The Incidence of Necrotizing Enterocolitis and Late-Onset Sepsis during the COVID-19 Pandemic in Sweden: A Population-Based Cohort Study.

INTRODUCTION: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. METHODS: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98-99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. RESULTS: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55-0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). CONCLUSION: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged.

Experiences and satisfaction of video follow up of children with paediatric gastrointestinal conditions linking tertiary centre with guardians and clinicians at the local hospital: a cross-sectional study.

BACKGROUND: Children with complicated gastrointestinal conditions are dependent on follow up by tertiary care specialists throughout childhood to prevent and treat complications. In Sweden, paediatric surgical- and intestinal rehabilitation centres are centralised which means that many patients and guardians have to travel long distances to access tertiary referral centres. Our tertiary referral centre has developed a model of shared care with video conferences for follow up with our centre and the patient and guardians attending together with the responsible professionals at the local hospital. This study aimed to investigate the experiences and satisfaction with video follow-up visits (VFV) between a tertiary referral centre and guardians and clinicians at their local hospital. METHODS: Eligible participants were families with children with oesophageal atresia, intestinal failure and intestinal motility disorders and their local clinicians attending VFV with our tertiary referral centre from 2015 to 2020. Questionnaires included fixed-response alternatives, a 6-point Likert scale and open questions. RESULTS: Fifty-seven out of 102 families (56%) and 19 out of 27 local clinicians (70%) responded the questionnaires. In 68% of the VFV, two guardians attended compared to 35% in the physical visits. Of the guardians attending VFV, 82% lost ≤ half a working day and 91% attending physical visits lost ≥ one full working day. Median distance to the tertiary referral centre was 267 km and attending VFV avoided emissions of 7.2 metric tonnes of CO2. Of the guardians, 90% and of the clinicians 95% were satisfied with VFV. Advantages were avoidance of travelling and the participants shared the same information. CONCLUSIONS: VFV is an appropriate alternative to physical visits with a high grade of satisfaction among the guardians and clinicians. VFV was time-saving for the families and reduced CO2 emissions.

A nordic multicenter study on contemporary outcomes of pediatric short bowel syndrome in 208 patients.

BACKGROUND & AIMS: Despite advances in the management of short bowel syndrome related intestinal failure (SBS-IF), large-scale contemporary pediatric studies are scarce. The aim of this multicenter study was to assess key outcomes and clinical prognostic factors in a recent Nordic pediatric SBS-IF population. METHODS: Patients with SBS-IF treated during 2010-2019, whose parenteral support (PS) started at age <1 year and continued >60 consecutive days were included and retrospectively reviewed. All six participating centers followed multidisciplinary SBS-IF management. Risk factors for PS dependency, intestinal failure associated liver disease (IFALD) and mortality were assessed with Cox regression and Kaplan Meier analyses. IFALD was defined with serum liver biochemistry levels. RESULTS: Among 208 patients, SBS-IF resulted from NEC in 49%, gastroschisis w/wo atresia in 14%, small bowel atresia in 12%, volvulus in 11%, and other diagnoses in 14%. Median age-adjusted small bowel length was 43% (IQR 21-80%). After median follow up of 4.4 years (IQR 2.5-6.9), enteral autonomy was reached by 76%, none had undergone intestinal transplantation, and overall survival was 96%. Half of deaths (4/8) were caused by septic complications. Although biochemical cholestasis occurred only in 3% at latest follow-up and none of deaths were directly caused by IFALD, elevated liver biochemistry (HR 0.136; P = 0.017) and shorter remaining small bowel (HR 0.941; P = 0.040) predicted mortality. Shorter remaining small bowel and colon, and presence of end-ostomy were the main predictors of PS dependency, but not IFALD. Patients with NEC reached enteral autonomy more efficiently and had decreased incidence of IFALD compared to other etiologies. CONCLUSIONS: Although with current multidisciplinary management, prognosis of pediatric SBS is encouraging, septic complications and IFALD still associated with the remaining low mortality rate.

Surgical management of necrotising enterocolitis in Sweden: A national cohort study.

