non-isolated ARM 122 (69.7) 92 (64.8) 30 (90.9) .005 Isolated ARM 53 (30.3) 50 (35.2) 3 (9.1) Down syndrome No 134 (76.6) 105 (73.9) 29 (87.9) .11 Yes 41 (23.4) 37 (26.1) 4 (12.1) VACTERL No 141 (80.6) 121 (85.2) 20 (60.6) .001 Yes 34 (19.4) 21 (14.8) 13 (39.4) CHD No 102 (58.3) 90 (64.8) 10 (30.3) < .001 Yes 73 (41.7) 50 (35.2) 23 (69.7) CHD severity Severe CHD 38 (21.7) 20 (14.1) 18 (54.5) < .001 Non-Severe CHD 35 (20.0) 30 (21.1) 5 (15.2) No CHD 102 (58.3) 92 (64.8) 10 (30.3) ARM type Major clinical group 163 (93.1) 133 (93.7) 30 (90.9) .70 Rare‎/regional variant 12 (6.9) 9 (6.3) 3 (9.1) (%), percentage within the outcome ARM, anorectal malformation; CHD, congenital heart disease Table II: Distribution and severity of congenital heart disease among infants with anorectal malformation CHD Total, N (%) CHD severity Severe CHD, n (%) Non-Severe CHD, n (%) VSD 29 (39.7) 6 (15.8) 23 (65.7) TOF 10 (13.7) 10 (26.3) 0 (0.0) PAVSD 7 (9.6) 7 (18.4) 0 (0.0) ASD 6 (8.2) 0 (0.0) 6 (17.1) PDA 6 (8.2) 4 (10.5) 2 (5.7) PS 3 (4.1) 0 (0.0) 3 (8.6) TAPVD 3 (4.1) 3 (7.9) 0 (0.0) DORV 2 (2.7) 2 (5.3) 0 (0.0) HLHS 2 (2.7) 2 (5.3) 0 (0.0) AVSD 1 (1.4) 1 (2.6) 0 (0.0) CoA 1 (1.4) 0 (0.0) 1 (2.9) D-TGA 1 (1.4) 1 (2.6) 0 (0.0) AS 1 (1.4) 1 (2.6) 0 (0.0) IAA 1 (1.4) 1 (2.6) 0 (0.0) Total 73 (100.0) 38 (100.0) 35 (100.0) (%), percentage within total CHD and severity CHD, Congenital heart disease; VSD, ventricular septal defect; ASD, atrial septal defect; PDA, patent ductus arteriosus; TOF, tetralogy of Fallot; PAVSD, pulmonary atresia with VSD; TAPVD, total anomalous pulmonary venous drainage; DORV, double outlet right ventricle; PS, pulmonary stenosis; HLHS, hypoplastic left heart syndrome; AVSD, atrioventricular septal defect; CoA, coarctation of aorta; D-TGA, transposition great arteries; AS, aortic stenosis; IAA, interrupted aortic arch Table III. Univariate and multivariate analysis of factors associated for mortality of infants with anorectal malformation Variables All Mortality Crude HR (95% CI) P-value *Adjusted HR (95% CI) P-value N N (%) Sex Female 70 17 (24.3) 1.71 (0.87–3.39) .122 1.82 (0.91–3.62) .088 Male 105 16 (15.2) Reference Reference Ethnicity Malay 136 28 (20.6) 1.56 (0.60–4.03) .362 1.41 (0.54–3.62) .483 Non-Malay 39 5 (12.8) Reference Reference Gestation Term 141 29 (20.6) 0.64 (0.22–1.81) .399 - Premature 34 4 (11.8) Reference Birth weight (kg) < 2.5 60 12 (20.0) 1.21 (0.59–2.47) .591 - ≥ 2.5 115 21 (18.3) Reference Birth Year 2006–2010 42 10 (23.8) 1.04 (0.46–2.55) .854 - 2011–2015 75 12 (16.0) 0.86 (0.38–1.94) .707 - 2016–2019 58 11 (19.0) Reference VACTERL Yes 34 13 (38.2) 2.77 (1.38–5.58) .004 1.39 (0.64–3.03) .403 No 141 20 (14.2) Reference Reference Trisomy-21 Yes 41 4 (9.8) .37 (0.13–1.05) .061 0.49 (0.16–1.48) .206 No 134 29 (21.6) Reference Reference CHD severity Severe 38 18 (47.4) 4.66 (2.34–9.27) < .001 4.03 (1.93–8.42) < .001 Non-severe/no CHD 137 15 (10.9) Reference Reference *Analyzed with cox regression analysis, corrected for sex and ethnicity A p-value is considered significant if a 95% confidence interval does not include 1 HR; hazard ratio, CI; confidence interval; CHD, congenital heart disease Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Oct, 2023 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Major revision 25 May, 2023 Reviews received at journal 01 May, 2023 Reviewers agreed at journal 30 Apr, 2023 Reviews received at journal 27 Apr, 2023 Reviewers agreed at journal 13 Apr, 2023 Reviewers agreed at journal 04 Apr, 2023 Reviewers invited by journal 31 Mar, 2023 Editor assigned by journal 27 Mar, 2023 Submission checks completed at journal 27 Mar, 2023 First submitted to journal 20 Mar, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2712306","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":186708150,"identity":"71d44a00-bca7-44db-97a6-b650a5cc5ea4","order_by":0,"name":"Mohd Nizam MAT BAH","email":"","orcid":"","institution":"Ministry of Health Malaysia","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohd","middleName":"Nizam MAT","lastName":"BAH","suffix":""},{"id":186708152,"identity":"6eed6d67-f942-4252-8e1f-87b1db57cc3d","order_by":1,"name":"Norazah ZAHARI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYPCCAwz8YJqNFC2SDSRrMThArBZz9t6HH3/U3LE3vpGdwPCh7DCD7owE/Fose44bS0gce8ZsdiN3A+OMc4cZzG4Q0GJwI41BwoDtMBtICzNvG3FamH8k/DvMYzwDqOUvkVrYJA62HZYwkABqYSRKy5ljbJaNfYcNJM683XCw51w6j9mZBwS0HG9jvvnj22F7/vbcjQ9+lFnLmR0nYAsKOADEPAwCpGiBAP4DJGsZBaNgFIyC4Q0A1J1JFrowpBMAAAAASUVORK5CYII=","orcid":"","institution":"University of Malaya","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Norazah","middleName":"","lastName":"ZAHARI","suffix":""},{"id":186708153,"identity":"30f0f86a-4038-4e7d-a226-f6dd3058ab5f","order_by":2,"name":"Aina Salwa KASIM","email":"","orcid":"","institution":"Ministry of Health","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aina","middleName":"Salwa","lastName":"KASIM","suffix":""},{"id":186708155,"identity":"4d20bd3d-19bc-42f8-93c8-c18255140ee3","order_by":3,"name":"Noorintan Liana MOHAMED SHARIF","email":"","orcid":"","institution":"University Malaya Medical Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Noorintan","middleName":"Liana MOHAMED","lastName":"SHARIF","suffix":""}],"badges":[],"createdAt":"2023-03-20 04:29:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2712306/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2712306/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-023-05292-7","type":"published","date":"2023-10-23T15:01:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":34945175,"identity":"da1544a7-9ba4-4327-84df-5ee143ae77a1","added_by":"auto","created_at":"2023-03-28 22:32:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6899,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves for an infant with non-isolated versus isolated anorectal malformation.\u003c/p\u003e","description":"","filename":"OnlineFigure1IsolatedARM.png","url":"https://assets-eu.researchsquare.com/files/rs-2712306/v1/5923f43342280e10b240bb1c.png"},{"id":34945177,"identity":"1c380297-bae2-4b4c-bf1b-8d7c838e84be","added_by":"auto","created_at":"2023-03-28 22:32:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6897,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves for anorectal malformation patients with and without VACTERL association.\u003c/p\u003e","description":"","filename":"OnlineFigure2VACTERL.png","url":"https://assets-eu.researchsquare.com/files/rs-2712306/v1/24956b213e0305e59defc104.png"},{"id":34945176,"identity":"b5ecdd9c-572a-493e-998c-ceb7fa4228f5","added_by":"auto","created_at":"2023-03-28 22:32:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6762,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves for anorectal malformation patients with severe, non-severe, and no congenital heart disease.\u003c/p\u003e","description":"","filename":"OnlineFigure3CHD.png","url":"https://assets-eu.researchsquare.com/files/rs-2712306/v1/583b9e071cc703fd39b70839.png"},{"id":45453893,"identity":"bba5b58e-73d7-424b-8f30-20046281d6bd","added_by":"auto","created_at":"2023-10-30 15:07:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":265237,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2712306/v1/b0312acf-3200-48fa-bc0d-d4edc81ce848.