Exclusive Breastfeeding Protects Against Bacterial

Exclusive Breastfeeding Protects Against Bacterial Colonization and
Day Care Exposure to Otitis Media
Linda C. Duffy, PhD*‡; Howard Faden, MD*; Raymond Wasielewski, MS‡; Judy Wolf, MS*;
Debra Krystofik, RN*; and Tonawanda/Williamsville Pediatrics§
ABSTRACT. Objective. We followed a cohort (N 5
306) of infants at well-baby visits in two suburban pediatric practices to assess the relation of exclusive breastfeeding, and other environmental exposures, to episodes
of acute otitis media (AOM) and otitis media with effusion (OME).
Methods. Detailed prospective information about the
exclusiveness of breastfeeding, parental smoking, day
care attendance, and family history was obtained at
scheduled clinic visits. Tympanometric and otoscopic examinations were used in the diagnosis of otitis media
(OM). Nasopharyngeal cultures were performed at 1– 6
months, and at 8, 10, 12, 15, 18, and 24 months of age to
detect colonization with middle-ear pathogens.
Results. Between 6 and 12 months of age, cumulative
incidence of first OM episodes increased from 25% to
51% in infants exclusively breastfed and from 54% to
76% in infants formula-fed from birth. Peak incidence of
AOM and OME episodes was inversely related to rates of
breastfeeding beyond 3 months of age. A twofold elevated risk of first episodes of AOM or OME was observed in exclusively formula-fed infants compared with
infants exclusively breast-fed for 6 months. In the logistic
regression analysis, formula-feeding was the most significant predictor of AOM and OME episodes, although age
at colonization with middle-ear pathogens and day care
(outside the home) were significant competing risk factors. A hazard health model suggested additionally that
breastfeeding, even for short durations (3 months), reduced onset of OM episodes in infancy.
Conclusions. Modifiable factors in the onset of AOM
and OME episodes during the first 2 years of life include
early age at colonization (<3 months of age), day care
outside the home, and not being breastfed. Pediatrics
1997;100(4). URL: http://www.pediatrics.org/cgi/content/
full/100/4/e7; acute otitis media; otitis media with effusion; nasopharyngeal colonization; breastfeeding; day
care; proportional hazards.
ABBREVIATIONS. AOM, acute otitis media; OME, otitis media
with effusion; OM, otitis media; CI, confidence interval; RR, relative risk.
From the Departments of *Pediatrics, Children’s Hospital, and ‡Social and
Preventive Medicine and Statistics, School of Medicine and Biomedical
Sciences, State University of New York, Buffalo, New York; and
§Tonawanda/Williamsville Pediatrics, Buffalo, New York.
Received for publication Feb 18, 1997; accepted May 15, 1997.
Reprint requests to (L.C.D.) Pediatrics, Children’s Hospital, SUNY, 888
Delaware Ave, Buffalo, NY 14209.
PEDIATRICS (ISSN 0031 4005). Copyright © 1997 by the American Academy of Pediatrics.
D
espite general agreement that breastfeeding
moderates gastrointestinal and respiratory
infections in childhood, many questions underlying the beneficial effects of breast milk in preventing acute otitis media (AOM) and otitis media
with effusion (OME) remain unanswered. Design
issues and sample size variation account for much of
the variability reported. Summarized in Table 1, recent studies in well-defined cohorts have yielded
equivocal results. Among 5356 infants in Turku,
Finland, followed for 1 year, those with breastfeeding durations of ,9 months were associated with a
30% to 50% elevated risk of developing otitis media
(OM).1 A cohort of 1661 infants born in Dunedin,
New Zealand, were assessed at 3 years of age; after
adjustment for number of siblings, type of day care,
and passive smoking, duration of breastfeeding was
associated with reduced prevalence of OM disease,
but the difference was not significant.2 In Greater
Boston, among 877 children still being followed at 1
year of age, breastfeeding was found to be significantly protective for one or more episodes (odds
ratio 5 0.64; 95% confidence interval [CI]: .44-.91).3 In
another large cohort of 2130 children still being followed at 2 years, breastfeeding for ,3 months was
associated with a 20% to 60% elevated risk of AOM
and OME.4 A metaanalysis of recent follow-up studies concluded that breastfeeding even for 3 months
was protective in decreasing the risk of OM.5– 8
In the United States, the bacteria most predominantly associated with OM infections in childhood
include Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis.9,10 Bacterial infections are thought to play a more significant role in AOM compared with OME.11 Given the
problem of recognizing the occurrence of OME and
measuring the duration of an asymptomatic event,
however, the role of bacterial and viral infection in
OME needs additional study.
