PEDIATRICS Vol. 106 No. 6 December 2000, pp. 1413-1421

Trends in Intussusception-Associated Hospitalizations and Deaths Among US Infants

Umesh D. Parashar, MBBS, MPH^*, , Robert C. Holman, MS^§, Kate C. Cummings, MPH, N. Wayne Staggs, MS^¶, Aaron T. Curns, MPH^§, Christopher M. Zimmerman, MD^*, Stephen F. Kaufman, MS^#, Jon E. Lewis, PhD^¶, Duc J. Vugia, MD, MPH, Kenneth E. Powell, MD, MPH^**, and Roger I. Glass, MD, PhD^*

From the ^* Viral Gastroenteritis Section, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;  Preventive Medicine Residency Program, Centers for Disease Control and Prevention, Atlanta, Georgia; ^§ Office of the Director, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia;  Disease Investigations and Surveillance Branch, Division of Communicable Disease Control, California Department of Health Services, Berkeley, California; ^¶ Epidemiology Resource Center, Indiana State Department of Health, Indianapolis, Indiana; ^# Indian Health Service, US Department of Health and Human Services, Rockville, Maryland; and the ^** Division of Public Health, Georgia Department of Human Resources, Atlanta, Georgia.

	ABSTRACT

Top Abstract Methods Results Discussion Conclusion References

Context.  The newly licensed tetravalent rhesus-human reassortant rotavirus vaccine has been withdrawn following reports of intussusception among vaccinated infants.

Objective.  To describe the epidemiology of intussusception-associated hospitalizations and deaths among US infants.

Design.  This retrospective cohort study examined hospital discharge data from the National Hospital Discharge Survey for 1988-1997, Indian Health Service (IHS) for 1980-1997, California for 1990-1997, Indiana for 1994-1998, Georgia for 1997-1998, and MarketScan for 1993-1996, and mortality data from the national multiple cause-of-death data for 1979-1997 and linked birth/infant death data for 1995-1997.

Patients.  Infants (<1 year old) with an International Classification of Diseases, Ninth Revision, Clinical Modification code for intussusception (560.0) listed on their hospital discharge or mortality record, respectively.

Results.  During 1994-1996, annual rates for intussusception-associated infant hospitalization varied among the data sets, being lowest for the IHS (18 per 100 000; 95% confidence interval [CI] = 9-35 per 100 000) and greatest for the National Hospital Discharge Survey (56 per 100 000; 95% CI = 33-79 per 100 000) data sets. Rates among IHS infants declined from 87 per 100 000 during 1980-1982 to 12 per 100 000 during 1995-1997 (relative risk =7.6, 95% CI = 3.2-18.2). Intussusception-associated hospitalizations were uncommon in the first 2 months of life, peaked from 5 to 7 months old, and showed no consistent seasonality. Intussusception-associated infant mortality rates declined from 6.4 per 1 000 000 live births during 1979-1981 to 2.3 per 1 000 000 live births during 1995-1997 (relative risk = 2.8, 95% CI = 1.8-4.3). Infants whose mothers were <20 years old, nonwhite, unmarried, and had an education level below grade 12 years were at an increased risk for intussusception-associated death.

Conclusions.  Intussusception-associated hospitalization rates varied among the data sets and decreased substantially over time in the IHS data. Although intussusception-associated infant deaths in the United States have declined substantially over the past 2 decades, some deaths seem to be related to reduced access to, or delays in seeking, health care and are potentially preventable.intussusception, hospitalizations, deaths, risk factors, infants.

Intussusception, a condition in which a portion of the intestine invaginates into a distal portion, is the most common cause of intestinal obstruction among children 3 months to 5 years old.^1-3 Approximately two-thirds of all intussusceptions in children occur among infants <1 year old. Some intussusceptions resolve spontaneously and, if treated early, almost all can be reduced by enema or surgery^4,5; if untreated, many would be fatal. The cause of most intussusceptions is unknown. Some children with intussusception, particularly those who are older, have a predisposing anatomic condition (eg, everted Meckel's diverticulum) or develop the disease after an operation.^6-9 Several pathogens, especially respiratory adenoviruses, have also been implicated as causative agents.^10-18

