We identified a number of factors that increased the risk of hospitalization for influenza among children 6–59 months of age in the EIP population during 3 consecutive US influenza seasons. Maternal age <26 years, household income below the poverty threshold, lack of household member influenza vaccination and smoking by >50% of household members were identified as independent risk factors for hospitalization with laboratory-confirmed influenza. Consistent with prior studies,7–9 specific chronic illnesses logically increased the risk for hospitalization with influenza. Among younger children, full immunization for influenza decreased the risk of hospitalization.
Our findings that several caregiver- and household-level factors increased the risk of an influenza-associated hospitalization were not unexpected. For example, an inverse relationship was demonstrated between maternal age and the risk of acute lower respiratory tract infection among children <59 months of age in a study conducted in Western Australia,16 and a US study found that maternal age <25 years was associated with increased risk of lower respiratory tract infection deaths among children <1 year of age.17 Young maternal age may increase the risk of hospitalization with influenza because younger mothers and their peers may have less experiential knowledge and/or less social support. Younger women also may be more susceptible to respiratory infections than older women18 and thus may be more likely to transmit influenza infections to their young children.
We collected data for several factors related to socioeconomic status, including household income, household crowding and receipt of Medicaid insurance. In other studies, a number of such indicators of low socioeconomic status have been identified as risk factors for hospitalization with common acute infectious diseases among young children. For example, receiving Medicaid insurance has been identified as risk factors among young children for hospitalization with rotavirus gastroenteritis.19,20 In our analysis, only household income was identified as an independent risk factor for an influenza hospitalization, suggesting it may be a more encompassing predictor of risk than type of insurance. Low family income has been shown to increase the risk of lower respiratory tract infections, asthma attacks and respiratory-related hospitalizations among children21 and has been associated with worse outcomes in infants with respiratory syncytial virus infection.22 A recent study examining risks of hospitalization with 2009 H1N1 influenza found an inverse association between odds of hospitalization and neighborhood poverty among adults and children.23 Of course, lower socioeconomic status is associated with other factors, including poor access to medical care because of lack of transportation and fewer general available resources, which might mediate this increased risk.24
Smoking by the mother and other household members is known to increase the risk of infectious and noninfectious respiratory illness in children. In a recent meta-analysis,25 exposure to smoking by any household member was associated with an OR of 1.5 for lower respiratory infections among children <2 years of age. Our findings are consistent with those of other studies and provide evidence that exposure to passive smoking specifically increases the risk of serious outcomes related to influenza infection.
Our finding that full immunization for influenza decreased the risk of hospitalization among younger children (6–23 months of age) but not among older children (24–59 months of age) was unexpected, but may be because of an unmeasured case ascertainment bias related to differences in health-seeking behavior. Advisory Committee on Immunization Practices recommendations for influenza vaccination were expanded during our study enrollment to include children in the older age group. It is possible that older children who received the vaccination in line with the new recommendations were more likely to have seen a physician in general and therefore more likely to seek medical attention for a respiratory illness and be identified as a case.
Neither child race nor ethnicity was associated with an increased risk for influenza hospitalization in our case-control study. Although racial disparities for hospitalization associated with acute respiratory illness including influenza have been reported,26,27 it is likely that other data we collected in our study, including household income and the presence of specific chronic medical conditions, accounted for any greater risk of influenza hospitalization among select racial/ethnic groups. For example, other studies have found that black children have higher asthma prevalence,28 black and Hispanic women have lower maternal age at first parity29 and blacks and Hispanics have highest US poverty rates.30 It also should be noted that our sample size of non-Caucasian children was small, and therefore it is unlikely that this study was powered to detect small differences in risk, especially after controlling for the factors mentioned above.
This study has several limitations. First, cases were identified by influenza laboratory tests ordered by clinicians and not through use of a standardized protocol. Therefore, our results may not be representative of all children hospitalized (but not necessarily diagnosed) with influenza. Second, the diagnostic tests used to diagnose influenza infection were of variable sensitivity and specificity. In particular, there is concern with the use of commercially available influenza antigen detection assays, as the sensitivity and specificity of these tests can be quite variable.31,32 In the context of a case-control study, the specificity of the test used to provide laboratory confirmation of influenza infection in the cases is of great importance, as false positives can lead to substantial bias in the results.32 Third, because household member vaccination status was collected by self-report and not verified by physician records and because the date of household member vaccination was not collected, some household members may have reported incorrect information about their vaccination status and/or may have been vaccinated after the case was hospitalized. Fourth, recall bias may have affected parental responses to some questions; differential recall bias by case or control status is possible, as the controls as a group were interviewed later than cases were compared with the reference period. Fifth, selection bias is always a possibility in observational studies and may be of particular concern in case-control studies. Children eligible to be controls of higher socioeconomic status may have been easier to reach and enroll than other eligible controls, which would likely bias the strength of associations, especially for sociodemographic indicators, away from the null. However, it is also possible that case children of lower socioeconomic status were less likely to be enrolled if their caregivers were more difficult to reach because of lack of contact information or difficulty traveling to the hospital. As a lower proportion of controls were enrolled compared with cases, the potential for selection bias may be a greater concern among controls.