The present study was, in part, designed to examine the role of breastfeeding relative to selected risk
factors, including host susceptibility (age, gender),
colonization with potential pathogens, parental
smoking, and day care exposures, in identifying a
subgroup of infants at greatest risk of AOM and
OME. Using otoscopy and tympanometry to diagnosis OM episodes, we followed intensively a cohort of
infants from birth through 24 months of age. Beneficial effects of human milk were assessed at the end
of the first and second years of life. Outcomes in-
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PEDIATRICS Vol. 100 No. 4 October 1997
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TABLE 1.
Cohort Studies Examining Breastfeeding and Development of Otitis Media
Study (Year)
N
Kero and Piekkala (1982)
5356
Comparison Groups
1.5 (1.2–1.8)
1.4 (1.3–1.6)
1.3 (1.1–1.5)
1.07 (P 5 0.86)
0.64 (P 5 0.23)
0.57 (P 5 0.11)
Zielhuis et al (1989)
1661
Duration of breastfeeding
2–3 mo vs 0–4 wk
4–6 mo vs 0–4 wk
$7 mo vs 0–4 wk
Teele et al (1989)
1067
Breastfeeding as a protective factor in first year of life
One or more episodes
Three or more episodes
Alho et al (1990)
2512
Howie et al (1990)
674
Duncan et al (1993)
1220
Uhari et al (1996)
RR (95% CI)*
Duration of breastfeeding
#3 mo vs $9 mo
3–5 mo vs $9 mo
6–8 mo vs $9 mo
Duration of breastfeeding and risk of AOM
,3 mo vs 3–6 mo
,3 mo vs 7–11 mo
,3 mo vs $12 mo
Duration of breastfeeding and risk of OME
,3 mo vs 3–6 mo
,3 mo vs 7–11 mo
,3 mo vs $12 mo
.64 (0.4–0.9)
.51 (0.3–0.9)
1.4 (1.2–1.6)
1.5 (1.3–1.8)
1.6 (1.3–2.0)
1.2 (0.9–1.6)
1.4 (1.1–1.8)
1.5 (1.1–2.0)
Breastfeeding protective effects on AOM
.70 (0.5–1.0)
Effects of exclusive breastfeeding on acute and
recurrent OM
.50 (0.3–0.7)
Metaanalytic review of breastfeeding effects for AOM
$3 months
0.87 (0.8–0.9)
* For Zielhuis et al, 1989, P values were reported instead of 95% CIs.
cluded (1) frequency of OM episodes in the major
feeding groups (exclusive or partially breastfed, exclusive formula); (2) effect of breastfeeding on delaying age at colonization (.3 months) and first episodes of OM; and (3) changes to risk of AOM and
OME after breastfeeding is discontinued.
METHODS AND PROCEDURES
Study Population
A cohort of 306 infants were enrolled consecutively at wellbaby visits shortly after birth in two large pediatric practices in
Buffalo, NY. Infants with craniofacial abnormalities, genetic disorders, and immune deficiencies were excluded from the study.
Informed consent was obtained from all maternal guardians at
entry, and infants were followed intensively monthly for the first
6 months of life, and then at 8, 10, 12, 15, 18, 21, and 24 months of
age. Cumulative incidence of OM episodes and colonization patterns of disease in this present cohort are described in detail in
recent reports.12–14 Interim visits after diagnosis of middle-ear
disease and recent illnesses were scheduled as necessary. Maternal
interviews (family medical history, demographics, prenatal maternal exposures) and physical examinations of eligible infants
were completed at study enrollment. Changes in feeding modes
(breast milk, formula) and environmental exposures (parental
smoking, day care attendance of siblings and index child) were
assessed at scheduled office visits. Sibling history of recurrent OM
was defined as more than three episodes before enrollment of the
index child. Accuracy and reliability of data collected were quality-assured during phone interviews and home visits and by
mailed questionnaires at 6, 12, and 24 months of age. When the
child was 2 years old, maternal guardians completed a questionnaire to determine the reliability of various postnatal parameters.
