Aims Non-specific abdominal pain (NSAP) is the most common diagnosis on discharge following admission for abdominal pain in childhood. Our aim was to determine the risk of subsequent hospital diagnosis of organic and functional gastroenterological conditions following a diagnosis of NSAP, and to assess the persistence of this risk.
Methods An NSAP cohort of 268 623 children aged 0–16 years was constructed from linked English Hospital Episode Statistics from 1999 to 2011. The control cohort (1 684 923 children, 0–16 years old) comprised children hospitalised with unrelated conditions. Clinically relevant outcomes were selected and standardised rate ratios were calculated.
Results From the NSAP cohort, 15 515 (5.8%) were later hospitalised with bowel pathology and 13 301 (5%) with a specific functional disorder. Notably, there was a 4.84 (95% CI 4.45 to 5.27) times greater risk of Crohn's disease following NSAP and a 4.23 (4.13 to 4.33) greater risk of acute appendicitis than in the control cohort. The risk of irritable bowel syndrome (IBS) was 7.22 (6.65 to 7.85) times greater following NSAP. The risks of inflammatory bowel disease (IBD), IBS and functional disorder (unspecified) were significantly increased in all age groups except <2-year-olds. The risk of underlying bowel pathology remained raised up to 10 years after first diagnosis with NSAP.
Conclusions Only a small proportion of those with NSAP go on to be hospitalised with underlying bowel pathology. However, their risk is increased even at 10 years after the first hospital admission with NSAP. Diagnostic strategies need to be assessed and refined and active surveillance employed for children with NSAP.
- Evidence Based Medicine
- General Paediatrics
- Adolescent Health
- Paediatric Practice
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What is already known on this topic
In adults with non-specific abdominal pain (NSAP), underlying bowel pathology is found in anything between 2% and 30% of cases according to the literature.
One small study found that 1.6% of children with a diagnosis of NSAP were later found to have an identifiable organic cause (Barker et al6).
In those adults and children where no underlying bowel pathology is found (the majority), psychological factors may play a role.
What this study adds
Data with strong statistical power in support of the fact that only a small number (5.8%) of those with non-specific abdominal pain (NSAP) go on to be diagnosed in hospital with underlying bowel pathology.
Clinically relevant age-stratified risks of specific organic diseases following a diagnosis of NSAP.
Statistically powerful data showing an increased rate of diagnosis of bowel pathology among patients with NSAP, even beyond 10 years after first hospital admission with abdominal pain.
Non-specific abdominal pain (NSAP) is the most common diagnosis recorded following admission for abdominal pain in childhood.1 It is used both as a diagnosis of exclusion and as a transient label while further investigations are undertaken. Literature regarding adults with NSAP reports an organic cause found in 2%–30% of cases,2–5 but little data is available regarding children with NSAP. One small study found that 1.6% of children diagnosed with NSAP were later found to have an organic cause.6 We have used linked hospital discharge records to study all children discharged with a diagnosis of NSAP in England between 1999 and 2011, to identify selected functional and organic gastroenterological conditions that were subsequently diagnosed. Our aim was to determine the proportion of patients diagnosed with underlying bowel pathology and with specific functional gastroenterological conditions, to compare them with a control group, and to assess the persistence of any change found. The use of an all-England dataset, in a population of over 50 million people over a 14-year period, provides unrivalled statistical power in this area of study.