However, a strength of our study is that the eligible controls represented the true population from which the cases arose and included all children exposed to influenza viruses. Recently, a variation of traditional case-control study design known as the test negative design has become widely used in studies of influenza vaccine effectiveness. In such studies, all subjects are tested for influenza infection; cases are those testing positive and “controls” are those testing negative.33,34 These studies are popular because they permit investigators to enroll cases and non-cases from only those persons tested for influenza. For example, in a study of risk factors for influenza-related hospitalizations, one would only enroll children tested in the hospital for influenza infection. Such studies do have limitations, however, and by not limiting control selection to children tested for influenza, we were able to evaluate factors that might lead children to have more intense exposure to influenza viruses (such as daycare attendance or household crowding) as well as factors potentially associated with more severe influenza infections (including chronic illnesses and having household members who smoke).
We found child, caregiver and household factors associated with hospitalization with influenza infection among young children eligible for influenza vaccination (ie, 6 months of age and older). Our findings that chronic illnesses, young maternal age, poverty, household smoking and lack of household member influenza vaccination increase the risk of an influenza hospitalization may help providers to identify young children at greatest risk for poor outcomes from influenza illness, including those for whom early interventions such as treatment with influenza antivirals is of paramount importance.
The authors acknowledge the following persons: Deborah Aragon and Becky Rosenblatt, Colorado Department of Public Health and Environment, Denver, CO; Meredith Vandermeer, MPH, Oregon Public Health Division, Portland, OR; Darcy Fazio, Kimberly Yousey-Hindes, MPH, CPH, and John Palumbo, MT (ASCP) MS, MBA, Connecticut Emerging Infections Program, New Haven, CT; Kyle Openo, Norisse Tellman, Olivia Almendares and Suzanne Segler, Georgia Emerging Infections Program, Atlanta, GA; Brenda Barnes, RN, Sandra Gray, RN, Terri McMinn and Katie Dyer, Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN and Emily Hancock, New Mexico Department of Health, Santa Fe, NM.
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METHODS: COUNTIES PARTICIPATING IN THE EIP PEDIATRIC INFLUENZA HOSPITALIZED SURVEILLANCE PROJECT
Selected counties in 9 states that participated in the EIP Pediatric Influenza Hospitalized Surveillance Project: California (Alameda, Contra Costa, San Francisco); Colorado (Adams, Arapahoe, Denver, Douglas, Jefferson); Connecticut (New Haven); Georgia (Clayton, Cobb, DeKalb, Douglas, Fulton, Gwinnett, Newton, Rockdale); Minnesota (Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, Washington); New Mexico (2006–08: Bernalillo, Doña Ana, Grant, Luna; 2007–2008: Chaves and Santa Fe added), New York (Genesee, Livingston, Monroe, Ontario, Orleans, Wayne, Yates), Oregon (2005–2006: Clackamas, Multnomah, Washington; 2006–2008: all 36 Oregon counties) and Tennessee (Cheatham, Davidson, Dickson, Robertson, Rutherford, Sumner, Williamson, Wilson).
CODE FOR MULTIVARIABLE ANALYSES PRESENTED IN TABLES 5 AND 6
Table 5: Matched multivariable regression analysis of factors associated with hospitalization with laboratory-confirmed influenza virus infection, main effects model without interaction term
proc logistic data=a;
model enrolltype = perccat hemeonccat lungcat neurocat othchron totalpersonsvax matagecat poverty_status immunstatus / clodds=wald;
Table 6: Matched multivariable regression analysis of factors associated with hospitalization with laboratory-confirmed influenza virus infection, with interaction term
proc logistic data=a;
model enrolltype = perccat hemeonccat lungcat neurocat othchron totalpersonsvax matagecat
poverty_status immunstatus agegrouprecat agegrouprecat*immunstatus / clodds=wald;
CONTRAST agegrouprecat 0 immunstatus -1 agegrouprecat*immunstatus -1 / estimate=exp;
CONTRAST agegrouprecat 0 immunstatus -1 agegrouprecat*immunstatus 0 / estimate=exp;
perccat: >50% of household members smoked
hemeonccat: hematologic or oncologic condition
lungcat: pulmonary condition
neurocat: neurologic condition
othchron: other condition
totalpersonsvax: no household member vaccinated for influenza
matagecat: maternal age<26 years
poverty_status: household income below the poverty threshold
immunstatus: child vaccinated for influenza (vs. unvaccinated reference group)
agegrouprecat: age category of child (6–23 months vs. 24–59 months)
influenza; risk factors; hospitalization; children; household