Antibiotics, passive smoking, high socioeconomic status and sweetened foods contribute to the risk of paediatric inflammatory bowel disease: A systematic review with meta-analysis.

OBJECTIVE: Genetic and environmental factors influence pathogenesis and rising incidence of paediatric inflammatory bowel disease (PIBD). The aim was to meta-analyse evidence of diet and environmental factors in PIBD. METHODS: A systematic search was conducted to identify diet and environmental factors with comparable risk outcome measures and had been reported in two or more PIBD studies for inclusion in meta-analyses. Those with ≥2 PIBD risk estimates were combined to provide pooled risk estimates. RESULTS: Of 4763 studies identified, 36 studies were included. PIBD was associated with higher risk with exposure to ≥/=4 antibiotic courses (includes prescriptions/purchases/courses), passive smoking, not being breastfed, sugary drink intake, being a non-Caucasian child living in a high-income country and infection history (odds ratio [OR] range: 2-3.8). Paediatric Crohn's disease (CD) was associated with higher risk with exposure to antibiotics during early childhood, ≥/=4 antibiotic courses, high socioeconomic status (SES), maternal smoking, history of atopic conditions and infection history (OR range: 1.6-4.4). A history of infection was also associated with higher risk of paediatric ulcerative colitis (UC) (OR: 3.73). Having a higher number of siblings (≥2) was associated with lower risk of paediatric CD (OR: 0.6) and paediatric UC (OR: 0.7). Pet exposure was associated with lower risk of paediatric UC (OR: 0.5). CONCLUSION: Several factors associated with PIBD risk were identified that could potentially be used to develop a disease screening tool. Future research is needed to address risk reduction in PIBD.

History of paediatric gastroenterology in Australia.

Paediatric gastroenterology in Australia has undergone remarkable changes over the more than six decades since Charlotte Anderson's pioneering work, and is now a well-established specialty in its own right. Australian paediatric gastroenterologists have made important contributions nationally and internationally.

Long term follow up of persistence of immunity following quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children.

BACKGROUND: Human Papillomavirus (HPV) causes significant burden of HPV-related diseases, which are more prevalent in immunosuppressed compared to immunocompetent people. We conducted a multi-centre clinical trial to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. Here we present the immunogenicity results 5 years post vaccination. METHODS: We followed up immunocompromised children (5-18 years) with a range of specified underlying conditions who were previously recruited from three Australian paediatric hospitals. Participants received three doses of quadrivalent HPV vaccine (Gardasil Quadrivalent HPV Types 6, 11, 16, 18) and were followed up between 2007 and 2016 (60 months post-vaccination). The immunogenicity primary outcome was seroconversion and geometric mean titres (GMT) of the quadrivalent HPV vaccine serotypes in the study. RESULTS: Of the 59 original participants, 37 were followed up at 60 months. The proportion of participants who seroconverted were: 86.5%, 89.2%, 89.2%, 91.9% by competitive Luminex immunoassay (cLIA) and 83.8%, 83.8%, 94.6%, 78.4% by total immunoglobulin G assays (IgG) for serotypes 6, 11, 16 and 18 respectively. GMT values ranged from 118 (95%CI: 79-177) for serotype 11, to 373 (95%CI: 215-649) for serotype 16 by cLIA. For IgG, serotype 16 had the highest GMT of 261 (95%CI: 143-477) and serotype 18 had the lowest value of 37 (95%CI: 21-68). All antibody titres were lower in females compared to males but the difference was not statistically significant except for serotype 16. No serious adverse event was reported during this follow-up period. CONCLUSION: Our evidence, although limited by small numbers, is reassuring that a three dose schedule of HPV vaccine remains immunogenic in immunocompromised children to five years post vaccination. Large scale studies are required to determine long term protection in immunocompromised children. CLINICAL TRIAL REGISTRATION: NCT02263703 (ClinicalTrials.gov).

Early Posthepatoportoenterostomy Predictors of Native Liver Survival in Biliary Atresia.