AIM: Necrotising enterocolitis (NEC) is the dominating surgical emergency in preterm neonates. The aims were to investigate indications, surgical management and mortality for surgically treated neonates with NEC. METHODS: Data were retrieved from the Swedish Neonatal Quality Register for Swedish neonates with surgically treated NEC from 1 January 2017 to 31 December 2021. Diagnosis was validated by surgical records and histopathology. Neonates with isolated spontaneous intestinal perforation were excluded. RESULTS: In total, 109 neonates were included. Median gestational age was 25 weeks (22-38), and median birth weight was 771 g (269-3920). Preoperative pneumoperitoneum was found in 32%, portal venous gas in 25% and clinical deterioration on conservative treatment in 26% of the neonates. Among the 97 neonates presenting with small bowel necrosis, single-focal NEC occurred in 38 (39%), multifocal NEC in 35 (36%) and panintestinal NEC in 24 (25%). A primary anastomosis was performed in 10/87 (11%) of the neonates with bowel resection at primary surgery. Clip-and-drop technique was applied in 24/87 (28%).Mortality rate was 37%. CONCLUSION: Mortality was well comparable with earlier reports considering exclusion of spontaneous intestinal perforation (SIP) and the low gestational age of the study population. Resection of necrotic bowel with stoma formation was the dominating surgical method.

Effect of proton pump inhibitors in infants with esophageal atresia on the gut microbiome: a pilot cohort.

BACKGROUND: The effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint. RESULTS: A longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users. CONCLUSION: Prolonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.

Postoperative morbidity and health-related quality of life in children with delayed reconstruction of esophageal atresia: a nationwide Swedish study.

BACKGROUND: In 10-15% of children with esophageal atresia (EA) delayed reconstruction of esophageal atresia (DREA) is necessary due to long-gap EA and/or prematurity/low birth weight. They represent a patient subgroup with high risk of complications. We aimed to evaluate postoperative morbidity and health-related quality of life (HRQOL) in a Swedish national cohort of children with DREA. METHODS: Postoperative morbidity, age-specific generic HRQOL (PedsQL™ 4.0) and condition-specific HRQOL (The EA-QOL questionnaires) in children with DREA were compared with children with EA who had primary anastomosis (PA). Factors associated with the DREA group's HRQOL scores were analyzed using Mann-Whitney U-test and Spearman's rho. Clinical data was extracted from the medical records. Significance level was p < 0.05. RESULTS: Thirty-four out of 45 families of children with DREA were included and 30 returned the questionnaires(n = 8 children aged 2-7 years; n = 22 children aged 8-18 years). Compared to children with PA(42 children aged 2-7 years; 64 children aged 8-18 years), there were no significant differences in most early postoperative complications. At follow-up, symptom prevalence in children aged 2-7 with DREA ranged from 37.5% (heartburn) to 75% (cough). Further digestive and respiratory symptoms were present in ≥ 50%. In children aged 8-18, it ranged from 14.3% (vomiting) to 40.9% (cough), with other digestive and airway symptoms present in 19.0-27.3%. Except for chest tightness (2-7 years), there were no significant differences in symptom prevalence between children with DREA and PA, nor between their generic or condition-specific HRQOL scores (p > 0.05). More children with DREA underwent esophageal dilatations (both age groups), gastrostomy feeding (2-7 years), and antireflux treatment (8-18 years), p < 0.05. Days to hospital discharge after EA repair and a number of associated anomalies showed a strong negative correlation with HRQOL scores (2-7 years). Presence of cough, airway infection, swallowing difficulties and heartburn were associated with lower HRQOL scores (8-18 years), p < 0.05. CONCLUSIONS: Although children with DREA need more treatments, they are not a risk group for postoperative morbidity and impaired HRQOL compared with children with PA. However, those with a long initial hospital stay, several associated anomalies and digestive or respiratory symptoms risk worse HRQOL. This is important information for clinical practice, families and patient stakeholders.

Understanding of the transition to adult healthcare services among individuals with VACTERL association in Sweden: A qualitative study.

