Systematic review of the evidence base for the medical treatment of paediatric inflammatory bowel disease.

OBJECTIVE: To systematically review the evidence base for the medical (pharmaceutical and nutritional) treatment of paediatric inflammatory bowel disease. METHODS: Key clinical questions were formulated regarding different treatment modalities used in the treatment of paediatric (not adult-onset) IBD, in particular the induction and maintenance of remission in Crohn disease and ulcerative colitis. Electronic searches were performed from January 1966 to December 2006, using the electronic search strategy of the Cochrane IBD group. Details of papers were entered on a dedicated database, reviewed in abstract form, and disseminated in full for appraisal. Clinical guidelines were appraised using the AGREE instrument and all other relevant papers were appraised using Scottish Intercollegiate Guidelines Network methodology, with evidence levels given to all papers. RESULTS: A total of 6285 papers were identified, of which 1255 involved children; these were entered on the database. After critical appraisal, only 103 publications met our criteria as evidence on medical treatment of paediatric IBD. We identified 3 clinical guidelines, 1 systematic review, and 16 randomised controlled trials; all were of variable quality, with none getting the highest methodological scores. CONCLUSIONS: This is the first comprehensive review of the evidence base for the treatment of paediatric IBD, highlighting the paucity of trials of high methodological quality. As a result, the development of clinical guidelines for managing children and young people with IBD must be consensus based, informed by the best-available evidence from the paediatric literature and high-quality data from the adult IBD literature, together with the clinical expertise and multidisciplinary experience of paediatric IBD experts.

Interventions for growth failure in childhood Crohn's disease.

BACKGROUND: Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians. OBJECTIVES: To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth. SEARCH STRATEGY: Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed. SELECTION CRITERIA: Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible. MAIN RESULTS: Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group. AUTHORS' CONCLUSIONS: In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.

Thermal stress, sleeping position, and the sudden infant death syndrome.

We review the evidence than overheating or disordered thermoregulation may be responsible for some cases of the Sudden Infant Death Syndrome (SIDS). Possible mechanisms for an interaction of thermal stress and the prone position are discussed with an emphasis on heat production and loss via the infant head. After the reduction in the prevalence of the prone position following "Back to Sleep" campaigns, and the emergence of cigarette smoking as a key risk factor, the role of disordered thermoregulation continues to be important in many cases of SIDS.

Night-time non-nutritive sucking in infants aged 1 to 5 months: relationship with infant state, breastfeeding, and bed-sharing versus room-sharing.

AIM: Epidemiological studies suggest that pacifier use may be protective against SIDS but little is known of the relationship between pacifier use and other forms of non-nutritive sucking (NNS) in infancy, or of patterns of NNS during the night, when most SIDS deaths occur. We report the first longitudinal study of NNS by direct overnight observations in healthy infants in a sleep laboratory. METHODS: Healthy, breast fed term infants (n = 10) were enrolled at birth, and sequential overnight polygraphic and infrared video recordings of infants with their mothers performed at monthly intervals from 1 to 5 months. Each month, mother baby pairs were randomized to 1 night bed-sharing (BN) then 1 room-sharing (RN), or vice versa. 'Episodes' of pacifier, own digit and mother's digit sucking (> 1 min) were identified and compared with state-matched control periods without sucking or feeding before and after each such episode. RESULTS: 329 episodes of NNS were identified in 749 h of video recording. The prevalence of pacifier sucking decreased with age, whilst digit sucking increased. Routine pacifier users rarely sucked their digits. There were temporal differences throughout the night in the distribution of different types of sucking and in infant state during and around sucking episodes. Sleeping in the 'non-routine' location was associated with a larger percentage of nights with sucking episodes and increased sleep latency. Bed sharing (routinely or on a given night) was associated with less sucking behavior and more breastfeeding. Non-nutritive sucking was not, however, associated with decreased total time breastfeeding per night or number of feeds per night. CONCLUSION: Patterns of NNS during the night change with age and are affected by maternal proximity. Digit sucking has state modulating effects, and may be suppressed by pacifier use. Thus any benefits of pacifier use must be set against the potential loss of a self-directed ability to modulate state during the night, and possible shortening of breastfeeding duration.

Newer diarrheal syndromes.

Aetiological diagnosis of protracted diarrhoea remains obscure in as many as 30% of cases despite extensive investigations. A number of newer syndromes have been recognized amongst this "idiopathic group" which includes microvillous inclusion disease, "tufting" enteropathy and epithelial dysplasia, autoimmune enteropathy and "syndromic" immunodeficiency with characteristic facial abnormalities, woolly hair and intractable diarrhea. The molecular basis of some of these syndromes has been reviewed but in only a small series of patients has the functional defect been characterized. If a case is suspected the antenatal history, family history and history of consanguinity should be sought. Extra-intestinal manifestations, presence of gut or other auto-antibodies, together with phenotypic abnormalities should be looked for. Careful light and electron microscopy is done of small bowel biopsies, although microvillous inclusion disease can be usually suspected on PAS staining. Large bowel biopsy may be needed to exclude an unsuspected microscopic colitis. The prognosis of this group of conditions is poor with an overall 50-85% mortality. Although successful gut transplantation has been reported, genetic counselling may be one of the more important aspects of the clinicians' role.