OBJECTIVES: Most infants with biliary atresia (BA) require liver transplantation (LT) after hepatoportoenterostomy (HPE), including those who initially clear jaundice. The aim of the present study was to identify clinical and routine laboratory factors in infants with BA post-HPE that predict native liver survival at 2 years. METHODS: A retrospective cohort study was conducted in 217 patients with BA undergoing HPE in Sydney, Australia and Toronto, Canada between January 1986 and July 2009. Univariate and multivariate logistic regression using backwards-stepwise elimination identified variables at 3 months after HPE most associated with 2-year native liver survival. RESULTS: Significant variables (P < 0.05) on univariate analysis included serum total bilirubin (TB) and albumin at 3 months post-HPE, bridging fibrosis or cirrhosis on initial liver biopsy, ascites of <3 months post-HPE, type 3 BA anatomy, age at HPE of >45 days, change in length z scores within 3 months of HPE, and center. On multivariate analysis, TB (P < 0.0001) and albumin (P = 0.02) at 3 months post-HPE, and center (P = 0.0003) were independently associated with native liver survival. Receiver operating characteristic analysis revealed an optimal cut-off value of TB <74 µmol/L (4.3 mg/dL; area under the receiver operating characteristic curve 0.8990) and serum albumin level >35 g/L (3.5 mg/dL; area under the receiver operating characteristic curve 0.7633) to predict 2-year native liver survival. TB and albumin levels 3 months post-HPE defined 3 groups (1: TB ≤74 µmol/L, albumin >35 g/L; 2: TB ≤74 µmol/L, albumin ≤35 g/L; 3: TB >74 µmol/L) with distinct short- and long-term native liver survival rates (log-rank P < 0.001). Length z scores 3 months post-HPE were poorer for group 2 than group 1 (-0.91 vs -0.30, P = 0.0217) with similar rates of coagulopathy. CONCLUSIONS: Serum TB and albumin levels 3 months post-HPE independently predicted native liver survival in BA when controlling for center. Serum albumin level <35 g/L in infants with BA who were no longer jaundiced at 3 months post-HPE was a poor prognostic indicator. Poorer linear growth and absence of significant coagulopathy suggest a role for early aggressive nutritional therapy in this group.

Are We Overdoing Pediatric Lower Gastrointestinal Endoscopy?

INTRODUCTION: Lower gastrointestinal endoscopy (LGIE)/colonoscopy is frequently performed for rectal bleeding, recurrent abdominal pain, and the diagnosis of inflammatory bowel disease (IBD). Although these are common indications, the causes of isolated rectal bleeding and recurrent abdominal pain in the otherwise well child have not been described. METHODS: A retrospective analysis of patients who had had an LGIE/colonoscopy from January 2001 to December 2010 was performed. The following data were collected: demographic data, indication, distance reached, macroscopic findings, microscopic findings, diagnosis, additional procedures, and complications. RESULTS: There were a total of 999 colonoscopies. The colonoscopy was normal in 390 of 999 (39%). The commonest indication for colonoscopy was a diagnosis of suspected IBD, 449 of 999 (45%). IBD was confirmed in 282 of 449 (63%), but colonoscopy was normal in 143 of 449 (32%) of suspected IBD. Colonoscopy was performed for rectal bleeding in 197 of 999 (20%) of whom 141 of 197 (72%) were normal. There were 46 (5%) colonoscopies performed for recurrent abdominal pain, which were all normal. Our completion rate to the cecum and beyond was 521 of 999 (52%). Our perforation rate during the 10 years was 0.2%. CONCLUSIONS: Colonoscopy is a safe procedure in pediatrics; however, 39% of colonoscopies in this series were normal. Many of these could have been avoided by eliminating colonoscopy in patients with recurrent abdominal pain in the absence of other clinical features, conservative management with laxatives for those with fresh blood per rectum typical of anal fissures, and fecal calprotectin screening before endoscopy in patients with suspected IBD.

Family Impact and Infant Emotional Outcomes Following Diagnosis of Serious Liver Disease or Transplantation in Infancy.

OBJECTIVES: Research is lacking into the emotional effects on families of serious chronic illness in infants. We examined the effect of the diagnosis of serious liver disease in infants upon parent psychological symptoms and family functioning. We hypothesized that parent psychological symptoms, family functioning, and father engagement will predict infant emotional outcomes. METHODS: Parents of infants recently diagnosed with serious liver disease completed validated questionnaires about parent stress, family function, impact of the illness on the family, and father engagement. The measures were repeated after 1 year, with the addition of the Child Behavior Checklist (CBCL). RESULTS: Parents of 37 infants participated. Parent stress and family functioning scores were not elevated. Parent psychological symptoms, family function, and father engagement did not predict infant outcome. For mothers, infant diagnosis other than biliary atresia, number of outpatient visits, and impact of the illness on the family explained 32% of the variation in CBCL (P = 0.001). For fathers, socioeconomic status, infant diagnosis other than biliary atresia, whether the infant had had a transplant, and impact of the illness on the family explained 44% of the variation in CBCL (P < 0.001). CONCLUSIONS: Parents and families appear to be resilient in coping with serious infant illness. Infant diagnosis other than biliary atresia and parental perceptions of high impact of the illness on the family are indicators of negative emotional outcomes for infants with serious liver disease. Psychosocial interventions for infants with chronic illness should target reducing the impact of illness on the family.

Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children.

AIM: The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. METHODS: A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine. RESULTS: Fifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV. CONCLUSION: Immunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children. CLINICAL TRIAL REGISTRATION: NCT02263703 (ClinicalTrials.gov).

Family adjustment and parenting stress when an infant has serious liver disease: the Australian experience.

OBJECTIVES: Parenting stress, problems in family functioning, and lack of fathers' engagement in treatment are associated with poor quality of life in children with chronic illnesses. The aim of the present study was to examine these characteristics in families of infants with serious liver disease in Australia, to inform the provision of mental health care for these families. METHODS: From September 2009 to May 2013, 42 parents of infants recently diagnosed as having serious liver disease (defined as liver disease that may require transplantation in the future) completed questionnaires about family function, impact of the infant's illness on the family, parent stress symptoms, and fathers' engagement in the care of the child. Participants were recruited from 4 metropolitan children's hospitals in Australia. RESULTS: Parents reported psychological symptoms at similar rates to normative populations. Their reports of family functioning were significantly below mean scores in previously published populations with a medically ill family member (population mean 1.89; mothers mean 1.59; fathers mean 1.61, P < 0.001). Disruption to family roles was significantly correlated with psychological symptoms for mothers (r = 0.48, P < 0.01) and fathers (r = 0.31, P < 0.05). Greater helpfulness of fathers was correlated with lower depression in mothers (r = -0.35, P < 0.05), and fathers' anxiety was correlated with their increased engagement (r = 0.40, P < 0.01). CONCLUSIONS: When parents report the presence of psychological symptoms, symptoms are likely to be present in both parents and are associated with difficulties adjusting to disrupted family roles. Father engagement may be protective of mothers' mental health.

Antireflux surgery in children with neurological impairment: caregiver perceptions and complications.

OBJECTIVES: The aim of the present study was to report caregiver perceptions to antireflux surgery and gastrostomy in children with severe neurological impairment and to report the complications of the surgery. METHODS: Children were identified from a clinic database and clinical information and surgical complications were extracted from the database and hospital medical records. A cross-sectional questionnaire addressing severity of symptoms was administered to parents/caregivers and scored with a 5-point Likert scale (1 is much better to 5, much worse). RESULTS: A total of 122 children, median age 74 months (interquartile range 29-124), 63% spastic quadriplegic cerebral palsy, had antireflux surgery. Laparoscopic surgery was performed in 77 of 122 (63%) and 117 of 122 (96%) had gastrostomy insertion. Questionnaire was completed by 89 of 122 (73%) children; median duration of time from fundoplication to questionnaire was 77 months (43-89). The majority of caregivers indicated that surgery improved or greatly improved weight gain, chest infections, vomiting, and feeding tolerance. Only 2 caregivers reported that they regretted consenting to surgery. Serious surgical complications occurred in 10%. CONCLUSIONS: Serious complications were uncommon in this series of antireflux surgery in neurologically impaired children. Although gagging and retching were common following surgery, a high percentage of caregivers reported improved nutrition, reflux-related symptoms, and high levels of satisfaction.

Nutritional rehabilitation increases the resting energy expenditure of malnourished children with severe cerebral palsy.

