Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Proton pump inhibitors, antibiotics, and atopy increase the risk of eosinophilic esophagitis in children with esophageal atresia.

OBJECTIVE: To determine whether proton pump inhibitor (PPI) exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA). STUDY DESIGN: A retrospective chart review of children with EA from January 1, 2005 to December 31, 2020 was undertaken at Sydney Children's Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression. RESULTS: Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR], 7.317; 95% confidence interval [CI], 2.244-23.742), family history of atopy (aOR, 3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR, 1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort. CONCLUSIONS: Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.

Intestinal dysbiosis and inflammation in children with repaired esophageal atresia.

OBJECTIVES: This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS: A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS: Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS: Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.

Disparities in resource utilisation by families of children with cardiac conditions.

OBJECTIVES: There are limited data documenting sources of medical information that families use to learn about paediatric cardiac conditions. Our study aims to characterise these resources and to identify any disparities in resource utilisation. We hypothesise there are significant variations in the resources utilised by families from different educational and socio-economic backgrounds. METHODS: A survey evaluating what resources families use (websites, healthcare professionals, social media, etc.) to better understand paediatric cardiac conditions was administered to caretakers and paediatric patients at Morgan Stanley Children's Hospital. Patients with a prior diagnosis of CHD, cardiac arrhythmia, and/or heart failure were included. Caretakers' levels of education (fewer than 16 years vs. 16 years or more) and patients' medical insurance types (public vs. private) were compared with regard to the utilisation of resources. RESULTS: Surveys completed by 137 (91%) caretakers and 27 (90%) patients were analysed. Websites were utilised by 72% of caretakers and 56% of patients. Both private insurance and higher education were associated with greater reported utilisation of websites, healthcare professionals, and personal networks (by insurance p = 0.009, p = 0.001, p = 0.006; by education p = 0.022, p < 0.001, p = 0.018). They were also more likely to report use of electronic devices (such as a computer) compared to those with public medical insurance and fewer than 16 years of education (p < 0.001, p < 0.001, respectively). CONCLUSION: Both levels of education and insurance status are associated with the utilisation of informative resources and digital devices by families seeking to learn more about cardiac conditions in children.

Congenital Heart Disease with Congenital Diaphragmatic Hernia: Surgical Decision Making and Outcomes.

OBJECTIVE: To describe the types of congenital heart disease (CHD) in a congenital diaphragmatic hernia (CDH) cohort in a large volume center and evaluate surgical decision making and outcomes based on complexity of CHD and associated conditions. STUDY DESIGN: A retrospective review of patients with CHD and CDH diagnosed by echocardiogram between 01/01/2005 and 07/31/2021. The cohort was divided into 2 groups based on survival at discharge. RESULTS: Clinically important CHD was diagnosed in 19% (62/326) of CDH patients. There was 90% (18/20) survival in children undergoing surgery for both CHD and CDH as neonates, and 87.5 (22/24) in those undergoing repair initially for CDH alone. A genetic anomaly identified on clinical testing was noted in 16% with no significant association with survival. A higher frequency of other organ system anomalies was noted in nonsurvivors compared with survivors. Nonsurvivors were more likely to have unrepaired CDH (69% vs 0%, P < .001) and unrepaired CHD (88% vs 54%, P < .05), reflecting a decision not to offer surgery. CONCLUSIONS: Survival was excellent in patients who underwent repair of both CHD and CDH. Patients with univentricular physiology have poor survival and this finding should be incorporated into pre and postnatal counseling about eligibility for surgery. In contrast, patients with other complex lesions including transposition of the great arteries have excellent outcomes and survival at 5 years follow-up at a large pediatric and cardiothoracic surgical center.

Measurement of Physical Activity by Actigraphy in Infants and Young Children with Pulmonary Arterial Hypertension.