The response rate to the questionnaires among infants still being
followed at 2 years of age (N 5 238) was .85%. k Statistics
revealed consistent agreement (r .. 90) of maternal respondents to
questionnaire items related to classification and duration of feeding modes (birth and 3, 6, and 12 months of age).
Bacterial infection of the middle ear often contributes to a
continuum of disease with AOM leading to OME and vice versa.
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AOM was defined by presence of one or more symptoms such as
fever, irritability, ear pain, pulling at the ears, and tympanic
membrane changes including increased thickness, bulging, loss of
landmarks, decreased mobility, and a flattened tympanogram,
type b curve.12 Tympanograms were performed in children $6
months of age; the lowest negative pressure on the tympanometer
used was 2400 daPa.
OME was defined as the presence of a middle-ear effusion in
the absence of symptoms. The tympanic membrane was not thickened, but it was immobile and the tympanogram had to show a
flattened tracing in children .6 months of age. In our study, de
novo OME episodes appeared spontaneously and were not related
to a preceding episode of AOM. For episodes of either AOM or
OME, children were examined monthly until the ear examination
was entirely normal; duration was calculated from the start of the
episode until all evidence of disease had resolved.
Physicians and trained nurse interviewers used standard criteria in evaluating clinical symptoms as well as in determining
resolution and new episodes of disease. Ears were examined with
pneumatic otoscopy and tympanometry by the same group of
physicians for the duration of the study. Infants were examined
monthly after the initial diagnosis of OM until resolution of middle-ear disease. New episodes were defined after resolution of at
least 30 days, with the unit of analysis being the child (avoiding
problems of interdependence when the ear is used in the analysis).11
Feeding groups were defined as 1) exclusively breast milk-fed;
2) combined breast- and formula-fed; and 3) exclusively formulafed. Maternal and paternal smoking history was defined for current smoking status at birth of index child and was reviewed
retrospectively at 24 months of age (k . .70). Number of cigarettes
smoked per day was not determined. Day care contact by index
children and their siblings was recorded at scheduled visits.
Laboratory Procedures
Nasopharyngeal cultures were obtained with a small rayon
swab. Swabs were placed in transfer medium for laboratory processing using standard techniques. Collected specimens were cultured on trypticase soy agar with 5% sheep blood, chocolate agar,
and MacConkey agar within 8 hours of collection. Bacteriology
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procedures used for identification of S pneumoniae, nontypeable H
influenzae, and M catarrhalis are described extensively in previous
reports from our laboratory.12–14
Data Analysis
Cumulative incidence was used to express rates of unilateral or
bilateral OM episodes in the various feeding groups. Tests of
association for categoric comparisons were expressed as relative
risk (RR) and their appropriate 95% CI values. Because a large
number of infants (N 5 96) had only single acute episodes of OM
in the first year, the distribution was highly skewed. A logistic
regression model was used to test the relative effect of independent etiologic factors on first OM episodes.15 Additionally, Cox
proportional hazard analyses16 h(tux) 5 c(t)zf(x) were performed to
examine the role of breastfeeding and time-dependent factors (age
at first pathogen colonization) in mediating OM episodes. The
proportional hazard at time t is the probability of an episode
occurring at time t given no event up to time t and for a specific
value of a predictor variable (full or partially breastfed, formula).
Covariables were entered in the chronologic sequence of assumed
postnatal events (ie, feeding mode, age at colonization). The cumulative hazard functions for the two feeding groups are displayed graphically and are summarized as risk ratios in the results. SAS and SPSS/BMDP statistical software was used in the
analysis.
RESULTS
Demographic and clinical characteristics of the
study population are given in Table 2. Mean age of
mothers was 29.6 6 4.3 years (range, 19 to 42 years),
TABLE 2.
