Increasing Burden and Risk Factors for Bronchiolitis-Related Medical Visits in Infants Enrolled in a State Health Care Insurance Plan
OBJECTIVES. The goals were to estimate the year-round burden of health care visits attributable to bronchiolitis and to identify risk factors for bronchiolitis in term healthy infants.
METHODS. We conducted a population-based, retrospective cohort study of 103 670 term, non–low birth weight infants enrolled in Tennessee Medicaid in 1995–2003. We monitored infants through the first year of life. Risk factors for bronchiolitis during infancy and rates of inpatient, emergency department, and outpatient visits during the study period were calculated by using claims data.
RESULTS. Over the 9 study years, rates of bronchiolitis visits were 238 outpatient visits per 1000 infant-years, 77 emergency department visits per 1000 infant-years, and 71 hospitalizations per 1000 infant-years. Average annual rates of bronchiolitis visits increased 41%, from 188 visits per 1000 infant-years to 265 visits per 1000 infant-years, from 1996–1997 to 2002–2003. Analysis of the linear trend in 500-g increments demonstrated a negative association between increasing birth weight and bronchiolitis diagnosis. There was a significant negative trend between maternal age and infant bronchiolitis diagnosis. Compared with infants of mothers 20 to 29 years of age, infants of mothers 15 to 19 years of age had a small increase in risk of having a bronchiolitis visit, whereas infants of older mothers (30–39 or 40–44 years of age) were less likely to have a visit.
CONCLUSIONS. The disease burden of bronchiolitis is substantial, with increasing rates of all types of visits among term, otherwise-healthy infants enrolled in Tennessee Medicaid between 1995 and 2003. Protective factors in this cohort of term infants included higher birth weight and older maternal age.
Bronchiolitis is a disease of the lower respiratory tract that is characterized clinically by cough, tachypnea, wheezing, and/or rales.1 Yearly, up to 3% of healthy infants in the United States are hospitalized with bronchiolitis, resulting in an estimated 120 000 hospitalizations, with reports of increasing hospitalization rates between 1988 and 1996.2,3 Several viruses cause bronchiolitis, including respiratory syncytial virus (RSV), influenza virus, human rhinovirus, and human metapneumovirus.4–6 RSV infects most children in the first year of life and typically causes yearly epidemics of bronchiolitis between November and April, resulting in an estimated 80 000 infant hospitalizations per year.3,7 Although children with chronic lung disease, children with cardiac disease, and children born prematurely are at increased risk of developing severe RSV bronchiolitis, the majority of illness occurs in term, otherwise-healthy infants. Efforts to develop a vaccine for RSV have been ongoing over the past several decades, with challenges in developing a safe effective vaccine.8 Although national estimates of bronchiolitis visits exist,9–12 there have been no population-based studies examining the full spectrum of the health care burden of bronchiolitis in term infants by examining outpatient and inpatient visits attributable to bronchiolitis during both RSV and non-RSV peaks.
By using a large, population-based, administrative database linked with vital records, we examined outpatient and inpatient visits attributable to bronchiolitis among term infants enrolled in the Tennessee Medicaid Program. To investigate risk factors associated with bronchiolitis, we assembled a cohort of term, otherwise-healthy infants, to avoid potential confounders such as chronic lung disease and prematurity. The objectives of this study were to estimate the year-round burden of health care visits attributable to bronchiolitis, to determine whether rates have continued to increase since the last report on hospitalization trends (1988–1996),3,13 and to estimate risk factors for bronchiolitis diagnoses in term healthy infants. These data are important to establish the burden and trends in disease for both outpatient and inpatient visits, to establish potentially modifiable risk factors for term, otherwise-healthy infants, and to inform biological research on the mechanisms of disease.
We conducted a population-based, retrospective, cohort study of >100 000 term, otherwise-healthy infants enrolled in the Tennessee Medicaid Program, in 1995–2003. Approximately 50% of infants born in Tennessee are enrolled in the Tennessee Medicaid Program. By using previously described methods, we obtained study data from linked Tennessee Medicaid administrative data files and Tennessee State vital records.14,15 The protocol was approved by the institutional review boards of Vanderbilt University and the Tennessee Department of Health.
