Helene Engstrand Lilja - Academia.edu (original) (raw)

Papers by Helene Engstrand Lilja

Biochemical and Biophysical Research Communications, Jun 1, 2000

ABSTRACT In fulminant hepatic failure, survival is not possible without recovery of sufficient he... more ABSTRACT In fulminant hepatic failure, survival is not possible without recovery of sufficient hepatocyte mass. Remarkably, only a few studies exist that provide insight into the mechanisms that control proliferation of residual hepatocytes after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors, including pro-inflammatory cytokines such as interleukin-6 (IL-6), is not well understood. In the present study we show that in rats with critically low (10%) hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels. Under these conditions, the signal transducer and activator of transcription (Stat3) DNA binding activity was lowered at the time of G1/S cell-cycle transition. We further demonstrate that the protein inhibitor of activated Stat3 (PIAS3) and the suppressor of cytokine signaling (SOCS-1) were up-regulated early after induction of liver failure (6–12 h). In vitro, IL-6 induced PIAS3 expression in HGF stimulated rat hepatocytes. These findings suggest that after massive hepatocyte loss, an early and rapid rise in blood IL-6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.

PLOS ONE, Jun 29, 2023

Background Studies on neurodevelopmental outcomes in individuals with congenital anomalies who un... more 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 VAC-TERL 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 VAC-TERL 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.

PLOS ONE, Oct 21, 2020

Aim Several studies in animal models have found that exposure to anesthetics in early life can ca... more 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).

European Journal of Pediatrics, Apr 5, 2023

Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEF... more 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 welldefined 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.

Acta Paediatrica, Mar 28, 2019

Aim: Improved survival rates for premature infants have also increased the population at risk of ... more Aim: Improved survival rates for premature infants have also increased the population at risk of necrotising enterocolitis (NEC). This study evaluated the outcomes of surgically treated NEC and identified risk factors for mortality, intestinal failure (IF) and IF associated liver disease (IFALD). Methods: This was a retrospective observational study of 131 infants with surgically treated

Diseases of The Esophagus, Dec 20, 2022

Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD)... more 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.

Journal of Pediatric Surgery

Acta Paediatrica

AimNecrotising enterocolitis (NEC) is the dominating surgical emergency in preterm neonates. The ... more AimNecrotising 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.MethodsData 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.ResultsIn 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...

Background: Children with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbi... more Background: Children with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children’s development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden. Method: Twenty-six children with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child’s school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared to that from 95 children with EA who had primary anastomosis (PA), a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal≥90 percentile. Data were analyzed using ...

European Journal of Pediatrics

Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEF... more 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 w...

Diseases of the Esophagus

Summary Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorde... more Summary 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 ...

Journal of Pediatric Surgery

Journal of Pediatric Surgery

Human Genetics and Genomics Advances, 2022

Summary Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common ... more Summary Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes.

Additional file 1: Table S1. Infection types of the progenitor isolate 11–281 and derived 30 muta... more Additional file 1: Table S1. Infection types of the progenitor isolate 11–281 and derived 30 mutants of Puccinia striiformis f. sp. tritici on 18 wheat Yr single-gene differentials. Table S2. Reads, rates and qualities of 30 Puccinia striiformis f. sp. tritici mutants mapped to the reference genome. Table S3. The distribution and density of SNPs and Indels on each scaffold. Table S4. Statistics of Indels of each mutant isolate in terms of insertions, deletions, and different lengths. Table S5. Number of SNPs, Indels, insertions and deletions of each mutant isolate identified from the isolate 11–281 haplotigs. Table S6. Genes highly associated to avirulence with P-value

BMC Pediatrics, 2020

Background Anastomotic stricture (AS) is the most frequently occurring complication that occurs a... more Background Anastomotic stricture (AS) is the most frequently occurring complication that occurs after esophageal atresia (EA) repair. Nevertheless, the pathogenesis remains primarily unknown and there is inadequate knowledge regarding the risk factors for AS. Therefore, a systematic review of the literature and a meta-analysis was performed to investigate whether gender and birth weight were risk factors for the development of AS following EA repair. Methods The main outcome measure was the occurrence of AS. Forest plots with odds ratios (OR) and 95% confidence intervals (CI) were generated for the outcomes. Quality assessment was performed using the Newcastle–Ottawa scale. Results Six studies with a total of 495 patients were included; 59% males, and 37 and 63% of the patients weighed < 2500 g and ≥ 2500 g, respectively. Male gender (OR, 0.96; 95% CI, 0.66–1.40; p = 0.82) and birth weight < 2500 g (OR, 0.74; 95% CI, 0.47–1.15; p = 0.18) did not increase the risk of AS. The ma...

BJS Open, 2020

Background Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and a... more Background Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. Methods An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. Results Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3–33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5–156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged ...

The British journal of surgery, 2014

Serial transverse enteroplasty (STEP) was first described in 2003 as a method for lengthening and... more Serial transverse enteroplasty (STEP) was first described in 2003 as a method for lengthening and tapering of the bowel in short bowel syndrome. The aim of this multicentre study was to review the outcome of a Swedish cohort of children who underwent STEP. All children who had a STEP procedure at one of the four centres of paediatric surgery in Sweden between September 2005 and January 2013 were included in this observational cohort study. Demographic details, and data from the time of STEP and at follow-up were collected from the case records and analysed. Twelve patients had a total of 16 STEP procedures; four children underwent a second STEP. The first STEP was performed at a median age of 5·8 (range 0·9-19·0) months. There was no death at a median follow-up of 37·2 (range 3·0-87·5) months and no child had small bowel transplantation. Seven of the 12 children were weaned from parenteral nutrition at a median of 19·5 (range 2·3-42·9) months after STEP. STEP is a useful procedure f...

