The vast majority of children and adolescents with recurrent abdominal pain have functional gastrointestinal disorders (FGIDs), defined as chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities (1,2). Founded on 2 decades of work in classifying adult FGIDs, the international pediatric Rome II criteria (PRC-II) were introduced in 1999 as a first attempt at classifying specific diagnostic entities on the basis of typical constellations of gastrointestinal symptoms in children and adolescents (3). Studies have shown that 55% to 89% of patients with functional abdominal pain or symptoms referred to tertiary gastroenterology centers fulfilled the PRC-II criteria for a specific FGID diagnosis (4–6). Recent clinical guidelines recommend making a positive diagnosis of the categories functional dyspepsia, irritable bowel syndrome (IBS), abdominal migraine, and functional abdominal pain (FAP) on the basis of the PRC combined with a normal physical examination and the absence of alarm symptoms (7). The foundation for a positive, symptom-based approach is the existence of well-defined categories that are able to capture distinct and recognizable constellations of gastrointestinal symptoms.
The PRC-II were recently revised as the PRC-III (Table 1) on the basis of evolving research that pointed out the need for refinement and clarification (2). Notable changes are introduction of new entities (eg, adolescent rumination syndrome), modification of established categories (abdominal migraine, functional constipation, and FAP), reduction of the required duration of symptoms for all disorders except cyclic vomiting and abdominal migraine (from 3 to 2 months), and reduction of the required number of episodes of pain for the 2 cyclic disorders (from ≥3 to ≥2 episodes in the preceding year) (2).
The aims of this study were primarily to determine the proportion of referred patients with nonorganic abdominal pain who met the criteria for 1 or more diagnoses of an FGID, and explore the distribution of diagnoses according to the PRC-III. A secondary aim was to investigate reasons for failure to meet the criteria for diagnosis.
MATERIALS AND METHODS
This prospective study was conducted in 4 general pediatric outpatient clinics at the Innlandet Hospital Trust (secondary care) over approximately 26 months (minimum of 25 months, maximum of 27 months) from 2006 to 2008. The 4 clinics are the only pediatric referral clinics serving approximately 330,000 inhabitants in the counties of Oppland and Hedmark in Norway, with the exception of 1 pediatrician working part time in a small practice. Pediatric consultations are only accepted on the basis of referrals from general practitioners.
All children (4–15 years) consecutively referred for the evaluation of recurrent abdominal pain were eligible for the study. The exclusion criteria were abdominal pain of known organic etiology, recent evaluation of abdominal pain by a pediatrician, or language problems that interfered with the completion of questionnaires.
To describe the symptoms associated with FGIDs according to the PRC-III, the parent report version of the Questionnaire on Pediatric Gastrointestinal Symptoms–Rome III Version (QPGS-RIII) was used. This form is recommended for use by parents of 4- to 18-year-old children (8). The QPGS-RIII is a structured questionnaire and is an adaptation and abbreviation of the original QPGS on the basis of the PRC-II, which has undergone preliminary validation (5,9). The QPGS-RIII comprises 5 sections: pain or discomfort in the upper abdomen above the umbilicus, pain or discomfort in the lower abdomen around and/or below the umbilicus, bowel habits, other gastrointestinal symptoms (nausea and vomiting), and impairment (limitation in activities). The QPGS-RIII parent report was translated from English into Norwegian according to standard procedures, which included independent translation back into English. The questionnaire was completed by the parents at home before the first consultation. At the clinic and before the medical evaluation, a member of the research team assisted the parents in completing missing answers. If the parents did not know the answer, then the child was given an opportunity to answer to avoid missing values.
