Evaluation and prevalence of associated anomalies in children with anorectal malformations at a tertiary referral center

Abstract

Background

Anorectal malformations (ARMs) comprise a spectrum of congenital anomalies frequently associated with multisystem congenital defects. Early recognition of associated anomalies is essential for appropriate surgical planning and long-term management. This study aimed to investigate the prevalence of associated anomalies with ARMs in the Children’s Tertiary Center.

Materials and methods

This retrospective cross-sectional study included all children diagnosed with ARM who were admitted to the Children’s Medical Center Hospital between 2020 and 2022. Associated anomalies were categorized by organ system and by syndromic patterns, including VACTERL association. Data were extracted from medical records. Descriptive statistics were used, and associations with sex and gestational age were analyzed using Chi-square or Fisher’s exact tests.

Results

Fifty-seven children with ARM were included (52.6% male). Associated anomalies were detected in 73.7% of patients. The most common associated anomalies involved the cardiovascular (52.6%), genitourinary (36.8%), and vertebral (24.6%) systems. No significant association was found between gestational age and the prevalence of anomalies. Female sex was associated with a higher prevalence of cardiac anomalies.

Conclusion

Associated anomalies are highly prevalent in children with ARM, particularly affecting the cardiovascular, genitourinary, and vertebral systems. Systematic screening and multidisciplinary management are essential to reduce morbidity and improve long-term outcomes.

Introduction

Anorectal malformations (ARMs) represent a heterogeneous group of congenital anomalies involving abnormal development of the distal anus and rectum. The condition occurs in approximately 1 in 5,000 live births, although reliable epidemiological data from Iran are lacking [1, 2]. ARMs range from minor perineal defects to complex cloacal malformations associated with urinary and genital fistulas. More severe cases require specialized diagnostic and therapeutic management in tertiary care centers [3–5]. In males, anorectal malformations are most frequently associated with recto-urinary fistulas, including recto-bulbar, recto-prostatic, and, less commonly, recto-vesical variants. In females, the commonest lesion is a vestibular fistula, whereas rectovaginal fistula is exceedingly rare [6, 7].

A major consideration in ARMs is their frequent association with other congenital anomalies, which may occur either as individual organ system anomalies (e.g., isolated genitourinary or cardiac defects) or as part of syndromic patterns such as VACTERL association. The estimated incidence of VACTERL is approximately 1 in 10,000 to 40,000 live births [1]. This association encompasses vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal anomalies, renal anomalies, and limb abnormalities [1, 8]. Classically, the VACTERL association is defined by the presence of at least three component anomalies [1]. The presence of associated anomalies has a decisive impact on the choice and timing of therapeutic interventions, as well as on prognosis and long-term quality of life [4, 9]. The exact etiology of ARMs remains unknown, though a multifactorial origin is presumed [2, 3].

Evidence regarding risk factors for ARMs is limited. Nevertheless, several studies suggest potential associations with maternal overweight, obesity, diabetes mellitus, and paternal smoking [2, 10]. Associated congenital anomalies commonly involve the vertebral, cardiac, genitourinary, and gastrointestinal systems and significantly influence early morbidity and mortality [11, 12]. Children with anorectal malformations may experience a spectrum of postoperative complications following definitive repair. Wound dehiscence, anal stenosis, and mucosal prolapse are recognized as expected postoperative sequelae. In contrast, true iatrogenic complications may arise from technical errors during surgery and include misplacement of the neoanus, residual fistula, urethral injury, or damage to the sphincter complex [6, 9, 11, 12]. Accurate distinction between expected sequelae and iatrogenic complications is essential for appropriate postoperative surveillance and timely intervention. Even after successful surgical repair, lifelong follow-up remains essential [3, 9].

Studies have reported varying frequencies of associated anomalies in patients with ARMs, with approximately 50–60% of affected patients presenting with at least one additional congenital anomaly [2, 4]. The most common associated malformations involve the genitourinary system, cardiovascular system, and vertebral column [4, 13–15]. These anomalies can contribute to serious complications and increased mortality [4, 16, 17]. Most cases of ARMs are diagnosed during the neonatal period. However, despite routine physical examinations after delivery, delayed diagnosis occurs in approximately one out of every five newborns, potentially increasing morbidity and mortality [3, 7]. Timely recognition and management of associated anomalies are critical for reducing complications. Outcomes depend largely on the presence and severity of associated anomalies and clinical features, and optimal care requires multidisciplinary collaboration among pediatricians, surgeons, and other specialists [5, 9].

