Maternal metabolomic profiling and congenital heart disease risk in offspring: A systematic review of observational studies.

Aetiological understanding and screening methods for congenital heart disease (CHD) are limited. Maternal metabolomic assessment offers the potential to identify risk factors and biomarkers. We performed a systematic review (PROSPERO CRD42022308452) investigating the association between fetal/childhood CHD and endogenous maternal metabolites. Ovid-MEDLINE, Ovid-EMBASE and Cochrane Library were searched between inception and 06/09/2022. Case control studies included analysing maternal blood or urine metabolites in pregnancy or postpartum where there was foetal/childhood CHD. Risk of bias assessment utilised the Scottish Intercollegiate Guidelines Network methodology checklist and narrative synthesis was performed. A total of 134 records were screened with eight eligible studies (n = 3242 pregnancies, n = 842 CHD-affected offspring). Five studies performed metabolomic analysis in pregnancy. Metabolites distinguishing case and control groups spanned lipid, glucose and amino-acid pathways, with the development of sensitive risk prediction models. No single metabolite consistently distinguished cases and controls across studies. Three studies performed targeted analysis postnatally with altered lipid and amino acid metabolites and raised homocysteine and markers of oxidative stress identified in cases. Included studies reported small sample sizes, analysing different biosamples at variable time points using differing techniques. At present, there is not enough evidence to confidently associate maternal metabolomic profiles with offspring CHD risk. However, several identified pathways warrant further investigation.

Factors influencing enteral autonomy after autologous gastrointestinal reconstructive surgery: A two-centre UK perspective.

BACKGROUND AND AIMS: The implementation of multidisciplinary care and improvements in parenteral nutrition (PN) in patients with short bowel syndrome (SBS) have led to better outcomes and higher survivability. Autologous gastrointestinal reconstructive (AGIR) surgery can reduce the duration on PN and lead to earlier enteral autonomy (EA). Our aim was to investigate the effect of SBS aetiology and other predictors on the achievement of enteral autonomy following AGIR surgery. METHODS: Retrospective review of all patients undergoing AGIR surgery in two tertiary paediatric surgical units, between 2010 and 2021. Continuous data is presented as median (range). RESULTS: Twenty-seven patients underwent 29 AGIR procedures (20 serial transverse enteroplasties (STEP), 9 longitudinal intestinal lengthening and tailoring (LILT)) at an age of 6.6 months (1.5 - 104.5). EA rate was 44% at 13.6 months after surgery (1 - 32.8). AGIR procedures achieved an increase in small bowel length of 70% (pre-operative 46.5 vs 77 cm, p = 0.003). No difference was found between STEP and LILT (p = 0.84). Percentage of expected small bowel length (based on the child's weight) was a strong predictor of EA (bowel length >15% - EA 80% vs bowel length ≤15% - EA 17%, p = 0.008). A diagnosis of gastroschisis showed a negative non-significant correlation with the ability to achieve EA (25% vs 60%, p = 0.12). Overall survival rate was 96%. CONCLUSION: AGIR surgery is an important tool in the multidisciplinary management of children with SBS. Percentage of expected small length and aetiology of SBS are likely predictors of achievement of EA in patients undergoing AGIR surgery. LEVEL OF EVIDENCE: IV: Retrospective Case-Series.

