Acute lower respiratory infections in childhood: opportunities for reducing the global burden through nutritional interventions

Estimation of the global burden of child mortality attributable to undernutrition has played a crucial role in refocusing the attention of researchers and policy-makers on the importance of optimal maternal–child nutrition for promoting neonatal, infant and child survival,13 including the prevention of mortality due to severe acute lower respiratory infection (ALRI).25 To advance the public health application of knowledge about the interrelated burdens of childhood ALRI and poor nutrition in developing countries, we have critically reviewed available data regarding the efficacy and effectiveness of specific nutritional interventions for reducing global childhood ALRI incidence, morbidity and ALRI-specific mortality. This review included meta-analyses and large-scale randomized controlled trials of micronutrient supplementation, breastfeeding promotion, complementary food provision or counselling, and antenatal nutritional interventions, in which at least one childhood ALRI outcome (incidence, morbidity or mortality) was measured. Smaller studies or those with non-randomized designs were included where higher-quality data were unavailable. The literature review was based primarily on several systematic reviews that formed the evidence base for the Lancet Undernutrition Series (LUS) published earlier this year (available at: http://www.globalnutritionseries.org/web_appendices). To include articles published after completion of the systematic reviews, we searched PubMed (1990–January 2008) and reference lists of selected recent articles published on each topic. PubMed search terms included nutrient-specific keyword(s) and a string that broadly captured childhood ALRI-related articles (“ALRI” OR “ARI” OR “pneumonia” OR “lower respiratory tract infection” OR “lower respiratory infection” OR “bronchiolitis” OR “bronchopneumonia” OR “morbidity” OR “mortality”) without age or language restrictions. Titles/abstracts were scanned for relevant interventional studies or key supportive articles, for which full-text articles were retrieved.

ALRI outcome definition

As there is no standard definition of childhood ALRI,6 studies were included if they applied an outcome definition incorporating at least one specific lower respiratory tract sign reported by a caregiver or study personnel (fast or difficulty breathing, chest wall indrawing) and/or abnormal auscultatory findings (crackles/crepitations or bronchial breath sounds). Authors occasionally differentiated ALRI subtypes on the basis of wheeze versus crepitations/crackles (probable bronchiolitis versus pneumonia, respectively); however, viral diagnostics, isolation of pathogenic bacteria from a sterile fluid (i.e. blood culture, lung aspirate), or unequivocal radiographic findings (i.e. lobar consolidation or pleural effusion) were not documented in the reviewed trials.

Burden of disease

Estimates of the burden of ALRI attributable to selected nutritional factors were extracted from an analysis performed for LUS3,7 [where “burden” refers to ALRI-related deaths and disability-adjusted life years (DALYs) lost], and are discussed in the context of related interventions. The ALRI-specific attributable fractions (Table 1) were not reported in LUS.

Results

Breastfeeding promotion

A lack of exclusive breastfeeding in the first half of infancy is a risk factor for ALRI incidence, morbidity and death.3,5 In the LUS analysis,3 approximately 44% of infection-related neonatal deaths/DALYs (including those due to ALRI) and 20% of postnatal ALRI deaths/DALYs lost were attributed to suboptimal breastfeeding (Table 1). A causal effect of breastfeeding is plausible given the maternal–infant transfer of innate immune effectors (e.g. lactoferrin, lysozyme, secretory IgA, leukocytes)8 and influences of breast milk on immune-system maturation.9 Breastfeeding may enhance the antibody response to important pneumonia-causing pathogens (e.g. pneumococci, Haemophilus influenzae),10 but the specific mechanisms by which breastfeeding ameliorates ALRI resistance are less obvious than those that underlie diarrhoea risk reduction.

Eliminating the fraction of the ALRI burden due to suboptimal breastfeeding relies on effective breastfeeding promotion and education; however, few studies have quantified the effect of breastfeeding programmes on ALRI risk reduction.11 Four studies that reported respiratory outcomes did not distinguish upper and lower respiratory tract infections.1215 PROBIT, a large cluster-randomized trial of breastfeeding promotion (based on the WHO baby-friendly hospital initiative) in Belarus,16 was the only study from which an effect of breastfeeding promotion on ALRI outcomes could be inferred. Success of the promotion efforts was evidenced by increased breastfeeding continuation and a significant 40% decrease in diarrhoea incidence in the intervention group. The trial showed a 15% decrease in respiratory-disease-related hospitalizations (presumably due to ALRI), but despite the large sample size (n = 17 046) and high event rate (20.5% of infants in control arm had ≥ 1 respiratory disease hospitalization), the reported confidence intervals crossed the null after adjustment for confounders and design effects (Table 2).

The overall benefits of breastfeeding promotion are now widely accepted, and it seems doubtful that future similar trials will be deemed ethical or be more rigorously conducted than PROBIT, even though the magnitude of the effect might differ across populations or alternative behaviour-change strategies. Therefore, we concluded that the benefit of breastfeeding promotion on ALRI morbidity in PROBIT was consistent with observational data, and alongside the other known health benefits of breastfeeding (e.g. diarrhoea prevention, lactational amenorrhoea), reinforces the need to continue to support breastfeeding promotion policies and programmes in resource-poor settings.