Helicobacter pylori in children: think before you kill the bug!

Since the discovery of Helicobacter pylori (H. pylori) as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless numbers of studies have been conducted and papers published, on the efficacy of various management strategies to eradicate the infection. In adults, a global consensus by the experts in the field concluded that H. pylori gastritis is an infectious disease and requires treatment irrespective of the presence or absence of symptoms due to the potential for serious complication like peptic ulcer disease and gastric neoplasia. However, although more than half the world's population harbors H. pylori, these serious complications occur only in a small minority of the infected population, even less so in childhood. More importantly, there is accumulating evidence for beneficial role of H. pylori against many chronic health conditions, from several epidemiological and laboratory studies. No doubt, eradication therapy is indicated in children with H. pylori-related peptic ulcer disease. Even though the pediatric guidelines from various learned societies recommend against a "test and treat" strategy, this is not always adhered to. With the accumulating evidence of the possible beneficial role of H. pylori, it is time to pause and think, are we causing more harm than good by eradicating H. pylori in every child who has this bug?

Survival of children and adolescents with intellectual disability following gastrostomy insertion.

BACKGROUND: Positive health outcomes have been observed following gastrostomy insertion in children with intellectual disability, which is being increasingly used at younger ages to improve nutritional intake. This study investigated the effect of gastrostomy insertion on survival of children with severe intellectual disability. METHODS: We used linked disability and health data of children and adolescents who were born in Western Australia between 1983 and 2009 to compare survival of individuals with severe intellectual disability by exposure to gastrostomy status. For those born in 2000-2009, we employed propensity score matching to adjust for confounding by indication. Effect of gastrostomy insertion on survival was compared by pertinent health and sociodemographic risk factors. RESULTS: Compared with children born in the 1980s-1990s, probability of survival following first gastrostomy insertion for those born in 2000-2009 was higher (2 years: 94% vs. 83%). Mortality risk was higher in cases than that in their matched controls (hazard ratio 2.9, 95% confidence interval 1.1, 7.3). The relative risk of mortality (gastrostomy vs. non-gastrostomy) may have differed by sex, birthweight and time at first gastrostomy insertion. Respiratory conditions were a common immediate or underlying cause of death among all children, particularly among those undergoing gastrostomy insertion. CONCLUSIONS: Whilst gastrostomy insertion was associated with lower survival rates than children without gastrostomy, survival improved with time, and gastrostomy afforded some protection for the more vulnerable groups, and earlier use appears beneficial to survival. Specific clinical data that may be used to prioritise the need for gastrostomy insertion may be responsible for the survival differences observed.

Tricho-hepatic-enteric syndrome (THES) without intractable diarrhoea.

Tricho-hepatic-enteric syndrome (THES) is a genetically heterogeneous rare syndrome (OMIM: 222470 (THES1) and 614602 (THES2)) that typically presents in the neonatal period with intractable diarrhoea, intra-uterine growth retardation (IUGR), facial dysmorphism, and hair and skin changes. THES is associated with pathogenic variants in either TTC37 or SKIV2L; both are components of the human SKI complex, an RNA exosome cofactor. We report an 8 year old girl who was diagnosed with THES by the Undiagnosed Disease Program-WA with compound heterozygous pathogenic variants in SKIV2L. While THES was considered in the differential diagnosis, the absence of protracted diarrhoea delayed definitive diagnosis. We therefore suggest that SKIV2L testing should be considered in cases otherwise suggestive of THES, but without the characteristic diarrhoea. We expand the phenotypic spectrum while reviewing the current knowledge on SKIV2L.

Accelerated Step-Up Infliximab Use Is Associated with Sustained Primary Response in Pediatric Crohn's Disease.

BACKGROUND: Earlier introduction of infliximab (IFX) in Crohn's disease (CD) may be associated with a sustained remission. METHODS AND AIMS: Children on scheduled IFX therapy for predominant luminal CD after successful induction (drop in PCDAI by ≥ 15) and a minimum of 2-year IFX follow-up were included. We compared outcomes of children treated with early (within 3 months from diagnosis) versus later IFX (after failing conventional therapy ≥ 3 months) and identify clinical predictors of sustained primary response (SPR) in our cohort. SPR was defined as CS-free clinical remission without requiring IFX dose escalation and/or surgical excision and/or switch to second anti-TNFs due to LOR or allergic reaction. RESULTS: Sixty-four children received IFX therapy for CD during the study period. Forty-three children on scheduled IFX therapy for luminal CD met the inclusion criteria. During the median follow-up of 3.05 years (IQR 2.6-3.5 years), SPR was observed in 17/43 (40%). SPR was associated with shorter time from diagnosis to the initiation of IFX (5.4 vs. 18.7 months, p = 0.006). Binary logistic regression using multiple variables also confirmed that only early use of IFX is associated with SPR. CONCLUSION: Early step-up use of IFX in children with CD with inadequate clinical response to conventional therapies leads to sustained primary response over 2 years.