Identification of organic disease was based on the case history, physical examination by a pediatrician, and supplementary investigations. All patients had blood tests for hemoglobin, total leukocyte and differential count, sedimentation rate, C-reactive protein, ferritin, total IgE and IgE screen for food allergies, and anti-endomysial and anti-gliadin antibodies (IgG and IgA) and anti-tissue transglutaminase antibodies for celiac disease, urine analyses for protein, blood and leukocytes, 3 stool specimens for occult blood, and 1 stool specimen for quantification of calprotectin. The following tests were performed at the pediatrician's discretion: endoscopies, 24-hour esophageal pH measurements, ultrasonographic and radiographic examinations of the abdomen and pelvis, and lactose malabsorption tests (either hydrogen breath tests or blood glucose measurements after a standard oral lactose challenge—tests considered positive for lactose malabsorption if H2 increased more than 20 ppm or blood glucose more than 1.1 mmol/L, combined with clinical symptoms). If organic disease was suspected individual follow-up was scheduled to confirm or exclude a diagnosis. After the first consultation, the medical records were reviewed for evidence of alarm symptoms (blood in the stools, involuntary weight loss, deceleration of linear growth, significant vomiting, chronic severe diarrhea, persistent right upper or right lower quadrant pain, unexplained fever, and a family history of inflammatory bowel disease), organic disease, and results of supplementary investigations. Furthermore, all patients were invited to a follow-up by their pediatrician 6 to 9 months after the first consultation. After the follow-up, the medical records of all patients, including those who did not meet for follow-up, were reviewed again for evidence of organic disease. The study was approved by the Regional Committee on Medical Research Ethics and the Norwegian Data Inspectorate, Oslo.
Descriptive analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 15.0 (SPSS Inc, Chicago, IL). Frequency distributions were computed to examine the prevalence of each FGID.
Overall, 192 consecutive patients were referred for evaluation of abdominal pain. Fourteen patients canceled the appointment because of spontaneous improvement and 1 because of emergency admission. Of the 177 eligible patients evaluated for abdominal pain, 25 (14%) were excluded (22 because of missing consent from 1 parent, 2 had recently been evaluated by a pediatrician, and 1 because of language problems), leaving 152 (86%) patients in the study. A total of 140 (92%) met for the follow-up consultation after 6 to 9 months.
Eleven children (7%) had alarm symptoms. Thirty-seven (24%) had blood values outside the normal range, but none were considered significant for their abdominal pain (20 had positive IgE screen for food and 11 for pollen allergens, 6 had low serum ferritin values but no anemia, 1 had an elevated sedimentation rate because of a skin infection). In 134 patients investigated for fecal calprotectin, elevated levels (>50 mg/kg) were found in 11 (8%). All patients with a value beyond 100 (6 patients) underwent gastroscopy and colonoscopy (with exception of 1 child with a slightly elevated value and who recovered from pain before the endoscopies). At the pediatricians' discretion, a total of 50 children (33%) had investigations in addition to the standard laboratory tests (19 lactose malabsorption tests, 16 radiographic examinations of the abdomen and pelvis, 12 gastroscopies, 7 colonoscopies, 6 ultrasonographic examinations of the abdomen and pelvis, 6 esophageal pH measurements, and 1 Meckel scan).
Organic disease was found in 8 patients following the first visit (1 Crohn disease, 1 unspecific gastrointestinal inflammation, 2 gastroesophageal reflux disease [GERD], 4 lactose malabsorption) and in another 2 (1 GERD and 1 celiac disease) on follow-up. The 2 children with Crohn disease and unspecific gastrointestinal inflammation had alarm symptoms (blood in the stools) and elevated fecal calprotectin. The 8 children with organic disease but no alarm symptoms would have fulfilled criteria for various FGIDs if the investigation had been limited to medical history, clinical examination, and stool examination for blood. The patients with organic etiology were excluded from further analyses.
Of the 142 children with nonorganic etiology, the mean age was 9.4 (SD 2.7) years and 89 (63%) were girls. Both parents were Nordic for 138 (97%) of the children. A total of 102 (72%) children were living with both parents. The education and occupational status of the parents are shown in Table 2. All 142 children had experienced abdominal pain more than 2 months, 139 (98%) for more than 3 months, and 97 (68%) children for more than 1 year.
Distribution of FGID Diagnoses and Reasons for Not Meeting the Criteria
Of the 142 children with nonorganic etiology, 124 (87%) met the criteria for at least 1 specific diagnosis of an FGID. IBS was the most common diagnosis (43%), followed by abdominal migraine (23%), aerophagia (15%), FAP (15%), and functional dyspepsia (10%) (Table 3). Of the 22 children with FAP, 13 (59%) also met the criteria for functional abdominal pain syndrome (FAPS). Of the 124 children with specific diagnoses, 82 (66%) were given 1 FGID diagnosis, 36 (29%) 2, and 6 (5%) 3 (Table 4). The most frequent combinations were IBS and aerophagia and IBS and abdominal migraine (Table 4). Eighteen patients (13%) did not fulfill any diagnostic criteria (Table 5). A pain frequency less than that required was the dominating cause (83%).