Demographic and Clinical Characteristics of
Infant Cohort
Characteristics
N
Gender
Male
Female
Ethnicity
Caucasian
African-American (and other minorities)
History of recurrent OM (more than three episodes)
Maternal
Paternal
12 Months
Siblings*
24 Months
Siblings†
Current smokers
Maternal
Paternal
Day care (outside house)
12 Months
Sibling(s)‡
Infant
24 Months
Sibling(s)§
Infant
Enteral feeding at entry
Exclusive breast
Combined breast and formula
Exclusive formula
(%)
160 (52)
146 (48)
302 (99)
4 (1)
93 (31)
58 (19)
110 (58)
117 (59)
36 (12)
54 (18)
68 (35)
110 (36)
88 (44)
151 (49)
178 (58)
18 (6)
110 (36)
* The percentage of infants for sibling history of recurrent OM at
12 months is based on the number of infants with siblings with
available data (N 5 191).
† The percentage of infants for sibling history of recurrent OM at
24 months is based on the number of infants with siblings with
available data (N 5 200).
‡ The percentage of infants with siblings in day care at 12 months
is based on the number of infants with siblings with available data
(N 5 192).
§ The percentage of infants with siblings in day care at 24 months
is based on the number of infants with siblings with available data
(N 5 201).
with the majority of maternal guardians having completed a high school education (average education,
14 6 2 years). The vast majority of study infants
(99%) in the two suburban practices were Caucasian,
and all infants were full term at birth. Despite problems of generalizing, the high compliance of this
homogenous cohort is notable. Infants were enrolled
between 1 and 6 weeks postnatally, 86% of infants
completed 9 or more of the 13 scheduled visits over
the 24 months of study follow-up. Home contact was
maintained with the families, which minimized attrition rates (moving out of area, loss to follow-up).
In all, 58% of infants were exclusively breastfed at
birth, 6% were combined breast- and formula-fed at
birth, and 36% were exclusively formula-fed. The
rate of exclusive breastfeeding in this infant cohort
was ;30% at 3 months and 16% at 6 months.
As shown in Fig 1, the cumulative incidence of OM
was #20% for the first 3 months of age, regardless of
feeding mode. At 6 months, cumulative incidence of
first episodes of OM remained ,30% in infants exclusively breastfed (10/40), whereas cumulative incidence was .50% in infants formula-fed from birth
(53/99). Peak incidence of OM rose earlier (3 to 6
months) in formula-fed infants compared with exclusively breastfed infants (6 to 12 months). Slightly
more than 50% of infants exclusively breastfed for 6
months had first episodes of OM by the end of the
first year (20/39), whereas 76% of exclusively formula-fed infants had first episodes of OM by 12 months
of age (74/98).
The incidence of AOM and OME episodes is described separately in Fig 2 relative to changes in
feeding mode and number of infants still being followed. Peak incidence of AOM and OME episodes
was inversely related to rates of breastfeeding beyond 3 months of age. Rates of OM in breastfed
infants partially supplemented with formula remained between rates reported for exclusively
breast- and formula-fed infants during the first year.
The effects of breastfeeding (duration, amount) on
risk of AOM and OME episodes are examined further in the multivariate analyses reported later in
“Results.”
Summarized in Fig 3, rates of colonization with
potential middle-ear pathogens (any) were higher in
infants currently formula-fed at 3 months of age
(31.7%), 6 months (54.3%), and 12 months (48.9%)
compared with infants exclusively breastfed (28.4%,
27.3%, and 50%). However, rates of colonization
were only significantly different between the two
exclusive feeding groups at 6 months of age (P 5
.003). Colonization rates in combined breast- and
formula-fed infants were below or between rates
observed in the exclusive feeding groups reported
for the first 12 months (19.2%, 35.9%, 46.4%, respectively).
We summarized risk of first episodes of AOM and
OME as it related to changes in feeding mode during
the first 12 months of life (Table 3). Overall, first
episodes of OM were elevated, but not significantly,
in exclusively formula-fed infants compared with
exclusively breastfed infants at 3 months of age
(RR 5 1.22, 95% CI: .97, 1.54); risk increased signifi-
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Fig 1. Cumulative percent of otitis media first episodes in breast- and formula-fed infants, 0 to 24 months.
Fig 2. Incidence of OM episodes relative to changes in
feeding modes during the first
year of life.
cantly for the 6-month comparison in the exclusive
feeding groups (RR 5 1.59, 95% CI: 1.13, 2.24). Risk
was marginally elevated in infants exclusively
formula-fed versus those combined breast- and
formula-fed at 6 months (RR 5 1.28, 95% CI: 1.03,
1.59) and 12 months (RR 5 1.30, 95% CI: .99, 1.70),
respectively.