Current knowledge of transitional care from the perspective of individuals with congenital malformations is scarce. Their viewpoints are required for the development of follow-up programs and transitional care corresponding to patients' needs. The study aimed to describe expectations, concerns, and experiences in conjunction with transfer to adult health care among adolescents, young adults, and adults with VACTERL association, (i.e. vertebral defects, anorectal malformations (ARM), cardiac defects (CHD), esophageal atresia (EA), renal, and limb abnormalities). Semi-structured telephone interviews were performed and analyzed with qualitative content analysis. Of 47 invited individuals, 22 participated (12 males and 10 females). An overarching theme emerged: Leaving the safe nest of pediatric health care for an unfamiliar and uncertain follow up yet growing in responsibility and appreciating the adult health care. The participants described expectations of qualified adult health care but also concerns about the process and transfer to an unfamiliar setting. Individuals who were transferred described implemented or absence of preparations. Positive and negative experiences of adult health care were recounted including being treated as adults. The informants described increasing involvement in health care but were still supported by their parents. Ongoing follow up of health conditions was recounted but also uncertainty around the continuation, missing follow up and limited knowledge of how to contact health care. The participants recommended information ahead of transfer and expressed wishes for continued health care with regular follow up and accessibility to a contact person. Based on the participants' perspective, a transitional plan is required including early information about transfer and follow up to prepare the adolescents and reduce uncertainty concerning future health care. Meetings with the pediatric and adult team together with the patient and the parents are essential before transfer. Follow up should be centralized to centers with multi-professional teams well-experienced with the condition. Further studies are warranted to evaluate the transition process for adolescents and young adults with complex congenital health conditions.

Predictors of histopathological esophagitis in infants and adolescents with esophageal atresia within a national follow-up programme.

PURPOSE: Esophageal atresia (EA) is a congenital anomaly of the foregut. Although the survival has improved over the years there is a significant gastrointestinal morbidity affecting physical function and health-related quality of life. The aims of the study were to identify and evaluate predictors of histopathological esophagitis in infants and adolescents with EA. METHODS: Single centre, cross-sectional study including one and 15-year-old patients operated for EA that participated in the national follow-up programme between 2012 and 2020 according to a pre-established protocol including upper endoscopy with oesophageal biopsies and 24h-pH-test. Data was collected from patients' medical records and pH-analysis software. Regression models were used to identify predictors of histopathological oesophagitis. Possible predictors were abnormal reflux index, endoscopic esophagitis, hiatal hernia, symptoms of gastroesophageal reflux (GER) and age. RESULTS: 65 patients were included, 47 children and 18 adolescents. All children were treated with PPI during their first year of life. Symptoms of GER were reported by 13 (31.7%) of the infant's caregivers, 34 of the children (72.3%) had abnormal reflux index and 32 (68.1%) had histopathological esophagitis. The corresponding numbers for adolescents were 8 (50%), 15 (83.3%) and 10 (55.6%). We found no significant associations between histopathological esophagitis and endoscopic esophagitis, symptoms of GER, hiatus hernia or age group. Abnormal reflux index was an independent predictor of histopathological esophagitis. Seven patients with normal reflux index had histopathological esophagitis, all grade I. CONCLUSIONS: We found a high prevalence of histopathological esophagitis despite PPI treatment in accordance with recommendations. No significant difference between the two age groups was seen. Abnormal reflux index was an independent predictor of histopathological esophagitis. However, we cannot recommend the use of pH-metry as a substitute for esophageal biopsies; future studies are needed to elucidate if esophageal biopsies might be postponed in infants with normal reflux index.

Attention deficit hyperactivity disorder and educational level in adolescent and adult individuals after anesthesia and abdominal surgery during infancy.

AIM: Several studies in animal models have found that exposure to anesthetics in early life can cause cognitive dysfunction. Human studies show conflicting results and studies of cognitive function after anesthesia and neonatal surgery are scarce. The aim of this study was to investigate whether exposure to anesthesia and abdominal surgery during infancy was associated with cognitive dysfunction from the perspective of educational level, disposable income and attention deficit hyperactivity disorders (ADHD) in adolescent and adult individuals. METHODS: A cohort study with patients born 1976 to 2002 that underwent abdominal surgery during infancy at a pediatric surgical center were matched by age, sex, and gestational age to ten randomly selected individuals from the Swedish Medical Birth Register. Individuals with chromosomal aberrations were excluded. Data on highest level of education and annual disposable income were attained from Statistics Sweden and the diagnosis of ADHD were retrieved from the Swedish National Patient Register. RESULTS: 485 individuals and 4835 controls were included. Median gestational age was 38 weeks (24-44) and median age at surgery was seven days (0-365). Three hundred sixty-six individuals (70.0%) underwent surgery during the neonatal period (< 44 gestational weeks). Median operating time was 80 minutes (10-430). The mean age at follow-up was 28 years. Fisher's exact test for highest level of education for the exposed and unexposed groups were respectively: university 35% and 33%, upper secondary 44% and 47%, compulsory 21% and 20% (p = 0.6718). The median disposable income was 177.7 versus 180.9 TSEK respectively (p = 0.7532). Exposed individuals had a prevalence of ADHD of 5.2% and unexposed 4.4% (p = 0.4191). CONCLUSIONS: This study shows that exposure to anesthesia and abdominal surgery during infancy is not associated with cognitive dysfunction from the perspective of educational level, disposable income and ADHD in adolescent and adult individuals. Further studies in larger cohorts at earlier gestational ages are needed to verify these findings.