To our knowledge, this is the first study to assess the ability of PRC-III to classify FAP in children, and the first study in secondary health care to explore the distribution of diagnoses as specified in the PRC. The main findings were as follows: 87% of referred children with nonorganic abdominal pain met the criteria for 1 or more diagnoses of an FGID; IBS was the most frequent diagnosis (43%), both alone and in combination with others; and almost one third of the patients had overlapping FGID diagnoses. Low frequency of abdominal pain symptoms was the principal reason for failure to meet any diagnostic criteria for specific entities.
The rate of specific FGID diagnoses obtained with the PRC-III in the present study is in the upper range (87% vs 55%–89%) compared with previous studies conducted in tertiary pediatric gastroenterology centers based on the PRC-II (4–6), indicating that the PRC-III is at least as sensitive as the PRC-II in classifying FGIDs in children. This is not surprising because the revision has resulted in criteria that are more inclusive. New entities are defined, some established categories are redefined, and less restrictive time and frequency limits have been introduced (2).
The distribution of the different FGID diagnoses differs to some extent from that found in other studies of children referred for recurrent abdominal pain (4–6). Consistent with previous studies, IBS was the most common entity, with prevalence in the upper range compared with earlier reports (43% vs 20–45%) (4–6). However, the proportions of diagnoses of abdominal migraine (23%), aerophagia (15%), and FAP (15%) were notably higher than the previously reported figures of 1% to 5% (4–6), 1% to 2% (5), and 0% to 8% (4,5), respectively. Functional dyspepsia (10%) and functional constipation (6%) were somewhat less prevalent in our compared with other reports of 14% to 47% (4–6) and 13% to 19% (5), respectively. These differences may have several explanations. The modification of established categories is likely to explain the observed high frequencies of abdominal migraine and FAP. However, the introduction of less restrictive time and frequency limits alone does not seem sufficient to explain the observed differences. For example, the change in the required duration of symptoms from 3 to 2 months, which is the only change in the PRC-III for aerophagia, does not explain the observed prevalence of this entity in the present study because the majority of the children with aerophagia (91%) reported a duration of abdominal symptoms more than 3 months. Differences in study populations probably account at least partly for the observed differences in the prevalence of aerophagia, functional dyspepsia, and functional constipation. Comparable previous studies of referred children with abdominal pain have been conducted in tertiary health care, whereas the present study was undertaken in secondary health care. The low prevalence of functional dyspepsia and functional constipation may be related to our inclusion criterion of abdominal pain. Children referred for constipation without recognized pain or with dyspepsia with nausea as the presenting symptom were not included in our study.
In the present study, 15% of the children met the criteria for FAP compared with 0% to 8% in previous reports using the PRC-II (4,5). The observed difference is probably due to changes in the criteria for FAP in the PRC-III. In the more restrictive PRC-II, a substantial proportion of children with symptoms of abdominal pain were left without a specific diagnosis such as IBS, functional dyspepsia, or FAP (4). To make the PRC-III more inclusive, a distinction was introduced between unspecific FAP and FAPS (2). Unlike FAP, a diagnosis of FAPS requires some loss of daily functioning and/or additional somatic symptoms (Table 1). In our study, 13 of the 22 children with FAP also met the criteria for FAPS, suggesting that the PRC-III successfully includes more patients and at the same time allows differentiation according to severity.