10 Year Follow-Up of Randomized Trial of Laparoscopic Nissen Versus Thal Fundoplication in Children.

Introduction: The aim of this study was to compare the long-term outcomes of laparoscopic complete (Nissen) fundoplication (LNF) with laparoscopic partial (Thal) fundoplication (LTF) in children. This is the only prospective, randomized study to follow patients up for more than 10 years. Interim results published in 2011 at median 2.5 year follow-up showed that LNF had a significantly lower failure rate compared with LTF. Materials and Methods: A randomized, controlled trial of LNF versus LTF in children (<16 years) was performed. The primary outcome measure was "absolute" failure of the fundoplication-recurrence of symptoms that merited either reoperation or insertion of transgastric jejunostomy (GJ). Secondary outcomes were "relative" failure (need for postop antireflux medication), complications (e.g., dysphagia), and death. Results: One hundred seventy-five patients were recruited; 89 underwent LNF, and 86 underwent LTF. Eight patients had no follow-up recorded. At long-term follow-up, 59 patients had died (35%); LNF 37/85 (43.5%) and LTF 22/82 (26.8%), P = .02. Median length of follow-up in survivors was 132 months. There was no statistically significant difference in "absolute" failure rate between LNF 8/85(9.4%) and LTF 15/82 (18%), P = .14. There was no difference in "relative" failure between LNF 7/85 (8.2%) and LTF 12/82 (14%), P = .23. Long-term dysphagia affected 5 out of 108 (4.6%) patients; 3/48 (6.2%) of LNF and 2/60 (3.3%) of LTF (P = .65). Conclusions: There was no statistically significant difference in 'absolute' failure between LNF and LTF at long-term follow-up. Neurologically impaired children have a high mortality rate following fundoplication due to comorbidities. This trial commenced in 1998 and was approved by the Oxfordshire Research Ethics Committee (No. 04.OXA.18-1998).

Maternal micronutrient deficiency and congenital heart disease risk: A systematic review of observational studies.

BACKGROUND: Congenital anomalies affect over 2% of pregnancies, with congenital heart disease (CHD) the most common. Understanding of causal factors is limited. Micronutrients are essential trace elements with key roles in growth and development. We aimed to investigate whether maternal micronutrient deficiencies increase the risk of fetal CHD through systematic review of published literature. METHOD: We performed a systematic review registered at PROSPERO as CRD42021276699. Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library were searched from their inception until September 7, 2021. Case control trials were included with a population of biological mothers of fetuses with and without CHD. The exposure was maternal micronutrient level measured in pregnancy or the postpartum period. Data extraction was performed by one author and checked by a second. Risk of bias assessment was performed according to the Scottish Intercollegiate Guidelines Network guidance. We performed a narrative synthesis for analysis. RESULTS: 726 articles were identified of which 8 met our inclusion criteria. Final analysis incorporated data from 2,427 pregnancies, 1,199 of which were complicated by fetal CHD assessing 8 maternal micronutrients: vitamin D, vitamin B12, folate, vitamin A, zinc, copper, selenium, and ferritin. Studies were heterogenous with limited sample sizes and differing methods and timing of maternal micronutrient sampling. Definitions of deficiency varied and differed from published literature. Published results were contradictory. CONCLUSION: There is not enough evidence to confidently conclude if maternal micronutrient deficiencies increase the risk of fetal CHD. Further large-scale prospective study is required to answer this question.

Perianal/perineal rhabdomyosarcoma: Results of the SIOP MMT 95, Italian RMS 96, and EpSSG RMS 2005 studies.

BACKGROUND/OBJECTIVES: Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment. DESIGN/METHODS: International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed. RESULTS: Fifty patients (nonmetastatic) were identified, median age 6.4 years (range: 0.1-19.6): 29 male, 21 female. Tumors were >5 cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1 months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10 years and tumor size >5 cm impacting 5-year EFS and OS (p < .05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21. CONCLUSIONS: About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.

Surgical-PEARL protocol: a multicentre prospective cohort study exploring aetiology, management and outcomes for patients with congenital anomalies potentially requiring surgical intervention.