The putative beneficial effects of breastfeeding
were somewhat clearer for acute episodes of disease.
For short-term breastfeeding (3 months), first episodes of AOM were increased significantly in infants
exclusively formula-fed compared with those infants
exclusively breastfed from birth (RR 5 1.39, 95% CI:
1.00, 1.94). For longer durations of exclusive breastfeeding ($6 months), an approximately twofold elevated risk for AOM (RR 5 1.82, 95% CI: 1.15, 2.90)
and OME episodes (RR 5 2.06, 95% CI: 1.01, 4.18)
was observed. AOM, but not OME, episodes were
significantly elevated in infants exclusively formulafed compared with infants receiving breast milk
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combined with formula supplementation for 6
months. Recurrent episodes (at least two) of OM
were also examined intensively in this infant cohort.
Elevated risk for recurrent episodes of AOM (RR 5
1.35, 95% CI: .82, 2.22) and OME (RR 5 1.65, 95% CI:
.67, 4.07) was noted in exclusively formula-fed compared with full or combined breast- and formula-fed
infants, but the estimates were not significant.
Environmental exposures thought to intervene in
the onset and recurrence of OM disease of infancy
include infant and sibling day care outside the home,
parental smoking, family history of OM, and other
factors. A multivariate logistic regression including
only significant risk factors from the univariate analyses and OM episodes from birth to 24 months is
presented in Table 4. Formula-feeding remained the
single most consistent predictor of OM episodes at 3,
6, and 12 months. An additional risk factor of note
was day care contact (outside the home) by the index
child (b 5 1.08 6 .43; 95% CI: .22, 1.92). By 12 months
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Fig 3. Frequency of pathogen colonization in breast- and formula-feeding infants during first 12 months.
TABLE 3.
Univariate Analysis of Feeding Modes and Risk of First Episode of Otitis Media During First 12 Months
Risk Factors
Feeding mode during first 3 months
Feeding mode during first 6 months
Feeding mode during first 6 months
Feeding mode during first 12 months
Feeding mode during first 12 months
Value
1st OM Disease
RR
95% CI
1st AOM
RR
95% CI
1st OME
RR
95% CI
Exclusive formula*
Exclusive breast†
Exclusive formula*
Exclusive breast†
Exclusive formula*
Breast and formula‡
Exclusive formula
Breast and formula‡
Full formula§
Breast and formula‡
1.22
0.97, 1.54
1.59
1.13, 2.24
1.28
1.03, 1.59
1.30
0.99, 1.70
1.24
0.96, 1.60
1.39
1.00, 1.94
1.82
1.15, 2.90
1.40
1.04, 1.89
1.45
0.99, 2.13
1.35
0.94, 1.94
1.22
0.76, 1.95
2.06
1.01, 4.18
1.50
0.92, 2.43
1.47
0.83, 2.59
1.37
0.81, 2.31
* Exclusively formula-fed for the respective months above included children who had only formula (feed 5 2) for every month up to the
last month in the analysis.
† Exclusively breast-fed for the respective months above included children who had only breast (feed 5 1) for every month up to the last
month in the analysis.
‡ Combined breast and formula-fed for the respective months above included children who had either breast (feed 5 1) or both breast
and formula (feed 5 3) for every month up to the last month in the analysis.
§ Full formula-fed for the respective months above included children who were either formula (feed 5 2) for every month up to the last
month in the analysis or weaned (feed 5 4) at any time before or at the last month in the analysis.
of age, day care remained only marginally associated
with elevated risk of OM episodes in index children
(b 5 .81 6 .37, 95% CI: .08, 1.54).
Similar risk estimates for AOM episodes were observed in exclusively formula-fed infants compared
with breastfed infants at 3 months (b 5 .99, 95% CI:
.11, 1.88), and 6 months (b 5 1.52, 95% CI: .48, 2.56).
Despite the silent nature of OME episodes, the protective effect of breastfeeding at 3, 6, and 12 months
was remarkably similar to that observed for AOM in
this study cohort. Day care (outside the home) of the
index child appeared important, but of marginal sig-
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TABLE 4.
