PEDIATRICS Vol. 114 No. 3 September 2004, pp. 782-785 (doi:10.1542/peds.2004-0390)
Intussusception in Early Childhood: A Cohort Study of 1.7 Million Children
* Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
Departments of Epidemiology Research
|| Epidemiology, Statens Serum Institut
Department of Internal Medicine, Amager University Hospital, Copenhagen, Denmark
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ABSTRACT |
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Objective. To describe incidence and temporal trends of intussusceptions in Danish children during 1980 to 2001.
Methods. A population-based cohort study was conducted of 1.67 million children who were younger than 5 years during 1980 to 2001 and were followed up for 6.66 million person-years. The Danish National Patient Registry was used to identify cases of intussusception in the cohort. Age-specific incidence rates were main outcome measure.
Results. A total of 1814 cases of intussusception among children who were younger than 5 years were reported from 1980 to 2001. The incidence rate remained fairly constant during 1980 to 1990 but decreased by 55% (95% confidence interval: 43%–65%) from 1990 to 2001. The reduction was most pronounced among children aged 3 to 5 months.
Conclusions. The incidence of intussusception among Danish children declined significantly during the 1990s, particularly among infants 3 to 5 months of age.
Key Words: children • incidence • intussusception • population-based studies
Abbreviations: NPR, National Patient Registry • ICD, International Classification of Diseases • CI, confidence interval
Intussusception is the most common cause of intestinal obstruction in children younger than 2 years. The condition develops when a portion of the bowel (intussusceptum) telescopes into a distal portion (the intussuscipiens), often near the ileocecal valve, resulting in venous congestion leading to intestinal obstruction.1 Untreated intussusception is potentially fatal.
Among children, most intussusceptions develop in the first year of life.1,2 Cases rarely occur in children before 2 months of age, reach a peak in 5- to 7-month-old children, and then suddenly decline.3,4 In young children, the cause of intussusception is often unknown, but in children older than 2, predisposing anatomic conditions, such as inverted Meckel's diverticula or appendicitis, can be involved.5,6
The reported incidence of intussusception in some studies varies by time and geographic location. In recent studies of hospital discharge data from the United States,7,8 annual rates varied almost 3-fold between New York6 and the populations monitored by the Indian Health Survey.8 To our knowledge, few studies have investigated trends in the incidence of intussusception over time.1,9
In 1999, an oral rotavirus vaccine that had been introduced into the US Childhood Immunization Schedule was reported to be associated with intussusception among vaccine recipients. Although results from several investigations into this association were conflicting,10,11 the vaccine was voluntarily withdrawn from the market in 1999.10,11 Reliable measures of the frequency of intussusception in various parts of the world are needed to assist in understanding epidemiology of this disease. Such measures would be particularly useful for studies on the introduction and evaluation of future rotavirus vaccine candidates. To define the magnitude of the disease and to study temporal trends in the incidence of childhood intussusception in Denmark, we used population-based registries of hospital discharge diagnoses and vital status among Danish children aged 0 to 4 years during 1980 to 2001.
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METHODS |
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Study Population
The study population consisted of all live-born children in Denmark between January 1, 1975, and December 31, 2001. A total of 1 677 994 Danish children were identified: 861 612 (51.3%) boys and 816 382 (48.7%) girls. Children were followed from birth or January 1, 1980, whichever came last, to hospitalization for intussusception, emigration, death, their fifth birthday, or December 31, 2001, whichever came first.
Data Sources
All live-born children and new residents in Denmark are provided with a unique personal identification number, based on the date of birth combined with 4 digits. The personal identification number is registered in the Civil Registration System together with the child's name, gender, place of birth, address, and vital status (updated daily). All available information from national registries is kept under the personal identification number, making accurate linkage of information between registries possible. Data from the Civil Registration System were linked to the Danish National Patient Registry (NPR) to obtain data on discharge diagnoses from all Danish hospitals. The NPR contains data on all patients who were discharged from hospital departments since January 1, 1977. Data available in the NPR include patients' personal identification number, date of hospital admission and discharge, diagnosis(es), name of hospital, and zip code.
