Medical Presentation of Constipation From Childhood to Early Adulthood: A Population-Based Cohort Study

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5: Medical Presentation of Constipation From Childhood to Early Adulthood: A Population-Based Cohort Study DENESH K. CHITKARA,* NICHOLAS J. TALLEY, G. RICHARD LOCKE III, AMY L. WEAVER, SLAVICA K. KATUSIC, HEIKO DE SCHEPPER, and MARY JO RUCKER *University of North Carolina Center for Functional GI and Motility Disorders, Division of Pediatric Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Clinical Enteric Neuroscience Translational and Epidemiological Research Program, and the Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota Background & Aims: Constipation is a common disorder in children and adults, but the role of gender and early life risk factors remains undefined. The aims of the study were as follows: (1) to estimate the incidence of medical presentation for constipation in a population-based birth cohort, and (2) to examine factors associated with constipation presentation from childhood to adulthood. Methods: A birth cohort of all children born between 1976 and 1982 to mothers who were residents of Rochester, Minnesota, and who remained in the community until age 5 was used for this study. Medical visits for constipation were identified by diagnoses codes and chart review. Subjects were followed up based on their diagnoses accumulated while younger than 21 years old, and 80% of subjects remained in the area until 18 years of age. Results: Of 5299 birth cohort members without constipation presentation before age 5, the overall age- and sex-adjusted incidence was 3.9 per 1000 person-years. A higher incidence for constipation in females occurred beginning at 13 years to early adulthood (rate ratio, 2.6 for y and 4.2 for 17 to <21 y). Children with a diagnosis for constipation at younger than 5 years of age had a significantly higher incidence for subsequent medical visits for constipation through adolescence and early adulthood compared with the incidence rate of children without an early medical presentation (rate ratio, 4.5 for 5 8 y, 2.5 for 9 12 y, and 3.9 for y). Conclusions: Early medical presentation and female sex influence incident and repeat medical visits for constipation from childhood to early adulthood. Constipation is a common medical complaint both in children and adults. In children, studies of the general population have shown that the prevalence for constipation is approximately 9%. 1 Population-based studies estimate that 12% 19% of adults experience constipation. 2 Although constipation is a common condition, only a proportion of affected individuals will seek out health care for their symptoms. 3,4 Two surveys of the general population have shown that between 16% and 22% of subjects with constipation report seeing a physician because of their symptoms. 3,4 Although most individuals who experience constipation will not seek medical care, the use of health care resources attributable to constipation care are substantial. 5 Medical visits for constipation in children and adults have been estimated to account for 4 8 million ambulatory visits per year in the United States between 1993 and A number of factors influence whether individuals experience constipation between childhood and adulthood. van Ginkel et al 7 reported that among young children with symptoms of chronic constipation who were followed up until age 16 years and older, 30% continued to experience symptoms. In this study, experiencing an early onset of symptoms ( 4 y) was associated with a poorer prognosis of recovery from symptoms. 7 In addition, sex is a factor that influences whether individuals experience constipation during their lifetime. Epidemiologic studies in children report a similar prevalence of constipation between boys and girls, and sex does not appear to be an influential factor during childhood. 1 However, populationbased studies conducted in adults with constipation show a female to male gender distribution of 2.1 to 1. 2 The time of life in which sex plays a factor toward manifesting symptoms of constipation currently is unknown. It has been suggested that an increased prevalence of constipation in females vs males may be caused by hormonal changes related to puberty, 8 or by physiologic changes unique to the female pelvic floor or colonic smooth muscle that occur from progressive ageing, 9 childbearing, 10 medication use, 9 or comorbid diseases associated with ageing such as diabetes. 11 Experiencing an early onset of symptoms and female sex also may influence the health resource use in individuals who present for medical care with constipation in the general population. For this study, we examined the natural history of medical presentation for constipation in a population-based cohort who remained in a geographic area from childhood to early adulthood. The aims of the present study were as follows: (1) to describe the incidence and proportion of repeat medical visits for constipation in a population-based birth cohort in which 80% of the cohort remained in the area at least until age 18 years, and (2) to examine factors that may predispose to increased incident visits, and repeat medical visits for constipation from childhood to early adulthood such as early childhood presentation for constipation, female sex, and adverse sociodemographic factors. Abbreviations used in this paper: HICDA, hospital adaptation of International Classification of Diseases; ICD, International Classification of Diseases by the AGA Institute /07/$32.00 doi: /j.cgh