Biochemical and Biophysical Research Communications, Jun 1, 2000

ABSTRACT In fulminant hepatic failure, survival is not possible without recovery of sufficient he... more ABSTRACT In fulminant hepatic failure, survival is not possible without recovery of sufficient hepatocyte mass. Remarkably, only a few studies exist that provide insight into the mechanisms that control proliferation of residual hepatocytes after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors, including pro-inflammatory cytokines such as interleukin-6 (IL-6), is not well understood. In the present study we show that in rats with critically low (10%) hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels. Under these conditions, the signal transducer and activator of transcription (Stat3) DNA binding activity was lowered at the time of G1/S cell-cycle transition. We further demonstrate that the protein inhibitor of activated Stat3 (PIAS3) and the suppressor of cytokine signaling (SOCS-1) were up-regulated early after induction of liver failure (6–12 h). In vitro, IL-6 induced PIAS3 expression in HGF stimulated rat hepatocytes. These findings suggest that after massive hepatocyte loss, an early and rapid rise in blood IL-6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.

PLOS ONE, Jun 29, 2023

Background Studies on neurodevelopmental outcomes in individuals with congenital anomalies who un... more 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 VAC-TERL 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 VAC-TERL 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.

PLOS ONE, Oct 21, 2020

Aim Several studies in animal models have found that exposure to anesthetics in early life can ca... more 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).

European Journal of Pediatrics, Apr 5, 2023

Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEF... more 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 welldefined 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.

Acta Paediatrica, Mar 28, 2019

Aim: Improved survival rates for premature infants have also increased the population at risk of ... more Aim: Improved survival rates for premature infants have also increased the population at risk of necrotising enterocolitis (NEC). This study evaluated the outcomes of surgically treated NEC and identified risk factors for mortality, intestinal failure (IF) and IF associated liver disease (IFALD). Methods: This was a retrospective observational study of 131 infants with surgically treated

Diseases of The Esophagus, Dec 20, 2022

Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD)... more 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.

Journal of Pediatric Surgery

Acta Paediatrica

AimNecrotising enterocolitis (NEC) is the dominating surgical emergency in preterm neonates. The ... more AimNecrotising 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.MethodsData 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.ResultsIn 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...

Background: Children with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbi... more Background: Children with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children’s development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden. Method: Twenty-six children with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child’s school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared to that from 95 children with EA who had primary anastomosis (PA), a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal≥90 percentile. Data were analyzed using ...

European Journal of Pediatrics

Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEF... more 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 w...

Diseases of the Esophagus

Summary Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorde... more Summary 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 ...

Journal of Pediatric Surgery

Journal of Pediatric Surgery

Human Genetics and Genomics Advances, 2022

Summary Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common ... more Summary Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes.

Additional file 1: Table S1. Infection types of the progenitor isolate 11–281 and derived 30 muta... more Additional file 1: Table S1. Infection types of the progenitor isolate 11–281 and derived 30 mutants of Puccinia striiformis f. sp. tritici on 18 wheat Yr single-gene differentials. Table S2. Reads, rates and qualities of 30 Puccinia striiformis f. sp. tritici mutants mapped to the reference genome. Table S3. The distribution and density of SNPs and Indels on each scaffold. Table S4. Statistics of Indels of each mutant isolate in terms of insertions, deletions, and different lengths. Table S5. Number of SNPs, Indels, insertions and deletions of each mutant isolate identified from the isolate 11–281 haplotigs. Table S6. Genes highly associated to avirulence with P-value

BMC Pediatrics, 2020

Background Anastomotic stricture (AS) is the most frequently occurring complication that occurs a... more Background Anastomotic stricture (AS) is the most frequently occurring complication that occurs after esophageal atresia (EA) repair. Nevertheless, the pathogenesis remains primarily unknown and there is inadequate knowledge regarding the risk factors for AS. Therefore, a systematic review of the literature and a meta-analysis was performed to investigate whether gender and birth weight were risk factors for the development of AS following EA repair. Methods The main outcome measure was the occurrence of AS. Forest plots with odds ratios (OR) and 95% confidence intervals (CI) were generated for the outcomes. Quality assessment was performed using the Newcastle–Ottawa scale. Results Six studies with a total of 495 patients were included; 59% males, and 37 and 63% of the patients weighed < 2500 g and ≥ 2500 g, respectively. Male gender (OR, 0.96; 95% CI, 0.66–1.40; p = 0.82) and birth weight < 2500 g (OR, 0.74; 95% CI, 0.47–1.15; p = 0.18) did not increase the risk of AS. The ma...

BJS Open, 2020

Background Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and a... more Background Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. Methods An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. Results Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3–33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5–156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged ...

The British journal of surgery, 2014

Serial transverse enteroplasty (STEP) was first described in 2003 as a method for lengthening and... more Serial transverse enteroplasty (STEP) was first described in 2003 as a method for lengthening and tapering of the bowel in short bowel syndrome. The aim of this multicentre study was to review the outcome of a Swedish cohort of children who underwent STEP. All children who had a STEP procedure at one of the four centres of paediatric surgery in Sweden between September 2005 and January 2013 were included in this observational cohort study. Demographic details, and data from the time of STEP and at follow-up were collected from the case records and analysed. Twelve patients had a total of 16 STEP procedures; four children underwent a second STEP. The first STEP was performed at a median age of 5·8 (range 0·9-19·0) months. There was no death at a median follow-up of 37·2 (range 3·0-87·5) months and no child had small bowel transplantation. Seven of the 12 children were weaned from parenteral nutrition at a median of 19·5 (range 2·3-42·9) months after STEP. STEP is a useful procedure f...