Diagnoses are coded according to the International Classification of Diseases (ICD), which changed directly from ICD-8 to ICD-10 on January 1, 1994, without any intermediate use of ICD-9. The following codes for intussusception were used to identify cases: 560.00 to 560.09 (ICD-8), before January 1, 1994, and DK561 (ICD-10) after January 1, 1994. The analyses were restricted to the first intussusception-associated hospitalization, as some children experienced >1 event as it has similarly been observed in other studies.12
Validation of Intussusception Diagnosis
A stratified random sampling approach was used to generate a list of 3 large urban and 3 smaller regional hospitals from each of 3 major Danish geographic regions. Only hospitals with 10 or more cases of intussusception recorded during the study period were considered in the sampling. Medical files that were available at the sampled hospitals from temporal distinct periods of the study period and had equal numbers of cases from the period before and after the change in ICD codes were reviewed to validate intussusception diagnoses according to standard symptoms, paraclinical findings, and treatment performed.
Statistical Methods
Period-specific cumulative incidence rates of intussusception-associated hospitalizations per 10 000 person-years during the first 5 years of childhood were estimated as weighted sums of estimated age- and period-specific incidence rates.13 From here, all mentioning of incidence will refer to incidence of intussusception-associated hospitalizations. As the NPR was established in 1977, the first years of data registration are likely related with less accuracy, whereas the incidences used in this article are based on rates of intussusceptions among children aged 0 to 5 in January 1980, and on.
The annual change in incidence rates was estimated in a log linear Poisson regression model using the SAS procedure PROC GENMOD. Because of age- and gender-related differences in incidence rate, these factors were adjusted for in the model. The effect modification by age and gender was evaluated by including interaction terms.
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RESULTS |
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Secular Trends of Intussusception
From 1980 to 2001, a total of 1 673 392 Danish children who were younger than 5 years were followed for 6 663 432 person-years; 1814 cases of intussusception were diagnosed. The incidence among girls was approximately half that among boys (1.9 vs 3.5 cases/10 000 person-years). During the study period, the follow-up of 25 082 children was terminated before 5 years of age because of death (n = 11 059), emigration (n = 13 725), or disappearance (n = 298).
The annual incidence rates of intussusception were fairly constant from 1980 to 1989 but decreased almost linearly thereafter (Fig 1). During 1980–1989, the incidence rate of intussusception in the first 5 years of childhood was 17.2 cases per 10 000 person-years. During 2000–2001, the 5-year cumulative incidence rate had declined to 7.1 cases per 10 000 person-years. From 1990 to 2001, the incidence rate decreased annually by 7% (95% confidence interval [CI]: 5%–9%; Table 1), equivalent to a total reduction of the incidence rate of 55% (95% CI: 43%–65%) in the period. The observed annual decrease was similar (P = .46) for girls (8%; 95% CI: 5%–11%) and boys (7%; 95% CI: 4%–9%; Table 1). The annual decrease was observed in most age groups but differed in magnitude (P = .009). Age-specific secular changes in rates after 1990 were as high as 12% (95% CI: 8%–15%) in 3- to 5-month-old children, whereas the annual decrease only was 2% (95% CI: –7% to 9%) among 0- to 2-month-old children (Table 1). These age-specific differences were reflected in the overall age distribution of intussusception cases (Fig 2).
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The age distribution of intussusception cases was characterized by cases occurring only rarely during the first 2 months of life, peaking among infants 4 to 7 months of age, and then declining gradually through 12 months of age (Fig 2). Among children who were younger than 5 years, the median age at diagnosis increased from 6.7 months in the period 1980–1990 to 7.7 months in the period 1991–2001 (Fig 2).
Validation of Intussusception Diagnosis
To validate the diagnosis of intussusception reported on the hospital discharge forms, we reviewed medical records for 40 patients from 18 hospitals selected at random with equal number of records from the periods before and after change of ICD code, respectively. Two diagnoses were found to be registered incorrectly as intussusception; in one case the proper diagnosis was icterus, and in the other case, the postsurgery findings revealed a hernia with an "intussusception-like" condition. One of the misclassified cases was registered by the use of the ICD-8 code and the other by the ICD-10 code. The remaining 38 cases all were equally distributed over the study period and registered correctly as intussusception.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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This study documents a 55% reduction in the incidence of intussusception among children younger than 5 years in Denmark. The incidence decreased from 16 cases per 10 000 person-years in 1980 to 8.5 cases per 10 000 person-years in 2000 (Fig 1). Denmark has a unique and reliable national information system that provides regularly updated information on person-identifiable data, including vital status, migration, and hospitalizations. Reporting to these registries is mandatory, and the trends in incidence of disease over prolonged periods can be established reliably.