In August 1998, a tetravalent rotavirus vaccine (RRV-TV) was licensed in the United States and was subsequently recommended by the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics for routine vaccination of US infants, with 3 doses administered orally at ages 2, 4, and 6 months.^19,20 From September 1, 1998 through July 7, 1999, 15 cases of intussusception among children vaccinated with RRV-TV were reported to the Centers for Disease Control's Vaccine Adverse Event Reporting System.²¹ Because of these reports, the use of RRV-TV was suspended and studies were launched to assess the association between intussusception and vaccination.^21,22 Preliminary data from these studies suggested that intussusception occurs with significantly increased frequency in the first 1-2 weeks after vaccination with RRV-TV, particularly after the first dose.²³ Consequently, in November 1999, the recommendation for vaccination of US infants with RRV-TV was withdrawn by the ACIP. At the same time, the ACIP recommended further research of the relationship between intussusception and RRV-TV because the findings could impact directly on the usage of this and other rotavirus vaccines.

A knowledge of the epidemiology of intussusception-associated hospitalizations and deaths among US infants will assist in understanding the relationship between RRV-TV and intussusception. Currently, limited data on intussusception among US infants are available from reports of individual cases or a series of cases and from a study that examined hospital discharge data for 1993-1995 for children in New York.²⁴ In this report, we have examined hospital discharge and mortality data from a variety of sources to provide information on the epidemiology of intussusception among US infants.

	METHODS

Top Abstract Methods Results Discussion Conclusion References

Sources of Data

To examine intussusception-associated hospitalizations, we obtained data from the National Hospital Discharge Survey (NHDS) for the period 1988-1997, from the Indian Health Service (IHS) for 1980-1997 (Yolinda Cadman, IHS, written communication, September 27, 1999 for IHS data from October 1996 through December 1997), from California for 1990-1997, from Indiana for 1994-1998, from Georgia for 1997-1998, and from MarketScan for 1993-1996.^25-33 The NHDS data were compiled by the National Center for Health Statistics (NCHS), Center for Disease Control and Prevention, and consisted of a representative sample of patient discharge records obtained from short-stay, nonfederal, general, and children's hospitals in the United States.^25,26 National estimates of total hospitalizations are weighted according to NCHS procedures and do not include hospitalizations at federal facilities, including IHS, military, and Public Health Service hospitals.²⁷ The IHS data consist of patient discharge records obtained from IHS-operated, tribally-operated, and community hospitals that have contracted with IHS or tribes to provide care to eligible American Indians and Alaska Natives within the United States.^28,29 Ten of the 12 IHS administrative areas were included in this study. The California Area was excluded because it has no IHS-operated or tribally-operated hospitals and did not report contract health services inpatient data by diagnosis to the IHS.³⁰ The Portland area was excluded because it has no IHS-operated or tribally-operated hospitals and contract health services data provided very low hospitalization rates because of limited contract health service funds for inpatient care.³⁰ The California, Indiana, and Georgia hospitalization data bases consist of patient discharge records from all nonfederal, short-term, acute-care hospitals in the respective states.^31-33 The MarketScan database is a large proprietary database (The MEDSTAT Group Inc, Ann Arbor, MI) containing information on all inpatient and outpatient health care service use of individuals who are covered by the benefit plans of ~65 large US corporations. Intussusception-associated hospitalizations among infants (<1 year old) were defined as hospitalizations for which an International Classification of Diseases, Ninth Revision, Clinical Modification code for intussusception (560.0) was recorded as any one of the diagnoses listed on the discharge record.³⁴

To examine intussusception-associated deaths, we obtained multiple cause-of-death data for 1979-1997 and linked birth/infant death data for 1995-1997 from NCHS.^35-38 The multiple cause-of-death data include all death records in the United States.^35,36 The linked birth/infant death data include information from the death certificate and the period-linked birth certificate for infants who died in the United States.^37,38 The linkage allows the use of additional information from the birth certificate to conduct more detailed analysis of infant mortality patterns. Intussusception-associated deaths among infants were defined as deaths for which the International Classification of Diseases, Ninth Revision code 560.0 was listed anywhere on the death record.³⁹

