Swedish registry study showed that 50% of paediatric operations were performed in university hospitals and mortality was low.

AIM: To investigate the distribution of paediatric surgery in various hospitals and to study postoperative risk factors of mortality. METHODS: Retrospective registry-based cohort study of children aged 0-14 years undergoing surgery from 2017 to 2021. Data were extracted from the Swedish Perioperative Registry. A mixed logistic regression was applied for the all-risk mortality analysis. RESULTS: A total of 126 539 cases were identified, 50% in university, 36% in county and 14% in district hospitals. The dominating operations were appendectomy in 6667, orchidopexy in 5287, inguinal hernia repair in 4200 and gastrostomy in 1152 children. Among children under 1 year of age or American Society of Anesthesiologists Physical Status classification (ASA-PS-Class) 3-5, the majority underwent surgery in university hospitals. The 30-day mortality in university hospitals was 0.5% and in county hospitals 0%. The proportion of emergency surgery was similar in university and county hospitals. Independent risk factors of mortality were being under 1 year of age, ASA-PS-class 4-5, emergency surgery and surgery at university hospitals. CONCLUSION: Half of all operations in children were performed in university hospitals, with low postoperative mortality despite effective centralisation of high risk patients <1 year of age or ASA-PS-Class 3-5.

Neurodevelopmental outcomes in individuals with VACTERL association. A population-based cohort study.

BACKGROUND: Studies on neurodevelopmental outcomes in individuals with congenital anomalies who undergo neonatal surgery are scarce and have reported contradictory findings based on small study groups. The congenital condition VACTERL association includes at least three malformations: vertebral anomalies, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal anomalies and limb deformities. Most of these patients undergo surgery during their first days of life. Neurodevelopmental disorders include a broad group of disabilities involving some form of disruption to brain development. Attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability (ID) are diagnoses included in this group. The aim of the study was to investigate the risk of ADHD, ASD and ID in a cohort of individuals with VACTERL association. METHOD: Data was obtained from four Swedish national health registers and analyzed using the Cox proportional hazards model. Patients born 1973-2018 in Sweden with the diagnosis of VACTERL association were included in the study. For each case five healthy controls matched for sex, gestational age at birth, birth year and birth county were obtained. RESULTS: The study included 136 individuals with VACTERL association and 680 controls. Individuals with VACTERL had significantly higher risk of ADHD, ASD and ID than the controls; 2.25 (95% CI, 1.03-4.91), 5.15 (95% CI, 1.93-13.72) and 8.13 (95% CI, 2.66-24.87) times respectively. CONCLUSIONS: A higher risk of ADHD, ASD and ID was found among individuals with VACTERL association compared to controls. These results are of importance to caregivers and to professionals participating in follow ups of these patients in providing early diagnosis and support, aiming to optimize the quality of life of these patients.

Paediatric Adhesive Small Bowel Obstruction is Associated with a Substantial Economic Burden and High Frequency of Postoperative Complications.

BACKGROUND: Intra-abdominal adhesions can lead to adhesive small bowel obstruction (ASBO). The incidence of ASBO is higher in paediatric surgery than in adult surgery. However, ASBO related complications, economic burden and clear management guidelines in the treatment of ASBO are lacking. The aims of this study were to investigate underlying diagnoses, treatments, complications and costs in paediatric ASBO. METHOD: An observational retrospective study in children 0-15 years, hospitalised for ASBO during 2000-2020. Data were extracted from the medical records. Complications were classified based on Clavien Dindo Classification of Surgical Complications. Descriptive statistics were presented as median, continuous variables and categorical variables summarised with frequencies. Time to ASBO was presented as a Kaplan-Meier estimate. RESULTS: In total, 101 patients with 137 episodes of ASBO were included whereof 58.4% underwent first (index) surgery during the neonatal period. Median follow-up was 11.3 (0.6-19) years and median time to the first ASBO was 3.76 months (95%CI 2.23-12.02). The most common diagnoses at index surgery were necrotising enterocolitis, duodenal obstruction and primary ASBO. In 86.6% of the patients, first ASBO did not resolve with conservative treatment and a laparotomy was needed. Postoperative complications were found in 52%. Median cost for one episode of acute ASBO was 36 236 USD (1629-236 159). CONCLUSION: Neonatal surgery was the dominating cause of ASBO and surgical intervention the most common treatment with a high frequency of postoperative complications and significant healthcare costs. Future studies are needed to develop safe management guidelines for the treatment of paediatric ASBO. LEVELS OF EVIDENCE: III.