We used a linked English national dataset of hospital admissions (Hospital Episode Statistics (HES)) and mortality. HES comprises routinely collected administrative data on all hospital day cases (the term used in England for admissions when the patient does not stay overnight) and inpatient admissions in NHS hospitals in England, with brief statistical records that include coded diagnostic data. The HES data were provided by the Health and Social Care Information Centre, and the mortality data were derived from death registration data provided by the Office for National Statistics. Records were anonymised, by encryption of identifiers, before being provided to the Unit of Health-Care Epidemiology, Oxford University, where the data were analysed. Records were matched, for linkage, using an exact match on encrypted values of the NHS number (a unique number for each resident of England registered with the NHS) and the Hospital Episode Statistics Identification (a unique national HES number for each hospitalised patient). These are very well recorded in the period covered by this study; and the ‘hit rate’ for matching is upwards of 95%. The dataset spanned 1999–2011. We constructed a cohort of patients with NSAP in childhood, defined as a patient's HES record with the International Classification of Diseases (ICD) tenth revision code R10 (the code for ‘abdominal and pelvic pain’ without further specification), aged 0–16 years. We constructed a control cohort, comprising children (0–16 years old) hospitalised with a range of mainly minor medical conditions, surgical procedures and injuries (table 1). Following customary epidemiological practice in using hospital controls, we selected a wide range of different conditions that are unlikely to be related to either the exposure (NSAP) or the outcomes of interest. The ‘outcomes’ studied were Crohn's disease (ICD10 K50), ulcerative colitis (UC; K51), coeliac disease (K90.0), acute and unspecified appendicitis (K35 and K37), other appendicitis (K36), gastro-oesophageal reflux disease (K21), irritable bowel syndrome (IBS; K58), constipation (K59) and functional intestinal disorder unspecified (K59.9). From both cohorts we excluded anyone with a prior or concurrent HES record containing the outcome diagnosis.
Rates of outcome diseases were calculated based on person-days ‘at risk’. The ‘date of entry’ into either the NSAP or control cohort was that of the earliest recorded admission for NSAP or control condition. The ‘date of exit’ was that of the earliest recorded admission for the outcome disease, death or the end of the data collection period (31 December 2011), whichever was the earliest. An individual with multiple admissions for NSAP was counted only once; an individual with multiple admissions for an outcome condition (eg, Crohn's disease) was counted as only one outcome case; an individual with one outcome condition remained ‘eligible’ to be counted for a different outcome condition. We analysed the data in strata by clinically relevant age groups (0–2 years, 3–5 years, 6–12 years, 13–16 years), year of admission (in single years), sex (in the analyses of both sexes combined) and quintile of the Index of Multiple Deprivation and Government Office Region (nine in England). The indirect method of standardisation was used, taking the NSAP cohort and the control cohort, combined, as the standard population. The stratum-specific rates in the standard population were applied to the number of people in each equivalent stratum in the NSAP cohort, and, separately, in the control cohort. The calculations within each stratum (eg, within each age group), within each cohort, gave us an ‘expected’ number of cases of the ‘outcome’ disease (eg, Crohn's disease) to compare with the observed number of cases. We then summed the numbers of observed cases, and of expected cases, in each stratum in each cohort to give a total-cohort expected and observed number. We calculated the ratio of the rate of each outcome disease in the NSAP cohort relative to the control cohort using the formula (ONSAP/ENSAP) divided by (OCONT/ECONT), where O is the observed number and E is the expected number of each outcome disease in the NSAP and control cohorts respectively. We refer to it in the tables as the standardised rate ratio. The rate ratios and 95% CIs were calculated using published, standard methods.7
In analyses by time interval, the interval is that from the date of first record of NSAP to the date of first record of the outcome condition.
The Unit of Health-Care Epidemiology has ethical approval from the Central and South Bristol Multi-Centre Research Ethics Committee (04/Q2006/176) for a multistudy programme of work analysing these anonymised datasets.
There were 268 623 children in the NSAP cohort. Of these, 56% were female children; 1.9% were aged <2 years at first NSAP admission, 7.8% aged 3–5 years, 51.5% aged 6–12 years and 38.8% aged 13–16 years (table 1). There were 1 684 923 children in the control cohort. From the NSAP cohort, 15 515 (5.8%) went on to be hospitalised with a diagnosis of underlying bowel pathology compared with 13 301 (5.0%) hospitalised with a functional disorder (table 2). Notably, of the organic disorders, 12 867 developed acute appendicitis (4.2 times the rate in the control population) and 1249 developed Crohn's disease (4.8 times the rate in the control population). Notably, of the functional disorders, 2120 were eventually hospitalised with IBS (7.2 times the rate in the control population), and 9240 were hospitalised with constipation (4.3 times the rate in the control population).
