Acute viral respiratory infections (ARIs) are a leading cause of infant morbidity.1 Although viral upper respiratory tract infections (URIs) are common in infancy; currently, there are no effective vaccines to prevent the most common viral etiologies of ARIs, such as respiratory syncytial virus (RSV).2 Viral lower respiratory tract infections (LRTIs) are a leading cause of hospitalizations during infancy in the United States2,3 and are associated with subsequent wheeze and asthma.3
Breast-feeding is a protective factor for ARI.4,5 Exclusive breast-feeding has been associated with decreased risk of ARI;4–7 however, findings have been less consistent regarding partial breast-feeding.4,6,7 Our objective was to assess the association between history of breast-feeding (ever vs. never) and ARI severity in a cohort of 629 mother-infant dyads enrolled in the Tennessee Children’s Research Initiative (TCRI).
We investigated the association between history of breast-feeding and infant ARI severity, as measured by involvement of the lower respiratory tract and bronchiolitis severity score, using a cross-sectional analysis of data from the TCRI cohort.8 Briefly, TCRI is a prospective study of mother-infant dyads designed to assess the association between infant ARI and childhood asthma.8 Participants were recruited from September through May 2004–2008 during an acute visit (ambulatory or inpatient) for a URI or LRTI. Term infants without chronic medical conditions were eligible, with oversampling for hospitalized infants.8 At enrollment, trained research personnel administered a structured questionnaire to collect data on infant feeding, sociodemographics, medical history, environmental exposures and family history. Informed consent was obtained from the women. The Vanderbilt University Institutional Review Board approved the study.
Infants were classified as having a URI or LRTI based on physician discharge diagnosis and chart review, with LRTI considered as more severe.8 Symptoms indicative of a URI included fever, cough, congestion, hoarse cry, otitis media and/or rhinorrhea without lower respiratory symptoms. Infants with a LRTI had symptoms including grunting, nasal flaring and/or chest wall retractions, diffuse wheezing, rales or rhonchi. LRTI severity was assessed using the ordinal bronchiolitis severity score (BSS) and length of stay (LOS) for hospitalized infants. The BSS ranges from 0 to 12 (12 most severe) and scores (0–3) flaring/retraction, respiratory rate, wheezing and oxygen saturation.8 Length of hospital stay was measured in days.8 Viral testing for RSV and other viruses was conducted on infant nasopharyngeal specimens obtained at enrollment using RT-PCR.8
We obtained infant breast-feeding history using the questions, “was your child ever breastfed?” and “If yes, for how long? (specify in weeks)”. Responses were dichotomized as “ever” and “never” breast-fed. “Ever breast-fed” was categorized by a history of any breast-feeding and the minimum duration recorded was 1 week. We derived current breast-feeding by report of breast-feeding with length reported as current. We a priori selected covariates based on association with breast-feeding and ARI severity,9,10 including: maternal factors (ethnicity/race, age, asthma, enrollment year) and infant factors (estimated gestational age, birth weight, age at enrollment, insurance, daycare attendance, secondhand smoke exposure and siblings).
Univariate analyses compared breast-feeding and ARI severity using Pearson χ2 tests for categorical variables and Wilcoxon rank sum tests for continuous variables. We used multivariable regression models to investigate the association of breast-feeding with ARI severity. When our regression sample size was small for the number of adjustment covariates in subset analyses, we used propensity score adjustment method.11 We estimated the relative odds of LRTI versus URI in infants with a history of breast-feeding compared with those who were never breast-fed using multivariable logistic regression. In a subanalysis, we assessed the association between current breast-feeding and relative odds of LRTI versus URI. In the LRTI subset, we assessed the association between breast-feeding and BSS (ordinal dependent variable) using the proportional odds model. Finally, we used multivariable linear regression to evaluate the association of breast-feeding and BSS and LOS in hospitalized infants using log-transformed LOS. Multivariable regression models were controlled for maternal factors (age, asthma, ethnicity/race, enrollment year) and infant gender, estimated gestational age, birth weight, age, daycare attendance, insurance, enrollment year, secondhand smoke and sibling number. To potentially relate to RSV, we further assessed the association between breast-feeding and BSS among LRTI infants with RSV positivity. All analyses were performed using R version 2.15.2 software.
Overall 629 infants were included; median infant estimated gestational age was 39 weeks and age at enrollment was 12 weeks (Table 1). Fifty-seven percent had a history of breast-feeding. The median duration for breast-fed infants was 6 weeks (interquartile range 3–10). In univariate comparisons, women who breast-fed were older (median 26 vs. 23 years, P < 0.001) and less likely to be African-American (16% vs. 31%). Breast-fed infants were more likely to have private insurance (32% vs. 17%), higher median birth weight (3345 vs. 3232 g; P = 0.002) and lower secondhand smoke (47% vs. 66%, P < 0.001) compared with never breast-fed infants (Table 1). Seventy-two percent of infants in the study had a LRTI (n = 455). Compared with infants with a URI, infants with LRTI were younger (median age 11 vs. 23 weeks, P < 0.001), had older mothers (median 26 vs. 23 years, P < 0.001), higher median gestational age [39 (38–40) vs. 39 (39–40), P < 0.001) and sibling number [1(1–2) vs. 1 (0–2), P < 0.001] distributions, were less likely to have an African-American mother (19% vs. 33%) and more likely to have private insurance (31% vs. 11%).
