Methods of identifying surgical Necrotizing Enterocolitis-a systematic review and meta-analysis.

BACKGROUND: Current data suggests potential benefit of earlier surgery for necrotizing enterocolitis (NEC) however this requires accurate prognostication early in the disease course. This study aims to identify and determine the effectiveness of previously reported methods or tests for the identification of surgical NEC. METHODS: Systematic review and meta-analysis with registration on PROSPERO including articles describing a method of identifying surgical NEC. Outcomes of interest were effectiveness and repeatability of index test. RESULTS: Of the 190 full-text articles screened, 90 studies were included which contained 114 methods of identifying surgical NEC in 9546 infants. Of these methods, 44 were a scoring system, 37 a single biomarker, 24 an imaging method, and 9 an invasive method. Sensitivity and specificity ranged from 12.8-100% to 13-100%, respectively. Some methods (9.6%) provided insufficient methods for repeatability within clinical practice or research. Meta-analyses were possible for only 2 methods, the metabolic derangement 7 score and abdominal ultrasound. CONCLUSIONS: A range of methods for identifying surgical NEC have been identified with varying overall performance and uncertainties about reproducibility and superiority of any method. External validation in large multicentre datasets should allow direct comparison of accuracy and prospective study should evaluate impact on clinical outcomes. IMPACT: Earlier identification of need for surgery in necrotizing enterocolitis (NEC) has the potential to improve the unfavourable outcomes in this condition. As such, many methods have been developed and reported to allow earlier identification of surgical NEC. This study is the first synthesis of the literature which identifies previously reported methods and the effectiveness of these. Many methods, including scoring systems and biomarkers, appear effective for prognostication in NEC and external validation is now required in multicentre datasets prior to clinical utility.

Investigations, management and outcome of neonates presenting with distal intestinal obstruction: challenging the need for contrast enemas.

PURPOSE: To characterise the investigations, management and ultimate diagnosis of neonates with distal intestinal obstruction. METHODS: Retrospective review of term (> 37 weeks) neonates with admission diagnosis of distal intestinal obstruction over 10 years (2012-2022). Patient pathways were identified and associations between presentations, response to treatments and outcome investigated. RESULTS: A total of 124 neonates were identified and all included. Initial management was colonic irrigation in 108, contrast enema in 4, and laparotomy in 12. Of those responding to irrigations none underwent contrast enema. Ultimately, 22 neonates proceeded to laparotomy. Overall, 106 had a suction rectal biopsy and 41 had genetic testing for cystic fibrosis. Final diagnosis was Hirschsprung disease (HD) in 67, meconium ileus with cystic fibrosis (CF) in 9, meconium plug syndrome in 19 (including 3 with CF), intestinal atresia in 10 and no formal diagnosis in 17. Median length of neonatal unit stay was 11 days (7-19). CONCLUSIONS: Initial management of neonates with distal bowel obstruction should be colonic irrigation since this is therapeutic in the majority and significantly reduces the need for contrast enema. These infants should all have suction rectal biopsy to investigate for HD unless another diagnosis is evident. If a meconium plug is passed, testing for CF is recommended. Evaluation and therapy are multimodal and time consuming, placing burden on resources and families.

Long-gap esophageal atresia: gastric transposition or esophageal lengthening with delayed primary anastomosis? A systematic review.