OBJECTIVE: To evaluate the feasibility, tolerability, and adherence with wearable actigraphy devices among infants and children with pulmonary arterial hypertension (PAH). STUDY DESIGN: This multicenter, prospective, observational study included children ages 0-6 years with and without PAH. Participants wore the ActiGraph wGT3X-BT on the hip and FitBit Inspire on the wrist during waking hours for 14 days. Steps, vector magnitude counts per minute, activity intensity, heart rate, and heart rate variability were compared between groups. RESULTS: Forty-seven participants (18 PAH, 29 control) were enrolled from 10 North American sites. PAH patients were mostly functional class II (n = 16, 89%) and treated with oral medications at the time of enrollment. The number of wear days was not significantly different between the groups (ActiGraph: 10 [95% CI: 5.5, 12.2] in PAH vs 8 [4, 12] in control, P = .20; FitBit 13 [10, 13.8] in PAH vs 12 [8, 14] in control, P = .87). Complete data were obtained in 81% of eligible ActiGraph participants and 72% of FitBit participants. PAH participants demonstrated fewer steps, lower vector magnitude counts per minute, more sedentary activity, and less intense physical activity at all levels compared with control participants. No statistically significant differences in heart rate variability were demonstrated between the 2 groups. CONCLUSIONS: Measurement of physical activity and other end points using wearable actigraphy devices was feasible in young children with PAH. Larger studies should determine associations between physical activity and disease severity in young patients with PAH to identify relevant end points for pediatric clinical trials.

Prevalence, Predictive Factors, and Clinical Manifestations of Fungal Esophagitis in Children.

OBJECTIVES: Fungal esophagitis (FE) is the most common cause of esophageal infection and its prevalence in immunocompetent adults is rising. However, there is minimal data on FE in children without human immunodeficiency virus. Therefore, the objective of this study was to determine the prevalence, symptoms, endoscopic appearances, and predictive factors of FE in children, regardless of immune status. METHODS: A 2010-2020 retrospective case-control study was conducted on 1823 children presenting to Sydney Children's Hospital for elective endoscopy with esophageal biopsy. Histopathology reports were reviewed to identify FE cases and determine prevalence rates. Thirty-two patients with FE were age- and sex-matched (1:2) to 64 controls. Significant symptoms and risk factors of FE were identified via univariate and multivariate logistic regression analysis. RESULTS: The prevalence of FE in children was 1.76%. Common symptoms included dysphagia (25%), heartburn (25%), poor oral intake (21.9%), vomiting (18.8%), cough (15.6%), nausea (12.5%), and weight loss (9.4%). No significant differences in symptoms were found between cases and controls. On endoscopy, although white plaques were associated with FE ( P < 0.001), visually normal findings were reported in 28.1% of cases. Topical swallowed corticosteroids were a significant independent risk factor for FE (adjusted odds ratio = 10.740, 95% confidence interval: 1.213-95.101, P = 0.033). CONCLUSIONS: The prevalence of FE in this pediatric cohort reflects rates among immunocompetent adults. Given that many of these children presented with a wide range of gastrointestinal symptoms, esophageal biopsy is required to accurately diagnose FE. Pediatricians should consider the risk of FE when prescribing topical swallowed corticosteroids.

Ketogenic Diets in Children With Intractable Epilepsy and its Effects on Gastrointestinal Function, Gut Microbiome, Inflammation, and Quality of Life.

OBJECTIVES: The ketogenic diet (KD) is a treatment for children with intractable epilepsy (IE), can cause gastrointestinal symptoms, and have an adverse effect on growth, nutrition and quality of life (QOL). This study investigated the extent of these side effects by comparing children with IE on KDs to their counterparts on normal diets. METHODS: Patients with IE were categorized into patients with KD or control groups. Gastrointestinal side effects and QOL were assessed using the PedsQL Gastrointestinal Symptoms Module. Cross sectional growth, gut microbiome compositions, and inflammation levels were also analyzed. RESULTS: Fourteen patients on the KD and 13 control patients were enrolled. Patients had been on KD for a median duration of 15 months (interquartile range: 9.8-60 months). The patients on the KD reported a trend to lower total gastrointestinal symptoms scores (more symptoms) compared to control patients, at 71.1 and 84.9, respectively ( P = 0.06, not significant). Patients on the KD had significantly lower QOL scores compared to control patients ( P = 0.01). Patients on the KD were found to have consistently lower median height/length, weight, and body mass index z scores compared to the controls although these were not statistically significant. Patients on the KD had a lower microbial diversity, Both groups had a normal level of S100A12, a marker of gut inflammation. CONCLUSIONS: Patients on the KD reported a trend to more gastrointestinal symptoms and more QOL concerns compared to controls. Although microbial differences were noted in patients on the KD, this did not result in detectable gut inflammation.

