Bowel function and associated risk factors at preschool and early childhood age in children with anorectal malformation type rectovestibular fistula:An ARM-Net consortium study

Background: Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel function of RVF-patients at preschool/early childhood age and determine risk factors for poor functional outcome. Methods: A multi-center cohort study was performed. Patient characteristics, associated anomalies, sacral ratio, surgical procedures, post-reconstructive complications, one-year constipation, and Bowel Function Score (BFS) at 4–7 years of follow-up were registered. Groups with below normal (BFS < 17; subgroups ‘poor’ ≤ 11, and ‘fair’ 11 < BFS < 17) and good outcome (BFS ≥ 17) were formed. Univariable analyses were performed to detect risk factors for outcome. Results: The study included 111 RVF-patients. Median BFS was 16 (range 6–20). The ‘below normal’ group consisted of 61 patients (55.0%). Overall, we reported soiling, fecal accidents, and constipation in 64.9%, 35.1% and 70.3%, respectively. Bowel management was performed in 23.4% of patients. Risk factors for poor outcome were tethered cord and low sacral ratio, while sacral anomalies, low sacral ratio, prior enterostomy, post-reconstructive complications, and one-year constipation were for being on bowel management. Conclusions: Although median BFS at 4–7 year follow-up is nearly normal, the majority of patients suffers from some degree of soiling and constipation, and almost 25% needs bowel management. Several factors were associated with poor bowel function outcome and bowel management. Level of Evidence: Level III

Clinical Differentiation between a Normal Anus, Anterior Anus, Congenital Anal Stenosis, and Perineal Fistula: Definitions and Consequences—The ARM-Net Consortium Consensus

In the past, an anteriorly located anus was often misdiagnosed and treated as an anorectal malformation (ARM) with a perineal fistula (PF). The paper aims to define the criteria for a normal anus, an anterior anus (AA) as an anatomic variant, and milder types of ARM such as congenital anal stenosis (CAS) and PF. An extensive literature search was performed by a working group of the ARM-Net Consortium concerning the subject “Normal Anus, AA, and mild ARM”. A consensus on definitions, clinical characteristics, diagnostic management, and treatment modalities was estab-lished, and a diagnostic algorithm was proposed. The algorithm enables pediatricians, midwives, gynecologists, and surgeons to make a timely correct diagnosis of any abnormally looking anus and initiate further management if needed. Thus, the routine physical inspection of a newborn should include the inspection of the anus and define its position, relation to the external sphincter, and caliber. A correct diagnosis and use of the presented terminology will avoid misclassifications and allow the initiation of correct management. This will provide a reliable comparison of different therapeutic management and outcomes of these patient cohorts in the future

Perineal Groove : An Anorectal Malformation Network, Consortium Study

Objective: To review the Anorectal Malformation Network experience with perineal groove (PG) focusing on its clinical characteristics and management. Study design: Data on patients with PG managed at 10 participating Anorectal Malformation Network centers in 1999-2019 were collected retrospectively by questionnaire. Results: The cohort included 66 patients (65 females) of median age 1.4 months at diagnosis. The leading referral diagnosis was anal fissure (n = 20 [30.3%]): 23 patients (34.8%) had anorectal malformations. Expectant management was practiced in 47 patients (71.2%). Eight (17%) were eventually operated for local complications. The median time to surgery was 14 months (range, 3.0-48.6 months), and the median age at surgery was 18.3 months (range, 4.8-58.0 months). In the 35 patients available for follow-up of the remaining 39 managed expectantly, 23 (65.7%) showed complete or near-complete self-epithelization by a mean age 15.3 months (range, 1-72 months) and 4 (11.4%) showed partial self-epithelization by a mean age 21 months (range, 3-48 months). Eight patients showed no resolution (5 were followed for ≤3 months). Nineteen patients (28.7%) were primarily treated with surgery. In total, 27 patients were operated. Dehiscence occurred in 3 of 27 operated patients (11.1%). Conclusions: PG seems to be an underestimated anomaly, frequently associated with anorectal malformations. Most cases heal spontaneously; therefore, expectant management is recommended. When associated with anorectal malformations requiring reconstruction, PG should be excised in conjunction with the anorectoplasty

Bowel function and associated risk factors at preschool and early childhood age in children with anorectal malformation type rectovestibular fistula: An ARM-Net consortium study

Background: Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel function of RVF-patients at preschool/early childhood age and determine risk factors for poor functional outcome. Methods: A multi-center cohort study was performed. Patient characteristics, associated anomalies, sacral ratio, surgical procedures, post-reconstructive complications, one-year constipation, and Bowel Function Score (BFS) at 4–7 years of follow-up were registered. Groups with below normal (BFS < 17; subgroups ‘poor’ ≤ 11, and ‘fair’ 11 < BFS < 17) and good outcome (BFS ≥ 17) were formed. Univariable analyses were performed to detect risk factors for outcome. Results: The study included 111 RVF-patients. Median BFS was 16 (range 6–20). The ‘below normal’ group consisted of 61 patients (55.0%). Overall, we reported soiling, fecal accidents, and constipation in 64.9%, 35.1% and 70.3%, respectively. Bowel management was performed in 23.4% of patients. Risk factors for poor outcome were tethered cord and low sacral ratio, while sacral anomalies, low sacral ratio, prior enterostomy, post-reconstructive complications, and one-year constipation were for being on bowel management. Conclusions: Although median BFS at 4–7 year follow-up is nearly normal, the majority of patients suffers from some degree of soiling and constipation, and almost 25% needs bowel management. Several factors were associated with poor bowel function outcome and bowel management. Level of Evidence: Level III