Eligible infants had estimated gestational ages of ≥37 weeks, weighed ≥2500 g at birth, and were born to women who were continuously enrolled in the Tennessee Medicaid program. Continuous maternal enrollment was defined as no more than 45 days of nonenrollment during the year before pregnancy (last menstrual period minus 365 days) through delivery. To investigate risk factors for bronchiolitis in infants without the confounding of chronic disease, we excluded infants with any of the following during the first 3 months of life (3.11%): an International Classification of Diseases, Ninth Revision (ICD-9) code for congenital heart disease, chronic lung disease, or congenital anomaly of the airway, a Current Procedural Terminology code indicating surgery for treatment of congenital heart disease, or receipt of ≥1 dose of RSV immunoglobulin. Infant estimated gestational ages were determined by using the date of the last menstrual period on the birth certificate (91.7%), calculated on the basis of the median gestational period (in weeks) for the infant's race, birth weight, and birth year (8.22%), or determined by assigning the date of the last menstrual period as 270 days before birth (0.04%).16,17
We determined infant health care visits attributable to bronchiolitis by using ICD-9 codes for bronchiolitis (code 466.1) and/or RSV pneumonia (code 480.1). To investigate the full spectrum of the health care burden of bronchiolitis in term infants, we examined outpatient and inpatient visits attributable to bronchiolitis throughout the year. During the first few months of life, infant Medicaid visits may be billed to the infant's mother. Therefore, we attributed bronchiolitis visits in the mother's record to the infant, because bronchiolitis is a rare diagnosis in women of childbearing age.
To illustrate the pattern of the monthly distribution of bronchiolitis diagnoses, we captured all diagnoses by month from 1995 to 2003. All infants in the study cohort were monitored until they were 1 year of age, they had >21 days of nonenrollment in Tennessee Medicaid, or they died. We determined the numbers of bronchiolitis-associated outpatient visits (not associated with a same-day hospitalization or emergency department visit), emergency department visits (not associated with a same-day 23-hour observation or hospitalization), and combined 23-hour observations and hospitalizations per 1000 infant-years. To examine trends in bronchiolitis rates, we studied the years 1996 to 2003 only. During this time period, we determined the first and all ICD-9 diagnoses for all bronchiolitis visit types. The numerator consisted of bronchiolitis diagnoses. To estimate the denominator for each year, we determined the total number of infants who were <12 months of age on July 1 for each year from 1996 through 2003. We applied Poisson regression analyses to assess temporal trends in the rates.18
In this large cohort of term infants, we estimated the association between bronchiolitis during infancy and available demographic variables, including infant birth weight and maternal age at delivery.2,19–22 From infant birth certificate data, we identified infant birth weight, maternal age at delivery, infant gender, siblings (0, 1, 2, or more, on the basis of birth certificate reports of the number of previous live births), self-reported maternal smoking during pregnancy, maternal education level, and marital status. We identified infant race and region of residence (urban, suburban, or rural) from Tennessee Medicaid enrollment files. We identified mothers with asthma by capturing data on asthma-specific health care visits and medications, as described previously.17 To estimate independent predictors of ≥1 bronchiolitis health care visit during infancy, we included the aforementioned variables in a Cox proportional-hazard model with age as the time-dependent variable. As a measure of severe bronchiolitis, we also estimated predictors of bronchiolitis hospitalization. We performed a linear test of trend of the effects of infant birth weight, maternal age at delivery, number of cigarettes smoked during pregnancy, and number of siblings as ordered continuous variables by using Cox proportional-hazards models. We tested for interaction between maternal age and infant gender in bronchiolitis incidence.