AIM: The aim of this study was to measure resting energy expenditure (REE) and energy intake in children with quadriplegic cerebral palsy (CP), to relate these to anthropometric measurements, and to determine the influence of nutritional rehabilitation on REE. METHODS: Fifty-six children (20 females, 36 males; age range 3y 11mo-18y; mean age 10y; SD 3y 11mo) with CP (Gross Motor Function Classification System level V) participated in this cross-sectional study. Children were excluded if they had a known metabolic disorder, genetic syndrome, or chromosomal abnormality. Thirty-three of the children were tube fed and 23 were fed orally. A comparison group comprised 111 (42 females, 69 males) healthy children who had undergone anthropometric and REE measurements and were of similar age to the children with CP (4-19y). REE was measured by indirect calorimetry and energy intake was determined from weighed food records. RESULTS: The REE in the children with CP was low (79.5%) compared with that predicted and highly variable (SD 38.4%). Fat-free mass was the strongest predictor of REE, accounting for 27% of the variation. Energy intake as a percentage of REE in was greatly overestimated in oral-fed children with CP (293%). In a subset of children with CP (n=14), an increased energy intake by gastrostomy tube feeding resulted in an increase in REE from 70.0% to 101.9% of that predicted. INTERPRETATION: The REE of children with CP is low and variable and is not strongly related to any one anthropometric measurement. Food records in oral-fed children with CP are of little value owing to their inaccuracy. This study provided support for the hypothesis that the low REE found in malnourished children with CP is partly due to a low energy intake.

Mitochondrial respiratory chain hepatopathies: role of liver transplantation. A case series of five patients.

INTRODUCTION: Orthotopic liver transplantation (OLT) in patients with mitochondrial respiratory chain disorders (MRCD) is controversial because of possible multi-organ involvement. AIM: To illustrate the clinical diversity of MRCD, the difficulty in making an accurate tissue diagnosis and whether to undertake OLT in five patients with proven MRCD. A review of the reported cases in the literature is presented. METHODS: Retrospective chart review from 1995 to 2007 at a paediatric liver transplant centre where five children with hepatic MRCD were identified. RESULTS: Patient 1 was transplanted for 'cryptogenic' cirrhosis. The diagnosis of MRCD was made on the explant. The patient remains well 5 years after transplant. Patient 2 presented with fulminant liver failure at 3 months of age. Although no extrahepatic manifestations were identified, OLT was not considered. Patient 3 presented with recurrent hypoglycaemia and was transplanted for fulminant hepatic failure at 12 months of age. He died of pulmonary hypertension 9 months post OLT. Patient 4 was diagnosed with MRCD at the age of 2 years. Death occurred at the age of 14 years, while listed for combined liver-kidney transplant, after a stroke-like episode following severe sepsis. Patient 5 developed liver failure after valproic acid was instituted for seizures. Mitochondrial DNA depletion syndrome was diagnosed and transplantation was not offered. CONCLUSION: Hepatic MRCD has a variable presentation. Diagnosis requires the measurement of respiratory chain enzymes on tissue from liver biopsy. Whether to proceed to OLT is a difficult decision given a good outcome in a minority of cases, suggesting that MRCD should not be an absolute contraindication to liver transplantation.

Detection of Helicobacteraceae in intestinal biopsies of children with Crohn's disease.

BACKGROUND: Given that members of Helicobacteraceae family colonize the intestinal mucus layer, it has been hypothesized that they may play a role in Crohn's disease. This study investigated the presence of Helicobacteraceae DNA in biopsies collected from children with Crohn's disease and controls. MATERIALS AND METHODS: The presence of Helicobacteraceae DNA was investigated in intestinal biopsies collected from 179 children undergoing colonoscopy (Crohn's disease n = 77, controls n = 102) using a Helicobacteraceae-specific PCR. RESULTS: Members of the Helicobacteraceae were detected in 32/77 children with Crohn's disease (41.5%) and 23/102 controls (22.5%). Statistical analysis showed the prevalence of Helicobacteraceae detected in patients to be significantly higher than that in controls (p = .0062). Analysis of non-pylori Helicobacteraceae showed that their prevalence was also significantly higher in patients than in controls (p = .04). Helicobacter pylori was detected in 14.0% of the biopsies across all groups. Given that all children tested were negative for gastric H. pylori, this was a surprising finding. Phylogenetic analysis of H. pylori sequences detected in the biopsies showed that the H. pylori strains identified in the patients did not group with gastric H. pylori included in the analysis, but rather with other H. pylori strains detected in the intestine, gall bladder, and liver. CONCLUSIONS: The higher prevalence of Helicobacteraceae DNA in Crohn's disease patients would suggest that members of this family may be involved in this disease. In addition, phylogenetic analysis of H. pylori strains showed that extragastric sequences clustered together, indicating that different H. pylori strains may adapt to colonize extragastric niches.

Isolated liver transplantation in children with cystic fibrosis--an Australian experience.