Gastroesophageal reflux in children.

Gastroesophageal reflux (GOR) is a major cause of morbidity and failure to thrive particularly in neurologically impaired children. Clinical manifestations of GOR in children range from regurgitation, food refusal, irritability, failure to thrive, hematemesis, wheezing and aspiration pneumonia, apnoea and apparent life threatening events in infants to clinically silent reflux. Although, no one test is always best to diagnose GOR, 24 hour esophageal pH monitoring remains the 'gold standard' for diagnosis. Barium radiography is useful for the diagnosis of associated anatomical abnormalities and endoscopy enables a histological diagnosis of esophagitis. Therapy for gastroesophageal reflux disease is now well established. Proper positioning of the baby and thickening of feeds is beneficial in uncomplicated GOR. Prokinetic agents like cisapride should be tried if dietary management and antacids are ineffective. Metoclopramide or domperidone may be tried in neurologically impaired children. H2-receptor antagonists are indicated in GOR complicated by esophagitis. Ranitidine is regarded to be more potent. Cimetidine has additional spectrum of adverse effects and sufficient information is not available on famotidine. Omeprazole has been shown to be effective in treating GOR-esophagitis resistant to H2 antagonist therapy even in high risk patients.

Presenting features of inflammatory bowel disease in Great Britain and Ireland.

BACKGROUND: Reports from individual referral centres suggest that a significant proportion of children with inflammatory bowel disease (IBD) present after prolonged delays and with impaired growth. AIMS: To prospectively document the presenting features, delay in presentation, disease localisation, and growth in newly diagnosed cases of IBD. METHODS: For 13 months, between June 1998 and June 1999, 3247 paediatricians, adult gastroenterologists, and surgeons across the UK and Ireland were prospectively surveyed each month and asked to report every newly diagnosed case of childhood IBD. RESULTS: A total of 739 new IBD cases aged less than 16 years were identified. Only one quarter of Crohn's disease (CD) cases presented with the "classic triad" of diarrhoea, weight loss, and abdominal pain; nearly half did not report diarrhoea. The median delay from onset of symptoms to diagnosis was 5 months (mean 11 months), with one fifth having symptoms of more than one year. Delays were most common in CD and in younger children. Short stature was noted only in those with CD and not with ulcerative colitis. One fifth of CD cases had disease activity in the jejunum and this group had significantly reduced stature. Ileo-colonic involvement was documented in most CD cases, with only a small minority having isolated ileal or isolated colonic disease. Pan-colitis was reported in most UC cases, with very few having only an isolated proctitis. CONCLUSIONS: Many children are diagnosed after prolonged delays and have growth failure. Improved knowledge of the presenting features of IBD, and earlier investigation of suspected cases, may help reduce the delays noted.

Variations in initial assessment and management of inflammatory bowel disease across Great Britain and Ireland.

BACKGROUND: There are no published data from Great Britain and Ireland detailing the initial management of children with inflammatory bowel disease (IBD). AIMS: To prospectively record the initial investigation and treatment of children aged less than 16 years with newly diagnosed IBD. METHODS: For 13 months, between June 1998 and June 1999, 3247 paediatricians, adult gastroenterologists, and surgeons across the UK and Ireland were prospectively surveyed each month and asked to report every newly diagnosed case of childhood IBD. Reporters subsequently completed a postal questionnaire about each case. RESULTS: A total of 739 new IBD cases were reported from 172 institutions. Significant variations were observed in the investigation and treatment of these cases, when examined by number of cases reported per institution, or by the specialists providing care. There were wide regional variations in the proportion of children having access to paediatric gastroenterology services. Overall, one third of children received care from an adult service, and a tenth care exclusively from an adult gastroenterologist. Children with Crohn's disease who had some or all of their care from adult services were more likely to receive systemic steroids and less likely to receive dietary therapy; those with ulcerative colitis were more likely to receive rectal steroids and to have surgery. Height and weight were also less likely to be recorded in those whose care involved adult services. CONCLUSION: Current specialist provision, and initial investigation and treatment of IBD, is heterogeneous. Optimisation of care is likely to be achieved by greater access to specialist paediatric gastroenterology services for all those with suspected IBD.

Prospective survey of childhood inflammatory bowel disease in the British Isles.

The incidence of inflammatory bowel disease in children in western countries may be rising. Since there is no prospective national data on the incidence of inflammatory bowel disease in the UK and Republic of Ireland (ROI), we undertook a prospective survey to determine this incidence. The incidence during 1998 and 1999 was 5.2/100,000 per year in children aged younger than 16 years. Those from an Asian background were over-represented and more likely to have ulcerative colitis.