Analysis of Data

We examined intussusception-associated hospitalizations by age in months, sex, race/ethnicity, and admission month of year for each data source, as available. Annual hospitalization rates (per 100 000) were calculated by using live birth (natality) denominators for the NHDS, California, Indiana, and Georgia data.^40-44 Denominator data for IHS hospitalizations were determined by using the 1997 IHS user populations for the 10 administrative areas studied and adjusting for annual changes in the IHS infant service populations for those areas (based on March 1997 estimates).²⁹ Denominators for the MarketScan database were estimated by totaling unique identifiers recorded for inpatient and outpatient services use among infants for each year. Rate ratios (RRs) with 95% confidence intervals (CIs) were calculated by using Poisson regression analysis.⁴⁵ SUDAAN software was used to calculate annual standard errors (SEs) for the estimated NHDS hospitalization rates.⁴⁶ NHDS rate comparisons were made using 2-sided t tests incorporating weighted variance estimates.⁴⁷ Denominators obtained from vital records data were considered free from sampling error. Costs of intussusception-associated hospitalizations were assessed based on charges for each hospitalization in Georgia and total payments for inpatient services reported in the MarketScan database. Payments from the MarketScan database were converted into constant 1998 dollars by using the consumer price index for medical care services from the Bureau of Labor Statistics, US Department of Labor.⁴⁸

We examined intussusception-associated deaths by age, sex, race/ethnicity, and standard geographic region of residence. Multiple cause-of-death and natality data were used to calculate annual infant mortality rates (IMRs) (per 1 000 000 live births). To further assess characteristics associated with intussusception-associated death, 1995-1997 linked birth/infant death data were examined, and characteristics of infants who died with intussusception were compared with those of a random sample of ~0.1% of surviving infants. Infant characteristics evaluated included sex, birth weight (<2500 g and >2500 g), 5-minute Apgar score, plurality of birth, live birth order in the family, and geographic region of birth. Maternal characteristics evaluated included age, race, education, prenatal care, marital status, and tobacco use, and paternal characteristics included age. Odds ratios (ORs) with 95% CIs were calculated by using logistic regression analysis. Variables that were significantly associated ( = 0.05) with intussusception-associated death were further analyzed by fitting a series of hierarchical logistic regression models.⁴⁵

	RESULTS

Top Abstract Methods Results Discussion Conclusion References

Intussusception-Associated Hospitalizations

For the entire period for which data were available, the overall annual intussusception-associated infant hospitalization rates ranged from 22 per 100 000 for the MarketScan data to 56 per 100 000 for the NHDS data (Table 1). During 1994-1996, the 3-year period for which data were available from 5 of the 6 data sources, intussusception-associated hospitalization rates ranged from 18 per 100 000 for the IHS data to 56 per 100 000 for the NHDS data. Overall hospitalization rates were greater among males than among females for all sources of data, and these differences were significant for data from Indiana, California, Georgia, and the NHDS (Table 2).

Examination of intussusception-associated hospitalizations among Indiana infants by race showed that compared with the rate among white infants (27 per 100 000), the rate was significantly greater among black infants (50 per 100 000; RR = 1.8, 95% CI = 1.2-2.9) and among infants of other races (217 per 100 000; RR = 8.0, 95% CI = 4.6-14.1). In California, for the 3-year period (1995-1997) for which comparable data were available, compared with the rate among white infants (35 per 100 000), the rate among black infants was not significantly different (32 per 100 000; RR = 0.9, 95% CI = 0.7-1.2), but the rate among infants of other races was significantly greater (112 per 100 000; RR = 3.2, 95% CI = 2.7-3.7). In Georgia, compared with the rate among white infants (26 per 100 000), the rate was similar among black infants (30 per 100 000; RR = 1.1, 95% CI = 0.7-1.9), and was significantly greater among infants of other or unknown race (240 per 100 000; RR = 9.3, 95% CI = 5.0-17.0).

Rates of intussusception-associated hospitalization declined during the study period among infants in the IHS database (Fig 1). The rate during the first 3 years for which data were examined (1980-1982) was significantly greater than the rate for the latest 3-year period (1995-1997) (87 per 100 000 vs 12 per 100 000, respectively, RR = 7.6, 95% CI = 3.2-18.2). No significant decline in rates was seen among infants in Indiana, California, and the MarketScan data bases for the shorter period for which data were examined.