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Survival and Factors Associated with Mortality Among Infants with Anorectal Malformation: A Population- Based Study from A Middle-Income Country","fulltext":[{"header":"What Is Known","content":"\u003cul\u003e\n\u003cli\u003eVACTREL association and congenital heart disease is common in patient with anorectal malformation\u003c/li\u003e\n\u003cli\u003eLow birth weight and prematurity are associated with a lower rate of survival\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new:\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eCongenital heart disease is common in ARM patients in a middle-income country\u003c/li\u003e\n\u003cli\u003eSevere congenital heart disease plays a significant role in the survival of patients with an anorectal malformation in lower- and middle-income countries.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eCongenital anorectal malformation (ARM) comprises a broad spectrum of abnormalities of the anus and anal cavity, with a reported prevalence of 2 to 5 per 10 000 live births (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). It is the most common gastrointestinal malformation and can occur in isolation or associated with other malformations or syndromes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In addition to Down syndrome and VACTERL, ARM is also known to be associated with congenital heart disease (CHD). However, the reported prevalence of CHD among ARM patients is highly variable, ranging from as low as 9% to as high as 50% (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Furthermore, there is a conflicting report on the most common cardiac lesion in ARM patients, with ventricular septal defect (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), atrial septal defect (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), and tetralogy of Fallot (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) described as frequent lesions.\u003c/p\u003e \u003cp\u003eIn addition, the mortality and survival of ARM patients vary greatly depending on the economic status of the countries. For example, the reported mortality in high-income countries ranges from 1.7\u0026ndash;2.9% (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In comparison, a higher rate was observed in the lower-and-middle-income countries, with a reported rate ranging from 11.9\u0026ndash;29% (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Additionally, the prognosis of ARM patients was also affected by various factors such as the number of associated anomalies, prematurity, low birth weight, delayed presentation, and primary perforation (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, studies on the effect of CHD on the mortality and survival of ARM patients are limited (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, a population-based study from lower-and-middle-income countries is lacking. Therefore, with a lack of resources and expertise, we postulate that the survival of ARM patients is lower than in high-income countries, and CHD plays a significant role in the survival of ARM patients. Therefore, this study aims to assess the prevalence and pattern of CHD and its effect on the overall outcome of ARM patients.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eThis retrospective cohort study included all ARM patients born between January 2006 and December 2019 in the State of Johor. There was an estimated population of 3.4\u0026nbsp;million in the State of Johor, with an annual live births of 50,000 per year. All cases of ARM and CHD were referred to Hospital Sultanah Aminah, a tertiary government hospital that provides pediatric cardiology and surgical services for the State of Johor, Malaysia (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e This study was approved by the Medical Research and Ethics Committee, Ministry of Health, Malaysia (NMRR 21-1881-61323). A waived informed consent was given due to the study's retrospective nature. All procedures performed in this study followed the institutional and national research committee's clinical standards, the 1964 Declaration of Helsinki, and its later amendments or comparable ethical standards.\u003c/p\u003e \u003cp\u003eARM was diagnosed based on clinical features such as imperforate anus, presence of fistula, ectopic anus, or cloacal anomaly and was classified according to the Krickenbeck classification (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In addition, other congenital malformations were recorded and divided into four groups as described by Cuschieri et al. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e): 1) syndromes of known cause, 2) recognized syndromes and sequences of unknown etiology, 3) VACTERL association, and 4) multiple congenital anomalies. Patients with three or more defects (vertebral, anal atresia, cardiac septal defects, esophageal atresia or tracheoesophageal fistula, renal anomalies, and radial limb defects) were considered to have the VACTERL association (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). ARM was divided into two groups, those with associated other malformations or syndromes as non-isolated ARM (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) and, conversely, isolated ARM if there was no association with any syndrome or malformation.\u003c/p\u003e \u003cp\u003eCHD was defined as a significant structural abnormality of the heart or the great intrathoracic vessel that was of actual or potential significance (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). All CHD was confirmed with two-dimensional echocardiography. Patients with patent foramen ovale, mild branch pulmonary stenosis, isolated dextrocardia, isolated bilateral superior vena cava, isolated right arch, and spontaneous closure PDA in three months (for a term infant) and six months (for premature) were not considered as CHD (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In patients with multiple cardiac defects, the primary lesion that required the first intervention or was hemodynamic significant was regarded as the primary defect. The severity of CHD was divided into mild, moderate, and severe (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eData were retrieved from the Pediatric Cardiology Clinical Information System, a clinical database for acquired and congenital heart disease in the State of Johor (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Data collected included demographic data (gestational age, maternal gestational diabetes, syndrome, birth weight, sex, and ethnicity), ARM data (type and associated with other malformation), CHD data (type and severity), and finally the outcome at the last follow-up (alive or dead).\u003c/p\u003e \u003cp\u003eAll patients had a complete clinical examination by the medical and pediatric surgical team. This included a two-diemnsional echocardiogram for screening of CHD. Active screening for other congenital anomalies associated with ARM or syndrome was also conducted. Similar to CHD, further ARM management was done according to the severity of the disease.