2 1060 CHITKARA ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 5, No. 9 Methods Setting Olmsted County, Minnesota, is a metropolitan and rural area 90 miles southeast of Minneapolis, Minnesota. Census data from the 1990 population, representing the years the children from this birth cohort were in school, indicated the population was 70,745 (75% 45 y), and was estimated to be 96% Caucasian. 12 With the exception of the place of employment, the characteristics of the Rochester population are similar to those of the US Caucasian population. 12 Olmsted County has substantial local resources for primary and specialty care, including the Mayo Clinic and Olmsted Medical Center, and these centers provide more than 98% of the health care to the residents of the area. 12 Identification of the Rochester Birth Cohort The birth cohort consisted of all children born between January 1, 1976, and December 31, 1982, to mothers residing in the 5 townships in Olmsted County, Minnesota, comprising the Minnesota Independent School district 535 (N 8548) in the city of Rochester. 13 Subjects were identified through computerized birth certificate information from the Minnesota Department of Health, Division of Vital Statistics. The vital status for each member of the birth cohort during the school year were established using resources from the Rochester Epidemiology Project, Independent School District 535, and the Minnesota Department of Health. The target population for this study consisted of 5718 children, who at or after the age of 5 years all still lived in Rochester and whose family did not deny research authorization. A review of hospital and school records indicated that 80% of the target population continued to reside in the area until at least age 18 years. Authorization to review the medical records of birth cohort subjects was obtained and this study was approved by the Mayo Clinic and Olmsted Medical Center institutional review boards. Identification of Constipation Medical Visits From Age 5 to Younger Than 21 Years in the Birth Cohort The relative isolation from any major urban center and the presence of the Mayo Clinic and Olmsted Medical Center essentially provide self-contained medical practices, offering primary care and specialty services indicated to the local population. Through the Rochester Epidemiology Project, all diagnoses and surgical procedures recorded at Rochester medical facilities are indexed continuously for automated retrieval. 14 This diagnostic index expedites retrieval of the unit (or dossier) medical record, which includes the history of all encounters in the hospital, community and ambulatory medical and social services, emergency department, outpatient clinics, and home visits, as well as laboratory and psychologic test results from birth until patients no longer reside within the community. Relevant hospital adaptation of International Classification of Diseases (HICDA) and international classification of diseases, ninth revision (ICD-9) diagnostic codes to conduct the search were chosen based on the consensus of 2 clinical physicians (N.J.T., D.K.C.) and a biostatistician familiar with conducting searches for medical diagnoses using the database (A.L.W.). In addition, the HICDA and ICD-9 code diagnoses of all birth cohort members that were obtained for this time period also were collated and searched manually to ensure that all relevant diagnoses were identified. All children in the birth cohort with a diagnosis of constipation (HICDA codes and , and ICD-9 codes and ) from age 5 to younger than 21 years were identified from the database, and were designated as a potential case. The total number of subsequent medical visits for the same diagnosis codes for constipation also was recorded. Manual Chart Review of Identified Cases of Children With Constipation The medical records of all potential incident cases with a medical visit for constipation from 5 to younger than 21 years of age were reviewed using a standardized chart review instrument. 15 The information of the date of the initial visit and the presence of a medical visit for constipation in the chart was used to confirm the information from the search of the administrative diagnostic index. Data concerning the demographic characteristics, presenting complaints, and specific medical complaints and accompanying gastrointestinal symptoms leading to the diagnosis were abstracted from the medical record. Information on birth cohort subjects who had an initial visit for constipation at younger than 5 years of age has been reported previously. 