INTRODUCTION: Congenital anomalies affect over 2% of pregnancies. Surgical advances have reduced mortality and improved survival for patients with congenital anomalies potentially requiring surgical (CAPRS) intervention. However, our understanding of aetiology, diagnostic methods, optimal management, outcomes and prognostication is limited. Existing birth cohorts have low numbers of individual heterogenous CAPRS. The Surgical Paediatric congEnital Anomalies Registry with Long term follow-up (Surgical-PEARL) study aims to establish a multicentre prospective fetal, child and biological parent cohort of CAPRS. METHODS AND ANALYSIS: From 2022 to 2027, Surgical-PEARL aims to recruit 2500 patients with CAPRS alongside their biological mothers and fathers from up to 15 UK centres. Recruitment will be antenatal or postnatal dependent on diagnosis timing and presentation to a recruitment site. Routine clinical data including antenatal scans and records, neonatal intensive care unit (NICU) records, diagnostic and surgical data and hospital episode statistics will be collected. A detailed biobank of samples will include: parents' blood and urine samples; amniotic fluid if available; children's blood and urine samples on admission to NICU, perioperatively or if the child has care withdrawn or is transferred for extracorporeal membrane oxygenation; stool samples; and surplus surgical tissue. Parents will complete questionnaires including sociodemographic and health data. Follow-up outcome and questionnaire data will be collected for 5 years. Once established we will explore the potential of comparing findings in Surgical-PEARL to general population cohorts born in the same years and centres. ETHICS AND DISSEMINATION: Ethical and health research authority approvals have been granted (IRAS Project ID: 302251; REC reference number 22/SS/0004). Surgical-PEARL is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated widely through peer-reviewed publication, conference presentations and through patient organisations and newsletters. TRIAL REGISTRATION NUMBER: ISRCTN12557586.

Case report of a skip segment Hirschsprung's disease: A real phenomenon.

INTRODUCTION AND IMPORTANCE: Hirschsprung's disease is a congenital anomaly that results from an incomplete craniocaudal migration and maturation of intestinal ganglion progenitor cells leading to distal intestinal aganglionosis. Skip segment Hirschsprung's disease is an extremely rare phenomenon. We report a case involving only the small bowel with confirmed colonic ganglionosis. CASE PRESENTATION: A case report of a 14-month-old with a skipped segment involving the distal 50 cm of the small bowel associated with colonic ganglionosis is presented. A current review of the literature is discussed. CLINICAL DISCUSSION: Our patient had persistent obstructive symptoms despite undergoing a technically good, ganglionic pull-through operation at an outside institution. A laparoscopic-assisted pull-through might have documented a small bowel wall diameter discrepancy. CONCLUSION: Although rare, skip segment Hirschsprung's disease is a real phenomenon that paediatric surgeons should be aware of and could involve small and large bowels.

Does a standardized operative approach in cloacal reconstruction allow for preservation of a patent urethra?

BACKGROUND: Cloacal malformations are recognized as a particularly challenging congenital condition to manage and they present with a wide spectrum of anatomical configurations making surgical repair very complicated. Urethral necrosis or urethral loss is a known and devastating complication of cloacal repair. The surgical repair of these malformations has evolved over time and historically only common channel (CC) length was measured. More recently, it has been advocated that the urethral length and the CC are both important in determining surgical repair. The purpose of our study is to evaluate if this surgical approach allows for preservation of a patent urethra. METHODS: A prospective database of all cloaca patients maintained with IRB approval (IRB# STUDY00000721) was retrospectively reviewed. We included any girl with cloacal malformation who underwent primary repair at our institution between May 2014 and December 2019. Standardized preop evaluation with endoscopy and 3-dimentional imaging to assess urethral length and CC length. These measurements were used to determine operative approach. Girls with CC < 1 cm undergo posterior sagittal anorectoplasty and introitoplasty (PSARP + I), those with CC measuring 1-3 cm and urethra > 1.5 cm undergo total urogenital mobilization (TUM) and those with CC > 3 cm or urethra < 1.5 cm undergo urogenital separation (UGS). Postoperative urethral patency was determined at the time of cystoscopy and exam under anesthesia (EUA) 4-6 weeks postoperatively by visualizing a viable and healthy urethra that is catheterizable. RESULTS: A total of 59 patients met inclusion criteria with a median age of 11.6 months. Four girls underwent PSARP + I, 19 girls had a TUM and 36 girls underwent a UGS. All of the girls who had PSARP +I (n = 4) or TUM (n = 19) had a viable and patent urethra that was catheterizable at the cystoscopy and EUA 4-6 weeks postoperatively. Of the 36 girls who had UGS, all but 2 (5.6%) had a viable and patent urethra that catheterized without problems. Overall, 97% of girls in this cohort had a patent urethra after cloacal repair using this surgical protocol. CONCLUSIONS: The use of a standard protocol that considers urethral and common channel length for cloacal repairs results in a viable and patent urethra in 97% of patients. LEVEL OF EVIDENCE: Level II.