\u003c/p\u003e \u003cp\u003eThe primary outcome measured was the survival of the infant. Mortality (all causes of death) was verified with the National Registry Department, Malaysia. Cause of death was grouped into cardiac, infection, or other causes.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using Statistical Package for Social Science (SPSS) version 23 (IBM Corp., Armonk, NY, USA). Groups were compared using Student's t-test for normally distributed continuous data and a non-parametric test for non-normally distributed continuous data. Pearson's chi-square test for categorical variables. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. The incidence of ARM was calculated as the sum of newly diagnosed ARM divided by total live births in the State of Johor and expressed as per 10,000 live births.\u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier analysis was used to estimate survival at 1-,5-, and 10-years. Log-rank test was used to compare the difference between the group.\u003c/p\u003e \u003cp\u003eUnivariate Cox proportional hazards regression was used to identify the unadjusted effect of age, sex, ethnicity, gestational age, birth weight, birth year, VACTERL, trisomy-21, and CHD severity on mortality. Variables with p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in the univariate analyses were entered into the Cox proportional hazards regression to identify the independent risk factors associated with death. A hazard ratio was considered significant if the 95% confidence interval (CI) excluded one\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 175 ARM patients among 803850 live births during the study period, giving an overall ARM incidence of 2.2 (95% CI, 1.9 to 2.5) per 10,000 live births.\u003c/p\u003e \u003cp\u003eOf 175, 105 (60.0%) were male, 136 (77.7%) were Malay ethnicity, and 60 (34.3%) had low birth weight (Table\u0026nbsp;1). The mean age of diagnosis was 1.5 days (ranging from 0 to 75 days). All patients were followed up at a median age of 5.1 years (IQR from 0.4 to 8.8 years).\u003c/p\u003e \u003cp\u003eOf 175 ARM patients, 169 (96.6%) were detected during newborn examination, 2 (1.1%) patients presented at birth with abdominal distension, 2 (1.1%) were suspected antenatally, and 1 (0.6%) with an abnormal route of passing stools/meconium. In addition, one patient had her ARM detected at three months of life during pediatric intensive care admission for pneumonia. Of the 97 available data on the subtype of ARM, 51 (29.1%) had no fistula, 12 (6.9%) recto vestibular, 8 (4.6%) cloacal anomalies, 8 (4.6%) rectovaginal fistula, 7 (4.0%) rectourethral, 7 (4.0%) perineal and 4 (2.3%) rectal atresia.\u003c/p\u003e \u003cp\u003eOne hundred twenty-two (69.7%) ARM patients had an underlying syndrome or associated congenital malformation. Recognized syndrome with a known cause is seen in 49 (28%), with a majority (n\u0026thinsp;=\u0026thinsp;41) being Down syndrome. VACTREL association was observed in 34 (19.4%) patients. In addition, one patient had Omphalocele, Exstrophy, Imperforate anus, Spinal Bifida complexes, 2 Edward syndrome, and one each for Patau syndrome, Prune-Belly, Golden-Har syndrome, Wolf-Hirschhorn syndrome, chromosomes 18 and 16 disorder. Of 175 ARM patients, 6 (3.4%) were associated with neural tube defects and 2 (1.1%) with omphalocele. There was no significant difference in the proportion of non-isolated ARM between females and males (51/70 [72.9%] vs. 71/105 [67.6%], p\u0026thinsp;=\u0026thinsp;.46).\u003c/p\u003e \u003cp\u003eSeventy-three (41.7%) had CHD, of which 38 (52.1%) were severe CHD, and 35 (47.9%) were non-severe CHD (Table\u0026nbsp;2). The commonest lesions were ventricular septal defect (n\u0026thinsp;=\u0026thinsp;29, 39.76%), followed by Tetralogy of Fallot (n\u0026thinsp;=\u0026thinsp;10, 13.7%). Of 73 patients with CHD, 36 (49.3%) required surgery, and 11 (15.1%) patients had their cardiac defect closed spontaneously (all were small ventricular septal defects).\u003c/p\u003e \u003cp\u003eOf 175 ARM patients, nine (5.1%) were treated with comfort care, of which three were due to lethal congenital malformation, four were due to complex congenital cardiac defects, and two were for severe persistent pulmonary hypertension of the newborn. Overall, 33 (18.9%) patients died, with a median age of death of 5.7 months (IQR 25 days to 11.2 months). Of 33 death, 8 (24.2%) were cardiac-related, 11 (33.3%) infection-related, and 14 (42.4%) of other causes.\u003c/p\u003e \u003cp\u003eThe overall 1-, 5- and 10-year survival rate for ARM patients was 82.3% (95% CI, 76.0% \u0026ndash; 88.6%), 77.3% (95% CI, 70.4% \u0026minus;\u0026thinsp;84.2%), and 77.3% (95% CI, 70.4%- 84.2%), respectively. However, there was a significantly lower survival in ARM patients with non-isolated ARM, with survival at 1-, 5, and 10 years of 77.2% (95% CI 69.4% \u0026ndash; 85.0%), 72.4% (95% CI 64.0%- 80.8%) and 72.4% (95% CI, 64.0%- 80.8%), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Further analysis revealed ARM patients with VACTERL had a lower survival rate than the non-VACTERL, with estimated survival at 1- and 5 years of VACTERL were 66.0% (95% CI, 48.8% \u0026minus;\u0026thinsp;83.2%) and 55.6% (95% CI, 37.6% \u0026minus;\u0026thinsp;77.5%), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, a lower survival was observed in ARM patients with severe CHD, with estimated survival rates at 1 and 5 years of severe CHD were 61.7% (95% CI, 45.8% \u0026minus;\u0026thinsp;77.6%) and 50.5% (95% CI, 34.2% \u0026minus;\u0026thinsp;66.8%), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In comparison, there were no significant differences in the survival of ARM patients by sex, ethnicity, or gestational age. However, corrected for sex and ethnicity, multivariable Cox regression analysis shows severe CHD as the only significant factor associated with mortality with a hazard ratio of 4.03 (95% CI: 1.93\u0026ndash;8.42) (Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis first population-based study from lower-and-middle income countries examined the prevalence of CHD among ARM patients over a 14-year duration. In addition, it analyzed its effect on the overall survival of ARM patients. In this cohort, almost one in two ARM patients had CHD, and severe CHD was associated with poor outcomes. Previous studies showed wide variation in the prevalence of CHD among ARM patients, ranging from 9% to % 50% (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The broad difference in the prevalence of CHD among ARM patients is due to the nature of the study, which involved a single center, a small sample size, and patient selection. The prevalence of CHD among ARM patients in this study (41.7%) is slightly higher than the population-based studies in Italy and the United Kingdom, with a rate of 36% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). There are several possible explanations for this result. Firstly, due to the active screening for CHD with 2d-echocardiogram in all neonates with congenital anomalies. Secondly, it could be due to the inclusion of a small ventricular septal defect, which closed spontaneously. Nevertheless, our study shows that one in five ARM patients had a severe cardiac defect.