15 Information was abstracted for the presence or absence of active symptoms of constipation in the subsequent or second visit for constipation in subjects with an incident visit at younger than 5 years. Individuals were designated as cases for a constipation diagnosis if they met the following criteria from the chart abstraction: (1) HICDA or ICD-9 diagnosis, and (2) chart review that confirmed the presence of a medical visit for primarily constipation with and without other gastrointestinal symptoms. All children with a recognized or underlying disorder that would contribute to the gastrointestinal symptoms at the time of the visit from the chart review such as cerebral palsy, developmental delay, a metabolic disorder, diabetes mellitus, intestinal malformation or obstruction, Hirschsprung s disease, intestinal allergy, or inflammation were excluded from this study. Sociodemographic Factors Collected at Birth in the Birth Cohort To determine factors that may influence medical presentation for a condition, birth certificate information, including parental demographic characteristics, were evaluated. This information was available from the computerized birth certificate information obtained from the Minnesota Department of Health, Division of Vital Statistics. The specific information evaluated included whether or not the child was born to a single parent, maternal age, and maternal level of education. Age- and Sex-Matched Controls For each identified and reviewed case, we randomly selected 2 sex- and age-matched controls from the pool of subjects in the birth cohort who did not have one of the relevant HICDA or ICD-9 diagnoses for constipation. The controls were matched on sex and date of birth ( 6 mo) using an optimal matching algorithm applied to the values of each matching factor. 16

3 September 2007 CONSTIPATION PRESENTATION TO ADULTHOOD 1061 Table 1. Age- and Sex-Specific Incidence Density Estimates (per 1000 Persons) for Initial Constipation Presentation Between the Ages of 5 and Younger Than 21 Years Age at diagnosis, y No. Females Incidence (95% CI) a No. Males Incidence (95% CI) a Rate ratio for females vs males (95% CI) ( ) ( ) 0.9 ( ) ( ) ( ) 1.2 ( ) ( ) ( ) 2.6 ( ) ( ) ( ) 4.2 ( ) Overall ( ) ( ) 1.4 ( ) CI, confidence interval. a Incidence per 1000 person-years. Statistical Analysis The overall and age- and sex-specific incidence density estimates were derived based on the number of cases with an incident medical visit for constipation between the ages of 5 and younger than 21 years divided by the total person-time of observation for the subjects at risk. The subjects at risk were those without an incident medical visit for constipation before 5 years of age. The total person-time (ie, person-years) was the summation of the years of follow-up evaluation for all subjects at risk, from age 5 to the date of the medical visit of interest, death, emigration, or last medical visit before 21 years of age. As a secondary analysis, the overall and age- and sex-specific incidence density estimates of having a subsequent constipation visit between the ages of 5 and younger than 21 were determined. The subjects at risk were those with an incident medical visit for constipation before 5 years of age. The incidence density estimates were derived based on the number of cases with a subsequent visit divided by the total person-time of observation for the subjects at risk. Ninety-five percent confidence intervals were constructed about the incidence density estimates based on the assumption that the observed number of cases follows a Poisson distribution. Differences in the incidence density rates between independent groups were tested using a Poisson regression model. Results Incidence and Repeat Medical Presentation for Constipation in Individuals From Age 5 to Younger Than 21 Years of Age Of the 5299 subjects at risk after 5 years of age, 270 incident medical visits for constipation were identified. Five subjects were excluded on review of the medical record because of the presence of organic disease (3 with cerebral palsy and developmental delay, 1 with type 1 insulin-dependent diabetes, and 1 with Duchenne s muscular dystrophy). Based on the 265 incident cases, the overall age- and sex-adjusted incidence for constipation presentation in children 5 to younger than 21 years was 3.9 per 1000 person-years (95% confidence interval, ). Subjects without an incident visit for constipation were followed up until a median age of 20.2 years (interquartile range, y; 5% 6 y). The age- and sex-specific incidence density estimates for the medical presentation for constipation are summarized in Table 1. Males had a significantly lower incidence density of constipation presentation than females beginning at age 13 and continuing until adulthood (Table 1). Most subjects who presented for constipation (88% males; 82% females) had only one medical visit for constipation. The proportion of individuals who had repeated medical visits for constipation by sex is depicted in