Abdominal migraine and aerophagia showed a notable overlap with IBS. The tendency of different FGIDs to overlap is well known (8). However, only 1 study on pediatric patients in tertiary care has reported the total proportion of the diagnoses that overlapped (20%) (5). The high prevalence of both abdominal migraine and aerophagia in the present study must be viewed in connection with their significant overlap with IBS. Episodes of intense abdominal pain and increased flatulence and abdominal distension are not only symptoms for aerophagia and abdominal migraine but also common symptoms in patients with IBS (2). Hence, a pertinent question is whether abdominal migraine and aerophagia are distinct entities or common symptoms of other FGIDs. With respect to abdominal migraine, several studies support the existence of this diagnostic entity (10,11). There is less evidence to support the independent existence of aerophagia (12). In one study, aerophagia appeared to be distinct from functional dyspepsia, but the study did not assess symptoms of IBS (12). Another issue is whether a diagnosis of aerophagia is appropriate only when IBS and functional dyspepsia are excluded. Such hierarchical classifications of some of the FGIDs have been established in the adult Rome III criteria (8). For example, functional bloating exists only when IBS and dyspeptic conditions are excluded because bloating is a common symptom in both of these disorders (8). Opposed to our study, an overlap between functional dyspepsia and IBS has been reported in several studies, but their diagnostic criteria differed from ours (6,13). On the basis of the QPGS-RII parent report, an overlap of 10% between functional dyspepsia and IBS was reported for pediatric patients in a study conducted in tertiary health care (6). We have no convincing explanation for the low tendency of overlap between functional dyspepsia and other FGIDs in the present study.
Only 13% of the patients with nonorganic abdominal pain did not meet the PRC-III criteria for any of the FGID diagnoses. The main reason was a frequency of abdominal pain less than once per week. Unlike in earlier studies (4–6), too short a duration of abdominal pain (ie, a duration of 2 months or less) was not a reason for failing to meet diagnostic criteria for any of the patients. Similarly, failure to meet the criteria for symptoms associated with specific FGIDs (eg, changes in stool frequency or consistency) explained 66% and 73% of the cases of “no diagnoses” in previous studies (4,6), but none in ours. The differences may at least partly be explained by the revision of the criteria to make some PRC-III categories, such as FAP and abdominal migraine, more inclusive (2). Differences in study populations and cultural variations may be other explanatory factors. However, our results indicate that the PRC-III may be better at capturing distinct and recognizable constellations of gastrointestinal symptoms in children than the PRC-II, and thereby an improved diagnostic tool.
The strengths of this study were the high participation rate and the consecutive recruitment of patients referred from general to pediatric practice within a well-defined geographic area. This most likely makes the results representative for children with sufficient abdominal pain to need referral to secondary health care, at least in Norway. However, the results may not be similarly applicable to other nations or cultures because the tendency to seek medical advice for complaints and referral patterns within the medical community may differ. Other limitations should also be considered. First, this study included patients within a specific age range (4–15 years) referred for abdominal pain. Therefore, the results cannot be generalized to all FGIDs or other age groups. Second, the diagnoses of FGIDs were based on parent reports. Parents may have limited knowledge of their children's gastrointestinal symptoms, and the reliability of their answers may therefore be questionable. Furthermore, a bias may have been introduced because the children were given the opportunity to answer whether the parents could not describe symptoms in the questionnaire. A previous study on the QPGS-RII only showed a fair-to-good concordance between parents and the children on most items (9). Third, this study was not designed to determine the validity of the PRC-III to discriminate between functional disorders and organic diseases. As far as we know, no other study has fully explored this issue. Therefore, the criteria cannot be used to rule out organic disease. Fourth, supplementary investigations for organic disease and interpretation of some findings were left to the discretion of the patient's pediatrician, and some of the diagnoses, therefore, may be inaccurate. However, the extensive primary investigation and 6 to 9 months' follow-up makes it unlikely that significant organic disease was missed. This is also supported by previous studies where less than 5% of patients diagnosed with recurrent abdominal pain in a tertiary care center and 3% of patients diagnosed with an FGID in a primary care setting developed organic disease during the year following the first medical evaluation (14,15).
The present study found that 87% of children with FAP qualified for a specific diagnosis of FGIDs on the basis of the pediatric Rome III criteria. Therefore, we believe that the PRC-III provides clinicians with an important tool in their approach to children with abdominal pain. The criteria also provide an avenue for research into the causes and management of these disorders. However, the significant overlap between different diagnoses may indicate that some diagnoses defined in the PRC-III are better described as common symptoms of other FGIDs rather than as distinct disorders.
The authors gratefully acknowledge the children and their parents for their efforts, the pediatricians at the four outpatient clinics at the Innlandet Hospital Trust for performing the medical evaluations, and the nurses Anne Marie Skaaden, Aud Ryen Eide, and Turid Skundberg for invaluable help in recruitment and data collection. We also thank Professor L.S. Walker (Vanderbilt Children's Hospital, Nashville, Tennessee) for assistance in the translation of the QPGS-RIII.
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