Endoscopic management of esophageal mucosal bridges in children with esophageal atresia.

BACKGROUND AND STUDY AIMS: Esophageal mucosal bridge (EMB) may be diagnosed at the anastomotic site in children operated on for esophageal atresia (EA) but so far only a few cases (n = 4) have been reported. This study aimed to characterize EMB in children with EA, risk factors, and treatment. PATIENTS AND METHODS: This retrospective multicenter study recorded patient's characteristics, EMB diagnosis circumstances, endoscopic management, follow-up, and EMB recurrence in children with EA aged less than 18 years, compared with paired EA patients without EMB. RESULTS: Thirty patients were included (60% male, 90% EA/tracheoesophageal fistula, 43% associated malformations). Compared to 44 paired controls, EMB was associated with a history of nasogastric tube feeding (31% vs. 9.1%, p = 0.02) and severe gastroesophageal reflux disease (history of fundoplication: 41.4% vs. 13.6%, p < 0.01). 77% had symptoms (food impaction and/or dysphagia). Endoscopic management was performed in 53% of patients (83% electrocoagulation) with no technical difficulties or complications. 80% of the symptomatic patients with EMB improved after endoscopic treatment, independently of anastomotic stricture dilatation or not. CONCLUSION: EMB endoscopic management by electrocoagulation is safe and often leads to symptom improvement.

Ventricular function and tissue characterization by cardiac magnetic resonance imaging following hospitalization for multisystem inflammatory syndrome in children: a prospective study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe life-threatening manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that often presents with acute cardiac dysfunction and cardiogenic shock. While recovery from acute illness is excellent, the long-term myocardial impact is unknown. OBJECTIVE: To compare cardiac MRI findings in children 6-9 months after their hospitalization with MIS-C against MRI findings in healthy controls to assess for residual myocardial disease. MATERIALS AND METHODS: We prospectively performed cardiac MRI on 13 children 6-9 months following their hospitalization with MIS-C: eight of these children had a history of left ventricle ejection fraction (LVEF) < 50%, persistent symptoms, or electrocardiogram (ECG) abnormalities and underwent clinical MRI; five of these children without cardiac abnormalities during their hospitalization underwent research MRIs. We compared their native T1 and T2 mapping values with those of 20 normal controls. RESULTS: Cardiac MRI was performed at 13.6 years of age (interquartile range [IQR] 11.9-16.4 years) and 8.2 months (IQR 6.8-9.6 months) following hospitalization. Twelve children displayed normal ejection fraction: left ventricle (LV) 57.2%, IQR 56.1-58.4; right ventricle (RV) 53.1%, IQR 52.0-55.7. One had low-normal LVEF (52%). They had normal extracellular volume (ECV) and normal T2 and native T1 times compared to controls. There was no qualitative evidence of edema. One child had late gadolinium enhancement (LGE) with normal ejection fraction, no edema, and normal T1 and T2 times. When stratifying children who had MIS-C according to history of LVEF <55% on echocardiography, there was no difference in MRI values. CONCLUSION: Although many children with MIS-C present acutely with cardiac dysfunction, residual myocardial damage 6-9 months afterward appears minimal. Long-term implications warrant further study.

Outcomes and Risk Factors of Interventions for Pediatric Post-operative Pulmonary Vein Stenosis.

Pulmonary vein stenosis (PVS) in children is a challenging condition with poor outcomes. Post-operative stenosis can occur after repair of anomalous pulmonary venous return (APVR) or stenosis within native veins. There is limited data on the outcomes of post-operative PVS. Our objective was to review our experience and assess surgical and transcatheter outcomes. Single-center retrospective study was performed including patients < 18 years who developed restenosis after baseline pulmonary vein surgery that required additional intervention(s) from 1/2005 to 1/2020. Non-invasive imaging, catheterization and surgical data were reviewed. We identified 46 patients with post-operative PVS with 11 (23.9%) patient deaths. Median age at index procedure was 7.2 months (range 1 month-10 years), and median follow-up was 10.8 months (range 1 day-13 years). Index procedure was surgical in 36 (78.3%) and transcatheter in 10 (21.7%). Twenty-three (50%) patients developed vein atresia. Mortality was not associated with number of affected veins, vein atresia, or procedure type. Single ventricle physiology, complex congenital heart disease (CCHD), and genetic disorders were associated with mortality. Survival rate was higher in APVR patients (p = 0.03). Patients with three or more interventions had a higher survival rate compared to patients with 1-2 interventions (p = 0.02). Male gender, necrotizing enterocolitis, and diffuse hypoplasia were associated with vein atresia. In post-operative PVS, mortality is associated with CCHD, single ventricle physiology, and genetic disorders. Vein atresia is associated with male gender, necrotizing enterocolitis, and diffuse hypoplasia. Multiple repeated interventions may offer a patient survival benefit; however, larger prospective studies are necessary to elucidate this relationship further.