Paneth cell proteins DEFA6 and GUCA2A as tissue markers in necrotizing enterocolitis.

Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEFA6) and guanylate cyclase activator 2A (GUCA2A) are selective protein markers of Paneth cells. The objective was to explore DEFA6 and GUCA2A expression in intestinal tissue samples from newborn infants with and without NEC. Tissue samples from histologically intact intestine were analyzed from 70 infants: 43 underwent bowel resection due to NEC and 27 controls were operated due to conditions such as intestinal atresia, dysmotility, aganglionosis, pseudo-obstruction or volvulus. Each tissue sample was immunohistochemically stained for DEFA6 and GUCA2A. Semi-automated digital image analysis was performed to determine protein expression. Clinical data and protein expressions were compared between the groups. DEFA6 expression was lower in the NEC group (p = 0.006). Low DEFA6 correlated with risk of developing NEC in a logistic regression analysis, independently of gestational age and birth weight (OR 0.843 [CI 0.732-0.971]; p = 0.018). GUCA2A expression did not differ between the two groups. CONCLUSION: Lower expression of DEFA6 together with intact GUCA2A expression indicates that NEC patients have well-defined Paneth cells but diminished defensin activity. Our results suggest that DEFA6 could be used as a biomarker for NEC. WHAT IS KNOWN: • Previous studies of defensin activity in NEC have been inconsistent, showing that defensin levels may be increased or diminished in NEC. GUCA2A has to our knowledge never been studied in NEC. WHAT IS NEW: • This study benchmarks two specific Paneth cell markers (DEFA6 and GUCA2A) and their activity in individuals with and without NEC. • The key finding is that the NEC group had a lower DEFA6 expression compared to the Controls, while the expression of GUCA2A did not differ between the groups.

Prevalence of Mental Health Problems, Associated Factors, and Health-Related Quality of Life in Children with Long-Gap Esophageal Atresia in Sweden.

BACKGROUND: Children with long-gap esophageal atresia (LGEA) face a high risk of digestive and respiratory morbidity, but their mental health outcomes have not been investigated. We aimed to identify the prevalence of mental health problems in children with LGEA, associated factors and health-related quality of life (HRQOL). METHODS: Twenty-six children with LGEA aged 3-17 were recruited nationwide in Sweden. One of their parents and adolescents aged 11-17 completed information on the child's mental health (Strength and Difficulties Questionnaire), generic (PedsQL 4.0) and condition-specific HRQOL (EA-QOL). Parents gave information on current child symptomatology. Mental health level was determined using validated norms; abnormal≥90 percentile/borderline≥80 percentile/normal. Elevated levels were considered borderline/abnormal. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05. RESULTS: Twelve children with LGEA aged 3-17 (46%) had elevated scores of ≥1 mental health domain in parent-reports, whereas 2 adolescents (15%) in self-reports. In parent-reports, 31% of the children had elevated levels of peer relationship problems, with associated factors being child sex male (p = 0.037), airway infections (p = 0.002) and disturbed night sleep (p = 0.025). Similarly, 31% showed elevated levels of hyperactivity/inattention, and associated factors were male sex (p = 0.005), asthma (p = 0.028) and disturbed night sleep (p = 0.036). Elevated levels of emotional symptoms, seen in 20%, were related to swallowing difficulties (p = 0.038) and vomiting problems (p = 0.045). Mental health problems correlated negatively with many HRQOL domains (p < 0.05). CONCLUSIONS: Children with LGEA risk mental health difficulties according to parent-reports, especially peer relationship problems and hyperactivity/inattention, with main risk factors being male sex, airway problems and sleep disturbances. This should be considered in follow-up care and research, particularly since their mental health problems may impair HRQOL. LEVELS OF EVIDENCE: Prognosis study, LEVEL II.