Figure 1. Presenting symptoms from the initial visit for constipation was available for 243 (92%) of the 265 patients. In addition to symptoms of constipation and hard and infrequent stools (100%; n 243), the most common symptoms documented in the medical records were abdominal pain (32.1%; n 85), fecal incontinence (4.9%; n 13), rectal fissure or bleeding (3.0%; n 8), and rectal prolapse (0.4%; n 2). Early Medical Presentation for Constipation and the Risk for Repeat Presentation in Individuals From Age 5 to Younger Than 21 Years To determine if early life medical presentation of constipation was a risk for a subsequent medical presentation for constipation, the rate of subsequent presentation for birth cohort members who had an incident medical visit for constipation from birth to 5 years was determined. Among the 184 subjects identified with an incident visit for constipation before 5 years of age, 29 had a subsequent visit between the ages of 5 and younger than 21 years. Of the 184 subjects, those without a subsequent visit for constipation were followed up until a median age of 20.4 years (interquartile range, y; 5% 7 y). The incidence of a subsequent medical visit for constipation in children who had an initial visit for constipation at younger than 5 years was significantly higher from 5 12 years of age and years compared with the incidence of presentation for constipation in the remainder of the population (Table 2). A chart review of the subsequent visit for constipation in subjects with an incident visit at younger than 5 years showed that 86% of patients had documentation of the subjects continuing to experience symptoms of constipation. Parental Sociodemographic Factors at Birth and Presentation for Constipation There were no significant differences in the presence of adverse parental sociodemographic (single parent, maternal age, and education level) factors at birth in children who presented for constipation, and age- and sex-matched controls from the same birth cohort (data not shown).

4 1062 CHITKARA ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 5, No. 9 Figure 1. Proportion of birth cohort members with 1, 2, 3, and 4 medical visits for constipation from 5 to younger than 21 years by sex. Discussion In this study, we found the incidence of a clinical diagnosis for constipation in children from 5 to younger than 21 years to be 3.9 per 1000 person-years. We also showed that although males and females have a similar incidence density of presentation for constipation before adolescence, males have a significantly lower incidence of constipation presentation than females beginning at age 13 and continuing until adulthood. Children with a medical visit for constipation at younger than 5 years of age were significantly more likely to have a subsequent medical visit for active symptoms of constipation up to 12 years of age and from years of age compared with the rate of new visits in this age group. Sociodemographic factors at birth did not appear to influence this presentation. Certain limitations need to be considered in interpreting the results of this study. First, this study does not reflect symptom onset or recurrence, but reflects whether a child was brought to medical care for symptoms of constipation. Second, the definitions of constipation or symptom assessments were not standardized. The evaluating physician determined if the individual had constipation, and the information reflects retrospectively collected data documented in the medical record. However, this study does provide novel information on the patterns of medical presentation for constipation in a longitudinal populationbased inception cohort for which 80% of individuals remained in the area from childhood to early adulthood. For this study, we report the incidence and repeat presentation for medical visits owing to constipation from childhood to early adulthood. The incidence is significant when compared with other disorders that affect individuals in the same age range. The incidence for constipation is much higher than the incidence of presentation for other chronic disorders that affect children such as inflammatory bowel disease (.07 cases per 1000 person-years 17 ) and type 1 insulin-dependent diabetes (.08 cases Table 2. Age-Specific Incidence Density Estimates (per 1000 persons) for Constipation Presentation Between the Ages of 5 and Younger Than 21 Years, in Children With an Early Incident Visit for Constipation ( 5 y) Compared With Those Without an Early Visit Age at diagnosis, y Incidence of subsequent visit between the ages of 5 and 21 years among the 184 subjects with an early visit ( 5 y)for constipation Incidence of initial visit between the ages of 5 and 21 years among the subjects at risk without a visit for constipation before age 5 No. Incidence (95% CI) a No. Incidence (95% CI) a Rate ratio for those with vs those without an early visit (95% CI) ( ) ( ) 4.5 ( ) ( ) ( ) 2.5 ( ) ( ) ( ) 2.1 ( ) ( ) ( ) 3.9 ( ) Overall ( ) ( ) 3.3 ( ) CI, confidence interval. a Incidence per 1000 person-years.