This study aimed to evaluate the prevalence and pattern of associated anomalies in children with ARMs referred to the Children’s Medical Center Hospital during 2020–2022, and to analyze their distribution in relation to ARM subtypes. Although similar studies have been conducted in other countries [8, 14, 17, 18], research in Iran remains limited [11, 12], highlighting the need for further investigations. The findings of this study may assist in predicting associated anomalies, guiding surgical decision-making, and reducing complications in patients with anorectal malformations.

Methods

Study design and population

This retrospective cross-sectional study included all children diagnosed with anorectal malformations (ARMs) who were admitted to the Children’s Medical Center Hospital, Tehran University of Medical Sciences, between 2020 and 2022. The study aimed to determine the frequency and types of anomalies associated with ARMs. Given the three-year study period, all consecutive eligible patients were included (census sampling), ensuring that every child meeting the inclusion criteria was included.

Data collection

Demographic and clinical data were extracted from patients’ medical records, including gestational age, sex, clinical examination findings, and diagnostic investigations. The presence and type of associated anomalies were recorded and categorized as VACTERL component anomalies (vertebral, cardiac, tracheoesophageal, renal, and limb anomalies) and non-VACTERL associated anomalies (e.g., isolated genitourinary and other system anomalies). Although the formal diagnosis of VACTERL association requires ≥ 3 component features [1], individuals with any two component anomalies (especially ARM or tracheoesophageal fistula) are frequently found to have additional VACTERL-type anomalies [19]. Therefore, we also describe the distribution of cases with ≥ 2 features as an exploratory analysis to capture early patterns of multisystem involvement. All patients underwent systematic screening for associated anomalies. Cardiac defects were screened using echocardiography. Vertebral anomalies, including rare defects such as hemivertebra and caudal regression, were evaluated using spinal ultrasonography in neonates younger than 3 months, spinal magnetic resonance imaging (MRI) in older infants, and plain spinal radiography when indicated. Genitourinary anomalies were initially screened using renal and pelvic ultrasonography, and further evaluated with voiding cystourethrography in cases with suspected vesicoureteral reflux or posterior urethral valves. When additional clarification was required, supplementary information was obtained through direct contact with parents or caregivers. Data were systematically recorded using a structured data collection form.

Ethical considerations

This study was reviewed by the Ethics Committee of Tehran University of Medical Sciences. All data were collected after obtaining the appropriate institutional permissions.

Statistical analysis

Data were analyzed using SPSS software (IBM Corp., Armonk, NY, USA). Descriptive statistics, including frequencies, percentages, means, and standard deviations, were calculated for demographic variables and the prevalence of associated anomalies. Comparisons of anomaly prevalence according to sex and gestational age were performed using the Chi-square test or Fisher’s exact test, as appropriate. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated where applicable. A p-value < 0.05 was considered statistically significant.

Results

This retrospective descriptive-analytical study examined 57 children with anorectal malformation (ARM) who underwent surgery at Children’s Medical Center Hospital between March 2020 and March 2022. The cohort comprised 30 males (52.6%) and 27 females (47.4%). Gestational age analysis revealed that among 51 patients with available data, 39 (76.5%) were full-term and 12 (23.5%) were preterm neonates. Gestational age information was unavailable for 6 children (10.5%).

A critical finding was the high prevalence of vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities (VACTERL) association among children with ARM. Results demonstrated that 42 children (73.7%) presented with VACTERL association, while only 15 children (26.3%) did not exhibit this pattern of associated anomalies. Figure 1 shows the prevalence of associated anomalies in children with ARM, and Table 1 illustrates the distribution of subgroup analyses examining the relationships between gender, gestational age, and individual VACTERL components.

Fig. 1.

Prevalence of Associated Anomalies in Children with ARM

Table 1.