Among 103 670 term infants, there were 23 306 outpatient visits, 7511 emergency department visits, and 6936 hospitalizations for treatment of bronchiolitis. Overall, 20% of infants had ≥1 bronchiolitis visit, and 8.8% of infants had >1 health care visit for treatment of bronchiolitis during infancy. During the first year of life, 13.3% of infants had a clinic visit, 6.2% had an emergency department visit, and 5.5% had a 23-hour observation or hospitalization. Bronchiolitis visits peaked in December through February, which parallels the known epidemiological features of RSV (Fig 1), with 80% of visits occurring during the winter virus season between November and April.23 There were 98 080 eligible infant-years during the study, with 238 bronchiolitis outpatient visits, 77 emergency department visits, and 71 hospitalizations per 1000 infant-years.
Figure 2 demonstrates an overall increase in yearly bronchiolitis rates from 1996 through 2003 for infants with ≥1 visit attributable to bronchiolitis (first visit during infancy, combined inpatient and outpatient), with rates stratified according to visit type. In a comparison of the average of years 1996 and 1997 with that of years 2002 and 2003, the rates of infants having any bronchiolitis diagnosis increased 41%, from 188 cases per 1000 infants to 265 cases per 1000 infants. There was a positive trend in increased rates of bronchiolitis from 1996 to 2003 (test of trend, P < .001). The average rates of having ≥1 hospitalization attributable to bronchiolitis increased from 5.5% to 6.4% in the same time period. We also estimated the total burden of all visits for treatment of bronchiolitis (repeat visits included) from 1996 through 2003. The average burden of all visits for treatment of bronchiolitis increased 48%, from 304 cases per 1000 infants in 1996–1997 to 449 cases per 1000 infants in 2002–2003.
Differences in rates of outpatient visits, emergency department visits, and hospitalizations according to sociodemographic factors are listed in Table 1. In a multivariate analysis, we compared the risk of having a visit attributable to bronchiolitis according to sociodemographic factors (Table 2). As illustrated in Table 2 and Fig 3, analysis of the linear trend for birth weight in 500-g increments demonstrated a significant negative association with bronchiolitis risk (P < .0001). In addition, there was a significant negative relationship between maternal age and infant bronchiolitis diagnosis (test of trend, P < .0001). Compared with infants of mothers who were 20 to 29 years of age at the time of delivery, infants of younger mothers had a small increase in the risk of bronchiolitis diagnosis, whereas infants of older mothers were much less likely to have a bronchiolitis diagnosis (Table 2). Similar to results for any bronchiolitis health care visit, a negative linear relationship was found between maternal age at delivery and risk of bronchiolitis hospitalization (data not shown). With adjustment for other factors, female and black infants remained less likely to have a visit attributable to bronchiolitis in the first year of life, compared with male and white infants, respectively (Table 2). Although female infants had a lower bronchiolitis risk than male infants, increasing maternal age was protective for both genders (Fig 4). Statistically significant differences in the rates of visits attributable to bronchiolitis were not seen according to maternal education level. Infants whose mothers had asthma were more likely to have a bronchiolitis diagnosis than were infants whose mothers did not have asthma (hazard ratio: 1.35; 95% confidence interval: 1.28–1.41). There was a significant dose-response relationship between the number of cigarettes smoked and bronchiolitis incidence (test of trend, P < .001). In analyses stratifying infants according to their maternal asthma and smoking history, infants of women who had asthma and who smoked ≥10 cigarettes per day had the greatest risk of bronchiolitis. In addition, there was a significant graded association of number of siblings and bronchiolitis (test of trend, P < .0001). Infants with siblings were 20% (1 sibling) to 30% (≥2 siblings) more likely to have a bronchiolitis diagnosis than were infants without a sibling. Infants in rural and suburban areas were more likely to have a bronchiolitis diagnosis than were infants in urban areas. In addition, as indicated in Table 2, factors such as higher birth weight, older maternal age, residing in an urban area, and having no siblings were associated with a decreased risk or tended toward a decreased risk of bronchiolitis hospitalization in term infants.
This population of term, otherwise-healthy, low-income children experienced high rates of bronchiolitis diagnoses, with rates of 238 outpatient visits per 1000 infant-years and 71 hospitalizations per 1000 infant-years during the first year of life. Overall, 20% of children had a health care claim for bronchiolitis, with 13.3% having an outpatient visit, 6.2% an emergency department visit, and 5.5% hospitalization. In addition, overall rates of having ≥1 bronchiolitis visit increased by 41% from 1996 to 2003.