Perhaps unsurprisingly, given the diagnostic pathway, analysis of the results by time intervals (table 3) showed that organic diseases were diagnosed most frequently within the first year, with particularly high rate ratios for acute appendicitis (15.1 times the rate in the control population), other appendicitis (40.4 times the rate in the control population) and Crohn's disease (26.3 times the rate in the control population). However, up to 10 years after initial diagnosis with NSAP, the risk of being diagnosed with inflammatory bowel disease (IBD) or appendicitis (other) remained significantly raised. This was no longer statistically significant 10 years after initial diagnosis with NSAP, as opposed to RRs for coeliac disease, appendicitis (acute or unspecified) and the functional disorders which remained significantly raised even after 10 years.
In keeping with clinical experience, analysis of the results by age (table 4) found very low rates of diagnosis of IBS and IBD in neonates/infants and the results are non-significant. Later in childhood, the rate of diagnosis of these conditions is significantly increased in children who have had a diagnosis of NSAP. On the other hand, diagnosis of appendicitis, constipation and reflux are significantly increased in neonates/infants with NSAP and the relative risk of diagnosis of appendicitis following NSAP fell with increasing age.
Of those diagnosed with NSAP in hospital as a child, 5.8% were later hospitalised with underlying bowel pathology, while 5.0% were subsequently hospitalised with a functional disorder. In some cases it was more than 5 years before they received these diagnoses.
Interpretation and comparisons with the literature
The finding that only 5.8% of children hospitalised with NSAP (either as inpatients or day case) subsequently received a hospital-based diagnosis of underlying bowel pathology fits with the literature available that shows that re-admission and more invasive investigation is only associated with a change in diagnosis in a minority of children with NSAP.6 ,8 It is known that for many of the remainder, psychological factors play a key role.1 ,9 ,10 Hence, it is perhaps not surprising that the rate of diagnosis of IBS (a functional disorder) in the NSAP cohort is more than seven times the rate of diagnosis in the control population.
Appendicitis is by far the most common of the diagnoses studied following a discharge with NSAP (table 2), and (as with all the outcomes) the rate of diagnosis is most increased within the first year (table 3). This fits with clinical experience and the pathways involved. What is perhaps more surprising is the increased risk of appendicitis and IBD up to 10 years after initial hospitalised episode of abdominal pain and coeliac disease more than 10 years later. Delay in diagnosis has been reported previously in the literature regarding both Crohn's disease and coeliac disease.11–13 Regarding coeliac disease, studies suggest that this delay is usually longer than for IBD, with an average time of between 5 and 10 years between initial presentation with abdominal pain and diagnosis.12 ,14 ,15 Abdominal pain is part of the presentation in as many as 72% of children with Crohn's disease,11 so it is possible that in some of these cases, the index presentation with abdominal pain was indeed a first presentation of Crohn's disease or other bowel pathology. This would suggest significant delays in diagnosis. However, it is not possible to be certain that this is the case, and indeed it is highly unlikely regarding some of the diagnoses studied, such as appendicitis. Perhaps children with NSAP are predisposed to certain pathologies at a later date through an as yet unknown mechanism, or perhaps there is no causal link at all.
When different age groups are considered (table 4), the data clearly suggests that the likelihood of a diagnosis of appendicitis is particularly high following NSAP in neonates/infants, while other conditions should be considered later in childhood, especially IBS and IBD.
