Gastrointestinal transit time of radiopaque ingested foreign bodies in children: experience of two paediatric tertiary centres.

Introduction: Foreign body (FB) ingestion is a common paediatric emergency. While guidelines exist for urgent intervention, less is known of the natural progress of FBs passing through the gastrointestinal tract (GIT). We reviewed these FB transit times in an outpatient cohort. Methods: A retrospective review was performed on all children (≤18 years) treated for radiopaque FB ingestion at two major tertiary paediatric centres from 2015 to 2016. Demographic data, FB types, outcomes and hospital visits (emergency department [ED] and outpatient) were recorded. All cases discharged from the ED with outpatient follow-up were included. We excluded those who were not given follow-up appointments and those admitted to inpatient wards. We categorised the outcomes into confirmed passage (ascertained via abdominal X-ray or reported direct stool visualisation by patients/caregivers) and assumed passage (if patients did not attend follow-up appointments). Results: Of the 2,122 ED visits for FB ingestion, 350 patients who were given outpatient follow-up appointments were reviewed (median age 4.35 years [range: 0.5-14.7], 196 [56%] male). The largest proportion (16%) was aged 1-2 years. Coins were the most common ingested FB, followed by toys. High-risk FB (magnets or batteries) formed 9% of cases (n=33). The 50th centile for FB retention was 8, 4 and 7 days for coins, batteries and other radiopaque FBs, respectively; all confirmed passages occurred at 37, 7 and 23 days, respectively. Overall, 197 (68%) patients defaulted on their last given follow-up. Conclusion: This study provides insight into the transit times of FB ingested by children, which helps medical professionals to decide on the optimal time for follow-up visits and provide appropriate counsel to caregivers.

Epidemiological characteristics of Asian children with inflammatory bowel disease at diagnosis: Insights from an Asian-Pacific multi-centre registry network.

BACKGROUND: There remains a dearth of Asian epidemiological literature for paediatric inflammatory bowel disease (PIBD). AIM: To describe the presenting features of PIBD from 7 Asia-Pacific pediatric gastroenterology centers via a central standardised electronic data platform. METHODS: Clinical, endoscopic and radiologic data at diagnosis from the registry were extracted between 1st January 1995 to 31st December 2019. Disease phenotypic characteristics were classified as per the Paris classification system. RESULTS: There was a distinct rise in new PIBD cases: Nearly half (48.6%) of the cohort was diagnosed in the most recent 5 years (2015-2019). The ratio of Crohn's disease (CD):Ulcerative colitis (UC):IBD-Unclassified was 55.9%:38.3%:5.8%. The mean age was 9.07 years with a high proportion of very early onset IBD (VEO-IBD) (29.3%) and EO-IBD (52.7%). An over-representation of the Indian/South Asian ethnic group was observed which accounted for 37.0% of the overall Singapore/Malaysia subcohort (6.8%-9.0% Indians in census). Indian/South Asian CD patients were also most likely to present with symptomatic perianal disease (P = 0.003). CD patients presented with significantly more constitutional symptoms (fever, anorexia, malaise/fatigue and muscle-wasting) than UC and higher inflammatory indices (higher C-reactive protein and lower albumin levels). CONCLUSION: We observed a high incidence of VEO-IBD and an over-representation of the Indian ethnicity. South Asian CD patients were more likely to have symptomatic perianal disease.

Antibiotic resistance patterns and therapeutic outcomes of pediatric Helicobacter pylori infection in a high-migrant Singaporean cohort.