CF liver disease is an uncommon indication for pediatric LT. Determining optimal timing and type (isolated liver versus multi-organ) of transplantation for those with severe liver disease can be challenging and involves consideration of the extent of liver disease (PHT, synthetic dysfunction) and extrahepatic factors such as pulmonary function. We present the experience of isolated LT for CF at our center. Eight children received one allograft each (3.9% of all grafts). One- and four-yr survivals are both 75%. The two deaths occurred within the first two months after LT, and in both cases, invasive fungal infections were implicated, one following treatment for acute severe rejection. All had significant PHT, and six had synthetic dysfunction. All had roux-en Y biliary anastomoses and none developed long-term biliary complications. Seven had pulmonary colonization with Pseudomonas aeruginosa and six with fungus at time of transplantation. Mean pre-LT FEV1 was 80% (range 59-116%) predicted, and lung function post-LT was stable. Isolated LT in children with CF is successful in those with relatively preserved pulmonary function, which does not appear to deteriorate as a consequence. Roux-en Y biliary anastomosis and antifungal prophylaxis should be a part of management of these patients.

Pneumomediastinum and subcutaneous emphysema in a child with ulcerative colitis.

We discuss the case of a young adolescent boy with ulcerative colitis who developed pneumomediastinum and subcutaneous emphysema in the neck and surrounding cervical soft tissues secondary to a probable retroperitoneal perforation of the colon. To our knowledge, this is the first reported case of this complication in the pediatric literature. Our experience provides insight into this unusual complication, how it may present, and its clinical significance in young patients with ulcerative colitis. The literature on this complication is also discussed.

Biliary strictures and hepatic artery flow abnormalities in split liver transplants.

The aim of this study was to examine the role of HA flow abnormalities in the development of biliary strictures following split liver transplants. Data was obtained from a prospective data base of all patients undergoing split liver transplants from 2000-2008 with a follow up time of at least six months. Forty-six transplants were performed in 44 patients. Fourteen of 46 developed strictures of whom four were intrahepatic and 10 anastomotic. Nine of 14 with strictures had either hepatic artery thromobosis (HAT, four) or abnormalities of HA flow identified by routine Doppler ultrasound (5) compared with two of 32 without strictures (p < 0.02, (one temporary loss of flow and one HA aneurysm). There were no differences between the stricture and non stricture group with regard to age or weight at transplant, donor age, cold and warm ischemia times or intraoperative portal vein flow though there was a significant decrease in intraoperative HA flow in the stricture group. In conclusion, both HAT and hepatic artery flow abnormalities are associated with biliary strictures in the majority of split liver transplants. However, unrecognised abnormalities in HA flow and or other factors are likely to contribute.

Chronic hepatitis B and C infection in children in New South Wales.

OBJECTIVE: To characterise epidemiological, clinical and laboratory features of children in New South Wales with chronic hepatitis B (HBV) or C (HCV) infections. DESIGN AND SETTING: Retrospective record review of epidemiological, clinical, laboratory, liver biopsy and treatment data for children (aged < 18 years) referred to tertiary referral paediatric and refugee clinics in NSW with chronic HBV or HCV during 2000-2007; and comparison with NSW Health notification data for the same period. MAIN OUTCOME MEASURES: Numbers and characteristics of referred children with HBV and HCV, and notifications to NSW Health. RESULTS: During 2000-2007, 79 children with chronic HBV and 29 with HCV infection were referred to specialist clinics, while 930 children with HBV and 777 with HCV infection were reported to NSW Health. Most of the referred children with HBV were born overseas, while most with HCV were born in Australia to mothers with a history of intravenous drug use. Of the 79 HBV-infected children, 56 were e-antigen positive. Most HCV-infected children (23/29) had alanine aminotransferase levels < or = 2 times the upper limit of normal, and more than half of those who had genotype determined had type 2 or 3. Fibrosis was evident in liver biopsies performed for both HBV and HCV. CONCLUSIONS: Although advanced liver disease was uncommon in children referred with HBV or HCV infection, a large number of infected children in NSW were not referred for specialist medical care, indicating that opportunities to intervene early in the natural history of these infections, particularly HCV, are being missed.

Detection and isolation of Campylobacter species other than C. jejuni from children with Crohn's disease.

The presence of Campylobacter species other than Campylobacter jejuni and antibodies to Campylobacter concisus in children were investigated. A significantly greater presence of C. concisus and higher levels of antibodies to C. concisus were detected in children with Crohn's disease (CD) than in controls. Campylobacter species other than C. jejuni were isolated from intestinal biopsy specimens of children with CD.