\u003c/p\u003e \u003cp\u003eSimilarly, there were contradicting reports of the most common CHD in ARM patients, with ventricular septal defect, atrial septal defect, and Tetralogy of Fallot as the commonest lesion (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In this study, a ventricular septal defect is the commonest cardiac defect among ARM patients and represents one-third of CHD. This result is similar to our general population, where a ventricular septal defect is the most common type of CHD (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe incidence of ARM in this study is within the lower range of the published population-based studies, ranging from 2 to 4 per 10,000 live births (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). A lower incidence of ARM in this study could be due to underreporting, as some infants have died before reaching a diagnosis or were referred to other surgical centers in a nearby state.\u003c/p\u003e \u003cp\u003eThe overall mortality of ARM varied, with a higher rate in the lower-and-middle income countries than in higher-income countries (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A slightly higher rate of mortality was observed in this study compared to the 12.5% reported by Wright et al.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). A higher rate of mortality could be due to the inclusion of those who were treated with comfort care secondary to lethal congenital malformation as well as hypoplastic left heart syndrome in our cohort. Another reason was that notable death was related to infection in this study, which is still a common scenario in other lower-and-middle income countries (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe overall estimated survival rate of ARM patients at one year was 82% and reached a plateau at three years with a rate of 77%, with a lower survival rate in non-isolated ARM. Our survival rate is lower than a recent study from high-income countries by Ford et al.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) from the United Kingdom and Cassina et al. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) from Italy. In these two high-income countries, the survival rate of non-isolated ARM patients ranged from 87\u0026ndash;89% compared to 72% in our cohort.\u003c/p\u003e \u003cp\u003eThere were many contributing factors associated with poor survival. Previous studies have shown that low birth weight, prematurity, late presentation, and a higher number of congenital anomalies as significant factors associated with mortality (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, this study shows that severe CHD plays a significant role in ARM survival. Almost half of the ARM patients with severe CHD did not survive by five years of age and were five times more likely to die than non-severe CHD or non-CHD. This result is not surprising, being a lower-and-middle income country lacking resources and expertise, especially in dealing with a non-isolated ARM with severe CHD. Therefore, in relation to Sustainable Development Goal 3.2, \"end preventable deaths in neonates and children under five by 2030, overall infection control and prompt access to congenital cardiac surgery are much needed to improve the survival of ARM patients. Early detection and surgical intervention of severe CHD are pivotal to achieving this goal.\u003c/p\u003e\n\u003ch3\u003eStrength Of The Study\u003c/h3\u003e\n\u003cp\u003eThe major strength of this study includes a population study over 14 years with an early cardiac evaluation with a 2d-echocardiogram. This allows early diagnosis of severe CHD, allowing a preoperative plan and subsequent management.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThere were a few limitations of the study. Firstly, as in other studies using clinical registry (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), missing data in the subtype of ARM and a small number of other congenital anomalies in this cohort prevent us from analyzing the effect of these variables on the overall survival of ARM patients. Secondly, we may miss some early and undiagnosed neonatal deaths, which may have underestimated the prevalence of CHD among ARM patients. Finally, the lack of surgical ARM data in the registry prohibits us from analyzing the roles of the surgical variable on the overall survival of the ARM in our cohort\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study explored the prevalence of CHD and its effect on the overall survival of ARM patients in lower-and-middle income countries. The present study shows that CHD is common among ARM patients, and severe CHD is associated with a lower survival rate. Hence, improved overall medical care, particularly for those with severe CHD in lower-and-middle income countries, is needed for better ARM survival.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eARM-anorectal malformation\u003c/p\u003e\n\u003cp\u003eCHD-congenital heart disease\u003c/p\u003e\n\u003cp\u003eCI-confidence interval\u003c/p\u003e\n\u003cp\u003eIQR-interquartile range\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eWe thank the Director-General of Health Malaysia for permission to publish this article. Additionally, we would like to thank the Biostatistics \u0026amp; Data Repository Sector, National Institute of Health, Setia Alam - for the data linkage service, and the National Registration Department (JPN) for their willingness to share their mortality records for research purposes.\u003c/p\u003e\u003cp\u003eFunding source: No funding was received for conducting this study\u003c/p\u003e\u003cp\u003eConflict of interest/Competing interests: All the authors declare that they have no conflict of interest. This work is original and has not been published or presented elsewhere, nor is it currently under consideration for publication elsewhere\u003c/p\u003e\u003cp\u003eAvailability of data and material: The data that support the findings of this study are available from the corresponding author upon reasonable request\u003c/p\u003e\u003cp\u003eCode availability: Not applicable\u003c/p\u003e\u003cp\u003eAuthors\u0026apos; contribution: All authors contributed to the study conception and design. AS, and NLMS performed material preparation, and data collection. MNMB performed the analysis. MNMB and NZ wrote the first draft of the manuscript, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003cp\u003eEthical approval: All procedures performed in studies involving human participants followed the clinical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Medical Research and Ethics Committee, Ministry of Health, Malaysia (National Medical Research Register (NMMR-21-1881-81323)\u0026nbsp;\u003c/p\u003e\u003cp\u003eConsent to participate: Medical Research and Ethics Committee, Ministry of Health, Malaysia waived the written informed consent.\u0026nbsp;\u003c/p\u003e\u003cp\u003eConsent for publication: Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFord K, Peppa M, Zylbersztejn A, Curry JI, Gilbert R. Birth prevalence of anorectal malformations in England and 5-year survival: a national birth cohort study. Arch Dis Child. 