PURPOSE: This study aims to evaluate different surgical approaches to long-gap esophageal atresia (LGEA) with or without tracheoesophageal fistula (TEF) is unclear. METHODS: A systematic literature review was done comparing gastric transposition versus esophageal lengthening with delayed primary anastomosis in infants with LGEA+/-TEF. The primary outcome was time to full oral feeds. Secondary outcomes were time to full enteric feeds, need for further surgery, growth, mortality, and postoperative adverse events. RESULTS: No comparative studies were found. However, the literature was re-interrogated for non-comparative studies. Four hundred thirty-eight articles were identified and screened, and 18 met the inclusion criteria. All were case series. Forty-three infants underwent gastric transposition, and 106 had esophageal lengthening with delayed primary anastomosis. One study on gastric transposition reported time to full oral feeds, and one study in each group reported growth. Time to full enteric feeds was reported in one study in each group. 30% of infants had further surgery following gastric transposition, including hiatus hernia repair (5/43, 12%) and esophageal dilation (7/43, 16%). Following esophageal lengthening, 62/106 (58%) had anti-reflux surgery, 58/106 (55%) esophageal dilatation and 11/106 (10%) esophageal stricture resection. Anastomotic complications occurred in 13/43 (30%), gastrointestinal in 16/43 (37%), respiratory in 17/43 (40%), and nerve injury in 2/43 (5%) of the gastric transposition group. In the esophageal lengthening group, anastomotic complications occurred in 68/106 (64%), gastrointestinal in 62/106 (58%), respiratory in 6/106 (6%), and none sustained nerve injury. Each group had one death due to a cause not directly related to the surgical procedure. CONCLUSIONS: This systematic review highlights the morbidity associated with both surgical procedures and the variety in reporting outcomes.

Assessing micro- vs macro-costing approaches for treating appendicitis in children with appendicectomy or non-operatively.

OBJECTIVES: We conducted a health economic sub-study within a feasibility RCT comparing a non-operative treatment pathway as an alternative to appendicectomy for the treatment of uncomplicated acute appendicitis in children. The objectives were to understand and assess data collection tools and methods and to determine indicative costs and benefits assessing the feasibility of conducting a full economic evaluation within the definitive trial. METHODS: We compared different methods of estimating treatment costs including micro-costing, hospital administrative data (PLICS) and health system (NHS) reference costs. We compared two different HRQoL instruments (CHU-9D and EQ-5D-5L) in terms of data completeness and sensitivity to change over time, including potential ceiling effects. We also explored how the timing of data collection and duration of the analysis could affect QALYs (Quality Adjusted Life Years) and the results of the cost-utility analysis (CUA) within the future RCT. RESULTS: Using a micro-costing approach, the total per treatment costs were in alignment with hospital administrative data (PLICS). Average health system reference cost data (macro-costing using NHS costs) could potentially underestimate these treatment costs, particularly for non-operative treatment. Costs incurred following hospital discharge in the primary care setting were minimal, and limited family borne costs were reported by parents/carers. While both HRQoL instruments performed relatively well, our results highlight the problem of ceiling effect and the importance of the timing of data collection and the duration of the analysis in any future assessment using QALYs and CUA. CONCLUSIONS: We highlighted the importance of obtaining accurate individual-patient cost data when conducting economic evaluations. Our results suggest that timing of data collection and duration of the assessment are important considerations when evaluating cost-effectiveness and reporting cost per QALY. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435.

'Cut and push' as an alternative to endoscopic retrieval of PEG type gastrostomy tubes.

PURPOSE: Percutaneous Endoscopically placed Gastrostomy (PEG) tubes are frequently used in children. The traditional endoscopic method to remove/change the PEG device requires general anaesthesia in children. A minimally invasive alternative is the 'Cut and Push' method (C&P): avoiding the risks/wait times of general anaesthesia and reducing resource burden. Data regarding the safety/effectiveness of C&P in children are lacking with concerns raised about the possibility of gastrointestinal obstruction. METHODS: We retrospectively reviewed all cases of PEG removal / change to button in children (< 18 years) between December 2020 and January 2022. Cases were identified from a prospectively maintained database and all cases of C&P included. Parents/carers were asked if the child had suffered any complications following C&P and if flange was visualised in stools. RESULTS: During the time period, 27 PEGs were either removed or changed to button via C&P. The average waiting time for C&P was 14.29 days, significantly shorter than the minimum 6-month waiting time for elective endoscopy. Our evaluation revealed no complications of C&P at median 70 days (range 25-301). In three cases the flange was visualised in the stool, at 2 days, 3 days and 5 weeks following C&P respectively. DISCUSSION: These data support the available literature suggesting C&P is an effective means to facilitate minimally invasive and prompt PEG removal/change to button in children. We recommend minimum weight and age parameters for this procedure and further evaluation of the safety and resource implications of this technique.