The risk of autism spectrum disorder and intellectual disability but not attention deficit/hyperactivity disorder is increased in individuals with esophageal atresia.

Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability (ID) in patients with esophageal atresia (EA) is scarce. The aims of this study were to investigate the prevalence and risk of ADHD, ASD and ID in individuals with EA. Data were obtained from four longitudinal population-based registries in Sweden and analyzed using Cox proportional hazards regression. Patients with EA born in Sweden in 1973-2018 were included together with five controls for each individual with the exposure matched on sex, gestational age at birth, birth year and birth county. Individuals with chromosomal aberrations and syndromes were excluded. In total, 735 individuals with EA and 3675 controls were included. Median age at time of the study was 20 years (3-48). ASD was found in 24 (3.9%), ADHD in 34 (5.5%) and ID in 28 (4.6%) individuals with EA. Patients with EA had a 1.66 times higher risk of ASD (95% confidence interval [CI], 1.05-2.64) and a 3.62 times higher risk of ID (95% CI, 2.23-5.89) compared with controls. The risk of ADHD was not significantly increased. ADHD medication had been prescribed to 88.2% of patients with EA and ADHD and to 84.5% of controls with ADHD. Individuals with EA have a higher risk of ASD and ID than individuals without the exposure. These results are important when establishing follow-up programs for children with EA to allow timely detection and consequentially an earlier treatment and support especially before school start.

Vascular adhesion protein-1 expression is reduced in the intestines of infants with necrotizing enterocolitis: an observational research study.

BACKGROUND: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC. METHODS: Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls. RESULTS: Mean gestational age was lower in NEC infants compared to controls, 26.6 ± 3.0 gestational weeks versus 36.5 ± 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression. CONCLUSION: VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.

Outcome and management in neonates with gastroschisis in the third millennium-a single-centre observational study.

Gastroschisis is one of the most common congenital malformations in paediatric surgery. However, there is no consensus regarding the optimal management. The aims of this study were to investigate the management and outcome and to identify predictors of outcome in gastroschisis. A retrospective observational study of neonates with gastroschisis born between 1999 and 2020 was undertaken. Data was extracted from the medical records and Cox regression analysis was used to identify predictors of outcome measured by length of hospital stay (LOS) and duration of parenteral nutrition (PN). In total, 114 patients were included. Caesarean section was performed in 105 (92.1%) at a median gestational age (GA) of 36 weeks (range 29-38) whereof (46) 43.8% were urgent. Primary closure was achieved in 82% of the neonates. Overall survival was 98.2%. One of the deaths was caused by abdominal compartment syndrome and one patient with intestinal failure-associated liver disease died from sepsis. None of the deceased patients was born after 2005. Median time on mechanical ventilation was 22 h. Low GA, staged closure, intestinal atresia, and sepsis were independent predictors of longer LOS and duration on PN. In addition, male sex was an independent predictor of longer LOS. CONCLUSION: Management of gastroschisis according to our protocol was successful with a high survival rate, no deaths in neonates born after 2005, and favourable results in LOS, duration on PN, and time on mechanical ventilation compared to other reports. Multicentre registry with long-term follow-up is required to establish the best management of gastroschisis. WHAT IS KNOWN: • Gastroschisis is one of the most common congenital malformations in paediatric surgery with increasing incidence. • There is no consensus among clinicians regarding the optimal management of gastroschisis. WHAT IS NEW: • Although primary closure was achieved in 82% of the patients, mortality rate was very low (1.8%) with no deaths in neonates born after 2005 following the introduction of measurement of intraabdominal pressure at closure. • Low gestational age, staged closure, intestinal atresia, sepsis, and male sex were independent predictors of longer length of hospital stay.

Early Postnatal Comprehensive Biomarkers Cannot Identify Extremely Preterm Infants at Risk of Developing Necrotizing Enterocolitis.