Long-term urologic and gynecologic follow-up and the importance of collaboration for patients with anorectal malformations.

Anorectal malformations (ARM) are well recognized to be associated with anomalies in other organ systems. The introduction of screening protocols has increased the diagnosis of these anomalies and greater collaboration with other specialties has influenced the treatment and follow-up of patients with ARMs. Much of the medical literature regarding the treatment of anorectal malformations has focused on technical details of operations and early post-surgical outcomes. Recently, an increase in published data regarding the long-term sequelae of an ARM diagnosis has resulted in an emphasis extended follow up in this population. Patient support groups have highlighted complex issues in ARM patients persist into adulthood have advocated for improved transitional care. This article describes the benefits of long-term follow-up and identifies key issues in ARM patients with respect to urologic and gynecologic health. A collaborative model of care is outlined and suggested timings of screening for potential problems is described.

Challenges in managing proximal hypospadias: A 17-year single-center experience.

BACKGROUND: There are only a few publications in the medical literature reporting on complication rates in proximal hypospadias surgery, particularly with regard to long-term follow-up. METHODS: Over a 17.5-year period, we operated 100 patients with penoscrotal, scrotal and perineal hypospadias. Sixty-four had a single-stage repair, including 15 who received a buccal mucosa inlay "Snodgraft" repair. Thirty-six had a two-stage Bracka repair of which 19 received buccal or lower lip grafts and 17 had preputial grafts. Overall, 34 patients received buccal grafts. The median follow-up was eight years (range 1-16 years). Three patients were operated for residual chordee years later. RESULTS: Urethral fistulae occurred in a total of 26/100 (26.0%) cases, meatal stenosis in 16/100 (16.0%), wound breakdown in six (6.0%) and graft failure in one (1.0%). The fistula rate after the single-stage approach was 15/64 (23.4%), whereas it was 11/36 (30.6%) following two-stage repair (P = 0.4811). CONCLUSIONS: Proximal hypospadias remains a challenging condition to treat. It is possible to perform a single-stage repair in 64.0% of cases. This brings down the median number of operations to only two. Lower lip grafts were used in 34.0% but are now used in redo-surgeries only. Our fistula rate was 26.0% but has decreased significantly in recent years. LEVEL OF EVIDENCE: Level III.

Menstrual, Sexual, and Obstetrical Outcomes after Vaginal Replacement for Vaginal Atresia Associated with Anorectal Malformation.