International Core Outcome Set for Acute Simple Appendicitis in Children: Results of a Systematic Review, Delphi Study, and Focus Croups With Young People.

OBJECTIVE: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children. SUMMARY OF BACKGROUND DATA: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS. METHODS: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS. RESULTS: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications. CONCLUSION: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

The Influence of the Introduction of Biologic Agents on Surgical Intervention in Paediatric Inflammatory Bowel Disease.

OBJECTIVES: To determine how the use of biological therapy is associated with surgical intervention for paediatric inflammatory bowel disease (PIBD) at a population level. METHODS: Hospital Episode Statistics data were obtained for all admissions within England (1997-2015), in children aged 0-18 years, with an ICD-10 code for diagnosis of Crohn disease (CD), ulcerative colitis (UC), or inflammatory bowel disease-unclassified (IBD-U). Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures codes for major surgical resection associated with PIBD and for biological therapy were also obtained. Data are presented as median values (interquartile range). RESULTS: In total, 22,645 children had a diagnosis of PIBD of which 13,722 (61%) had CD, 7604 (34%) had UC, and 1319 (5.8%) cases had IBD-U. Biological therapy was used in 4054 (17.9%) cases. Surgical resection was undertaken in 3212 (14%) cases, more commonly for CD than UC (17.5 vs 10.3%, P < 0.0001). Time from diagnosis to major surgical resection was 8.3 (1.2-28.2) months in CD and 8.2 (0.8-21.3) months in UC. As the time-frame of the dataset progressed, there was a decreased rate of surgical intervention ( P = 0.04) and an increased use of biological therapy ( P < 0.0001). Additionally, the number of new diagnoses of PIBD increased. CONCLUSIONS: The introduction of biologic agents has been associated with a reduction in cases undergoing surgery in children with a known diagnosis of PIBD. As time progresses we will be able to determine whether biological therapies prevent the need for surgery altogether or just delay this until adulthood.

One-year Outcomes of Congenital Duodenal Obstruction: A Population-based Study.

OBJECTIVES: Congenital duodenal obstruction (CDO) occurs in 1.2 per 10,000 live births and is frequently associated with other anomalies, most commonly cardiac. The aim of this study was to report important outcomes to 1 year following surgical repair. METHODS: This was a prospective population-based study using the British Association of Paediatric Surgeons Congenital Anomaly Surveillance System. Cases were identified at specialist pediatric surgical centres in the United Kingdom during a 12-month period starting in March 2016. Outcomes were recorded at 1 year following surgical repair. RESULTS: There were 100 infants with possible follow-up at 1 year and follow-up was achieved in 80 of these (80%) of whom 76 were alive at 1 year. The remainder had been discharged home, although one remained on parenteral nutrition. Five (6.1%) infants underwent repeat surgery for reasons related to CDO and overall 23 (23%) experienced at least 1 central venous catheter-related complication within 1 year. Overall mortality either before repair or within 1 year following surgical repair was 8.4% (95% CI 2.5%-14.4%), no deaths were related to CDO. CONCLUSIONS: One year outcomes for CDO are generally very good with poor outcomes typically related to comorbidities. These data are useful for national benchmarking and parental counselling.

Contemporary Outcomes for Infants with Necrotizing Enterocolitis-A Systematic Review.

