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Juraci A César a Departamento Materno Infantil, Fundação
Universidade do Rio Grande, Rio Grande do Sol, Brazil, b Departamento de Medicina Social,
Universidade Federal de Pelotas, Rio Grande do Sol, c Hospital
Pediátrico Santo Antônio, Porto Alegre, Rio Grande do Sol
Correspondence to: Professor J A César, Maternal and Child
Epidemiology Unit, London School of Hygiene and Tropical Medicine,
49-51 Bedford Square, London WC1B 3DP juraci.cesar{at}lshtm.ac.uk
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Abstract |
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Objective:
To determine whether breast feeding
protects infants against pneumonia and whether the protection varies
with age.
Design:
Nested case-control study.
Setting:
Pelotas, southern Brazil.
Subjects:
Cases were 152 infants aged 28-364 days who had been admitted to hospital for pneumonia. Controls were 2391 cases
in a population based case-control study.
Main outcome measure:
Odds ratio of admission for
pneumonia according to type of milk consumed (breast milk alone, breast
and formula milk, or formula milk and other fluids only), use of fluid
supplements apart from formula milk, and use of solid supplements.
Results:
Infants who were not being breast fed were 17 times more likely than those being breast fed without formula milk to
be admitted to hospital for pneumonia (95% confidence interval 7.7 to
36.0). This relative risk was 61 (19.0 to 195.5) for children under 3 months old, decreasing to 10 (2.8 to 36.2) thereafter. Supplementation
with solids was associated with a relative risk of 13.4 (7.6 to 23.5)
for all infants and 175 (21.8 to 1405.1) for those under 3 months old.
Conclusion:
Breast feeding protects young children
against pneumonia, especially in the first months of life. These
results may be used for targeting intervention campaigns at the most
vulnerable age groups.
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Key messages
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Introduction |
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Pneumonia is the leading cause of death in children under 5 years old worldwide, 1 2 and breast milk is the most important food in the first year of life.3
Several studies in less developed countries have assessed the effect of breast feeding on the risk of developing acute lower respiratory infections, particularly pneumonia.4 Most of these studies show a protective effect of breast milk on pneumonia, but causality has not yet been shown.4 In addition, whether this protection changes with age, as has been shown for diarrhoea,5 is not known.
We performed a nested case-control study in southern Brazil to assess
whether breast feeding protects young children against pneumonia and
whether this protection varies with age.
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Participants and methods |
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Study population
Throughout 1993 all women who lived in urban areas and had their
babies in Pelotas, southern Brazil, were interviewed soon after
delivery in the city's hospital. Over 99% of all births in this city
take place in such hospitals.6 A systematic sample of 655 newborn infants was selected for home visiting at 1 and 3 months of age
according to date and time of birth. In the first month the mothers of
99.1% (5256) of the children were interviewed and in the third month
98.3% (5214). These infants were also visited at the age of 6 months.
As additional funds were obtained for data collection, the sampling
fraction was increased to 1144, including the 655 visited at 1 and 3 months of age. These samples represent 12.3% (655) of all children
from the original cohort in the first and third months and 21.6%
(1144) in the sixth.
Defining cases
Cases of pneumonia were identified through daily visits to the
city's hospitals. Children who were born in 1993 and had been admitted
to a hospital when aged 28-364 days were considered for inclusion in
the study. Two independent referees (paediatricians) reviewed all the
available information on each child from hospital's records. Pneumonia
was diagnosed from the presence of all clinical signs (difficult or
rapid breathing, chest indrawing), presence of rales, and
whenever
available
results of laboratory and radiological tests. Whenever the
two referees disagreed, a third senior referee established the final diagnosis.
Defining controls
The control group was made up of children taking part in the
cohort study. For cases aged 28-89 days, controls were infants at the
first home visit, who were aged about 30 days. For cases aged 90-179 days, controls were infants at the second home visit, and for cases
aged 180-364 days, controls were infants at the third visit.
Questionnaire
The mothers of cases were interviewed at home soon after the
infant had been discharged from hospital using the same questionnaire
as was used for the mothers of controls. Information on diet was
collected for cases at the age of their corresponding controls at the
home visit. For example, for a case aged 45 days dietary information
was obtained for the exact age of 30 days. Three variables were
studied.
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breast milk alone, breast and formula
milk, or other fluids alone (water, teas, juices, formula milk, or any
other liquid supplement except breast milk; this group was considered
to be completely weaned)
whether infants received water, teas, juices,
or any other liquid supplements excluding formula milk
Sample size
The sample size studied was sufficient for detecting an odds ratio
of 2.0 for exposures present in 25% of the control children, with an
error of 0.05 and a power of 80%.9 An additional 40%
was added to adjust for confounding variables and to compensate for
possible refusals.10 According to this estimate, the final
sample size should have at least 143 cases and 572 controls (four
controls per case).