Background: Necrotizing enterocolitis (NEC) is a fatal disease where current diagnostic tools are insufficient for preventing NEC. Early predictive biomarkers could be beneficial in identifying infants at high risk of developing NEC. Objective: To explore early biomarkers for predicting NEC in extremely preterm infants (EPIs). Methods: Blood samples were collected on day 2 (median 1.7; range 1.5-2.0) from 40 EPI (median 25 gestational weeks; range 22-27): 11 developed NEC and 29 did not (controls). In each infant, 189 inflammatory, oncological, and vascular proteomic biomarkers were quantified through Proximity Extension Assay. Biomarker expression and clinical data were compared between the NEC group and Controls. Based on biomarker differences, controls were sorted automatically into three subgroups (1, 2, and 3) by a two-dimensional hierarchical clustering analysis. Results: None of the biomarkers differed in expression between all controls and the NEC group. Two biomarkers were higher in Control 1, and 16 biomarkers were lower in Control group 2 compared with the NEC group. No biomarker distinguished Control 3 from the NEC group. Perinatal data were similar in the whole population. Conclusions: Early postnatal comprehensive biomarkers do not identify EPIs at risk of developing NEC in our study. Future studies of predictors of NEC should include sequential analysis of comprehensive proteomic markers in large cohorts.

The Risk of Necrotizing Enterocolitis following the Administration of Hyperosmolar Enteral Medications to Extremely Preterm Infants.

INTRODUCTION: Necrotizing enterocolitis (NEC) is a disease predominantly affecting preterm infants. The administration of hyperosmolar solutions could lead to the development of NEC. The objective of this study was to measure the osmolality of enteral medications used in clinical practice and to assess the risk of NEC following exposure to hyperosmolar medications. METHODS: A retrospective cohort study in extremely preterm infants (gestational age <28 weeks) born between 2010 and 2016 at a tertiary neonatal intensive care unit in Sweden. 465 infants were identified via the Swedish Neonatal Quality register. Data relating to enteral administrations received during a two-week period were collected from the medical records. The osmolalities of medications were measured using an osmometer. Logistic regression was used to calculate the odds ratio of developing NEC. RESULTS: A total of 253 patients met the inclusion criteria. The osmolalities of 5 commonly used medications significantly exceeded the recommended limit of 450 mOsm/kg set by the American Academy of Paediatrics (AAP). Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found. CONCLUSION: The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC.

Improved Outcome of Intestinal Failure in Preterm Infants.

OBJECTIVE: The aim of the study was to evaluate the outcome and to identify predictors for survival and enteral autonomy in neonatal intestinal failure (IF). METHODS: A retrospective observational study in a Swedish tertiary centre of children born between 1995 and 2016 with neonatal IF, defined as dependency on parenteral nutrition (PN) ≥60 days, starting with PN before the age of 44 gestational weeks. Data were extracted from medical records and predictors for survival and enteral autonomy were identified by the Cox regression model. Time to death and weaning off PN analysis were performed with Kaplan-Meier curves including log rank test. RESULTS: In total, 105 children were included. Median gestational age was 28 weeks (22-42), 50% were born extremely preterm (<28 gestational weeks). PN started at a median age of 2 days (0-147) with a median duration of 196 days (60-3091). Necrotizing enterocolitis was the dominating cause of IF (61%). Overall survival was 88%, 5 children died of sepsis and 4 of intestinal failure-associated liver disease. Survival increased from 75% during 1995 to 2008 to 96% during 2009 to 2016 (P = 0.0040). Age-adjusted small bowel length of >50% and birth 2009 to 2016 were predictors for survival. Enteral autonomy was achieved in 87%, with positive prediction by small bowel length of >25% of expected for gestational age and remaining ileocecal valve. CONCLUSIONS: Preterm neonates with IF, at high risk of IF-associated morbidity, showed a high overall survival rate. Small-bowel length and being born 2009 to 2016 were predictors for survival and remaining ICV and small-bowel length were predictors for enteral autonomy.

Adhesive small bowel obstruction after appendectomy in children - Laparoscopic versus open approach.