In univariate analysis, the proportion of LRTI diagnoses was not statistically different in those with a history of breast-feeding compared with those never breast-fed, (70% vs. 76%, P = 0.087), respectively. In multivariable analyses, infants who were breast-fed had a 36% decreased relative odds of having a LRTI than a URI [adjusted odds ratio (OR) 0.64; 95% confidence interval (CI): 0.42–0.99] compared with infants who were never breast-fed. There were 140 infants who were currently breast-fed. The relative adjusted odds of LRTI versus URI by current breast-feeding was 0.69 (95% CI: 0.41–1.15). In the subset of infants with a LRTI, approximately 55% had a history of breast-feeding. The BSS was not significantly different by history of breast-feeding [median BSS ever 6 (4–8.5) vs. never 6.5 (4–9.0), P = 0.14]; in multivariable analysis, there was not a significant association between breast-feeding and BSS (adjusted OR 0.97, 95% CI: 0.69–1.39). Eighty-six percent of infants diagnosed with a LRTI were hospitalized. In univariate analyses, infants with a history of breast-feeding did not differ in their LOS compared with those who were never breast-fed but trended toward a lower BSS distribution (Table 1). In adjusted analyses, there was not a statistically significant association between breast-feeding history and BSS (adjusted OR: 0.79; 95% CI: 0.54–1.16) or LOS (Beta coefficient: −0.12; 95% CI: −0.27 to 0.03). In analysis of the RSV LRTI subset, we did not detect a statistically significant association between breast-feeding and BSS or LOS (data not shown).
Breast-feeding is the ideal form of infant nutrition and has protective effects on infant respiratory health,4–7 although findings regarding partial breast-feeding have been less consistent.4,6,7 In our cross-sectional study of mother-infant dyads, we found that infants with a history of breast-feeding compared with those who were never breast-fed had a 36% decreased relative odds of having a lower versus upper respiratory tract infection (adjusted OR 0.64; 95% CI: 0.42–0.99).
Studies have shown that exclusive breast-feeding is protective against LRTI7 and LRTI hospitalization,4,6 but results regarding partial breast-feeding yielded weaker associations.6 We investigated the association of a history of breast-feeding that included a minimal duration of 1 week versus infants who were not breast-fed and found a protective association between breast-feeding and LRTI versus URI. The association between current breast-feeding and LRTI versus URI was similar although not statistically significant, possibly because of smaller number of current breast-feeders and the heterogeneous comparison group. In our subset of children hospitalized with LRTI, we did not detect a statistically significant relationship between breast-feeding and LOS or BSS. Our findings may be impacted by cohort recruitment and composition which included a high prevalence of severe disease; therefore, a study with a greater spectrum of disease severity might detect differences by breast-feeding.
There are limitations to consider. We did not capture breast-feeding exclusivity and because of the cross-sectional nature of the study, we were not able to study the longitudinal association between breast-feeding duration and ARI severity. Previous studies have found a potential differential protective effect of breast-feeding on ARI by infant gender;12 however, because of limited power, we did not include interactions. There was an overrepresentation of infants with LRTI and a large proportion with severe disease, which might limit generalizability. Our study population may be disproportionately of lower socioeconomic status; however, women of lower socioeconomic status are at risk for lower breast-feeding duration and less exclusivity,7 so this population is important to study. Although we controlled for potential confounders, there may be unmeasured factors that affect the relationships studied.
We conclude that breast-feeding with a minimal duration of 1 week was associated with a decreased relative odds of having a LRTI versus a URI. Exclusive breast-feeding is the recommended feeding method within the first 6 months, but partial breast-feeding may provide some protection from LRTI.
1. Stockman LJ, Curns AT, Anderson LJ, et al. Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006. Pediatr Infect Dis J. 2012;31:5–9
2. Graham BS. Biological challenges and technological opportunities for respiratory syncytial virus vaccine development. Immunol Rev. 2011;239:149–166
3. Carroll KN, Wu P, Gebretsadik T, et al. The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma. J Allergy Clin Immunol. 2009;123:1055–61, 1061.e1
4. Lanari M, Prinelli F, Adorni F, et al.Italian Neonatology Study Group on RSV Infections. Maternal milk protects infants against bronchiolitis during the first year of life. Results from an Italian cohort of newborns. Early Hum Dev. 2013;89(suppl 1):S51–S57
5. Chantry CJ, Howard CR, Auinger P. Full breastfeeding duration and associated decrease in respiratory tract infection in US children. Pediatrics. 2006;117:425–432
6. Quigley MA, Kelly YJ, Sacker A. Breastfeeding and hospitalization for diarrheal and respiratory infection in the United Kingdom Millennium Cohort Study. Pediatrics. 2007;119:e837–e842
7. Duijts L, Jaddoe VW, Hofman A, et al. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics. 2010;126:e18–e25
8. Hartert TV, Carroll K, Gebretsadik T, et al.Vanderbilt Center for Asthma and Environmental Health Research Investigators and Collaborators. The Tennessee Children’s Respiratory Initiative: Objectives, design and recruitment results of a prospective cohort study investigating infant viral respiratory illness and the development of asthma and allergic diseases. Respirology. 2010;15:691–699
9. Kristiansen AL, Lande B, Øverby NC, et al. Factors associated with exclusive breast-feeding
in Norway. Public Health Nutr. 2010;13:2087–2096
10. Carroll KN, Gebretsadik T, Griffin MR, et al. Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan Pediatrics. 2008;122:58–64
11. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects Biometrika. 1983;70:41–55
12. Libster R, Bugna Hortoneda J, Laham FR, et al. Breastfeeding prevents severe disease in full term female infants with acute respiratory infection. Pediatr Infect Dis J. 2009;28:131–134