BACKGROUND: Variation in Helicobacter pylori (H. pylori) disease in terms of prevalence and antibiotic resistance prevails globally requiring a need to develop region-specific surveillance. We aimed to assess the influence of immigration factors upon the interpretation of local Singaporean epidemiological trends in antimicrobial susceptibility patterns and therapeutic outcomes in children with culture-positive H. pylori. MATERIALS AND METHODS: We retrospectively analyzed eradication outcomes of children with culture-proven H. pylori infections between 2011 and 2020 at our center, and we also analyzed the antimicrobial susceptibility profiles of the corresponding H. pylori isolates. The cohort was classified into two groups: (1) Native Singaporeans and (2) Non-native Singaporeans (First-/Second-generation immigrants and Non-residents) to correlate with resistance patterns and eradication outcomes. H. pylori culture was done via Kirby-Bauer disk diffusion for the era 2011-2016 and bioMérieux E test for 2016-2020. RESULTS: A total of 70 children (median age 14 [2-17] years) were included in the analysis. 42.9% (30/70) of the cohort displayed some form of antibiotic resistance; clarithromycin resistance was the most prevalent (30.0%), followed by metronidazole (27.5%) and amoxicillin (7.1%). Comparing to natives, non-native Singaporeans were significantly younger at presentation (mean 11.7 vs. 13.7 years, p = 0.043), and a significantly higher proportion of non-natives carried clarithromycin-resistant (51.4% vs. 8.6%, p < 0.001), metronidazole-resistant (47.1% vs. 8.6%, p < 0.001), or multidrug-resistant (resistant to ≥2 drugs) (40.0% vs. 2.9%, p < 0.001] strains. Non-natives were significantly more likely to fail first-line eradication therapy (48.5% failure vs. 23.3%, p = 0.038). The proportion of pan-sensitive H. pylori was significantly lower in first-generation (25.0%, p = 0.001) and second-generation (42.9%, p = 0.018) immigrants compared to natives (82.86%). These conclusions did not vary when the analysis was repeated for each culture method. CONCLUSIONS: An antibiotic susceptibility-based approach should be advocated for all patients but especially so for non-natives, who are at higher risk for antimicrobial resistant strains and poorer eradication outcomes.

Demographics, aetiology and outcome of paediatric acute liver failure in Singapore.

Introduction: The aetiology of paediatric acute liver failure (PALF) varies widely according to age, and geographic and socioeconomic factors. This study aimed to examine the epidemiology, aetiology and outcome of PALF in Singapore at a single centre. Methods: A retrospective review was performed of patients aged 0-18 years who were diagnosed with PALF from 2007 to 2019. PALF was defined by: absence of chronic liver disease; biochemical evidence of acute liver injury; and coagulopathy, non-correctible by vitamin K, defined as prothrombin time (PT) ≥20 seconds or international normalised ratio (INR) ≥2.0 regardless of hepatic encephalopathy (HE) or PT ≥15 seconds or INR ≥1.5 in the presence of HE. Results: 34 patients were included. Median age at diagnosis was 10 months (range 7 days to 156 months). The top three causes of PALF were indeterminate (41.2%), metabolic (26.5%) and infectious (26.5%) aetiologies. A metabolic disorder was the most frequent aetiology in infants <12 months (38.9%), whereas an indeterminate cause was the most common in children >12 months (50%). No cases of viral hepatitis A or B presenting with PALF were detected. Overall spontaneous recovery rate (survival without liver transplantation [LT]) was 38.2%, and overall mortality rate was 47.1%. Six patients underwent living-donor LT, and the post-transplant survival at one year was 83.3%. Conclusion: The aetiologic spectrum of PALF in Singapore is similar to that in developed Western countries, with indeterminate aetiology accounting for the majority. PALF is associated with poor overall survival; hence, timely LT for suitable candidates is critical to improve survival outcomes.

Cholestatic Jaundice in Sulphite Oxidase Deficiency - An Unusual Association.

Sulphite oxidase deficiency is an extremely rare inborn error of metabolism of sulphur containing amino acids. There are no reports of liver involvement in this condition. The authors describe a 9-y-old boy with known sulphite oxidase deficiency who presented with worsening cholestatic hepatitis which may be possibly related to underlying metabolic disorder. Although there is no current evidence that treating liver disease and ensuring normal hepatic function in sulphite oxidase deficiency would likely benefit patients, this could potentially contribute to optimising growth and development as well as improving the overall prognosis.

Characteristics and outcome of primary sclerosing cholangitis associated with inflammatory bowel disease in Asian children.

BACKGROUND: Current knowledge on the clinical features and natural history of childhood primary sclerosing cholangitis - inflammatory bowel disease in Asia is limited. We described the presenting features and natural history of primary sclerosing cholangitis-inflammatory bowel disease seen in a cohort of Southeast Asian children. METHODS: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia. RESULTS: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived. CONCLUSIONS: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease.

Parental concern of feeding difficulty predicts poor growth status in their child.