View larger version (16K): [in this window] [in a new window]   Fig. 1.   Intussusception-associated hospitalization rates among infants by year and data source.

Examination of intussusception-associated hospitalizations by month of age showed similar trends for all sources of data (Fig 2). Relatively few infants less than 3 months old were hospitalized with intussusception. By 5 months old, hospitalizations increased ~fivefold and remained elevated until 7 months old. Examination of intussusception-associated hospitalizations by month of year showed no consistent seasonal trend (Fig 3).

View larger version (23K): [in this window] [in a new window]   Fig. 2.   Percentage of intussusception-associated hospitalizations among infants by month of age and data source.

View larger version (29K): [in this window] [in a new window]   Fig. 3.   Composite percentage of intussusception-associated hospitalizations by month of year and data source.

The median length of stay for intussusception-associated hospitalizations from the various data sources ranged from 2 to 3 days. Based on MarketScan data, the median payments for each intussusception-associated hospitalization adjusted to 1998 constant dollars were $7743 (interquartile range, $3007-$16 308). Based on the Georgia data, the median charges for each intussusception-associated hospitalization were $6454 (interquartile range, $4320-$10 280). The hospital fatality rate among infants with intussusception was low for all study populations: 0% for MarketScan (0 deaths in 70 hospitalizations), 0% for IHS (0 deaths in 142 hospitalizations), 0% for Georgia (0 deaths in 78 hospitalizations), 0.2% for California (5 deaths in 2196 hospitalizations), and 1.5% for Indiana (2 deaths in 135 hospitalizations). The overall combined hospital fatality rate was 0.3% (7 deaths in 2621 hospitalizations).

Intussusception-Associated Deaths

During 1979-1997, a total of 323 intussusception-associated deaths were reported among US infants, for an overall rate of 4.4 deaths per 1 000 000 live births. Intussusception-associated IMRs declined over the study period (Fig 4); the rate during the first 3-year period (1979-1981) was significantly greater than the rate for the latest 3-year period (1995-1997) (6.4 per 1 000 000 vs 2.3 per 1 000 000, respectively; RR = 2.8, 95% CI = 1.8-4.3). The rates were greater among males than among females (5.1 per 1 000 000 vs 3.7 per 1 000 000, respectively; RR = 1.4, 95% CI = 1.1-1.7), and greater among blacks than among whites (8.7 per 1 000 000 vs 3.6 per 1 000 000, respectively; RR = 2.4, 95% CI = 1.9-3.1). By region, the rates were greatest among infants in the Midwest region (5.7 per 1 000 000), followed by those in the South (5.0 per 1 000 000), Northeast (3.6 per 1 000 000), and West (2.9 per 1 000 000).

View larger version (22K): [in this window] [in a new window]   Fig. 4.   Intussusception-associated deaths and mortality rates among infants in the United States, 1979-1997.

Examination of linked birth/infant death data showed that several characteristics of the mother including age <20 years, nonwhite race, unmarried status, education level lower than grade 12, and using tobacco, were associated with intussusception-associated infant death (Table 3). In multivariate analysis, nonwhite race (OR = 4.2, 95% CI = 1.6-10.7), unmarried status (OR = 4.2, 95% CI = 1.6-10.7), and education level lower than grade 12 (OR = 2.2, 95% CI = 1.0-4.9) were significantly associated with intussusception-associated infant death.