Previous studies reported increases in hospitalizations attributable to bronchiolitis through the 1990s.3 The reasons for the increase in hospitalizations are unclear. Increases in the rates of bronchiolitis visits over time could reflect true increases in disease incidence and severity or nonbiological factors such as improved access to medical care or changes in how physicians code for visits attributable to lower respiratory tract illnesses. It is debated whether increased use of pulse oximetry has influenced hospital admissions attributable to bronchiolitis, although several studies did not find increasing rates over time for hospitalizations during infancy attributable to other respiratory illnesses in which pulse oximetry is used routinely.3,24,25 Furthermore, we estimated trends in rates of all bronchiolitis diagnoses, not solely hospitalizations, and found that rates of both outpatient and inpatient bronchiolitis diagnoses were substantial and increasing.
We also determined risk factors for a bronchiolitis health care visit in the first year of life. Even among infants who were of normal birth weight, higher birth weight was protective for bronchiolitis and severe bronchiolitis. Hoo et al26 found that low birth weight for gestational age was associated with lower lung function in infancy, and lower lung function during early infancy has been associated with other respiratory illnesses later in life.27,28 There has been an increasing trend in the rates of elective induction of labor before term birth.29,30 This practice may affect the birth weight of infants and therefore decrease the protection that higher birth weight confers with respect to bronchiolitis risk. Elective induction of labor before term delivery may have important implications, particularly for infants with the highest risks of developing asthma, those born to mothers with asthma. Infants whose mothers have asthma are known to have lower birth weights corrected for gestational age, compared with infants whose mothers do not have asthma.31
Across the age continuum, infants born to younger women were at increased risk of bronchiolitis, compared with infants of older women, even after adjustment for number of living siblings, infant birth weight, infant race, region of residence, and maternal education level. Supporting this association was the finding that older maternal age was also protective against severe bronchiolitis, as indicated by the negative linear relationship across the age continuum. The association of younger maternal age and increased risk of wheezing lower respiratory illnesses during infancy, particularly in male infants, was described in a prospective cohort study of middle-class women and their infants.19 In our larger cohort of lower-income families, the increased risk of bronchiolitis in infants of younger women was detected for both male and female infants. It is unclear whether differences in bronchiolitis risk are attributable to protective factors associated with the in utero environment of older women or differences in sociodemographic factors, such as health care-seeking behaviors, breastfeeding, or day care use.32,33 For example, it is possible that less-experienced teen-aged mothers would be more likely to take their infants for medical care or that physicians would be more likely to admit infants of teenagers, for social reasons. As illustrated in Fig 4, however, the decreased likelihood of a bronchiolitis visit was seen across the continuum of maternal age, not simply in comparisons of the youngest women and the oldest women. For example, when women in the 40- to 44-year age group were compared with those in the 30- to 39-year age group, women in the 30- to 39-year age group had a 40% increased risk of having a bronchiolitis diagnosis, compared with women in the 40- to 44-year age group (data not shown). Furthermore, Martinez et al19 found decreased risk of wheezing lower respiratory illnesses in infants of older women even after adjustment for day care exposure and infant feeding method. Interesting work of others might provide additional insights into the association of familial and environmental prenatal exposures and the developing immune system that might explain this association.32,34
Previous findings for the Tennessee Medicaid population suggested that white infants were more likely to be hospitalized for treatment of bronchiolitis than were black infants, and we found that white infants were more likely to have a bronchiolitis diagnosis overall.2 The decreased incidence may reflect differences in illness incidence, health-seeking behavior, or access to care. In analyses according to visit type, black and Latino infants were more likely to have emergency department visits attributable to bronchiolitis than were white infants, which suggests differing use of services. In a previous investigation, we addressed the primary question of whether there were associations of familial predisposition to develop asthma and maternal smoking with the incidence and severity of bronchiolitis during infancy.35 We found that infants with maternal asthma or maternal smoking during pregnancy were more likely to have a bronchiolitis diagnosis than were infants without the maternal risk factors.35 In the current study, there was a dose-response relationship between maternal smoking during pregnancy and infants having ≥1 bronchiolitis diagnosis or more-severe bronchiolitis. In addition, infants with siblings were 20% to 30% more likely to have a bronchiolitis diagnosis than were infants without a sibling, which likely is explained by the greater likelihood of viral exposure and infection among infants with a sibling. Infants in rural and suburban areas were more likely to have a bronchiolitis diagnosis than were infants in urban areas, which is an interesting and unexplained finding. Maternal smoking during pregnancy, having siblings, and living in a rural region were associated with increased risk of severe bronchiolitis, compared with no maternal smoking, no siblings, or living in an urban region, respectively.