Multivariate Logistic Regression of Risk Factors and First OM Episode During First 24 Months
OM
Coefficient 6
SE
AOM
95% CI
OME
Coefficient 6
SE
95% CI
Coefficient 6
SE
95% CI
Intercept
Gender
Age of pathogen colonization
Day care
Mother smoking
Feed*
0.07 6 0.39
0.15 6 0.41
0.55 6 0.42
1.08 6 0.43
0.69 6 0.81
0.93 6 0.42
20.71,
20.67,
20.27,
0.22,
20.91,
0.10,
0.85
3.26
1.38
1.92
2.29
1.76
20.30 6 0.43
0.27 6 0.43
0.38 6 0.44
0.98 6 0.45
0.31 6 0.85
0.99 6 0.45
21.16,
20.59,
20.50,
0.09,
21.37,
0.11,
0.55
1.12
1.26
1.87
1.99
1.88
21.16 6 0.51
20.34 6 0.54
0.88 6 0.52
1.50 6 0.56
1.18 6 0.90
0.91 6 0.53
22.17,
21.42,
20.15,
0.39,
20.62,
20.16,
20.15
0.73
1.91
2.61
2.99
1.97
Intercept
Gender
Age of pathogen colonization
Day care
Mother smoking
Feed‡
20.30 6 0.48
0.49 6 0.49
0.24 6 0.50
1.01 6 0.52
1.01 6 1.09
1.52 6 0.50
21.26,
20.49,
20.76,
20.02,
21.14,
0.54,
0.65
1.46
1.24
2.03
3.16
2.50
20.58 6 0.52
0.61 6 0.52
0.08 6 0.53
0.80 6 0.54
0.86 6 1.11
1.52 6 0.52
21.61,
20.43,
20.98,
20.28,
21.35,
0.48,
0.46
1.65
1.14
1.87
3.07
2.56
21.90 6 0.72
0.05 6 0.65
0.66 6 0.64
1.59 6 0.69
1.18 6 1.20
1.83 6 0.69
23.34,
21.26,
20.63,
0.20,
21.22,
0.44,
20.45
1.35
1.94
2.97
3.58
3.21
Intercept
Gender
Age of pathogen colonization
Day care
Mother smoking
Feed‡
0.14 6 0.39
0.38 6 0.42
0.42 6 0.43
0.81 6 0.43
1.10 6 1.07
1.12 6 0.44
20.64,
20.45,
20.43,
20.04,
21.02,
0.25,
0.91
1.21
1.27
1.66
3.22
1.99
20.32 6 0.44
0.45 6 0.45
0.38 6 0.46
0.82 6 0.45
1.04 6 1.09
1.19 6 0.46
21.18,
20.43,
20.53,
20.08,
21.13,
0.29,
0.55
1.34
1.29
1.72
3.21
2.10
20.96 6 0.50
20.18 6 0.52
0.55 6 0.52
0.86 6 0.52
1.16 6 1.16
1.10 6 0.54
21.94,
20.85,
20.48,
20.18,
21.16,
0.02,
0.03
1.22
1.59
1.91
3.48
2.17
Intercept
Gender
Age of pathogen colonization
Day care
Mother smoking
Feed§
20.21 6 0.43
0.36 6 0.37
0.91 6 0.41
0.81 6 0.37
1.55 6 1.05
1.10 6 0.40
21.06,
20.37,
0.10,
0.08,
20.52,
0.31,
0.64
1.09
1.70
1.54
3.62
1.90
20.70 6 0.48
0.48 6 0.39
0.91 6 0.43
0.82 6 0.39
1.29 6 1.08
1.13 6 0.43
21.65,
20.29,
0.06,
0.05,
20.84,
0.28,
0.24
1.24
1.77
1.59
3.42
1.98
21.24 6 0.55
0.05 6 0.45
1.02 6 0.47
0.78 6 0.45
1.82 6 1.08
1.19 6 0.52
22.32,
20.84,
0.08,
20.11,
20.33,
0.17,
20.16
0.94
1.95
1.66
3.97
2.21
* Exclusively breast- versus exclusively formula-feeding (3 months).
† Exclusively breast- versus exclusively formula-feeding (6 months).
‡ Combined breast and formula-feeding versus exclusively formula-feeding (6 months).