	DISCUSSION

Top Abstract Methods Results Discussion Conclusion References

The observed annual intussusception-associated infant hospitalization rates (ranging from 18 per 100 000 in the IHS data to 56 per 100 000 in the NHDS data during 1994-1996) probably underestimate the true incidence of intussusception because some children with this disease are managed as outpatients but they are consistent with recent estimates of hospitalization rates from New York State and the United Kingdom.^24,49 Although it is important to note that the rates from the different data sets may not be directly comparable because of heterogeneity of the populations being studied and methodological differences in estimating population denominators, other factors might account for some of the observed variability in rates. The low rate among infants in the MarketScan database may, in part, be explained by disincentives to hospitalize in managed care settings and the consequent shift of care to emergency departments and outpatient clinics.^50,51 The high rate among IHS infants in the 1980s might reflect a greater prevalence of infectious diseases in this population. This hypothesis is supported by the observation that rates declined substantially during 1980-1997, coincident with major improvements in access to safe water and adequate sanitation and documented declines in rates of diarrhea-associated hospitalizations during that period.^52,53 Increased ambulatory management of children with intussusception through non-surgical methods may also have contributed to the observed decline in the IHS rates over time. Although the reasons for the variability in rates from the other data sources are unclear, further studies in this area are needed because they may provide insights into the etiology of intussusception and thereby help in developing strategies for the prevention of this condition.

Our data provide some clues regarding the etiology of intussusception among infants. The low rate of intussusception-associated hospitalization among infants younger than 3 months old might be related to several factors such as the relative immaturity of the intestinal lymphoid tissue, protection from intestinal infections because of persisting maternal antibodies, breastfeeding, and low antigenic diversity of infant diets.^1,2 The observation that hospitalization rates were consistently greater among males than among females suggests that some unknown gender-related developmental or physiologic differences may also play an etiologic role. Although a variety of infectious agents have been associated with intussusception in previous studies,^10-18 the lack of a distinct seasonality in intussusception-associated hospitalizations among the populations we studied argues against a primary etiologic role for a single pathogen with a characteristic seasonality. In particular, no winter seasonal trend consistent with that of rotavirus disease in the United States was seen,^54,55 suggesting that natural rotavirus infection may not be a major cause of intussusception in infants.

Although we cannot be certain that vital statistics data capture all intussusception-associated deaths among US infants, the low fatality rate among infants hospitalized with intussusception is consistent with mortality rates observed in other industrialized countries and contrasts with the greater mortality rates among children in developing countries.^56-62 The risk profile of infants who died with intussusception suggests that some of these deaths are preventable and may be related to reduced access to, or delays in seeking, health care, factors known to be associated with mortality in children with intussusception.^60-62 Strategies to prevent intussusception-associated infant deaths should focus on increasing awareness of this condition among parents and caretakers and encouraging them to seek care in the early stages of illness.

Our findings raise three issues that are relevant to better understanding the relationship between RRV-TV vaccination and intussusception. First, the variable incidence of intussusception-associated hospitalizations among the different data sets should be considered in evaluating the excess number of intussusceptions (ie, the attributable risk) that may potentially be associated with RRV-TV vaccination and suggests that the attributable risk may vary greatly in different settings. Second, the fact that intussusception-associated hospitalization rates among infants younger than 3 months old were fivefold lower than those among infants 5 to 7 months old underscores the need to carefully assess the data from epidemiologic studies to determine the age-related risk of intussusception associated with rotavirus vaccine. Such analyses may provide clues to whether the risk for rotavirus vaccine-induced intussusception could be reduced by initiating immunization at a younger age. Third, although our data suggest that rotavirus is probably not a major cause of intussusception-associated hospitalizations, further epidemiologic and laboratory studies should systematically evaluate this association because the data from previous studies are conflicting.^14-16,24 Such studies may also shed light on the pathogenesis of RRV-TV-induced intussusception and help assess whether other rotavirus vaccines that are under development, including those based on human rotavirus strains, might be associated with intussusception.

	CONCLUSION

Top Abstract Methods Results Discussion Conclusion References

In summary, this study provides important insights into the epidemiology of intussusception among US infants, raises several issues that are relevant to better understanding the relationship between rotavirus vaccines and intussusception, and highlights areas where further research is needed. Additional research is particularly needed in developing countries because the epidemiology of intussusception in these settings could be quite different from that in the United States. The need for a rotavirus vaccine in developing countries is great, and the morbidity and mortality associated with natural intussusception and that which might be associated with vaccine-induced intussusception should be carefully examined so that the potential risks and benefits of a rotavirus vaccine in these settings can be assessed.

	ACKNOWLEDGMENTS

We thank John O'Connor for editorial assistance in the preparation of this manuscript, Lawrence B. Schonberger and David K. Shay for critical review of the manuscript, and the following for technical assistance: Yolinda Cadman, Glenn Melton, and Erika Matsudaira (IHS); Tammi L. Riggs (CDC); Maria F. Owings (NCHS); and Mohamed G. Qayad (GA).