BACKGROUND: The aims of this study were to compare the incidence of small bowel obstruction (SBO) requiring laparotomy after laparoscopic appendectomy (LA) and open appendectomy (OA) in children and to identify risk factors for SBO. METHODS: Medical records of patients who underwent appendectomy from 2000 to 2014 at our department of Pediatric Surgery were reviewed. Risk factors were analyzed using Cox proportional hazard regression. RESULTS: Totally 619 out of 840 patients were included. OA was performed in 474 (76.6%), LA in 130 patients (21%), and 15 (2.4%) were converted from LA to OA. Age, sex and proportion of perforated appendicitis were comparable in the LA and OA groups. Median follow-up time was 11.4 years (2.6-18.4). The incidence of SBO after LA was 1.5%, after OA 1.9% and in the converted group 6.7% (p = 0.3650). There were no significant differences in the incidence of postoperative intraabdominal abscess, wound infection or length of stay between LA and OA. Perforation and postoperative intra-abdominal abscess were identified as risk factors with 9.03 (p < 0.001) and 6.98 (p = 0.004) times higher risk of SBO, respectively. CONCLUSIONS: The risk for SBO after appendectomy in children was significantly related to perforated appendicitis and postoperative intra-abdominal abscess and not to the surgical approach. LEVEL OF EVIDENCE: Level III.

Surgical treatment and major complications Within the first year of life in newborns with long-gap esophageal atresia gross type A and B - a systematic review.

BACKGROUND: The surgical repair of long-gap esophageal atresia (LGEA) is still a challenge and there is no consensus on the preferred method of reconstruction. We performed a systematic review of the surgical treatment of LGEA Gross type A and B with the primary aim to compare the postoperative complications related to the different methods within the first postoperative year. METHODS: Systematic literature review on the surgical repair of LGEA Gross type A and B within the first year of life published from January 01, 1996 to November 01, 2016. RESULTS: We included 57 articles involving a total of 326 patients of whom 289 had a Gross type A LGEA. Delayed primary anastomosis (DPA) was the most applied surgical method (68.4%) in both types, followed by gastric pull-up (GPU) (8.3%). Anastomotic stricture (53.7%), gastro-esophageal reflux (GER) (32.2%) and anastomotic leakage (22.7%) were the most common postoperative complications, with stricture and GER occurring more often after DPA (61.9% and 40.8% respectively) compared to other methods (p < 0.001). CONCLUSION: The majority of patients in this review were managed by DPA and postoperative complications were common despite the surgical method, with anastomotic stricture and GER being most common after DPA. LEVEL OF EVIDENCE: Systematic review of case series and case reports with no comparison group (level IV).

Surgical repair of long-gap esophageal atresia: A retrospective study comparing the management of long-gap esophageal atresia in the Nordic countries.

BACKGROUND: Several surgical procedures have been described in the reconstruction of long-gap esophageal atresia (LGEA). We reviewed the surgical methods used in children with LGEA in the Nordic countries over a 15-year period and the postoperative complications within the first postoperative year. METHODS: Retrospective multicenter medical record review of all children born with Gross type A or B esophageal atresia between 01/01/2000 and 12/31/2014 reconstructed within their first year of life. RESULTS: We included 71 children; 56 had Gross type A and 15 type B LGEA. Delayed primary anastomosis (DPA) was performed in 52.1% and an esophageal replacement procedure in 47.9%. Gastric pull-up (GPU) was the most frequent procedure (25.4%). The frequency of chromosomal abnormalities, congenital heart defects and other anomalies was significantly higher in patients who had a replacement procedure. The frequency of gastroesophageal reflux (GER) was significantly higher after DPA compared to esophageal replacement (p = 0.013). At 1-year follow-up the mean body weight was higher after DPA than after organ interposition (p = 0.043). CONCLUSION: DPA and esophageal replacement procedures were equally applied. Postoperative complications and follow-up were similar except for the development of GER and the body weight at 1-year follow-up. Long-term results should be investigated. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Functional outcome and health-related quality of life in patients with sacrococcygeal teratoma - a Swedish multicenter study.