BACKGROUND: Parents often express concerns about feeding difficulties in their child. We hypothesized that these parental concerns were associated with adverse growth status in early childhood. We aimed to determine the prevalence of such concerns and whether these concerns were associated with adverse growth status in early childhood. METHODS: We performed a cross-sectional study among healthy children aged 12-36 months attending three well-baby clinics in three urban areas in Malaysia and Singapore between December 2016 and February 2017. Parents were interviewed for concerns about their child's feeding and presence of behavioral and organic red flags for feeding difficulties. We defined growth faltering as weight-for-age < 3rd centile and short stature as height-for-age < 3rd centile according to World Health Organization Growth Standards. RESULTS: Of the 303 children studied (boys = 160, 52.8%; mean [± SD] chronological age at interview 21.3 [± 4.0] months), 13% (n = 38/292) had growth faltering and 19.5% (n = 50/256) had short stature. Overall, 36.3% (n = 110) of parents expressed concerns about their child's feeding behavior. Sixty-eight percent (n = 206) of parents reported presence of at least one behavioral and 18.5% (n = 56) had at least one organic red flag for feeding difficulties, respectively. 9.9% (n = 30) had both behavioral and organic red flags for feeding difficulties. Growth faltering was significantly associated with parental concern about feeding (odds ratio [OR] 3.049, p < 0.001), food refusal (OR 4.047, p < 0.001) and presence of at least one organic red flag (OR 2.625, p = 0.012). CONCLUSION: We found that parental concerns about their child's feeding to be common. Presence of parental concern, food refusal in the child and presence of organic red flags for feeding difficulties are associated growth faltering in early childhood.

Growth Assessment and Monitoring during Childhood.

Growth is an indicator of the health and nutritional status of infants and children. Health organisations and professionals worldwide advocate monitoring the growth of children with the primary aim of identifying and preventing malnutrition and/or obesity. Growth monitoring should be part of every health care consultation for children. However, physicians during health care consultations are often so busy addressing acute health issues, that they miss the opportunity to monitor the child's growth and provide anticipatory guidance. Appropriate growth monitoring would enable health care providers to detect abnormal growth in a timely manner, as well as to reassure parents if their concerns are unfounded. To perform this effectively, physicians need to be familiar with measurement methods, use of appropriate growth charts and interpretation of results. As weight, height and growth rates may vary among children, physicians also need to understand what constitutes normal growth. This paper aims to clarify the purpose of growth monitoring and provide recommendations for physicians to assess, monitor and manage growth in infants and children in a primary care setting.

Risk factors and clinical outcomes of pediatric liver transplant recipients with post-transplant lymphoproliferative disease in a multi-ethnic Asian cohort.

BACKGROUND: We aimed to evaluate clinical characteristics, risk factors, and disease outcomes for liver transplant recipients (LTR) with post-transplant lymphoproliferative disease (PTLD) at our center. METHODS: Retrospective review of data of all pediatric LTR (1991-2015) was conducted. RESULTS: The overall incidence of PTLD was 16.4% (18/110), the majority (13/18) were early lesions, while 3/18 were polymorphic/monomorphic PTLD. The risk factors significant on univariate analysis were as follows: mean age (years) at transplant (1.66 vs 4.76, P = .006); age <2 years at transplant (odds ratio [OR] 3.53 [95% confidence interval [CI]: 1.16-10.73], P = .026); cytomegalovirus (CMV) primary infection (OR 11.39 [95% CI: 3.44-37.7], P < .001); recipient CMV seronegativity (OR 7.50 [95% CI: 2.02-27.78], P = .003); presence of CMV end-organ disease (OR 4.00 [95% CI: 1.22-13.16], P = .022); Chinese ethnicity; and higher mean duration of intravenous ganciclovir prophylaxis. In multivariate analysis, CMV primary infection (OR 5.22 [95% CI: 1.25-21.87], P = .024), CMV seronegativity (OR 5.91 [95% CI: 1.13-30.90, P = .035]), and having acute cellular rejections (ACR) prior to PTLD (OR 5.53 [95% CI: 1.43-21.48, P = .013]) were significant risk factors for PTLD, with the latter two factors having a synergistic effect in increasing PTLD risk in a stratified analysis. The final multivariate model in predicting the risk of PTLD, utilizing CMV primary infection, recipient CMV seronegativity, and ACR before PTLD as predictive variables, was statistically significant (likelihood ratio chi square statistic = 25.18, P < .0001 with df = 3). CONCLUSIONS: We report a unique clinicopathologic and risk factor profile in our cohort-early lesion PTLD accounts for the majority and the incidence of monomorphic PTLD remains low. In addition, we show a synergism between CMV naivety and ACR on PTLD risk, a higher prevalence of gastrointestinal manifestations, and a lack of significant association with Epstein-Barr virus seronegativity.