	FOOTNOTES

This article does not necessarily reflect the views of the Indian Health Service.

Received for publication Feb 9, 2000; accepted Apr 18, 2000.

Reprint requests to (U.D.P.) Viral Gastroenteritis Section, Mailstop G-04, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE, Atlanta, GA 30333. E-mail: uap2{at}cdc.gov

	ABBREVIATIONS

RRV-TV, rhesus rotavirus tetravalent vaccine; ACIP, Advisory Committee on Immunization Practices; NHDS, National Hospital Discharge Survey; IHS, Indian Health Service; IMR, infant mortality rate; RR, rate ratio; CI, confidence interval; OR, odds ratio.

	REFERENCES

Top Abstract Methods Results Discussion Conclusion References

1. Stringer MD, Pablot SM, Brereton RJ Paediatric intussusception. Br J Surg. 1992; 79:867-876 [Medline]
2. DiFiore JW Intussusception. Semin Pediatr Surg. 1999; 8:214-220 [Medline]
3. Roeyen G, Jansen M, Hubens G, Vaneerdeweg W, Eyskens E Intussusception in infants: an emergency in diagnosis and treatment. Eur J Emerg Med. 1999; 6:73-76 [Medline]
4. LeMasne A, Lortat-Jacob S, Sayegh N, Sannier N, Brunelle F, Cheron G Intussusception in infants and children: feasibility of ambulatory management. Eur J Pediatr. 1999; 158:707-710 [CrossRef][Medline]
5. Shiels WE II Childhood intussusception: management perspectives in 1995. J Pediatr Gastroenterol Nutr. 1995; 21:15-17 [Medline]
6. St-Vil D, Brandt ML, Panic S, Bensoussan AL, Blanchard H Meckel's diverticulum in children: a 20-year review. J Pediatr Surg. 1991; 26:1289-1292 [CrossRef][Medline]
7. Bemelman WA, Hugenholtz E, Heij HA, Wiersma PH, Obertop H Meckel's diverticulum in Amsterdam: experience in 136 patients. World J Surg. 1995; 19:734-736 [CrossRef][Medline]
8. Linke F, Eble F, Berger S Postoperative intussusception in childhood. Pediatr Surg Int. 1998; 14:175-177 [CrossRef][Medline]
9. Holcomb GW III, Ross AJ III, O'Neill JA Jr Postoperative intussusception: increasing frequency or increasing awareness? South Med J. 1991; 84:1334-1339 [Medline]
10. Ross JG, Potter CW, Zachary RB Adenovirus infection in association with intussusception in infancy. Lancet 1962; 2:221-223 [CrossRef][Medline]
11. Bell TM, Steyn JH Viruses in lymph nodes of children with mesenteric adenitis and intussusception. Br Med J. 1962; 2:700-702 [Free Full Text]
12. Gardner PS, Knox EG, Court SDM, Green CA Virus infection and intussusception in childhood. Br Med J. 1962; 2:697-700 [Free Full Text]
13. Clarke EJ, Phillips IA, Alexander ER Adenovirus infection in intussusception in children in Taiwan. JAMA. 1969; 208:1671-1674 [Abstract/Free Full Text]
14. Konno T, Suzuki H, Kutsuzawa T, Human rotavirus infection in infants and young children with intussusception. J Med Virol. 1978; 2:265-269 [Medline]
15. Nicholas JC, Ingrrand D, Fortier B, Bricout F A one-year virological survey of acute intussusception in childhood. J Med Virol. 1982; 9:267-271 [Medline]
16. Mulcahy DL, Kamath KR, de Silva LM, Hodges S, Carter IW, Cloonan MJ A two-part study of the aetiological role of rotavirus in intussusception. J Med Virol. 1982; 9:51-55 [Medline]
17. Montgomery EA, Popek EJ Intussusception, adenovirus, and children: a brief reaffirmation. Human Pathol. 1994; 25:169-174 [CrossRef][Medline]
18. Hsu HY, Kao CL, Huang LM, Viral etiology of intussusception in Taiwanese childhood. Pediatr Infect Dis J. 1998; 17:893-898 [CrossRef][Medline]
19. Rotavirus vaccine for the prevention of rotavirus gastroenteritis among children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1999;48(RR-2):1-20
20. Prevention of rotavirus disease: guidelines for use of rotavirus vaccine American Academy of Pediatrics. Pediatrics 1998; 102:1483-1491 [Abstract/Free Full Text]
