Pediatric Tumors and Developmental Anomalies: A French Nationwide Cohort Study.

OBJECTIVE: To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities. STUDY DESIGN: Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking. RESULTS: From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm. CONCLUSIONS: In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.

Long-Term Functional Outcomes of an Anorectal Malformation French National Cohort.

OBJECTIVES: The present study aimed to assess long-term functional outcomes of children with anorectal malformations (ARMs) across a network of expert centers in France. METHODS: Retrospective cross-sectional study of patients ages 6-30 years that had been surgically treated for ARM. Patient and ARM characteristics (eg, level, surgical approach) and functional outcomes were assessed in the different age groups. RESULTS: Among 367 patients, there were 155 females (42.2%) and 212 males (57.8%), 188 (51.2%) cases with, and 179 (48.8%) higher forms without, perineal fistula. Univariate and multivariate statistical analyses with logistic regression showed correlation between the level of the rectal blind pouch and voluntary bowel movements (odds ratio [OR] = 1.84 [1.31-2.57], P < 0.001), or soiling (OR = 1.72 [1.31-2.25], P < 0.001), which was also associated with the inability to discriminate between stool and gas (OR = 2.45 [1.28-4.67], P = 0.007) and the presence of constipation (OR = 2.97 [1.74-5.08], P < 0.001). Risk factors for constipation were sacral abnormalities [OR = 2.26 [1.23-4.25], P = 0.01) and surgical procedures without an abdominal approach (OR = 2.98 [1.29-6.87], P = 0.01). Only the holding of voluntary bowel movements and soiling rates improved with age. CONCLUSION: This cross-sectional study confirms a strong association between anatomical status and functional outcomes in patients surgically treated for ARM. It specifically highlights the need for long-term follow-up of all patients to help them with supportive care.

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020.

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections.ResultsPrevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

Spinal dysraphism as a new entity in V.A.C.TE.R.L syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.

Anorectal malformation (ARM) is the most common symptom in VACTERL syndrome (vertebral, anal, cardiac, tracheo-esophageal fistula, renal, and limb anomalies). The association of ARM and spinal dysraphisms (DYS) is well documented. We aim to better evaluate children with VACTERL association and ARM, considering the presence or not of DYS. Between 2000 and 2015, 279 children with VACTERL associations were identified in Necker Children's Hospital, Paris. We identified 61 VACTERL children (22%) with ARM. A total of 52 VACTERL children with ARM were included. DYS were identified in 36/52 of cases (69.2%). A total of 33 (63.5%) VACTERL children presented with sphincterial dysfunction. We constated that 28/33 (84.8%) of them had DYS + (p < 0.0001). More children in ARM (DYS +) subgroup are presenting with initial urinary sphincter dysfunction (58 vs 19%, p < 0.009) than ARM (DYS -). We identified 29 lipoma filum in our series, which were not statistically associated with urinary disorders (p = 0.143).Conclusion: We propose to refine the definition of VACTERL association, by adding S as Spinal defect to include it as an integral part of this syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.What is Known:• The VACTERL association: congenital anomalies of the bony vertebral column (V), anorectal malformation (A), congenital cardiopathy (C), tracheo-esophageal defects (TE), renal and urinary tract anomalies (R), and limb malformations (L).• VACTERL children needs a complete appraisal, as early as possible, to adopt the most appropriate therapeutic management.What is New:• Include spine dysraphism (DYS) as a part of this syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.• The significant correlation between VACTERL/DYS and urinary dysfunction requires to investigate the spine cord prenatally.

Long-term Outcome of Hirschsprung Disease: Impact on Quality of Life and Social Condition at Adult Age.

BACKGROUND: Hirschsprung disease is a rare congenital disease typically requiring surgical treatment during childhood. Quality of life and social condition at adult age can be impaired by disease-specific sequelae. OBJECTIVE: This study aimed to assess the quality of life and social outcome of adult patients operated on for Hirschsprung disease during childhood. DESIGN: Patients operated on for Hirschsprung disease during childhood were identified and specific questionnaires were sent to them. SETTINGS: Data from 2 referral centers were used. PATIENTS: Patients who completed the questionnaires regarding quality of life and social condition were included. MAIN OUTCOME MEASURES: The Hirschsprung's Disease and Anorectal Malformations Quality of Life disease-specific questionnaire (8 dimensions explored; each scored from 0 to 100 maximum score) and a sociodemographic questionnaire were sent to identified patients. Sociodemographic data were compared with those of the French general population. RESULTS: Thirty-four patients had Hirschsprung disease (men, 76%; mean age, 32 years) were included in the study. Mean total Hirschsprung's Disease and Anorectal Malformations Quality of Life score was 611 of 800 (maximum score 800). The 2 most impaired dimensions were "physical symptoms" and "diarrhea" (62.9/100 and 73.6/100). Fecal continence was only marginally affected (mean score, 89/100). Patients with Hirschsprung disease achieved better educational levels than the French general population. Parental and marital status did not differ between the 2 groups. LIMITATIONS: This study had the limitations inherent to a retrospective study. CONCLUSION: The quality of life of adult patients with Hirschsprung disease sequelae is marginally impaired in this study. Despite the consequences of this congenital abnormality, the condition eventually achieved can be considered as satisfactory. See Video Abstract at http://links.lww.com/DCR/A917.