2022;107(8):758\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassina M, Fascetti Leon F, Ruol M, Chiarenza SF, Scir\u0026egrave; G, Midrio P, Clementi M, Gamba P. Prevalence and survival of patients with anorectal malformations: A population-based study. J Pediatr Surg. 2019;54(10):1998\u0026ndash;2003.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuschieri A. Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet. 2002;110(2):122\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGokhroo RK, Gupta S, Arora G, Bisht DS, Padmanabhan D, Soni V. Prevalence of congenital heart disease in patients undergoing surgery for major gastrointestinal malformations: An Indian study. Heart Asia. 2015;7(1):29\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli S, Uzair M, Rehman F ur, Imran M, Khan EB, Khan MA. Frequency of congenital cardiac anomalies in patients with anorectal malformations. Prof Med J. 2020;27(12):2713\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamal JS, Azhar AS. Congenital cardiac anomalies and imperforate anus: A hospital's experience. J Cardiovasc Dis Res. 2013;4(1):34\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Ouml;r\u0026uuml;n UA, Bilici M, Demir\u0026ccedil;eken FG, Tosun M, \u0026Ouml;cal B, \u0026Ccedil;avuş\u0026ograve;glu YH, Erdoğan D, Senocak F, Karademir S. Gastrointestinal system malformations in children are associated with congenital heart defects. Anadolu Kardiyol Derg. 2011;11(2):146\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho S, Moore SP, Fangman T. One hundred three consecutive patients with anorectal malformations and their associated anomalies. Arch Pediatr Adolesc Med. 2001;155(5):587\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJonker JE, Liem ET, Elzenga NJ, Molenbuur B, Trzpis M, Broens PMA. Congenital Anorectal Malformation Severity Does Not Predict Severity of Congenital Heart Defects. J Pediatr. 2016;179:150\u0026ndash;153.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShenoy NS, Kumbhar V, Basu KS, Biswas SK, Shenoy Y, Sharma CT. Associated anomalies with anorectal malformations in the Eastern Indian population. J Pediatr Neonatal Individ Med. 2019;8(2):6\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMathew P, Gupta AK, Gupta R, Sharma D. Anorectal malformations: Early outcome analysis in a tertiary care center in India. J Neonatal Surg. 2021;10:1\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavi Nagaprasad YVS, Muralidhar A. A Study of Incidence of Congenital Cardiac Anomalies in the NewBorns with Ano-Rectal Malformation: Our Hospital Experience. Indian J Anesth Analg. 2018;5(12):1973\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeixeira OHP, Malhotra K, Sellers J, Mercer S. Cardiovascular anomalies with imperforate anus. Arch Dis Child. 1983;58(9):747\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWright NJ, Leather AJM, Ade-Ajayi N, Sevdalis N, Davies J, Poenaru D, et al. Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study. Lancet. 2021;398(10297):325\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGandjehou H, Karl E, Chowdhury G, Manneh A, Amoah M, Nimako B, et al. Paediatric surgical outcomes in sub-Saharan Africa: A multicentre, international, prospective cohort study. BMJ Glob Heal. 2021;6(9):e004406.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar A, Agarwala S, Srinivas M, Bajpai M, Bhatnagar V, Gupta DK, Gupta AK, Mitra DK. Anorectal malformations and their impact on survival. Indian J Pediatr. 2005;72(12):1039\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMat Bah MN, Sapian MH, Alias EY. Birth prevalence and late diagnosis of critical congenital heart disease: A population-based study from a middle-income country. Ann Pediatr Cardiol. 2020;13(4):320\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Steeg HJJ, Schmiedeke E, Bagolan P, Broens P, Demirogullari B, Garcia\u0026ndash;Vazquez A, et al. European consensus meeting of ARM-Net members concerning diagnosis and early management of newborns with anorectal malformations. Tech Coloproctol. 2015;19(3):181\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan de Putte R, van Rooij IALM, Marcelis CLM, Guo M, Brunner HG, Addor MC, Cavero-Carbonell C, Dias CM, Draper ES, Etxebarriarteun L et al. Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study. Pediatr Res. 2020;87(3):541\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitchell S, Korones S, Berendes H. Congenital Heart Disease in 56,109 Births Incidence and Natural History. Circulation. 1971 Mar 1;43(3):323\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMat Bah MN, Sapian MH, Jamil MT, Abdullah N, Alias EY, Zahari N. The birth prevalence, severity, and temporal trends of congenital heart disease in the middle-income country: A population-based study. Congenit Heart Dis. 2018;13(6):1012\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoffman JIE, Kaplan S. The incidence of congenital heart disease. Vol.\u0026nbsp;39, Journal of the American College of Cardiology. 2002. p.\u0026nbsp;1890\u0026ndash;900.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMat Bah MN, Alias EY, Razak H, Sapian MH, Foo FH. Epidemiology, clinical characteristics, and immediate outcome of Kawasaki disease : a population-based study from a tropical country. Eur J Pediatr. 2021;180(8):2599\u0026ndash;606.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUmar Nisar M, Iqbal A, Javed N, Sikander S, Burki SA, Chaudhry MA. Factors affecting the outcome of neonates with anorectal malformation in a developing country. J Pediatr Adolesc Surg. 2021;1(2):66\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table I. The characteristic and immediate outcome of an infant with an anorectal malformation\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tabc\" style=\"width: 457px;\" border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eVariable\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74px;\" colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTotal (n\u0026thinsp;=\u0026thinsp;175)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" colspan=\"4\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFinal Outcome\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eP-value\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 95px;\" colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSurvivor (n\u0026thinsp;=\u0026thinsp;142)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.953px;\" colspan=\"3\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-survivor (n\u0026thinsp;=\u0026thinsp;33)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSex\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e105\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(60.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e89\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(62.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e16\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(48.5)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.13\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e70\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(40.