Whole genome sequencing of familial isolated oesophagus atresia uncover shared structural variants.

BACKGROUND: Oesophageal atresia (OA) is a life-threatening developmental defect characterized by a lost continuity between the upper and lower oesophagus. The most common form is a distal connection between the trachea and the oesophagus, i.e. a tracheoesophageal fistula (TEF). The condition may be part of a syndrome or occurs as an isolated feature. The recurrence risk in affected families is increased compared to the population-based incidence suggesting contributing genetic factors. METHODS: To gain insight into gene variants and genes associated with isolated OA we conducted whole genome sequencing on samples from three families with recurrent cases affected by congenital and isolated TEF. RESULTS: We identified a combination of single nucleotide variants (SNVs), splice site variants (SSV) and structural variants (SV) annotated to altogether 100 coding genes in the six affected individuals. CONCLUSION: This study highlights rare SVs among candidate gene variants in our individuals with OA and provides a gene framework for further investigations of genetic factors behind this malformation.

From crisis to self-confidence and adaptation; Experiences of being a parent of a child with VACTERL association - A complex congenital malformation.

AIM: Knowledge is scarce regarding mothers' and fathers' experiences of being a parent of a child with VACTERL association-a complex malformation. The aim of the study was to describe experiences of being a parent of a child with VACTERL association. METHOD: Semi-structured interviews were performed with ten mothers and nine fathers face-to-face or by telephone and analyzed by using Qualitative content analysis. RESULTS: The parents described crisis reactions at the discovery of malformations in their child. Involvement in care was reported from the initial hospital admission until actively taking responsibility for treatments at home. Eventually the health condition became an integrated part of everyday life. The parents expressed the importance of meeting other families with a child with VACTERL. Descriptions were given of more or less professionalism with perceived discrepancies of knowledge and experience between the healthcare professionals in the tertiary hospital and those in the local hospital. Difficulties in receiving medical support during the initial period at home were described. Furthermore, emotional support and practical arrangements regarding parental accommodation and transportation varied. CONCLUSION: Being a parent of a child with VACTERL association involves crisis, mixed emotional reactions and shared responsibility for the child´s treatment and care with the professional care providers. Psychological processing, good medical care and support from experts, and peer support from other parents is essential in the parents' struggle to reach self-confidence and adaptation. A care plan with individualized tailored care for each child including a training and support plan for the parents is warranted. To reduce the described discrepancies in knowledge and experience between the local and tertiary hospital, video sessions with the parents and responsible professionals at the local and tertiary hospital could be an appropriate mode of transferring information at discharge and follow up of the child.

Intestinal dysbiosis in children with short bowel syndrome is associated with impaired outcome.

BACKGROUND: The composition of the intestinal microbiota seems to be an important factor in determining the clinical outcome in children with short bowel syndrome (SBS). Alterations in the microbiota may result in serious complications such as small bowel bacterial overgrowth (SBBO) and intestinal mucosal inflammation that lead to prolonged parenteral nutrition (PN) dependency with subsequently increased risk of liver failure and sepsis. To date, there are no reported mappings of the intestinal microbiome in children with SBS. Here, we present the first report on the intestinal microbial community profile in children with SBS. FINDINGS: The study includes children diagnosed with SBS in the neonatal period. Healthy siblings served as controls. Fecal samples were collected, and microbial profiles were analyzed by using 16S rRNA gene sequencing on the Illumina MiSeq platform. We observed a pronounced microbial dysbiosis in children with SBS on PN treatment with an increased and totally dominating relative abundance of Enterobacteriacae in four out of five children compared to children with SBS weaned from PN and healthy siblings. CONCLUSIONS: The overall decreased bacterial diversity in children with SBS is consistent with intestinal microbiome mappings in inflammatory bowel diseases such as Crohn's disease and necrotizing enterocolitis in preterm infants. Our findings indicate that intestinal dysbiosis in children with SBS is associated with prolonged PN dependency.