The distribution of subgroup analyses examining the relationships between gender, gestational age, and individual VACTERL components

Anomaly Type	Gender (Male/Female) OR (95% CI)	P-value	Gestational Age (Preterm/Term) OR (95% CI)	P-value
VACTERL overall	1.50 (0.45–4.96)	0.506	0.60 (0.14–2.46)	0.478
Vertebral	3.00 (1.02–8.86)	0.318	0.96 (0.21–4.29)	0.964
Genitourinary	1.01 (0.34–2.98)	0.976	2.00 (0.53–7.43)	0.300
Tracheoesophageal	1.13 (0.29–4.45)	0.854	0.30 (0.03–2.67)	0.282
Cardiac	3.00 (1.02–8.86)	0.044*	0.85 (0.23–3.12)	0.815
Skeletal	1.12 (0.14–8.55)	0.913	1.68 (0.13–20.34)	0.682

Vertebral anomalies

Vertebral anomalies were identified in 14 children (24.6%). Sacral anomalies were the most prevalent, occurring in 9 patients (15.8%), followed by hemivertebra in 3 patients (5.3%) and caudal regression in 3 patients (5.3%). Rare vertebral malformations, including tethered cord, thoracic anomalies, and spina bifida, were each documented in 1 patient (1.8%). Some patients presented with multiple concurrent vertebral anomalies.

Genitourinary anomalies

Genitourinary anomalies were observed in 21 children (36.8%). The most common structural renal anomalies were renal agenesis or solitary kidney (5, 8.8%) and horseshoe kidney (3, 5.3%), while ectopic kidney and renal dysplasia were each found in 1 patient (1.8%). Functional and collecting-system anomalies included vesicoureteral reflux (5, 8.8%), posterior urethral valves (3, 5.3%), and neurogenic bladder (2, 3.5%). Genital anomalies comprised hypospadias, epispadias, and urogenital sinus (combined 6, 10.5%); ambiguous genitalia (3, 5.3%); and bicornuate uterus (1, 1.8%). Rare complex anomalies such as bladder exstrophy were encountered in a single patient. Multiple genitourinary anomalies coexisted in some patients.

Gastrointestinal anomalies

Gastrointestinal system anomalies were detected in 8 children (14%). The most frequent malformations included tracheoesophageal fistula and esophageal atresia, each occurring in 3 children (5.3%), intestinal atresia in 2 children (3.5%), and biliary atresia in 1 child (1.8%). Some patients presented with multiple gastrointestinal anomalies simultaneously.

Cardiac anomalies

Cardiac anomalies represented the most prevalent associated defects, observed in 30 patients (52.6%). The most frequently identified cardiac malformations were atrial septal defect (ASD) in 24 patients (42.1%), patent ductus arteriosus (PDA) in 14 patients (24.6%), and ventricular septal defect (VSD) in 11 patients (19.3%). Less common cardiac defects included partial or total anomalous pulmonary venous connection (PAPVC/TAPVC) in 4 patients (7%), bilateral superior vena cava in 4 patients (7%), and pulmonary artery atresia in 3 patients (5.3%). Rare cardiac anomalies such as transposition of the great arteries (TGA), atrial aneurysm, and Tetralogy of Fallot were each observed in 2 patients (3.5%), while double outlet right ventricle, coarctation of the aorta, dextrocardia, and aberrant subclavian artery were each documented in 1 patient (1.8%). Multiple cardiac anomalies were seen in several patients.

Skeletal anomalies

Limb anomalies were documented in 4 children (7%). Specific skeletal malformations included limb length discrepancy, wrist anomalies, developmental dysplasia of the hip (DDH), arthrogryposis, and limb hypoplasia, each observed in 1 child (1.8%) (Fig. 1).

Miscellaneous anomalies

Miscellaneous anomalies, including single umbilical artery, depressed nasal bridge, and rib anomalies, were each reported in 1 child (1.8%).

ARM and associated anomalies relationship

Statistical analysis using the Chi-square test revealed no significant associations between gestational age and the prevalence of associated anomalies. Similarly, no overall significant relationship was observed between gender and anomaly prevalence. However, subgroup analyses evaluating associations between gender and gestational age with VACTERL components demonstrated a statistically significant association between female sex and cardiac anomalies (P χ² = 0.044, OR = 3.00, 95% CI: 1.02–8.86). No significant associations were identified between gestational age (preterm versus term) and any specific anomaly category.