Ninety percent of celiac disease is being missed.

Serological screening of 5470 children age 7.5 years from a cohort of 13,971 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) suggested the prevalence of celiac disease (CD) to be at least 1%. ALSPAC is an anonymous study, and hence seropositive children could not be individually identified or undergo biopsy. Inasmuch as all children within ALSPAC suspected of having CD are referred to just 1 center, we aimed to identify children with biopsy-confirmed CD who were likely to be in this cohort and to estimate the magnitude of discrepancy between serology-positive cases and biopsy-confirmed cases. The results suggest that more than 90% of CD in children goes undiagnosed.

Epidemiology of inflammatory bowel diseases in childhood.

Inflammatory Bowel Disease (IBD) is common in most industrialised countries and childhood IBD accounts for nearly 30% of total cases. Various studies, mostly from Europe and USA have reported epidemiological characteristics of childhood IBD. The incidence figures vary greatly from region to region and within a region over time. Almost all reported studies have documented an increase in the incidence, mainly of Crohn's disease over the last few decades. The reasons for the increase are not clear but epidemiological observations have led to many postulates. Incidence in developing countries is perceived to be low, but limited data suggest that it may not be as uncommon as previously thought. IBD can occur at any age but is rare in infancy. Among childhood IBD, early onset IBD appears to be different epidemiologically and is characterised by predominance of colonic involvement and high positive family history. It has become apparent that only about 25% of childhood Crohn's disease presents with classical triad of abdominal pain, diarrhoea and weight loss. Pediatricians should be aware of atypical manifestations and should maintain high index of suspicion. Though epidemiological studies of childhood IBD done so far have contributed towards understanding of IBD, they have differed in study design, population, time period, age group and case definitions. Unfortunately there are no uniform, clear diagnostic criteria which are evidence based. To address this problem, recently the IBD working group of European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has published "The Porto Criteria" which details a consensus based diagnostic criteria for the diagnosis of childhood IBD. This should bring uniformity in ascertainment of newly diagnosed IBD cases. An European multicentre prospective database has also been established to facilitate future epidemiological studies.

The changing clinical presentation of coeliac disease.

BACKGROUND: There has been a growing recognition that coeliac disease is much more common than previously recognised, and this has coincided with the increasingly widespread use of serological testing. AIM: To determine whether the age at presentation and the clinical presentation of coeliac disease have changed with the advent of serological testing. METHODS: A 21-year review of prospectively recorded data on the mode of presentation of biopsy confirmed coeliac disease in a single regional centre. Presenting features over the past 5 years were compared with those of the previous 16 years. Between 1983 and 1989 (inclusive), no serological testing was undertaken; between 1990 and 1998, antigliadin antibody was used with occasional use of antiendomysial antibody and antireticulin antibody. From 1999 onwards, anti-tissue transglutaminase was used. RESULTS: 86 patients were diagnosed over the 21-year period: 50 children between 1999 and 2004 compared with 25 children between 1990 and 1998 and 11 children between 1983 and 1989. The median age at presentation has risen over the years. Gastrointestinal manifestations as presenting features have decreased dramatically. In the past 5 years, almost one in four children with coeliac disease was diagnosed by targeted screening. CONCLUSION: This study reports considerable changes in the presentation of coeliac disease-namely, a decreased proportion presenting with gastrointestinal manifestations and a rise in the number of patients without symptoms picked up by targeted screening. Almost one in four children with coeliac disease is now diagnosed by targeted screening. Most children with coeliac disease remain undiagnosed. Paediatricians and primary care physicians should keep the possibility of coeliac disease in mind and have a low threshold for testing, so that the potential long-term problems associated with untreated coeliac disease can be prevented.

Early neonatal mortality in an intramural birth cohort at a tertiary care hospital.

Early neonatal mortality (ENM) occurring among 12,283 consecutive live births over a period of 3 years were analysed. The early neonatal mortality rate (ENMR) was 26.6/1000 live births. Birth weight less than 2,000 gm, lack of antenatal care, male sex, operative vaginal delivery, prematurity and multiple pregnancy were significantly associated with early neonatal deaths. Birth asphyxia was found to be the most important cause of death, followed by hyaline membrane disease and congenital malformations. Majority of the asphyxia related deaths were due to late intrapartum referral of the mothers. Forty-two per cent of early neonatal deaths occurred in babies weighing less than 1,500 gm. Early identification and referral of high risk mothers and health education would significantly reduce the early neonatal deaths.