Development of a Core Outcome Set for Children Aged 1-18 Years with Gastroesophageal Reflux Disease.

OBJECTIVE: To develop a core outcome set for clinical studies assessing gastroesophageal reflux disease (GERD) in children. STUDY DESIGN: This core outcome set was developed using a 2-round Delphi technique and adhering to the Outcome Measures in Rheumatology Initiative (OMERACT 2.0) recommendations. Healthcare professionals (HCPs) and (parents of) children (age 1-18 years) with a GERD diagnosis (ie, the presence of bothersome symptoms), listed up to 5 harmful and/or beneficial outcomes that they considered important in the treatment of GERD. Outcomes mentioned by more than 10% of participants were put forward and rated and prioritized by HCPs, parents, and children in a second round. Outcomes with the highest rank formed the draft core outcome set. The final core outcome set was created during an online consensus meeting between an expert panel. RESULTS: The first round was completed by 118 of 125 HCPs (94%), 146 of 146 parents (100%), and 69 of 70 children (99%). A total of 80 of 118 HCPs (68%), 130 of 140 parents (93%), and 77 children (100%) completed round 2. "Adequate relief," "evidence of esophagitis," "feeding difficulties," "heartburn (≥4 years)," "hematemesis," "regurgitation," "sleeping difficulties," "vomiting," and "adverse events" were included in the final core outcome set for GERD in children aged 1-18 years. CONCLUSIONS: We identified a total set of 9 core outcomes and suggest these outcomes to be minimally measured in clinical studies assessing GERD in children. Implementation of this core outcome set is likely to increase comparison between studies and may thus provide future recommendations to improve treatment of GERD in children.

Infectious Esophagitis in Children.

Infectious esophagitis is the third most common cause of esophagitis after gastroesophageal reflux disease and eosinophilic esophagitis (EoE) and should always be considered in the differential of patients with dysphagia and odynophagia. The most common organisms causing disease are candida, Herpes simplex virus (HSV) and cytomegalovirus (CMV). It is well recognized that an impaired local or systemic immune system is a risk factor for disease; however, esophageal dysmotility and disruptions in esophageal homeostasis and the esophageal milieu are likely to represent additional risk factors in disease pathogenesis.

Management of Gastroesophageal Reflux Disease in Esophageal Atresia Patients: A Cross-Sectional Survey amongst International Clinicians.

OBJECTIVES: After surgical repair, up to 70% of esophageal atresia (EA) patients suffer from gastroesophageal reflux disease (GERD). The ESPGHAN/NASPGHAN guidelines on management of gastrointestinal complications in EA patients were published in 2016. Yet, the implementation of recommendations on GERD management remains poor.We aimed to assess GERD management in EA patients in more detail, to identify management inconsistencies, gaps in current knowledge, and future directions for research. METHODS: A digital questionnaire on GERD management in EA patients was sent to all members of the ESPGHAN EA working group and members of the International network of esophageal atresia (INoEA). RESULTS: Forty responses were received. Thirty-five (87.5%) clinicians routinely prescribed acid suppressive therapy for 1-24 (median 12) months. A fundoplication was considered by 90.0% of clinicians in case of refractory GERD with persistent symptoms despite maximal acid suppressive therapy and in 92.5% of clinicians in case of GERD with presence of esophagitis on EGD. Half of clinicians referred patients with recurrent strictures or dependence on transpyloric feeds. Up to 25.0% of clinicians also referred all long-gap EA patients for fundoplication, those with long-term need of acid suppressants, recurrent chest infections and feedings difficulties. CONCLUSIONS: Respondents' opinions on the optimal duration for routine acid suppressive therapy and indications for fundoplication in EA patients varied widely. To improve evidence-based care for EA patients, future prospective multicenter outcome studies should compare different diagnostic and treatment regimes for GERD in patients with EA. Complications of therapy should be one of the main outcome measures in such trials.

Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study.

OBJECTIVES: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. METHODS: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. RESULTS: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. CONCLUSIONS: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.

Australasian paediatric gastroenterologist practices of coeliac disease diagnosis before and during the COVID-19 pandemic.

AIM: To explore the perceptions and practices of Australasian paediatric gastroenterologists in diagnosing coeliac disease (CD) before and during the COVID-19 pandemic. METHODS: Paediatric gastroenterologists in Australasia were invited via email to complete an anonymous online questionnaire over a 2-week period in 2021. RESULTS: The questionnaire was completed by 39 respondents: 33 from Australia and six from New Zealand (NZ) equating to a 66% response rate. Thirty-four (87%) of the 39 respondents reported they currently practised non-biopsy diagnosis of CD in eligible children, while the rest diagnosed CD using biopsy confirmation only. All NZ respondents practised non-biopsy CD diagnosis. A majority of responders (76%) who practised non-biopsy CD diagnosis followed the 2020 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines. Twenty-two (56%) respondents reported that they started using a non-biopsy CD diagnosis protocol before the pandemic and did not change their practice during the pandemic, 10 (26%) started diagnosing non-biopsy CD during the pandemic, 5 (13%) stated their practices of CD were not impacted by the pandemic and 2 (5%) did not respond on whether the pandemic changed their practice. CONCLUSION: The majority of Australasian gastroenterologist respondents reported they routinely utilised the 2020 ESPGHAN diagnostic criteria in eligible children; half of them started prior to the pandemic and another quarter started this approach due to the pandemic. A minority of practitioners routinely rely only on biopsy confirmation to diagnose CD.

Fundoplication in children with esophageal atresia: preoperative workup and outcome.

Up to 45% of esophageal atresia (EA) patients undergo fundoplication during childhood. Their esophageal dysmotility may predispose to worse fundoplication outcomes compared with patients without EA. We therefore compared fundoplication outcomes and symptoms pre- and post-fundoplication in EA patients with matched patients without EA. A retrospective review of patients with- and without EA who underwent a fundoplication was performed between 2006 and 2017. Therapeutic success was defined as complete sustained resolution of symptoms that were the reason to perform fundoplication. Fundoplication indications of 39 EA patients (49% male; median age 1.1 [0.1-17.0] yrs) and 39 non-EA patients (46% male; median age 1.3 [0.3-17.0] yrs) included respiratory symptoms, brief resolved unexplained events, typical symptoms of gastroesophageal reflux disease, recurrent strictures and respiratory problems. Post-fundoplication, therapeutic success was achieved in 5 (13%) EA patients versus 29 (74%) non-EA patients (P<0.001). Despite therapeutic success, all 5 (13%) EA patients developed postoperative sustained symptoms/complications versus 12 (31%) non-EA patients. Eleven (28%) EA patients versus 3 (8%) non-EA patients did not achieve any therapeutic success (P=0.036). Remaining patients achieved partial therapeutic success. EA patients suffered significantly more often from postoperative sustained dysphagia (41% vs. 13%; P=0.039), gagging (33% vs. 23%; P<0.001) and bloating (40% vs. 17%; P=0.022). Fundoplication outcomes in EA patients are poor and EA patients are more susceptible to post-fundoplication sustained symptoms and complications compared with patients without EA. The decision to perform fundoplication in EA patients with proven gastroesophageal reflux disease needs to be made with caution after thorough multidisciplinary evaluation.

Clinician Knowledge of Societal Guidelines on Management of Gastrointestinal Complications in Esophageal Atresia.