BACKGROUND/PURPOSE: The aims of this study were to evaluate bowel and urinary tract function, to identify predictors for dysfunctional outcome and to evaluate health-related quality-of life (QoL) in patients treated for sacrococcygeal teratomas (SCT). METHODS: Medical records of patients with SCT born between 1985 and 2015 treated at three Swedish pediatric surgical centers were reviewed. Questionnaires regarding urinary tract function, bowel function and QoL were sent to patients and parents. Different QoL instruments were used for the different age groups. RESULTS: Totally 85 patients were identified. Four patients died in the neonatal period. Forty-nine patients answered the questionnaires (60%). Median age at follow-up was 8.9 years (range 3.6-28.8). Bowel dysfunction was reported by 36% and urinary tract dysfunction by 46% of the patients. Univariate analysis revealed that urinary tract dysfunction correlated with gestational age (p = 0.018) and immature histology (p = 0.008), and bowel dysfunction correlated with gestational age (p = 0.016) and tumor size (p = 0.042). Low gestational age was an independent predictor for both urinary tract and bowel dysfunction. Good or very good QoL was reported by 56% of children aged 4-7 years, 90% of children aged 8-17 years and 67% of the adults. CONCLUSION: Although a considerable proportion of bowel and urinary tract dysfunction was found, the reported QoL was good in a majority of the patients with SCT. Low gestational age was found to be a predictor for bowel- and urinary tract dysfunction. LEVEL OF EVIDENCE: Level III.

Diminished DEFA6 Expression in Paneth Cells Is Associated with Necrotizing Enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature infants with a high morbidity and mortality. Paneth cell dysfunction has been suggested to be involved in the pathogenesis of NEC. Defensin alpha-6 (DEFA6) is a specific marker for Paneth cells acting as part of the innate immunity in the human intestines. The aim of this study was to investigate the expression of DEFA6 in infants with NEC. MATERIALS AND METHODS: Infants who underwent bowel resection for NEC at level III NICU in Sweden between August 2004 and September 2013 were eligible for the study. Macroscopically vital tissues were selected for histopathological evaluation. All infants in the control group underwent laparotomy and had ileostomy due to dysmotility, and samples were taken from the site of the stoma. DEFA6 expression was studied by immunohistochemistry. Digital image analysis was used for an objective and precise description of the samples. RESULTS: A total of 12 infants were included in the study, eight with NEC and four controls. The tissue samples were taken from the colon (n = 1), jejunum (n = 1), and ileum (n = 10). Both the NEC and control groups consisted of extremely premature and term infants (control group: 25-40 gestational weeks, NEC group: 23-39 gestational weeks). The postnatal age at the time of surgery varied in both groups (control group: 4-47 days, NEC group: 4-50 days). DEFA6 expression in the NEC group was significantly lower than that in the control group and did not correlate with gestational age. CONCLUSION: The diminished DEFA6 expression in Paneth cells associated with NEC in this study supports the hypothesis that alpha-defensins are involved in the pathophysiology of NEC. Future studies are needed to elucidate the role of alpha-defensins in NEC aiming at finding preventive and therapeutic strategies against NEC.

Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. METHODS AND RESULTS: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using culture-independent molecular techniques and reported α and ß-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). CONCLUSIONS: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.

Risk factors for postoperative mortality in congenital diaphragmatic hernia: a single-centre observational study.

BACKGROUND: The management of congenital diaphragmatic hernia (CDH) is a major challenge. The mortality is dependent on associated malformations, the severity of pulmonary hypoplasia, pulmonary hypertension and iatrogenic lung injury associated with aggressive mechanical ventilation. The aims of the study were to investigate the mortality over time in a single paediatric surgical centre, to compare the results with recent reports and to define the risk factors for mortality. METHODS: The medical records of infants with CDH from two time periods: 1995-2005 and 2006-2016 were reviewed. Cox regression was used for statistical analysis. RESULTS: The study included 113 infants. The mortality rate was significantly decreased in the later time period, compared to the earlier, 4.4 and 17.9%, respectively. At the early time period five patients (7.5%) were treated with ECMO and in the later time period ECMO was used in three patients (6.5%). The mortality in ECMO-treated patients was 50% in both time periods. Prenatal diagnosis, intrathoracic liver, low Apgar score and low birth weight were defined as independent risk factors for mortality. CONCLUSION: Despite no significant differences in the incidence of independent risk factors and the use of ECMO between the two time periods, mortality decreased over time. The mortality was lower than previously reported. The results indicate that there are many important factors involved in a successful outcome after CDH repair. Large multicentre studies are necessary to define those critical factors and to determine optimal treatment strategies.