The specificity of the diagnosis was high, with 95% of the diagnoses in a subset of the medical files found to be classified correctly as intussusceptions. Additional factors that could influence the frequency of the reporting of intussusception in the Danish NPR were considered: the study period included a change in the diagnostic classification system from the ICD-8 to the ICD-10 system in 1994. However, the gradual decline in the incidence of intussusceptions had already begun in the late 1980s (Fig 1), and there is no indication of an unusual decline or increase around the time of change of classification codes. Moreover, the decline continued after the change in the classification system. It also is unlikely that the decline in incidence was attributable to a decrease in the rate of hospitalizations as a result of intussusception, because most cases of intussusception require hospitalization and only a small proportion resolve spontaneously.2,4,14 According to Danish physicians in several major hospitals nationwide, no changes in hospitalization practices, diagnostic criteria, or registration procedures occurred during the study period (O. Henricksen, MD, F. Jacobsen, MD, F. Ebbesen, MD, and E. A. Andersen, MD, verbal communication, 2003). We therefore consider the observed decrease in intussusception-associated hospitalizations over time likely to represent a true decrease in the occurrence of intussusceptions among Danish children during the study period.
Despite the last years’ focus on the cause and epidemiology of intussusception as a result of the potential association with the rotavirus vaccine, only a few studies addressing these issues have been published: a multistate study of US infants showed that the incidence of intussusception-associated hospitalizations substantially decreased during a 17-year period of observation from 1980 to 1997.8 It was suggested that a particularly significant decrease in 1 of the regions (data from the Indian Health Survey) might be at least partly explained by recent improvements in water and sanitation conditions and a concomitant decline in rates of diarrhea-associated hospitalizations during that period.8 This explanation is in agreement with the hypothesis of infections playing an important role in the cause of intussusceptions. However, using nationwide data, we could not support the findings from the Indian Health Survey because the incidence of diarrhea-related hospitalizations in Denmark increased steadily concomitantly with the decrease in intussusceptions (unpublished data). In another study from New York State, the incidence rate of intussusception was found to decline from 1989 to 1998.7 The decline in intussusception cases identified by a hospital surveillance system was explained by a decrease in the number of cases treated at the hospitals caused by a temporary increase in the number of outpatient facilities available. No outpatient facilities were available in Denmark during the study period for the treatment of intussusception, so this explanation does not apply to our findings either.
Viral infections such as those caused by adenovirus, rotavirus, and human herpesvirus 6 have been reported to be associated with intussusception, but the findings are somewhat conflicting.15–18 Lymphoid hyperplasia of the mesenteric tissue has been suggested as the "lead point" in the pathogenesis of infantile intussusceptions,14 but the influence of other factors that might alter the intestinal physiology and motility should be considered.14
The potential association of intussusception with oral vaccines against rotavirus9–11,19 and polio disease14,20–22 underscores the need for assessing this issue with reliable data. The temporal changes observed in the incidence rate of intussusceptions among young Danish children occurred gradually during a 10-year period and were most pronounced among 3- to 5-month-old children. For several decades, only inactivated polio vaccine has been used in Danish children younger than 1 year. No changes in the routine childhood vaccine regimen involving the use of oral vaccines took place during the study period. This study, the largest cohort study of intussusception to date, provides no evidence that the major mechanisms involved in the cause of intussusception are related to any routinely used oral childhood vaccine.
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CONCLUSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Our study shows a substantial decrease in intussusception among Danish children since the beginning of the 1990s. The decrease was observed mainly among children aged 3 to 5 months and analogous among boys and girls. Although our findings give rise to various hypotheses, the reason for the observed decrease is unknown.
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ACKNOWLEDGMENTS |
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We thank the Danish Medical Research Council for kind support through grant 22-02-0580, including the salaries of Dr Fischer and Ms Bihrman.
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FOOTNOTES |
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Accepted Apr 28, 2004.
Reprint requests to (T.K.F.) Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS-A34, Atlanta, GA 30333. E-mail: thf7{at}cdc.gov
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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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