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e53\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(37.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e17\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(51.5)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eGestational age\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePremature\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(19.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(21.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(12.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.33\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTerm\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e141\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(80.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e112\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(78.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e29\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(87.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eRace\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMalay\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e136\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(77.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e108\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(76.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e28\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(84.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.36\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-Malay\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e39\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(22.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(23.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(15.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBirth weight\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;2.5kg\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e60\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(34.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e48\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(33.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(36.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.78\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.5kg and more\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e115\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(65.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e94\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(66.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(63.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBirth Year\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2006\u0026ndash;2010\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e42\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(24.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e32\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(22.5)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(30.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.59\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2011\u0026ndash;2015\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e75\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(42.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e63\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(44.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(36.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2016\u0026ndash;2019\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e58\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(33.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e47\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(33.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e11\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(33.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMaternal Diabetic\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e148\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(84.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e122\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(85.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e26\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(78.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.30\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e27\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(15.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e20\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(14.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(21.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-isolated ARM\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-isolated ARM\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e122\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(69.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e92\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(64.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(90.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.005\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIsolated ARM\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e53\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(30.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e50\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(35.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(9.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDown syndrome\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e134\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(76.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e105\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(73.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e29\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(87.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.11\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e41\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(23.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e37\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(26.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(12.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eVACTERL\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e141\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(80.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e121\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(85.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e20\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(60.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(19.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(14.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e13\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(39.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCHD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e102\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(58.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e90\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(64.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(30.