Discussion

This retrospective study investigated the spectrum of congenital anomalies associated with anorectal malformations (ARM) in 57 surgically treated children at a tertiary referral center. Findings showed that the most common anomalies in children with ARM in our cohort were cardiac (52.6%), genitourinary (36.8%), and vertebral anomalies (24.6%). Compared with previous studies, our results are broadly consistent with the pattern of multisystem involvement reported in the literature, although the relative frequencies of affected systems vary across populations and study designs. As summarized in Table 2, Nah et al. reported associated anomalies in 78% of 99 patients, most commonly involving the genitourinary (28%) and spinal systems (26%) [20]. Similarly, in a large multicenter cohort of 460 patients, Oh et al. found that 65% had at least one associated anomaly, with genitourinary (28%), cardiac (25%), and vertebral (22%) systems most frequently involved [4]. Mittal et al. reported associated anomalies in 58.6% of 140 patients, predominantly affecting the urinary (37%), vertebral (34%), and cardiovascular systems (12%) [21]. Population-based data from Stoll et al. demonstrated a lower overall prevalence of associated anomalies (approximately 49–50%), with urogenital, cardiovascular, and skeletal systems most commonly involved [2, 22]. Collectively, these findings support the concept that ARM is frequently part of a broader multisystem congenital disorder.

Table 2.

Comparative summary of the most relevant international studies on associated anomalies in anorectal malformations

Author, Year (Reference)	Sample Size	Associated Anomalies (%)	Common Systems Involved
Nah et al., 2012 [20]	99 patients	78% had ≥ 1 anomaly	Genitourinary 28%, Spinal 26%
Oh et al., 2020 [4]	460 patients	65% had at-least one anomaly	Genitourinary 28%, Cardiac 25%, Vertebral 22%
Mittal et al., 2004 [21]	140 patients	58.6% had associated anomaly	Urinary 37%, Vertebral 34%, Cardiovascular 12%
Stoll et al., 2018 [2]	202 patients	~ 49.5% had associated anomalies	Urogenital, Cardiovascular, Skeletal
Stoll et al., 2007 [22]	174 patients	49.4% with associated malformations	Urogenital 81.1%, Skeletal 45.5%

Among them, cardiac anomalies were the most common associated defects (52.6%) in our study. The predominance of atrial septal defect, patent ductus arteriosus, and ventricular septal defect is consistent with previously published cohorts [8, 14]. The relatively high frequency observed in our study may reflect systematic echocardiographic screening in all patients, allowing detection of clinically silent lesions. These findings emphasize the critical importance of routine echocardiographic screening for all neonates with ARM. Many cardiac defects may be clinically silent in the neonatal period but require long-term follow-up for hemodynamic complications, arrhythmias, and pulmonary hypertension [6, 7, 9]. Although subgroup analysis showed a statistically significant association between female sex and cardiac anomalies, this finding should be interpreted cautiously, given the limited sample size.

Genitourinary anomalies were identified in 36.8% of patients. These included structural renal anomalies, vesicoureteral reflux, posterior urethral valves, and urogenital sinus. Similar rates (27–35%) have been reported internationally [14, 17, 18]. These anomalies significantly increase the risks of recurrent urinary tract infections, chronic kidney disease, and bladder dysfunction [3, 10, 14]. A comprehensive genitourinary evaluation is essential, including renal ultrasonography, voiding cystourethrography when indicated, and long-term nephrology follow-up [7, 9, 14]. The relatively higher proportion of genital anomalies observed in our study may be attributable to referral bias, as our center serves as a tertiary referral unit for complex anorectal and urogenital malformations.

Vertebral anomalies were present in 24.6% of patients, and sacral malformations were the most common of them, consistent with de Beaufort et al. (22.2%) [15]. Current guidelines recommend spinal ultrasonography for neonates under 3 months and MRI for older infants, as spinal cord anomalies, including tethered cord, can significantly impact neurological function and bowel/bladder control [12, 15]. Early identification of spinal anomalies, including tethered cord, is critical for neurological prognosis [12, 15].

Tracheoesophageal fistula (TEF) with or without esophageal atresia was detected in 14% of patients, and limb anomalies in 7%. The detection of severe anomalies such as TEF, bladder exstrophy, and major cardiac defects in a relatively small cohort likely reflects referral bias, as our center functions as a tertiary surgical institution receiving complex cases from a wide geographic area.