OBJECTIVE: To develop an accurate understanding of outcomes for necrotizing enterocolitis (NEC) to inform parental counseling, clinical care, and research agendas. STUDY DESIGN: A systematic review of recent (January 2010-January 2018) large cohort studies reporting outcomes of infants who developed NEC. Only studies reporting national, regional, or multicenter outcomes of NEC in high income countries were included. Outcomes assessed were mortality, neurodevelopmental outcome, and intestinal failure. Meta-analyses were used to generate summary statistics for these outcomes. RESULTS: Of 1375 abstracts, 38 articles were included. Overall mortality was 23.5% in all neonates with confirmed NEC (Bell stage 2a+) (95% CI 18.5%-28.8%), 34.5% (30.1%-39.2%) for neonates that underwent surgery for NEC, 40.5% (37.2%-43.8%) for extremely low birthweight infants (<1000 g), and 50.9% (38.1%-63.5%) for extremely low birthweight infants with surgical NEC. Studies examining causes of neonatal mortality showed NEC is responsible for around 1 in 10 of all neonatal deaths. Neurodevelopmental disability was reported in 4 studies at between 24.8% and 61.1% (1209 total NEC cases). Three studies reported intestinal failure with an incidence of 15.2%-35.0% (n = 1370). The main limitation of this review is the lack of an agreed definition for diagnosing NEC and the differences in the way that outcomes are reported. CONCLUSIONS: Mortality following NEC remains high. These contemporary data inform clinical care and justify ongoing research efforts. All infants with NEC should have long-term neurodevelopmental assessment. Data on the long-term risk of intestinal failure are limited. TRIAL REGISTRATION: CRD42018094791.

Association Between Administration of Antacid Medication and Anastomotic Stricture Formation After Repair of Esophageal Atresia.

BACKGROUND: Anastomotic stricture is a significant cause of morbidity after repair of esophageal atresia (EA). Exposure to gastric acid has been postulated to contribute to stricture development and severity leading to prophylactic antacid use by some surgeons. We investigated the association between administration of antacid medication and the development of anastomotic strictures. METHODS: Retrospective case-note review of consecutive infants undergoing repair of EA with distal tracheoesophageal fistula (type C) between January 1994 and December 2014. Only infants who underwent primary esophageal anastomosis at initial surgical procedure were included. Stricture-related outcomes were compared initially for infants who received prophylactic antacid medication (PAAM) versus no prophylaxis, and the role of PAAM in stricture prevention was explored in a multivariate model. Outcomes were also compared for infants grouped by antacid use at any stage. RESULTS: One hundred fourteen infants were included. Sixteen infants received PAAM at surgeon preference. Of the remaining 98 infants, 44 subsequently received antacid as treatment for gastroesophageal reflux (GER) and 54 never received antacid medication. There was no statistically significant association between incidence of stricture in the first year (10 of 16 versus 41 of 98; P = 0.18) nor time to first stricture (median, 57 d [41-268] versus 102 d [43-320]; P = 0.89) and administration of PAAM. Similarly, there were no statistically significant associations between incidence of stricture, age at first stricture and number of dilatations, and administration of antacid medication either as prophylaxis nor when given as treatment for symptoms or signs of GER. CONCLUSIONS: These data do not support the hypothesis that PAAM reduces the incidence or severity of anastomotic stricture after repair of EA. Treatment with antacids may be best reserved for those with symptoms or signs of GER. Further prospective investigation of the role of antacid prophylaxis on stricture formation after EA repair is warranted.

Application of the matched nested case-control design to the secondary analysis of trial data.

BACKGROUND: A nested case-control study is an efficient design that can be embedded within an existing cohort study or randomised trial. It has a number of advantages compared to the conventional case-control design, and has the potential to answer important research questions using untapped prospectively collected data. METHODS: We demonstrate the utility of the matched nested case-control design by applying it to a secondary analysis of the Abnormal Doppler Enteral Prescription Trial. We investigated the role of milk feed type and changes in milk feed type in the development of necrotising enterocolitis in a group of 398 high risk growth-restricted preterm infants. RESULTS: Using matching, we were able to generate a comparable sample of controls selected from the same population as the cases. In contrast to the standard case-control design, exposure status was ascertained prior to the outcome event occurring and the comparison between the cases and matched controls could be made at the point at which the event occurred. This enabled us to reliably investigate the temporal relationship between feed type and necrotising enterocolitis. CONCLUSIONS: A matched nested case-control study can be used to identify credible associations in a secondary analysis of clinical trial data where the exposure of interest was not randomised, and has several advantages over a standard case-control design. This method offers the potential to make reliable inferences in scenarios where it would be unethical or impractical to perform a randomised clinical trial.