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e73\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(41.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e50\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(35.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e23\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(69.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCHD severity\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSevere CHD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e38\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(21.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e20\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(14.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e18\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(54.5)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-Severe CHD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e35\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(20.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(21.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(15.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNo CHD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e102\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(58.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e92\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(64.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(30.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eARM type\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMajor clinical group\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e163\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(93.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e133\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(93.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(90.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.70\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 117px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eRare\u0026lrm;/regional variant\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 28px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(6.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 36px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 59px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(6.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 17px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 41px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(9.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 48.9531px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 392.953px;\" colspan=\"8\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(%), percentage within the outcome\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003eARM, anorectal malformation; CHD, congenital heart disease\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table II: Distribution and severity of congenital heart disease among infants with anorectal malformation\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tabb\" border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCHD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTotal, N (%)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCHD severity\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSevere CHD, n (%)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-Severe CHD, n (%)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eVSD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e29\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(39.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(15.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e23\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(65.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTOF\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(13.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(26.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePAVSD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(9.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(18.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eASD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(8.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(17.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePDA\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(8.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(10.5)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(4.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(8.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTAPVD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(4.1)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(7.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDORV\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHLHS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.7)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAVSD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCoA\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eD-TGA\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIAA\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1.4)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(0.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e73\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(100.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e38\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(100.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e35\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(100.0)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(%), percentage within total CHD and severity\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003eCHD, Congenital heart disease; VSD, ventricular septal defect; ASD, atrial septal defect; PDA, patent ductus arteriosus; TOF, tetralogy of Fallot; PAVSD, pulmonary atresia with VSD; TAPVD, total anomalous pulmonary venous drainage; DORV, double outlet right ventricle; PS, pulmonary stenosis; HLHS, hypoplastic left heart syndrome; AVSD, atrioventricular septal defect; CoA, coarctation of aorta; D-TGA, transposition great arteries; AS, aortic stenosis; IAA, interrupted aortic arch\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table III. Univariate and multivariate analysis of factors associated for mortality of infants with anorectal malformation\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Taba\" style=\"width: 673px;\" border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 204px;\" colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eVariables\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.141px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAll\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 54.875px;\" colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMortality\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCrude HR (95% CI)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eP-value\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e*Adjusted HR (95% CI)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eP-value\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eN\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eN\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(%)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSex\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e70\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e17\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(24.3)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.71 (0.87\u0026ndash;3.39)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.122\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.82 (0.91\u0026ndash;3.62)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.088\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e105\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e16\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(15.2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eEthnicity\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMalay\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e136\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e28\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(20.