21. Centers for Disease Control and Prevention Intussusception among recipients of rotavirus vaccine-United States, 1998-1999. MMWR Morb Mortal Wkly Rep. 1999; 48:577-581 [Medline]
22. Abramson JS, Baker CJ, Fisher MC, Possible association of intussusception with rotavirus vaccination. Pediatrics. 1999; 104:575 [Free Full Text]
23. Centers for Disease Control and Prevention Withdrawal of rotavirus vaccine recommendation. MMWR Morb Mortal Wkly Rep. 1999; 48:1007 [Medline]
24. Rennels MB, Parashar UD, Holman RC, Le CT, Chang HW, Glass RI Lack of an apparent association between intussusception and wild or vaccine rotavirus infection. Pediatr Infect Dis J. 1998; 17:924-925 [CrossRef][Medline]
25. National Center for Health Statistics. National Hospital Discharge Survey. Multi-Year Data Tape Information 1979-1992. Hyattsville, MD: National Center for Health Statistics; 1996. (Data for the years 1993-1997 were also used)
26. Graves EJ, Kozak LJ. National hospital discharge survey: annual summary, 1996. Vital Health Stat. 1996;13:i-iv:1-46
27. Gillium BS, Graves EJ, Jean L. Trends in hospital utilization: United States, 1988-92. Vital Health Stat. 1996;124:1:71
28. Indian Health Service. Hospital Inpatient Data Tapes Fiscal Years 1980-1996. Rockville, MD: Indian Health Service; 1997
29. Indian Health Service. Trends in Indian Health, 1997. Rockville, MD: Indian Health Service; 1998
30. Indian Health Service. Regional Differences in Indian Health, 1996. Rockville, MD: Indian Health Service; 1997
31. California Office of Statewide Health Planning and Development. Patient Discharge Data Program. Patient Discharge Data, 1990-1997. Berkeley, CA: California Office of Statewide Health Planning and Development; 1998
32. Indiana Hospital and Health Association. Indiana Hospital Discharge Data, 1994-1998. Indianapolis, IN: Indiana Hospital and Health Association; 1999
33. Georgia Hospital Association. Georgia Hospital Discharge Data, 1997-1998. Atlanta, GA: Georgia Hospital Association, 1999
34. Public Health Service and Health Care Financing Administration. International Classification of Diseases, 9th Revision, Clinical Modification. 6th ed. (CD-ROM). Hyattsville, MD: Centers for Disease Control and Prevention; 1998
35. National Center for Health Statistics. Public Use Data Tape Documentation. Multiple Cause-of-Death for ICD-9, 1979-1997 Data. Hyattsville, MD: US National Center for Health Statistics; 1999
36. National Center for Health Statistics. Vital Statistics of the United States, 1990, Vol. 1, Mortality, Part A. DHHS Pub. No. (PHS) 95-101. Washington, DC: US Government Printing Office; 1995
37. National Center for Health Statistics. Public Use Data Tape Documentation: 1995-1997 Period Linked Birth/Infant Death Data Sets. Hyattsville, MD: National Center for Health Statistics; 1999
38. MacDorman MF, Atkinson JO. Infant Mortality Statistics From the 1997 Period Linked Birth/Infant Death Data Set. National Vital Statistics Reports; Vol. 47, No. 23. Hyattsville, MD: US National Center for Health Statistics; 1999
39. World Health Organization. Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death, Based on the Recommendations of the Ninth Revision Conference, I, 1975. Geneva Switzerland: World Health Organization; 1977
40. National Center for Health Statistics. Natality Public-Use Tapes, 1979-1997. Hyattsville, MD: US National Center for Health Statistics; 1999
41. National Center for Health Statistics. Vital Statistics of the United States, 1992, Vol. 1, Natality. Washington, DC: US Government Printing Office; 1994. DHHS Publ. No. (PHS) 94-1113