5 September 2007 CONSTIPATION PRESENTATION TO ADULTHOOD 1063 per 1000 person-years 18 ). In a population-based study performed in the same community, Rozen et al 19 reported that the incidence for a medical presentation for migraine headache was 3.4 per 1000 person-years in subjects age years of age. For gastrointestinal disorders, the incidence of constipation presentation is almost twice the incidence of presentation for irritable bowel syndrome in adults (2 per 1000 person-years). 20 Constipation represents a significantly prevalent disorder from childhood to early adulthood for which individuals frequently present to medical attention, and probably contributes significantly to health care resource use compared with other common medical conditions. Previous studies examining the influence of sex on constipation symptoms and presentation in children have been conflicting. A number of studies have found either no gender difference or a male predominance of constipation. 1 However, studies performed in adults who report constipation have shown a consistent female predominance. 2 By using a population birth cohort, we have shown that adolescence appears to be the critical time period in which female sex influences constipation presentation. Pubertal-related differences in serum progesterone levels may be a responsible factor. Xiao et al 21 showed that smooth muscle cells isolated from women who had undergone a colectomy for slow transit constipation had a decreased contraction response to G-protein agonists, and an associated overexpression of progesterone receptors. Over time, progesterone may contribute to diminished colonic muscle transit function. 21 Pubertal-related changes in females may account for the increased medical presentation for constipation that occurs through adolescence and adulthood. Our study suggests that the female predominance of constipation in adulthood appears to begin in adolescence and hormonal changes that occur during this time period may be relevant. The predominance of constipation symptoms in adult females does not appear to be solely a consequence of progressive ageing. Children with constipation early in life appear to be at an increased risk for continued symptoms and medical presentation for constipation later in life. Staiano et al 22 examined factors that predicted treatment success in a group of 62 children 5 years after a child s initial diagnosis of constipation. In this study, a higher proportion of those children who persistently were constipated after 5 years had the onset of symptoms at less than 1 year of age (17 of 32; 53%). In a study examining the longitudinal outcomes of a group of 418 children enrolled in studies examining treatment for constipation, van Ginkel et al 7 showed that children who developed symptoms of constipation after age 4 had a higher likelihood for a successful treatment outcome compared with children who developed symptoms before age 1 (relative risk, 1.55; 95% confidence interval, ). Although these previous studies were performed on selected populations who may have had more severe or chronic symptoms of constipation, the results from our longitudinal community-based study show that individuals who present with early childhood constipation are at increased risk of having subsequent medical visits for constipation through early adulthood. These studies suggest that the initial manifestation of chronic constipation may occur in the childhood time period. In support of this, physiologic studies investigating the etiology of constipation have shown mechanisms such as slow colonic transit, dyssynergic defecation, 23,24,26 and abnormal rectal compliance 27,28 in both children and adults with chronic constipation. Because outcome and physiologic studies support the view that the initial manifestation of chronic constipation may occur during the early childhood period, long-term approaches such as education, behavioral treatments (eg, positive reinforcement and biofeedback), and dietary management along with medications should be considered in children with recurrent symptoms of constipation; we postulate that the childhood period may represent a time when early intervention may improve health outcomes in individuals who experience constipation throughout their lifespan. In conclusion, this population-based birth cohort study shows that constipation is a common complaint that frequently prompts a medical visit from childhood to adulthood. Preadolescence ( 12 y), males and females have a similar incidence for constipation