More than fetal urine:enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation

Item does not contain fulltextThe purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European newborns with congenital pre-gastric intestinal atresia, i.e., EA, to a European reference population. To account for the influence of the intestinal atresia on fetal growth per se, we compared adapted birth weights for each of 504 European newborns with post colonic intestinal atresia (anorectal malformation (ARM) with atresia of the anus) to the same European reference population. Analysis of the complete cohort showed (i) a significantly higher rate of small for gestational age newborns among EA compared to ARM newborns (p < 0.001) and (ii) significantly lower BW z-scores among EA compared to ARM newborns (p < 0.001). BW z-scores of EA newborns were significantly lower in term compared to preterm newborns with an inverse correlation with gestational age (GA) (Spearman correlation coefficient, r = -0.185, p < 0.001). CONCLUSIONS: Enteral uptake of AF seems to play a pivotal role in fetal growth during late gestation. WHAT IS KNOWN: * Peak velocity of fetal weight gain occurs at 33 weeks of gestation and continues until birth. During this period, fetal growth is mainly characterized by cellular hypertrophy. * Amniotic fluid (AF) comprises large amounts of hormones and growth regulators. What is New: * A significantly higher rate of small for gestational age and lower birth weights and z-scores are observed among newborn infants with congenital pre-gastric intestinal atresia. * These findings suggest that enteral uptake of AF is a major predictor for fetal growth during late gestation

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies

Background:The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Methods:Using molecular inversion probes, a candidate gene panel of 56 genes was sequenced in three patient groups: VACTERL (n= 211), ARM (n= 204), and EA/TEF (n= 95). Loss-of-function (LoF) and additional likely pathogenic missense variants, were prioritized and validated using Sanger sequencing. Validated variants were tested for segregation and patients were clinically re-evaluated. Results:In 7 out of the 510 patients (1.4%), pathogenic or likely pathogenic variants were identified inSALL1, SALL4, andMID1, genes that are associated with Townes-Brocks, Duane-radial-ray, and Opitz-G/BBB syndrome. These syndromes always include ARM or EA/TEF, in combination with at least two other VACTERL features. We did not identify LoF variants in the remaining candidate genes. Conclusions:None of the other candidate genes were identified as novel unequivocal disease genes for VACTERL. However, a genetics-first approach allowed refinement of the clinical diagnosis in seven patients, in whom an alternative molecular-based diagnosis was found with important implications for the counseling of the families

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies

Background: The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Methods: Using molecular inversion probes, a candidate gene panel of 56 genes was sequenced in three patient groups: VACTERL (n = 211), ARM (n = 204), and EA/TEF (n = 95). Loss-of-function (LoF) and additional likely pathogenic missense variants, were prioritized and validated using Sanger sequencing. Validated variants were tested for segregation and patients were clinically re-evaluated. Results: In 7 out of the 510 patients (1.4%), pathogenic or likely pathogenic variants were identified in SALL1, SALL4, and MID1, genes that are associated with Townes-Brocks, Duane-radial-ray, and Opitz-G/BBB syndrome. These syndromes always include ARM or EA/TEF, in combination with at least two other VACTERL features. We did not identify LoF variants in the remaining candidate genes. Conclusions: None of the other candidate genes were identified as novel unequivocal disease genes for VACTERL. However, a genetics-first approach allowed refinement of the clinical diagnosis in seven patients, in whom an alternative molecular-based diagnosis was found with important implications for the counseling of the families

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies

© Copyright © 2020 van de Putte, Dworschak, Brosens, Reutter, Marcelis, Acuna-Hidalgo, Kurtas, Steehouwer, Dunwoodie, Schmiedeke, Märzheuser, Schwarzer, Brooks, de Klein, Sloots, Tibboel, Brisighelli, Morandi, Bedeschi, Bates, Levitt, Peña, de Blaauw, Roeleveld, Brunner, van Rooij and Hoischen. Background: The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Methods: Using molecular inversion probes, a candidate gene panel of 56 genes was sequenced in three patient groups: VACTERL (n = 211), ARM (n = 204), and EA/TEF (n = 95). Loss-of-function (LoF) and additional likely pathogenic missense variants, were prioritized and validated using Sanger sequencing. Validated variants were tested for segregation and patients were clinically re-evaluated. Results: In 7 out of the 510 patients (1.4%), pathogenic or likely pathogenic variants were identified in SALL1, SALL4, and MID1, genes that are associated with Townes-Brocks, Duane-radial-ray, and Opitz-G/BBB syndrome. These syndromes always include ARM or EA/TEF, in combination with at least two other VACTERL features. We did not identify LoF variants in the remaining candidate genes. Conclusions: None of the other candidate genes were identified as novel unequivocal disease genes for VACTERL. However, a genetics-first approach allowed refinement of the clinical diagnosis in seven patients, in whom an alternative molecular-based diagnosis was found with important implications for the counseling of the families