42. California Department of Health Services. Center for Health Statistics, Birth Records, 1990-1997. Berkeley, CA: California Department of Health Services; 1998
43. Indiana State Department of Health. Indiana Natality Report: State, County, and City Data, 1994-1997. Indianapolis, IN: Indiana State Department of Health, 1998. (Data for 1998 were kindly provided separately)
44. Georgia Division of Public Health, Health Assessment Services Section. Natality Data: 1997 and 1998. Atlanta, GA: Georgia Division of Public Health; 1998
45. Kleinbaum DG, Kupper LL, Muller KE, Nizam A. Applied Regression Analysis and Other Multivariable Methods. Belmont, CA: Duxbury; 1998
46. Shah BV, Barnwell BG, Bieler GS. SUDAAN User's Manual, Release 7.0. Research Triangle Park, NC: Research Triangle Institute; 1996
47. Sirken MG, Shimizu BI, French DK, Brock DB. Manual on Standards and Procedures for Reviewing Statistical Reports. Hyattsville, MD: National Center for Health Statistics; 1992
48. US Department of Labor. Consumer Price Index, Medical Care Services, All Urban Consumers, Seasonally Adjusted City Average, Base-Period 1982-1984. Available at http://stats.bls.gov/sahome.html. Washington, DC: Bureau of Labor Statistics; 1998
49. Gay N, Ramsay M, Waight P Rotavirus vaccination and intussusception. Lancet. 1999; 354:956 [Medline]
50. Bodenheimer T The HMO backlash: righteous or reactionary? N Engl J Med. 1996; 335:1601-1604 [Free Full Text]
51. Parashar UD, Holman RC, Bresee JS, Epidemiology of diarrheal disease among children enrolled in four West Coast health maintenance organizations. Pediatr Infect Dis J. 1998; 17:605-611 [CrossRef][Medline]
52. Indian Health Service. The Sanitation Facilities Construction Program of the Indian Health Service, Public Law 86-121, Annual report for 1997. Rockville, MD: Indian Health Service; 1998
53. Holman RC, Parashar UD, Clarke MJ, Kaufman SF, Glass RI. Trends in diarrhea-associated hospitalizations among American Indian and Alaska Native children, 1980-1995. Pediatrics. 1999;103(1). URL: http://www.pediatrics.org/cgi/content/full/103/1/e11
54. Glass RI, Kilgore PE, Holman RC, The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. J Infect Dis. 1996; 174:S5-S11
55. Parashar UD, Holman RC, Clarke MJ, Bresee JS, Glass RI Hospitalizations associated with rotavirus diarrhea in the United States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus specific diagnostic code. J Infect Dis. 1998; 177:13-17 [Medline]
56. Simon RA, Hugh TJ, Curtin AM Childhood intussusception in a regional hospital. Aust N Z J Surg. 1994; 64:699-702 [Medline]
57. Ein SH, Alton D, Palder SB, Shandling B, Stringer D Intussusception in the 1990s: has 25 years made a difference? Pediatr Surg Int. 1997; 12:374-376 [Medline]
58. van Heek NT, Aronson DC, Halimun EM, Soewarno R, Molenaar JC, Vos A Intussusception in a tropical country: comparison among patient populations in Jakarta, Jogyakarta, and Amsterdam. J Pediatr Gastroenterol Nutr. 1999; 29:402-405 [CrossRef][Medline]
59. Meier DE, Coln CD, Rescorla FJ, OlaOlorun A, Tarpley JL Intussusception in children: international perspective. World J Surg. 1996; 20:1035-1039 [CrossRef][Medline]
60. Stringer MD, Pledger G, Drake DP Childhood deaths from intussusception in England and Wales, 1984-9. Br Med J. 1992; 304:737-739
61. Adejuyigbe O, Jeje EA, Owa JA Childhood intussusception in Ile-Ife, Nigeria. Ann Trop Paediatr. 1991; 11:123-127 [Medline]
62. Mangete ED, Allison AB Intussusception in infancy and childhood: an analysis of 69 cases. West Afr J Med. 1994; 13:87-90 [Medline]