How to Explore Fetal Sacral Agenesis Without Open Dysraphism: Key Prenatal Imaging and Clinical Implications.

The estimated prevalence of fetal caudal dysgenesis is 1 per 100,000 births. The functional prognosis of sacral agenesis is dominated by the large spectrum of associated caudal malformations. Except for cases associated with hydrocephalus secondary to open spinal dysraphism or chromosomal anomalies, association with mental deficiency is rare. We propose a systematic prenatal approach to cases of fetal sacral agenesis based on 9 etiologic items: clinical context, type of sacral dysgenesis, associated spinal cord malformations, mobility of lower limbs, investigation of the presacral region, analysis of the gastrointestinal tract, analysis of the genitourinary tract, associated vertebral defects, and cytogenetic analysis.

Consensus Review of Best Practice of Transanal Irrigation in Children.

Pediatric patients with either functional or organic bowel dysfunction may suffer from constipation and fecal incontinence and represent a complex group in whom management is often difficult. Many noninvasive and invasive treatments have been proposed, with variable efficacy and adverse effects. Transanal irrigation (TAI) is now an accepted alternative, in both children and adults, for bowel dysfunction that has not responded to conservative and medical therapies. There is, however, still some uncertainty about the use of TAI in pediatric populations. Hence, a group of specialists from different nations and pediatric disciplines, all with long-standing experience of bowel management in children, performed a literature search and had round table discussions to determine the best-practice use of TAI in the pediatric patient population. Based on these findings, this article provides best-practice recommendations on indications, patient selection, important considerations before treatment, patient and family training, treatment regimens, troubleshooting, and practical aspects of TAI. We conclude that careful patient selection, a tailored approach, directly supervised training, and sustained follow-up are key to optimize outcomes with TAI in children with functional or organic bowel dysfunction.

Validation of the French versions of the Hirschsprung's disease and Anorectal malformations Quality of Life (HAQL) questionnaires for adolescents and adults.

BACKGROUND: The Hirschsprung's disease Anorectal malformation QoL questionnaire (HAQL) is a disease-specific quality of life (QoL) questionnaire for patients with Hirschsprung's disease (HD) or anorectal malformations (ARM). It was originally proposed in Dutch and is currently being translated into other languages to obtain an internationally standardized instrument. In this work we validate a French adaptation of the HAQL for adolescents and adults. METHODS: The questionnaires were translated into French and sent to patients aged 12 years and older, followed for HD or ARM at three French university hospitals. Questionnaires were sent to 147 adolescents and 188 adults. The psychometric properties of the questionnaires were analyzed in terms of reliability and validity. RESULTS: The original HAQL structure was not satisfactory. A new structure was proposed, while aiming to remain close to the original structure. The proposed structure has acceptable reliability and validity properties and reflects both physical, as well as psychosocial aspects. CONCLUSIONS: A French version of the HAQL questionnaire for adults and adolescents is ready for use in France. In particular the score could discriminate between degrees of clinical status based on the Krickenbeck consensus, which can aid clinicians to inform patients about physical and psychosocial challenges they may expect.

Think of the Conus Medullaris at the Time of Diagnosis of Fetal Sacral Agenesis.