A striking finding was that 73.7% of children presented with anomalies fulfilling VACTERL association criteria or other associated malformations. This prevalence notably exceeds comparable studies: Tanasan et al. (2021) identified VACTERL association in 25% of 127 Iranian neonates [18], while Ahn and Choi (2021) reported 23% among 155 Korean patients [17]. The higher prevalence can be attributed to our definition of VACTERL association as at least two component anomalies (vertebral, anal, cardiac, tracheoesophageal, renal, and limb abnormalities), whereas most studies require three or more features [4, 8]. In the present study, we used a pragmatic definition of VACTERL association as the presence of at least two component anomalies. Although the classical and widely accepted definition of VACTERL association requires the presence of three or more component features, previous studies have shown that patients with two component anomalies (particularly those with anorectal malformations or tracheoesophageal fistula) frequently harbor additional VACTERL-type anomalies upon systematic evaluation [19]. Therefore, we adopted a lower threshold for descriptive and exploratory purposes to capture early multisystem involvement and avoid under-recognition of associated anomalies in this high-risk population. This approach may partially explain the higher prevalence of VACTERL association observed in our cohort compared with previous reports. Nevertheless, our findings should be interpreted with caution, and future studies using standardized diagnostic criteria (≥ 3 components) and prospective screening protocols are needed to enable direct comparison across cohorts. Additionally, as a tertiary referral center, our institution receives disproportionately complex cases, creating selection bias toward patients with multiple congenital anomalies [4, 13].

The high prevalence of multisystem involvement necessitates a comprehensive systematic evaluation for all neonates with ARM, including detailed physical examination, nasogastric tube insertion, plain radiography, renal ultrasonography, echocardiography, and spinal imaging. Management requires coordinated multidisciplinary care involving pediatric surgery, cardiology, nephrology, urology, orthopedics, neurosurgery, and genetics [1, 7, 9]. Long-term follow-up must address anorectal function, urinary continence, renal function, cardiac status, and neurological development [7, 9, 12].

Stratifying associated anomalies according to the severity of ARM has important clinical implications. Previous studies have demonstrated that vertebral and genitourinary anomalies are more frequent in severe ARMs (high-type and cloacal malformations), whereas cardiac anomalies tend to be distributed across all ARM subtypes [20, 21]. Although our study did not systematically classify ARMs according to international standards (e.g., Krickenbeck), these established patterns emphasize the importance of risk-adapted screening strategies based on ARM severity.

Because this study focused on the prevalence of associated anomalies, long-term survival and morbidity outcomes were not systematically analyzed. However, most patients survived to surgical intervention and discharge, reflecting advances in neonatal intensive care and staged surgical management. The presence of severe associated anomalies emphasizes the importance of longitudinal follow-up studies.

The study has several limitations: single-center design, relatively small sample size, referral bias toward complex cases, retrospective methodology, absence of standardized ARM severity stratification, and lack of long-term functional outcome data. These factors limit generalizability and preclude causal inference. Given the single-center design and limited sample size, our findings primarily reflect local referral patterns in a tertiary care center and should be interpreted as exploratory rather than population-level estimates.

Conclusion

This retrospective study demonstrates a high prevalence of associated congenital anomalies in children with anorectal malformations (ARM), most commonly involving the cardiac, genitourinary, and vertebral systems. A clear distinction between the classical VACTERL association and individual organ-system anomalies is essential for accurate interpretation. The findings support routine comprehensive screening and multidisciplinary management for all neonates with ARM. Larger prospective multicenter studies are required to further clarify risk patterns and long-term outcomes.

Abbreviations

ARM

Anorectal malformation

VACTERL

Vertebral, Anal atresia, Cardiac, Tracheo-Esophageal fistula, Renal, Limb

ASD

Atrial septal defect

PDA

Patent ductus arteriosus

VSD

Ventricular septal defect

TEF

Tracheoesophageal fistula

MRI

Magnetic resonance imaging

OR

Odds ratio

CI

Confidence interval

Authors’ contributions

This study was led by Mastaneh Moghtaderi. All authors contributed to the analysis, manuscript drafting, and final revisions. All authors have read and approved the final version of the manuscript. Mastaneh Moghtaderi had full access to all of the data in this study and takes complete responsibility for the integrity and accuracy of the data and analysis. All authors have read and approved the final version of the manuscript.

Funding

No funding was received for this study.

Data availability

The data supporting the findings of this study are available on request from the corresponding author. The datasets created during this study are not publicly accessible due to the possibility of compromising the privacy of individuals.

Declarations

Ethics approval and consent to participate

This retrospective study was conducted in full accordance with the ethical principles of the Declaration of Helsinki and national guidelines. The study protocol was approved by the Institutional Ethics Committee of the Children’s Medical Center Hospital, Tehran University of Medical Sciences (Ethics Code: IR.TUMS.CHMC.REC.1403.027). All parents or guardians provided written informed consent prior to inclusion.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.