There are several potential limitations of this work that should be considered. In this retrospective cohort study using existing data to categorize study variables, misclassification of the predictor variables is possible. However, because all predictors were measured before the infant outcome of bronchiolitis, it is likely that any misclassification would be nondifferential. If nondifferential misclassification occurred, then this would bias results toward the null hypothesis, which would lead conservatively to underestimation of the associations of the predictor variables with the bronchiolitis outcome. In addition, the cases of bronchiolitis might have been overdetected or underdetected. However, ICD-9 diagnoses of bronchiolitis represent objective, physician-characterized outcomes determined at the time of illness, which would not be influenced by recall bias. Hospitalization attributable to bronchiolitis has been used for decades in epidemiological investigations as a measure of severity; however, it is possible that social factors might have influenced providers’ decisions to hospitalize infants.36–40 Because of the retrospective nature of this cohort study, it is also possible that study findings were influenced by other unmeasured factors. Although we determined risk factors for bronchiolitis, we cannot conclude that these factors are causal. We conducted our study in a cohort of children enrolled in Tennessee Medicaid (approximately one half of the infants born in Tennessee are enrolled in Tennessee Medicaid). Population-based cohort investigations with non–Medicaid-enrolled populations would provide additional insights into the disease burden in different socioeconomic populations. Although results may not be generalizable to the non–Medicaid-enrolled population, this study cohort represents a substantial proportion of children born in the state and in other areas in the United States.
Rates of health care visits for treatment of bronchiolitis during infancy are substantial, with 1 in 5 infants having ≥1 health care visit attributable to bronchiolitis during infancy. In addition, rates of clinic visits, emergency department visits, and bronchiolitis hospitalizations are all increasing in this otherwise-healthy, term, low-income cohort of infants. Protective factors in this cohort of term infants included older maternal age and higher birth weight. These data reinforce the importance of determining why bronchiolitis rates are increasing and acting to prevent or to lessen the severity of this cause of significant infant morbidity.
This study was supported by grants from the National Institutes of Health (grants UO1 HL 72471, MO1 RR00095, KO1 AI 070808, and K12 RR17697), the Agency for Healthcare Research and Quality, Centers for Education and Research (grant U18-HS10384), the Geriatric Research Education and Clinical Center, Department of Veterans Affairs, and the Thrasher Research Fund, Parker B. Francis Foundation Grant.
We are indebted to the Bureau of TennCare of the Tennessee Department of Finance and Administration and the Tennessee Department of Health, Office of Policy, Planning, and Assessment, for providing the data. We are grateful to Fernando Martinez, MD, University of Arizona College of Medicine, for critical review of the manuscript.
- Accepted October 23, 2007.
- Address correspondence to Tina V. Hartert, MD, MPH, Center for Health Services Research, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, 6107 Medical Center East, Nashville, TN 37232-8300. E-mail:
Financial Disclosure: Dr Griffin reports receiving investigator-initiated grant support from MedImmune; the other authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject
National trends and risk factors for bronchiolitis hospitalizations (1988–1996) and risk factors for wheezing lower respiratory tract illness in infants have been reported in observational studies.
What This Study Adds
This study estimates more-recent population-based burdens and increasing trends of inpatient and outpatient visits for bronchiolitis (1995–2003) and confirms birth weight and maternal age as risk factors for bronchiolitis among term infants.
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