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.56 (0.60\u0026ndash;4.03)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.362\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.41 (0.54\u0026ndash;3.62)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.483\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-Malay\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e39\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(12.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eGestation\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTerm\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e141\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e29\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(20.6)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.64 (0.22\u0026ndash;1.81)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.399\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePremature\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(11.8)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBirth weight (kg)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;2.5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e60\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv 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(1.93\u0026ndash;8.42)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 94px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 110px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon-severe/no CHD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 20px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e137\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 11px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e15\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 34px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(10.9)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40.7031px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 694.719px;\" colspan=\"9\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e*Analyzed with cox regression analysis, corrected for sex and ethnicity\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003eA p-value is considered significant if a 95% confidence interval does not include 1\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003eHR; hazard ratio, CI; confidence interval; CHD, congenital heart disease\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Anorectal malformation, Congenital heart disease, Middle-income country, Mortality, Survival.","lastPublishedDoi":"10.21203/rs.3.rs-2712306/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2712306/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLimited data on the survival of anorectal malformation (ARM) patients from lower-and-middle income countries is available. This retrospective population-based study from the State of Johor, Malaysia, determines the incidence, mortality rate, and survival of ARM patients and factors associated with mortality. Kaplan-Meier survival analysis was used to estimate the survival of ARM patients at 1-, 5- and 10- years. In addition, multivariate cox-regression analysis was used to analyze mortality-related factors. There were 175 ARM patients among 803850 live births, giving an overall ARM incidence of 2.2 (95% confidence interval [CI], 1.9 to 2.5) per 10,000 live births. The male-to-female ratio was 1.5: 1. There was 122 (69%) non-isolated ARM, of which 41 were Down syndrome and 34 had VACTERL. Seventy-three (41.7%) had CHD, with 38 severe and 35 non-severe CHD. Overall, 33 (18.9%) patients died, with a median age of death of 5.7 months (Interquartile range 25 days to 11.2 months). The overall estimated 1-, 5- and 10-year survival rate for ARM patients was 82.3% (95% CI, 76.0% – 88.6%), 77.3% (95% CI, 70.4% - 84.2%), and 77.3% (95% CI, 70.4%- 84.2%), respectively. Univariate analysis shows that non-isolated ARM, VACTREL association, and severe CHD were associated with mortality. However, only severe CHD is the independent factor associated with mortality, with a hazard ratio of 4.03 (95% CI: 1.93-8.42).\u003c/p\u003e\n\u003cp\u003eConclusion: CHD is common among ARM patients, and one in five ARM patients had a severe cardiac defect, significantly affecting their survival\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Survival and Factors Associated with Mortality Among Infants with Anorectal Malformation: A Population- Based Study from A Middle-Income Country","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-28 22:32:37","doi":"10.21203/rs.3.rs-2712306/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-05-25T19:14:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-05-01T05:21:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0875a5e0-28ca-4ccb-8d04-9b1671004cdd","date":"2023-05-01T02:32:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-04-27T11:29:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4777439f-9332-4c3f-896b-3651b945b86b","date":"2023-04-13T23:46:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6a79752f-99e9-4a2f-a067-8b8438f73833","date":"2023-04-04T12:36:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-03-31T19:00:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-03-27T06:38:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-03-27T06:38:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2023-03-20T04:22:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e77564db-889f-4ce5-8c46-2793cfae4cd0","owner":[],"postedDate":"March 28th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-30T15:04:58+00:00","versionOfRecord":{"articleIdentity":"rs-2712306","link":"https://doi.org/10.1007/s00431-023-05292-7","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2023-10-23 15:01:46","publishedOnDateReadable":"October 23rd, 2023"},"versionCreatedAt":"2023-03-28 22:32:37","video":"","vorDoi":"10.1007/s00431-023-05292-7","vorDoiUrl":"https://doi.org/10.1007/s00431-023-05292-7","workflowStages":[]},"version":"v1","identity":"rs-2712306","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2712306","identity":"rs-2712306","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}