Background The authors of this article became aware of significant differences in the management of two females with a rectovestibular fistula and associated vaginal agenesis. In one patient, a sigmoid colovaginoplasty was performed at the time of the posterior sagittal anorectoplasty (PSARP), and the other underwent repair of the rectovestibular fistula with a primary PSARP, but the surgeons elected to delay the timing of vaginal reconstruction. We decided to review the literature, to establish if recommendations could be made to optimize the management of these children based on current evidence. Methods A literature review was conducted to determine the management and long-term outcomes in patients with an anorectal malformation and associated vaginal atresia. Specific gynecological outcomes assessed were menstrual egress and adequacy of the vaginal replacement for penile-vaginal intercourse. Results Eighty-eight cases were included in the review. Age at diagnosis had a bimodal distribution: 0 to 5 years, 56%; >10 years, 37%. Vaginal atresia was recognized before the operation in 45 patients. Types of vaginal atresia encountered were: (a) distal vaginal atresia (n = 17), (b) vaginal agenesis with absent Mullerian development (n = 47), (c) vaginal agenesis with variable Mullerian development (n = 17), and (d) cervico-vaginal agenesis (n = 7). Types of vaginal replacement used were sigmoid colovaginoplasty (n = 26), distal rectal fistula as neovagina (n = 30), terminal ileum (n = 5), vaginal pull-through (n = 9), and others/unknown (n = 8). Two patients followed a perineal dilatation program and nine patients await reconstruction. Median follow-up was 18 months (6 weeks to 31 years). Long-term menstrual outcomes were reported in 18 (21%) patients. Sexual function was reported in 10 (11%) patients. Three pregnancies were reported but none resulted in live births. Conclusion Vaginal atresia is often missed in association with ARMs. Management should be in collaboration with pediatric gynecologists. Due to a lack of long-term outcome data, no definite conclusion can be drawn for the best technique, tissue, or timing of vaginal replacement. The opportunity to perform vaginal replacement in conjunction with the rectal repair may be worth considering because of a shallower pelvis, nonscarred tissue planes, and the excellent surgical exposure.

A standardized approach for the assessment and treatment of internationally adopted children with a previously repaired anorectal malformation (ARM).

INTRODUCTION: A significant number of internationally adopted children have congenital birth defects. As a specialist center for colorectal diagnoses, we evaluate such children with an anorectal malformation (ARM) and have found that a significant number need a reoperation. Knowledge of the common complications following ARM surgery has led us to develop treatment algorithms for patients with unknown past medical and surgical history, a situation typically encountered in the adopted population. METHODS: The results of investigations, indications, and rate of reoperation were assessed for adopted children with an ARM evaluated between 2014 and 2016. RESULTS: 56 patients (28 males) were identified. 76.8% required reoperative surgery. Mislocation of the anus outside the sphincter complex was seen in 50% of males and 39.3% of females. Anal stricture, rectal prolapse, retained vaginal septum, and a strictured vaginal introitus were also common. CONCLUSION: The reoperative surgery rate in the internationally adopted child with an ARM is high. Complete, systematic evaluation of these children is required to identify complications following initial repair. Development of mechanisms to improve the primary surgical care these children receive is needed.

Early reported rectal sensation predicts continence in anorectal anomalies.

BACKGROUND: Straining at stool is an automatic reflex in babies and implies the presence of rectal sensation. We hypothesised that early reported rectal sensation would predict future continence in children with anorectal anomalies. AIM OF THE STUDY: The aim of this study is to determine if early straining at stool was a useful predictor of future continence in infants born with high anorectal malformations. METHODS: A retrospective case note review of prospectively collected clinical information was performed with institutional review board approval. All patients with intermediate/high anorectal malformation operated on by a single surgeon from 1984 to 2010 were included. After stoma closure, parents were asked: The responses were noted within the first year of stoma closure and then all patients were followed up until they were at least 3 ½years old and continence could be assessed using the Krickenbeck outcome classification. Data were compared using Fisher's exact test and sensitivity, specificity and positive predictive value (PPV) were calculated. MAIN RESULTS: Forty-eight patients were included in the study. Sixteen (33%) were female (12 cloacal malformation, 3 rectovaginal fistula, 1 rectal atresia) and 32 (66%) were male (6 rectovesical fistulae, 22 rectourethral fistulae, 4 no fistula). Median follow-up was 9.7years (range 3.5-17.9). Twenty-one children were noted by their parents to exhibit early straining at stool after stoma closure. Twenty of them achieved long term continence. The sensitivity of early straining as a predictor for long term continence was 77%, specificity 95% and positive predictive value 95%. CONCLUSION: The presence of early rectal sensation reported by parents is a good predictor of long term continence. This allows more informed discussion with families in the early years of life.