Enhancing communication, informed consent and recruitment in a paediatric urgent care surgical trial: a qualitative study.

BACKGROUND: Recruiting patients to paediatric trials can be challenging, especially in trials that compare markedly different management pathways and are conducted in acute settings. We aimed to enhance informed consent and recruitment in the CONTRACT trial (CONservative TReatment of Appendicitis in Children a randomised controlled Trial; ISRCTN15830435) - a feasibility trial that compared non-operative treatment (antibiotics) versus appendicectomy for uncomplicated acute appendicitis. METHODS: Qualitative study embedded within CONTRACT and conducted across three UK children's hospitals. Data were transcribed audio-recordings of 85 CONTRACT recruitment consultations with 58 families; and semi-structured interviews with 35 health professionals and 28 families (34 parents, 14 children) invited to participate in CONTRACT. Data analysis drew on thematic approaches. Throughout CONTRACT, we used findings from the ongoing qualitative analysis to inform bespoke communication training for health professionals recruiting to CONTRACT. Before and after training we also examined qualitative changes in communication during consultations and quantitative changes in recruitment rates. RESULTS: Bespoke communication training focussed on presenting the trial arms in a balanced way, emphasising clinical equipoise, exploring family treatment preferences and managing families' expectations about the trial's treatment pathways. Analysis of recruitment consultations indicated that health professionals' presentation of treatment arms became increasingly balanced following training, (e.g. avoiding imbalanced terminology) and recruitment rose from 38 to 62%. However, they remained reluctant to explore families' treatment preferences and respond with further information to balance these preferences. Analyses of interviews identified the time constraints of the urgent care setting, concerns about coercion, and reservations about exposing children to conversations about treatment risks as reasons for this reluctance. Interviews with families indicated the importance of clear explanations of trial treatment timings and sensitive communication of treatment allocation for both recruitment and retention. CONCLUSIONS: Following bespoke training based on the qualitative analyses, health professionals presented CONTRACT to families in clearer and more balanced ways and this was associated with an increase in the recruitment rate. Despite training, health professionals remained reluctant to explore families' treatment preferences. We provide several recommendations to enhance communication, informed consent, recruitment and retention in future trials in urgent care settings.

The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study.

PURPOSE: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down's syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. METHODS: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. RESULTS: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23-41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). CONCLUSIONS: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21.

The development of a consensus-based nutritional pathway for infants with CHD before surgery using a modified Delphi process.

IntroductionDespite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.Materials and methodsThe modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation. RESULTS: Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting. CONCLUSIONS: Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.

Intrauterine death rate in gastroschisis following the introduction of an antenatal surveillance program: Retrospective observational study.

AIM: To investigate whether an antenatal surveillance protocol including ultrasound and cardiotocograph monitoring reduces intrauterine death (IUD) in cases of gastroschisis. Secondary outcomes included neonatal death rate, mode of delivery and rate of intervention before planned time of delivery. METHODS: This was a retrospective observational study of all women with antenatally diagnosed gastroschisis who were managed according to the surveillance program between 2002 and 2015 in a tertiary fetal medicine and pediatric surgical center covering the Wessex region of England. We reviewed and analyzed data from the Wessex Antenatally Detected Anomalies (WANDA) database as well as prospectively managed maternity, ultrasound and neonatal databases over the given time period. Case notes were reviewed when delivery was expedited. RESULTS: The IUD rate was 2.2%, a 58% reduction since the introduction of the surveillance protocol. Delivery was expedited in 35.4% of cases, and in 86% of these, delivery was by cesarean section. In women being induced as planned at 38 weeks, the vaginal delivery rate was 88%, and for those in spontaneous labor before 38 weeks it was 75%. CONCLUSIONS: An antenatal surveillance program appears to reduce the IUD in gastroschisis. In one-third of cases, delivery was indicated before the planned date of delivery. When expedited delivery was indicated, the chance of cesarean section was high.