BACKGROUND: There is no precise prenatal indicator to refine an accurate prognosis in case of sacral agenesis and to define the diagnostic approach and outcome criteria in case of fetal sacral agenesis using 3 characteristics of the conus medullaris (CM): its position, its appearance, and associated spinal abnormalities. METHODS: Ten cases of prenatally diagnosed sacral agenesis were included between 1995 and 2014 after collating ultrasound findings and prenatal computed tomography data. RESULTS: Two cases of total sacral agenesis and 8 of partial agenesis were included. There were 1 or more spinal abnormalities in 8/10 cases: 6 lipomas, 4 low-lying tethered cords, 2 diastematomyelias, and 1 syringomyelia. Three situations were distinguished: sacral agenesis with low-lying tethered cord, sacral agenesis with a truncated CM, and sacral agenesis with CM in place. If the sacral agenesis is isolated, a lipoma should be sought. Lipomas of the filum have a good prognosis, whereas lipomas of the CM cause neurological deficits in 1/3 of cases. When there is a low-lying tethered cord, a diastematomyelia or a syringomyelia may be associated. In truncated CM, there may be a severe form suggestive of caudal regression syndrome. Serious ultrasound signs are immobility of the lower limbs, talipes equinovarus, impaired bladder emptying, and dilatation of the upper urinary tract. CONCLUSION: A precise description of the morphology of the CM, its position, and associated spinal malformations are important in defining the neurological, urinary, gastrointestinal, and motor functions prognosis in cases of fetal sacral agenesis.

European Reference Network eUROGEN Guidelines on the Management of Anorectal Malformations, Part II: Treatment.

INTRODUCTION: Anorectal malformations (ARMs) are rare birth defects affecting the anorectum and oftentimes the genitourinary region. The management of ARM patients is complex and requires highly specialized surgical and medical care. The European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM applicable on a European level. METHODS: The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence, expert opinion, and the European context. RESULTS: Surgical and medical treatment of ARM, postoperative instructions, toilet training, and management of fecal and urinary incontinence were addressed. Seven new studies were identified. The panel adapted 23 recommendations, adopted 3, and developed 8 de novo. The overall level of newly found evidence was considered low. CONCLUSION: Treatment of ARM patients requires a multidisciplinary team and expertise about anatomical and surgical aspects of the disease, as well as long-term follow-up. This guideline offers recommendations for surgical and medical treatment of ARM and associated complications, according to the best available evidence and applicable on a European level.

ERN eUROGEN Guidelines on the Management of Anorectal Malformations Part III: Lifelong Follow-up and Transition of Care.

INTRODUCTION: Anorectal malformations (ARMs) are complex congenital anomalies of the anorectal region, oftentimes also affecting the genitourinary system. Although successful surgical correction can often be achieved in the neonatal period, many children will experience functional problems in the long term. The European Reference Network for rare and complex urogenital conditions (eUROGEN) assembled a panel of experts to address these challenges and develop comprehensive guidelines for the management of ARM. METHODS: The Dutch Quality Standard for ARM served as the foundation for the development of guidelines applicable on a European level. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from 7 European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence and/or expert consensus. RESULTS: Lifelong follow-up, integration, and transition of care were assessed. A total of eight new studies were identified. The panel adapted 18 recommendations, adopted 6, and developed 6 de novo. Overall, the level of evidence was considered low. CONCLUSION: Successful lifelong follow-up and transition of care require a dedicated team of pediatric and adult specialist and an individually tailored patient-centered approach. This guideline summarizes the best available evidence on follow-up of ARM patients and provides guidance for the development of structured transition programs.

ERN eUROGEN Guidelines on the Management of Anorectal Malformations, Part IV: Organization of Care and Communication between Providers.

INTRODUCTION: Being born with an anorectal malformation (ARM) can have profound and lifelong implications for patients and parents. Organization of care and communication between health care providers is an overlooked area of patient care. The European Reference Network eUROGEN for rare and complex urogenital conditions assembled a panel of experts to address these challenges and develop comprehensive guidelines for the management of ARM. METHODS: The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering all available evidence, expert consensus, and the European context. RESULTS: Aspects pertaining to organization of care, patient/parent/health care provider communication, and referral and collaboration between providers caring for ARM patients were assessed. Two new studies were identified. In total, the panel adapted 12 recommendations, adopted 7, and developed 2 de novo. The overall level of newly found evidence was considered low and most recommendations were based on expert opinion. CONCLUSION: Collaborative care and organization of care are gaining importance in the field of ARM. This guideline gives practical guidance on how to achieve better communication and collaboration between all involved parties, applicable at the European level.

ERN eUROGEN Guidelines on the Management of Anorectal Malformations Part I: Diagnostics.

INTRODUCTION: Anorectal malformations (ARMs) are rare congenital anomalies that involve the anus, rectum, and oftentimes the genitourinary tract. The management of ARM patients is complex, and many controversies exist. To address this issue, the European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM. METHODS: The Dutch Quality Standard for ARM served as the basis for the development of guidelines applicable on a European level. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from 7 European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected, and recommendations were formed considering current evidence and/or expert consensus. RESULTS: Prenatal and neonatal diagnostic workup as well as postsurgical follow-up of anorectal, genitourinary tract, and neurologic system were reviewed. Seven new studies were identified. The panel adapted 13 recommendations, adopted 7, and developed 8 de novo. The availability of high-quality evidence was limited, and most recommendations were based on retrospective studies, case series, or expert opinion. CONCLUSION: Patients with ARM and their families require highly specialized and comprehensive care from the prenatal period to adulthood. This guideline provides recommendations for a comprehensive diagnostic workup of children with ARM throughout their life that is applicable on a European level.

Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis.

BACKGROUND: Hirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis. METHODS: A multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements. RESULTS: The consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus. CONCLUSIONS: Total colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center. TYPE OF STUDY: Clinical consensus statement. LEVEL OF EVIDENCE: 3a.

Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-reactive CD3+CD4+CD154+ T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4+ T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4+ T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2-reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Transitional Care for Patients with Congenital Colorectal Diseases: An EUPSA Network Office, ERNICA, and eUROGEN Joint Venture.

BACKGROUND: Transition of care (TOC; from childhood into adulthood) of patients with anorectal malformations (ARM) and Hirschsprung disease (HD) ensures continuation of care for these patients. The aim of this international study was to assess the current status of TOC and adult care (AC) programs for patients with ARM and HD. METHODS: A survey was developed by members of EUPSA, ERN eUROGEN, and ERNICA, including patient representatives (ePAGs), comprising of four domains: general information, general questions about transition to adulthood, and disease-specific questions regarding TOC and AC programs. Recruitment of centres was done by the ERNs and EUPSA, using mailing lists and social media accounts. Only descriptive statistics were reported. RESULTS: In total, 82 centres from 21 different countries entered the survey. Approximately half of them were ERN network members. Seventy-two centres (87.8%) had a self-reported area of expertise for both ARM and HD. Specific TOC programs were installed in 44% of the centres and AC programs in 31% of these centres. When comparing centres, wide variation was observed in the content of the programs. CONCLUSION: Despite the awareness of the importance of TOC and AC programs, these programs were installed in less than 50% of the participating centres. Various transition and AC programs were applied, with considerable heterogeneity in implementation, content and responsible caregivers involved. Sharing best practice examples and taking into account local and National Health Care Programs might lead to a better continuation of care in the future. LEVEL OF EVIDENCE: III.

Research perspectives in the etiology of congenital anorectal malformations using data of the International Consortium on Anorectal Malformations: evidence for risk factors across different populations.

PURPOSE: The recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities. METHODS: The consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case-parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data. RESULTS: Currently, 701 ARM cases have been recruited throughout Europe. Clinical data are available from all cases, and DNA samples and questionnaire data mainly from the Dutch and German cases. Preliminary analyses on environmental risk factors in the Dutch and German cohort found associations between ARM and family history of ARM, fever during first trimester of pregnancy and maternal job exposure to cleaning agents and solvents. CONCLUSION: First results show that both genetic and environmental factors may contribute to the multifactorial etiology of ARM. The International Consortium on Anorectal Malformations will provide possibilities to study and detect important genes and environmental risk factors for ARM, ultimately resulting in better genetic counseling, improved therapies, and primary prevention.

Variations in the Detection of Anorectal Anomalies at Birth among European Cities.

INTRODUCTION: The diagnosis of anorectal malformations (ARMs) is made at birth by perineal examination of the newborn, yet small series reported late diagnosis in almost 13%. No large series to date have looked into the magnitude of missed ARM cases in the neonatal period across Europe. This study aimed to define the rate of missed ARM at birth across four United Kingdom and European Union centers. MATERIALS AND METHODS: All ARM cases treated at two United Kingdom tertiary centers in the past 15 years were compared with two tertiary European centers. Demographic and relevant clinical data were collected. Late diagnosis was defined as any diagnosis made after discharge from the birth unit. Factors associated with late diagnosis were explored with descriptive statistics. RESULTS: Across the four centers, 117/1,350, 8.7% were sent home from the birth unit without recognizing the anorectal anomaly. Missed cases showed a slight female predominance (1.3:1), and the majority (113/117, 96.5%) were of the low anomaly with a fistula to the perineum. The rate of missed ARM cases was significantly higher in the United Kingdom centers combined (74/415, 17.8%) compared with those in the European Union (43/935, 4.6%) (p < 0.00001), and this was independent of individual center and year of birth. CONCLUSION: Significant variation exists between the United Kingdom and other European countries in the detection of ARM at birth. We recommend raising the awareness of accurate perineal examination at the time of newborn physical examination. We feel this highlights an urgent need for a national initiative to assess and address the timely diagnosis of ARM in the United Kingdom.

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. AIMS: This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. METHODS: Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. RESULTS: Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. CONCLUSION: In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.