Serologic Responses After Hepatitis B Vaccination in Preterm Infants Born to Hepatitis B Surface Antigen-Positive Mothers: Singapore Experience.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends a 4-dose vaccination schedule for preterm low birth weight infants (<2 kg) and a 3-dose vaccination schedule for preterm infants (≥2 kg) born to hepatitis B surface antigen (HBsAg)-positive mothers. However, data remain limited for these high-risk infants, and the optimal dosing schedule in Asia is not well established. AIM: The aim of this study was to evaluate the serologic vaccine responses in preterm infants born to HBsAg-positive mothers using current vaccination guidelines. METHODS: Preterm babies of gestation less than 37 completed weeks born to HBsAg-positive mothers were prospectively recruited during 6 years (June 2009 to December 2015) and retrospectively recruited via convenience sampling in 2 years (June 2013 to April 2015) in 2 tertiary pediatric centers. The preterm infants were given 4 or 3 vaccine doses as per ACIP 2005 guidelines. Vaccine response was defined as achieving hepatitis B surface antibody values of >10 IU/L [Abbott Architect (Abbott Laboratories, Chicago, IL)] at 9 months of chronologic age. RESULTS: A total of 24 preterm infants were recruited. Four had a birth weight <2 kg. Of 23 surviving infants, all were negative for HBsAg. One baby (4.5%) did not achieve adequate vaccine response. All 4 infants with birth weight <2 kg achieved seroprotective values. CONCLUSION: The current ACIP-recommended vaccination schedule results in adequate antibody responses in preterm infants of HBsAg-positive mothers.

Endoscopic Evaluation in Children With End-Stage Liver Disease-Associated Portal Hypertension Awaiting Liver Transplant.

OBJECTIVES: Routine oesophago-gastro-duodenoscopy (OGD) pre-liver transplantation (LT) for evaluation and management of gastrointestinal (GI) pathology, in particular GI varices secondary to portal hypertension, is common practice in adult LT programmes. There is no universal consensus for this practice in children. We report our endoscopic experience in children with end-stage liver disease (ESLD) pre-LT. METHODS: Retrospective audit of LT database and review of OGD findings of patients who had undergone endoscopy preceding LT. RESULTS: Of 69 patients with ESLD, 50 (72.4%) had pre-LT OGD, 37 of which were done electively, whereas the remaining 13 were event driven. Forty-eight (96%) patients who underwent OGD had abnormalities, in which 38 (76%) patients had varices and 23 (46%) had portal hypertensive gastropathy. Eleven (22%) patients required therapeutic intervention at initial OGD either with endoscopic variceal band ligation or endoscopic sclerotherapy. Compared with the group who underwent elective OGDs, the group who had event-driven OGDs had a significantly higher requirement for endoscopic intervention (P < 0.0001), occurrence of rebleeding (P < 0.029) and requirement for repeat OGDs (P = 0.014). There was no significant difference in terms of patient (P = 0.2746) or graft survival (P = 0.3192) between the 2 groups. CONCLUSIONS: The role of pre-LT OGDs in patients with ESLD associated with portal hypertension is possibly limited to control of bleeding during episodes of GI bleed, where the aim would be to stabilize the patient until eventual LT. Multicentre prospective studies are required to provide more evidence on the use of routine endoscopy for pre-LT assessment in children.

Long-term outcome of mycophenolate mofetil rescue therapy for resistant acute allograft rejection in pediatric liver transplant recipients.

Mycophenolate mofetil (MMF) has been used to rescue liver allografts with steroid-resistant rejection (SRR). However, the long-term outcome of these patients is not known. This study evaluates the long-term outcome of MMF rescue therapy for SRR in pediatric liver allograft recipients. Twenty-six children (who received 28 liver transplants), including 16 girls, were given MMF for SRR. The median age at transplant was 1.7 (range 0.4-13.6) years. Primary immunosuppression was cyclosporine-based in 22 and tacrolimus-based in 6. All patients except one had been converted to tacrolimus prior to MMF, having already received a median of 2 (1-5) courses of high-dose intravenous methylprednisolone. The median time to MMF rescue therapy was 1.8 (0.4-35.8) months. Twenty-one of 28 episodes of SRR responded to MMF therapy. The median follow-up was 8.8 (7.7-11.5) years. In responders, there was 1 death from posttransplant lymphoproliferative disease, and no grafts were lost to chronic rejection. In the 7 nonresponders, 3 grafts were lost to chronic rejection with 2 patient deaths. Surviving children are clinically well with good liver function, and 17 remain on MMF. Three children have glomerular filtration < 80 mL/minute/1.73 m(2). Side effects of MMF were seen in 12 patients; diarrhea (n = 5) and leukopenia (n = 5) being the most common. MMF was found to be effective in treating SRR in pediatric allograft recipients, with good long-term graft function and an acceptable side-effect profile.