OBJECTIVES: The aim of this study was to assess whether clinicians approached the management of children with esophageal atresia (EA) in accordance with the 2016 European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)/North American Society of Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines on the management of gastrointestinal and nutritional complications in this cohort. METHODS: We invited expert physicians and surgeons closely involved in the care of children with EA (members of the International network on esophageal atresia [INoEA], ESPGHAN EA working group, French national EA registry, European pediatric surgical association (EUPSA), and European rare disease reference network [ERNICA]) to participate in an anonymous online survey containing 15 multiple choice questions concerning the management of gastrointestinal and nutritional complications in children with EA. Questions were based on the management of gastroesophageal reflux disease (GERD) dysphagia, cyanotic spells, feeding and nutrition, anastamotic strictures, and transition to adult care as detailed in the 2016 guidelines. RESULTS: Median concordance with ESPGHAN/NASPHAN EA Guidelines was 69% (16-100%, SD 16%) across all responders. Areas of greatest concordance were in the fields of surveillance endoscopy and medical management of GERD. Areas for potential educational opportunities include: the differential diagnosis and appropriate investigation of dysphagia and the diagnostic evaluation of extraesophageal symptoms. CONCLUSIONS: This survey highlights the importance of improving the understanding and adherence to the EA guidelines amongst clinicians involved in the care of these patients.

Cholestatic jaundice in neonates: How common is biliary atresia? Experience at an Australian tertiary centre.

AIM: To (i) review the aetiologies of neonatal cholestasis among term and preterm neonates at a single tertiary centre in Australia; (ii) identify clinical variables associated with biliary atresia (BA) and non-BA aetiology of neonatal cholestasis; (iii) investigate the utility of hepatobiliary scintigraphy in predicting BA among term and preterm neonates. METHODS: A retrospective cohort study of neonates born and investigated for cholestasis at two co-located neonatal and children facilities from January 2013 to December 2017. RESULTS: Of the 139 neonates with cholestasis, BA and intestinal-failure-associated liver-disease was the most common cause of neonatal cholestasis in term (18%) and preterm (66%) cohorts, respectively. Incidence of BA was higher in term (1:6) than preterm (1:50) neonates (OR 10.29; 95% CI 2.06-49.97, P = 0.0024). Higher birthweight, acholic stool, absent or abnormal gallbladder on ultrasound was significantly associated with BA while gestational age ≤32 weeks, total parenteral nutrition ≥14 days and low albumin were associated with non-BA aetiology of cholestasis. In diagnosing BA, non-draining hepatobiliary scintigraphy demonstrated a lower specificity (73% vs. 90%) and lower positive predictive value (25% vs. 78%) in preterm compared to term neonates. CONCLUSION: Aetiology of cholestasis among preterm neonates differs from those in term neonates and currently existing diagnostic algorithm for neonatal cholestasis may need to be modified for preterm cohort, taking into account the prevalence for each aetiology, potential predictors and cost-efficiency.

Presence of Gastric Pepsinogen in the Trachea Is Associated with Altered Inflammation and Microbial Composition.

Gastroesophageal reflux is a common gastrointestinal issue that can lead to aspiration and contribute to respiratory problems. Little is known about how reflux can alter the respiratory microenvironment. We aimed to determine if the presence of gastric pepsinogen in the trachea was associated with changes in the microbial and inflammatory microenvironment. A pediatric cohort at high risk of reflux aspiration was prospectively recruited, and the tracheal microenvironment was examined. Pepsinogen A3 (PGA3) and cytokines were measured. The microbiome (bacterial and fungal) was profiled using 16S rRNA and internal transcribed spacer 2 (ITS2) amplicon sequencing. Increased bacterial richness and an altered composition driven by an enrichment of Prevotella correlated with high PGA3 levels. Fungal richness increased with PGA3, with higher Candida relative abundances observed in a subset of samples with high PGA3 levels. Source tracking of tracheal microbial taxa against taxa from matched oral and gastric samples revealed a significantly greater contribution of oral than of gastric taxa with higher PGA3 levels. Tracheal cytokines were differentially produced when stratified according to PGA3, with higher levels of interleukin-1 (IL-1)-related cytokines and IL-8 being associated with high PGA3 levels. Network analysis across cytokine and microbiome measures identified relationships between IL-1-related proteins and microbial taxa, with the presence of respiratory issues associated with higher levels of IL-1ß, IP-10, and Prevotella In conclusion, PGA3 levels in the trachea are correlated with increases in specific microbial taxa and inflammatory molecules, with an increase in oral microbes with increasing PGA3.