Statistical analysis
We measured odds ratios with 95% confidence intervals and used
the
2 test for contingency tables in
analyses.11 We adjusted analyses using unconditional
multiple logistic regression according to a previously determined
hierarchical framework (figure). In this model some variables are
assumed to mediate their effects through other variables as well as
directly. The outcome variable was admission for pneumonia. The
significance level for the inclusion of each variable in the model was
measured by the likelihood ratio test. The final model included all
variables that had a P value up to 0.10 after adjustment for variables
in the same and higher levels of the framework. In addition, each
ordinal variable
for example, family income group
was evaluated for
linear tendency. When this association was significant and did not
deviate from linearity, the variable was included in the model as a
linear component. When missing values were less than 5% of all cases, they were recorded as the mode. Data on social class were missing in
7% of interviews,12 and we therefore created a separate
category for missing values for this variable. All data were analysed
with SPSS for Windows13 and
Egret.14
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Results |
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Of the 5304 infants in the original cohort, 152 (2.9%) were admitted to a hospital with pneumonia in the postneonatal period.
Among 250 variables tested, only social class, family income, and maternal schooling, age, parity, and weight gained during pregnancy were associated with outcome (table 1).
Table 2 shows the frequency distributions of cases and controls according to these variables. The fact that there were more controls aged 6-11 months was due to the sampling scheme used in the cohort study. This does not affect the analyses since all information on feeding was referred to the exact age at the start of each age range.7
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Table 3 shows that the relative risk of admission for pneumonia for infants receiving breast and formula milk or other fluids alone was 3.8 and 16.7 respectively in comparison with infants who were exclusively breast fed. When infants who received fluid supplements were compared with those who did not the risk disappeared after adjusted analysis. Infants receiving solid and semisolid supplements had a relative risk of 8.5 of being admitted in comparison with those who did not receive such supplements.
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Table 4 shows that after adjustment infants receiving breast and formula milk at the age of 1-2.9 months were 2.9 times more likely to be admitted for pneumonia than were those who received breast milk alone. The relative risk for infants who were completely weaned was 61.1. From age 3-5.9 months these relative risks were 3.4 and to 10.1 respectively. From age 6-11.9 months the odds ratios were 3.7 and 9.2 respectively. The interaction between age and the type of milk consumed was significant (P<0.001).
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The crude analysis showed that the risk associated with the intake of
supplementary foods in the first months was 175 for children aged 1-2.9 months, 9.1 for children aged 3-5.9 months, and 0.7 for children
aged 6-11.9 months. The odds ratio of pneumonia admission for all
children who received supplementary food was 13.4.
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Discussion |
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Methodological limitations
Case-control studies may be affected by several biases.
4 15-18
Reverse causality bias
that is, repeated
respiratory illnesses leading to a change in breastfeeding pattern
was
avoided by regarding as still breastfed infants who had stopped breast feeding because of a respiratory infection up to two months before admission. Another possibility is recall bias, since mothers of cases
in a given age range (1-2.9, 3-5.9, and 6-11.9 months) were asked to
provide retrospective information on feeding patterns at the beginning
of that interval, while mothers of control children were interviewed
within a few days of that date. To assess how this could affect the
estimates of relative risk we analysed the reported feeding patterns of
32 infants who had been both a case and a control. For 26 infants the
type of milk consumed was the same in both interviews (three were
receiving breast milk alone, five were receiving breast and formula
milk, and 18 were completely weaned). The kappa index was 0.81, reflecting good concordance. Of the six mothers whose information was
discordant, five overestimated and one underestimated the intake of
breast milk. With this adjustment the odds ratio for breast and formula
milk increased from 3.5 to 5.6 and that for formula milk decreased from
9.9 to 6.9 (table 5). Therefore, recall bias may have reduced the
estimate of risk for children receiving both breast and formula milk
and increased the risk for infants who had been completely weaned.
However, our main conclusions remain unchanged. Berkson paradox was
controlled for during adjusted analysis,19 and limitation
related to diagnostic criteria was reduced by using
referees.12
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Previous studies
Recent publications have emphasised the need for using standard
definitions of feeding patterns to allow comparison between
studies.20 In our sample few infants were exclusively breast fed
20% in the first month and 1.6% at three months
because formula milk and herbal teas are widely used.21 The low
rate of exclusive breast feeding precludes the use of such infants as
the baseline category with the lowest expected risk. We therefore used
three different variables (type of milk consumed, intake of fluid
supplements, and intake of solid and semisolid supplements) to
characterise feeding patterns. With this approach the dose-response effect of the type of milk consumed could be assessed
most studies treat breast feeding as a dichotomous variable
4 18
and
the effects of milk, fluids, and other foods could be separated.
Conclusions
The relative risks of pneumonia associated with the introduction
of supplementary foods also varied markedly with age. To our knowledge,
this interaction had not been previously described in the literature.
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Acknowledgments |
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We particularly thank Alexander M Walker, Department of Epidemiology, Harvard School of Public Health, and Saul S Morris, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine for their critical reading of the manuscript and their generous comments. We thank the three independent referees who diagnosed pneumonia from hospital records: Drs Elaine P Albernaz, Luciani M Oliveira, and Ricardo Halpern.
Contributors: All authors participated in the study proposal. JAC collected and analysed the data and wrote the paper. CGV helped in the data analysis and in editing the paper. FCB, ISS, and JAF discussed main ideas and helped to edit the paper. JAC and CGV are guarantors.
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Footnotes |
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Funding: This study was supported by the European Community, World Health Organisation, and Fundação de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS), Brazil.
Competing interests: None declared.
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References |
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(Accepted 26 February 1999)