The Value of Trainee Networks in Pediatric Surgical Research.

In 2007, the first trainee-led surgical research network was founded in the United Kingdom (UK). The West Midlands Research Collaborative was started by a group of enthusiastic adult surgical trainees who saw the benefits of altruistic collaboration to generate high quality, multicenter research. Seeing the success of their research projects, including randomized controlled trials, trainees in other regions and specialties were spurred on to founding their own research collaboratives. The Pediatric Surgical Trainee Research Network was started in 2011 by a group of UK trainees with the aim to promote, facilitate, and encourage trainee-led research in pediatric surgery. This article summarizes the history and evolution of the trainee collaborative surgical research. It examines the challenges which multicenter research entails and the steps the collaboratives have taken to overcome them. We describe some of the projects which have been successfully completed and the benefits that the trainee networks have for patients and surgeons alike.

Recent Development in Pulmonary Valve Replacement after Tetralogy of Fallot Repair: The Emergence of Hybrid Approaches.

An increasing number of patients with tetralogy of Fallot require repeat surgical intervention for pulmonary valve replacement secondary to pulmonary regurgitation. Catheter-based interventions have emerged as an attractive alternative to surgery in this patient population but it is limited by patient size or the anatomy of the right ventricular outflow tract. Hybrid approaches involving both cardiac interventionists and surgeons are being developed to overcome these limitations. The purpose of this review is to highlight the recent advances in the hybrid field of pulmonary valve replacement, summarizing the advantages and disadvantages of the "traditional" surgical and the new catheter-based techniques and discuss the direction future research should take to determine the optimal management for individual patients.

Laparoscopic fundoplication in children with ventriculo-peritoneal shunts.

BACKGROUND: Children with ventriculo-peritoneal (V-P) shunts have a significant risk of morbidity and mortality from infections. Many of these patients have other co-morbidities and may require subsequent abdominal surgery, including fundoplication with or without gastrostomy placement. The aim of our study was to assess the outcomes of laparoscopic fundoplication in children with a V-P shunt in situ. SUBJECTS AND METHODS: A retrospective review of a prospectively maintained database on children who underwent laparoscopic fundoplication with a V-P shunt in situ at the time of surgery between July 1998 and March 2011 was conducted. Primary outcomes included intra- and postoperative complications as well as shunt-related problems within a 6-month period after surgery. The subset of children with V-P shunts was compared with those who underwent fundoplication without shunts. Variables were compared using the two-tailed Student's t test, chi-squared test, or Fisher's exact test. Significance was defined as P≤.05. RESULTS: Out of a total of 343 children who underwent fundoplication, 11 (6 girls, 5 boys) had a V-P shunt in situ at the time of surgery (3.2%). The median age at laparoscopy was 2.2 years (range, 0.7-13.8 years). Weight at surgery ranged from 5.8 to 39.0 kg (median, 12.0 kg). The operating time (without gastrostomy placement) was 105 minutes (range, 80-140 minutes). In 6 patients (55%) moderate to severe adhesions were documented, but only 1 child required conversion to open surgery because of bleeding from the omentum. In a second patient the colon was perforated during insertion of the percutaneous endoscopic gastrostomy (PEG) and repaired laparoscopically. There was no postoperative shunt dysfunction or infection related to the laparoscopic procedure. There was no significant difference between V-P shunt patients and the main cohort regarding operating time, conversion to open surgery, need for admission to a high-care unit, opiate requirements, time to full feeds, and length of hospital stay. CONCLUSIONS: These data suggest that laparoscopic fundoplication is feasible in children with previous V-P shunt placement. Although there were considerable adhesions in approximately half of these patients, the rate for conversion to open surgery was low. Complications associated with simultaneous PEG insertion occur and should be anticipated by placing the gastrostomy under laparoscopic guidance.