Patient-reported Swedish nationwide outcomes of children and adolescents with total colonic aganglionosis.

BACKGROUND: The aim of this study was to evaluate the nationwide outcome of children with total colonic aganglionosis (TCA) during the last 20years. METHODS: This was an observational, cross-sectional study where all patients with TCA, including aganglionosis of 0-50cm of ileum, born in Sweden 1995-2014 were included. Data were collected from the medical records. Patients >4years old without stoma answered a questionnaire regarding bowel function (bowel function score, BFS, score 1-20), medical treatment and nutrition. RESULTS: Twenty-seven children were included. Twenty-five children were reconstructed at median age of 56 (4-236) weeks. Reconstruction procedures included Swenson (6), Soave (5), mucosectomy with short muscular cuff with or without J-pouch (9), Duhamel (3) and Rehbein (2). There was no mortality. The median follow-up time was 9.5years (8months-20years). At follow-up 7 (26%) patients had an ileostomy, 4 with a syndrome. Eight patients required parenteral support, until a median age of 11 (2-24) months. Oral energy support was used by 5/27 (15%), still 5/22 (23%) were underweighted. Obstructive symptoms were reported by 7/20 (31%). All 17 patients >4years old completed the BFS questionnaire at median age of 10 (4-20) years. Median stool frequency/24h was 5 (1-30). Fecal accidents at least once per week was reported by 4 (24%), and social problems by 8 (47%). The median BFS was 15 (11-19) without any gender differences. CONCLUSION: One-third of patients with TCA report obstructive symptoms, one-third need additional nutrition and one-fifth require a permanent stoma. TCA have a negative impact on social life. Subsequently, children with TCA need a careful lifelong follow-up of specialized teams.

Risk Factors for Anastomotic Strictures after Esophageal Atresia Repair: Prophylactic Proton Pump Inhibitors Do Not Reduce the Incidence of Strictures.

Background Since 2005, infants with esophageal atresia (EA) in our unit are given prophylactic proton pump inhibitors (PPI) after repair until 1 year of age. The aims of this study were to identify risk factors for anastomotic strictures (AS) and to assess the efficacy of postoperative PPI prophylaxis in reducing the incidence of AS compared with symptomatic PPI. Methods Patients who underwent EA repair from 1994 to 2013 in our unit were included in this retrospective observational study approved by the local ethics review board. They were divided into two subgroups; symptomatic PPI-group with EA repair from 1994 to 2004 and prophylactic PPI-group with EA repair from 2005 to 2013. Data were collected from the patient records. Potential risk factors for AS analyzed were gender, long gap EA, birth weight, premature birth (<37 gestational weeks), anastomotic tension, and anastomotic leakage. Number of dilatations until the age of 1 and 5 years were recorded. To evaluate risk factors for AS and the effect of prophylactic PPI Logistic, Cox and Poisson regression models were used. For descriptive statistics Fisher exact test and Wilcoxon rank sum test were used. Results A total of 128 patients were included. Patient characteristics, surgical method, grading of anastomotic tension, complications, and survival rates did not differ significantly between the symptomatic PPI-group (n = 71) and the prophylactic PPI-group (n = 57). Comparing the symptomatic and prophylactic PPI-group, there was no significant difference in the median age at the first AS (9.3 vs 6 mo), the number of dilatations until 1 year (2 vs 2) and 5 years (5 vs 4), or the incidence of anastomotic stricture (56.5% vs 50.9%). Long gap EA, high birth weight, and anastomotic tension were found to be independent risk factors. Conclusion Surgeons should aim to perform anastomosis under less tension at EA repair. Prophylactic PPI-treatment does not appear to reduce the rate of AS. Randomized controlled trials with larger study populations are needed to further evaluate the efficacy of prophylactic PPI.