presentation. Postadolescence ( 12 y) to early adulthood, males have a significantly lower incidence of medical visits for constipation compared with females. Children who have an early ( 5 y) medical visit for constipation are approximately 3 times more likely to have a subsequent medical visit and report symptoms through early adulthood compared with children who did not present early in life. Early medical presentation and sex do influence incident and repeat medical visits for constipation from childhood to early adulthood. References 1. van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol 2006;101: Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol 2004;99: Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci 1993;38: Galvez C, Garrigues V, Ortiz V, et al. Healthcare seeking for constipation: a population-based survey in the Mediterranean area of Spain. Aliment Pharmacol Ther 2006;24: Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics 2005;23: Shah N, Locke GR III, Meek P, et al. Ambulatory care for constipation in the United States, Am J Gastroenterol 2006;101:S van Ginkel R, Reitsma JB, Buller HA, et al. Childhood constipation: longitudinal follow-up beyond puberty. Gastroenterology 2003;125: Preston DM, Lennard-Jones JE. Severe chronic constipation of young women: idiopathic slow transit constipation. Gut 1986; 27: Locke GR 3rd, Pemberton JH, Phillips SF. AGA technical review on constipation. American Gastroenterological Association. Gastroenterology 2000;119: Derbyshire EJ, Davies J, Detmar P. Changes in bowel function: pregnancy and the puerperium. 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6 1064 CHITKARA ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 5, No. 9 ester and Olmsted County, Minnesota, In: Kessler II, Levin ML, eds. The community as an epidemiologic laboratory. Baltimore: The Johns Hopkins University Press, 1970: Chitkara DK, Talley NJ, Weaver AL, et al. Incidence of presentation of common functional gastrointestinal disorders in children from birth to 5 years: a cohort study. Clin Gastroenterol Hepatol 2007;5: Bergstralh EJ, Kosanke JL, Jacobsen SJ. Software for optimal matching in observational studies. Epidemiology 1996;7: Kugathasan S, Judd RH, Hoffmann RG, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide populationbased study. J Pediatr 2003;143: Kadiki OA, Roaeid RB. Incidence of type 1 diabetes in children (0-14 years) in Benghazi Libya ( ). Diabetes Metab 2002;28: Rozen TD, Swanson JW, Stang PE, et al. Incidence of medically recognized migraine: a study in Olmsted County, Minnesota. Headache 2000;40: Locke GR 3rd, Yawn BP, Wollan PC, et al. Incidence of a clinical diagnosis of the irritable bowel syndrome in a United States population. Aliment Pharmacol Ther 2004;19: Xiao ZL, Pricolo V, Biancani P, et al. Role of progesterone signaling in the regulation of G-protein levels in female chronic constipation. Gastroenterology 2005;128: Staiano A, Andreotti MR, Greco L, et al. Long-term follow-up of children with chronic idiopathic constipation. Dig Dis Sci 1994; 39: Benninga MA, Voskuijl WP, Akkerhuis GW, et al. Colonic transit times and behaviour profiles in children with defecation disorders. Arch Dis Child 2004;89: Chitkara DK, Bredenoord AJ, Cremonini F, et al. The role of pelvic floor dysfunction and slow colonic transit in adolescents with refractory constipation. Am J Gastroenterol 2004;99: Grotz RL, Pemberton JH, Talley NJ, et al. Discriminant value of psychological distress, symptom profiles, and segmental colonic dysfunction in outpatients with severe idiopathic constipation. Gut 1994;35: Minguez M, Herreros B, Sanchiz V, et al. Predictive value of the balloon expulsion test for excluding the diagnosis of pelvic floor dyssynergia in constipation. Gastroenterology 2004;126: Voskuijl WP, van Ginkel R, Benninga MA, et al. New insight into rectal function in pediatric defecation disorders: disturbed rectal compliance is an essential mechanism in pediatric constipation. J Pediatr 2006;148: Mertz H, Naliboff B, Mayer E. Physiology of refractory chronic constipation. Am J Gastroenterol 1999;94: Address requests for reprints to: Denesh K. Chitkara, MD, Assistant Professor of Pediatrics, University of North Carolina Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, 130 Mason Farm Road, CB#7220, 5144 Bioinformatics Building, Chapel Hill, North Carolina chitkara@med.unc.edu; fax: (919) Supported in part by a research grant from Novartis pharmaceuticals and the Mayo Family Endowment in Gastroenterology at Children s Hospital, Boston, Massachusetts.