Strengths and weaknesses
This study benefits from its size, enabling high statistical power and precision of estimates. The main weakness in the dataset is that it relies on coding of discharge diagnoses: we cannot be certain of their accuracy. Privacy regulations preclude checking on samples of HES records in individual studies such as ours. However, at least for diagnoses that are straightforward, formal validity studies of HES have concluded that diagnostic information is ‘of sufficient reliability for epidemiological analyses’ and ‘sufficiently robust to support their use for research’.16 ,17 There are two main weaknesses in the use of HES data for this study. First, it only covers hospital day cases and admissions, thereby not taking into account diagnoses made in outpatient clinics or general practice. Since patients in this cohort would usually need endoscopy to diagnose any underlying bowel pathology it is unlikely that the lack of outpatient and general practice data would have missed many organic diagnoses (this may change in the future, however, with recent changes in coeliac disease diagnostic techniques). On the other hand, it is highly likely that inclusion of outpatient and general practice statistics would increase the rate of diagnosis of functional disorders. The second disadvantage of using HES data is that we have no way of knowing how long these patients had been presenting to primary care with abdominal pain or what signs and symptoms they presented with and how thoroughly (or not) they were investigated before a diagnosis was made. Particularly in children, clinicians will have exercised judgement about how far to investigate pain in children that may be self-limiting.
These results have two main clinical implications. First, a large proportion of those admitted to hospital with abdominal pain do not have an organic condition that requires hospital investigation or management. This does not automatically mean that the admission is unnecessary. Admission to rule out an underlying organic process, with a period of observation in hospital can be extremely useful to reassure children, families and the medical practitioners responsible for their care. However, while the process may have therapeutic benefit for some of the children admitted with NSAP, it is known that early recognition of functional abdominal problems in children can enable faster recovery.18 This means that in some cases, admission may not be appropriate where there is no concern regarding underlying diagnosis. Numerous authors have suggested symptoms and signs that should be used as ‘red flags’ for organic causes,19–22 which are often used in clinicians’ diagnostic decision making. Perhaps a consensus view could be reached regarding the diagnostic workup and management of children with abdominal pain in the community and the value of a screening test or panel of tests that could be done in primary care to try to avoid preventable admissions to hospital. It is now possible to diagnose coeliac disease in those with suggestive symptoms using blood tests (antiendomysial Ab, tissue transglutaminase and genetic susceptibility) where, previously, endoscopic biopsies would have been required. Faecal calprotectin (a neutrophil cytosolic protein) is a marker of intestinal inflammation in IBD.23 It is a highly sensitive test, making it a good candidate for screening;24 however, it must be noted that it has low specificity and clinicians should not be falsely reassured in the presence of red flag symptoms such as rectal bleeding or weight loss.
Second, the results indicate that children who have received hospital-based care for NSAP continue to be at increased risk of developing bowel pathology beyond 10 years after the index admission. While in some cases there may be no causal link, and in some cases there may be an underlying association between NSAP and the bowel pathology that is not yet understood, it may be that in some cases there is a substantial delay between the first presentation of bowel pathology with abdominal pain (even if this was not at the index admission) and diagnosis (perhaps because of the label of NSAP). Numerous studies have shown the negative effects of such delay.3 ,11 ,25 ,26 As mentioned previously, the data does not consider how these patients presented or how thoroughly they were investigated. Radiological imaging is rapidly becoming a key part of paediatric diagnostics, and data available suggests that it is reliable in the diagnosis of many of the conditions we have studied.27–30 Accordingly, perhaps greater use of imaging should be undertaken before children with persistent or recurrent pain are labelled with NSAP. At the least, this data would suggest that more active surveillance is required in patients presenting with recurrent NSAP.6
This study provides data with strong statistical power in support of the fact that only a small proportion of those with NSAP subsequently receive a hospital-based diagnosis of underlying bowel pathology. However, there is an increased rate of diagnosis of bowel pathology in this patient group, even beyond 10 years after first hospital admission with abdominal pain. This implies a need to assess and refine diagnostic strategies in primary and secondary care, as well as to employ active surveillance in order to improve patient care and minimise unnecessary use of resources.
We thank David Yeates who wrote the in-house software used in this study.
Contributors The data has been analysed by RG and MJG and the report written by GCDT with input from MJG, LJH and RG.
Funding The datasets were constructed with funding from the English National Institute for Health Research (grant reference number RNC/035/02). RG is part-funded by Public Health England. The funding sources had no involvement in the study design, data collection, data analysis and interpretation, writing of the manuscript, or the decision to submit the article for publication. The views expressed are not necessarily those of the funding bodies.
Competing interests None declared.
Ethics approval Central and South Bristol Multi-Centre Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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