§ Combined breast and formula-feeding versus exclusively formula-feeding or weaned at 12 months.
nificance, as an intervening variable for both AOM
and OME episodes in the present study.
Given the importance of the time-dependent covariables (age at colonization, duration of breastfeeding), proportional hazards regression health models16 are presented graphically in Fig 4 and Fig 5.
Results indicate that breastfeeding for at least 3
months (b 6 SE 5 .48 6 .18, P , .01) mediated age
at colonization (b 6 SE 5 2.11 6 .02) and onset of
OM episodes. Exclusive breastfeeding for 6 months
(b 6 SE 5 .78 6 .24, P 5 .001) appeared to mediate
age at colonization (b 6 SE 5 2.10 6 .03) and onset
of OM episodes even more strongly. Expressed as
relative risk, after controlling for age at colonization,
risk in exclusive formula-feeding infants increased
substantially between 3 months (RR 5 1.62, 95% CI:
1.12, 2.30) and 6 months of age (RR 5 2.17, 95% CI:
1.36, 3.48). In addition, the results indicated that for
each month pathogen colonization was delayed, a
corresponding decrease in first OM episodes was
observed.
DISCUSSION
The risk estimates presented for formula-feeding
compared with breastfeeding in this study cohort are
similar to those reported in several metaanalytic
Fig 4. Cumulative hazard function for onset of first OM:
3-month feeding. h(t;z) 5 h0(t)exp[(20.1097)z(1stPathAge)
1 (0.4793)z(3 month feeding)]. Hazard functions are plotted at the mean level of the covariate age of first colonization (5.49) and for each category of 3-month feeding.
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BREASTFEEDING AND OTITIS MEDIA
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Fig 5. Cumulative hazard function for onset of first OM:
6-month feeding. h(t;z) 5 h0(t)exp[(20.0999)z(1stPathAge)
1 (0.7770)z(6-month feeding)]. Hazard functions are plotted at the mean level of the covariate age at first colonization (5.45) and for each category of 6-month feeding.
studies published recently.3,6,7 These studies indicate
a beneficial effect of breastfeeding (even for short
durations) on reducing AOM episodes in infancy.
Day care outside the home was an important risk
factor in our study and has been reported to be a
significant risk factor for AOM in larger cohorts described in metaanalytic reports.3,5,11 Risk of recurrent
AOM increases with number of contacts with other
children; these contacts increase as children shift
from family to day care centers outside the home.
Additional investigation is needed to determine
which factors (hygiene, size, duration) associated
with day care attendance may be responsible for
increased risk of otitis media onset in infancy.
The lack of information on dose exposures of infants to tobacco smoke makes interpretation of parental smoking risk more difficult. In the present
study, maternal smoking appeared to be associated
with increased risk of AOM and OME in infancy. No
association between parental smoking and risk of
OM episodes was found, however, when duration of
breastfeeding, age at colonization with middle-ear
pathogens, and day care contact outside the home
were also considered in the multivariate logistic regression analyses. Our findings are consistent with
those of other cohort studies published recently.1,2
Selecting a causal model, when possible, may lead
to clearer interpretation of scientific and clinical results than simply using data-driven analyses.17 Time
dependence, as used in the proportional hazards
causal model reported here, assumes that the status
of the covariate (ie, age at pathogen colonization)
may change with time, and that it has to be effective
in the correct temporal sequence relative to disease;
ie, its effect must precede the disease. Early age (#3
months) of colonization with nontypeable H influenzae, S pneumoniae, or M catarrhalis has been associated
with increased risk of OM episodes in infancy. The
strong correlation (r 5 .37, P , .001) between pathogen colonization rates and frequency of OM episodes
found in the cohort is described more fully in a
recent microbiology report by the coauthors (HF, LD,
RW, et al).14 Early age at colonization (#3 months)
with middle-ear pathogens correlated with onset of
OM episodes in infants ,6 months of age. Alternatively, although our own extensive studies provide
evidence that human milk has immunologic and
nonimmunologic protective properties,13,18 data from
our laboratories and elsewhere do not conclusively
show whether breast milk is protective or whether
components of formula-feeding are conducive to onset and recurrence of OM.2,3,19
The protective effect of breastfeeding may be explained by several mechanisms, including exposure
to infectious microorganisms, improved nutrition,
and bioactive and antibacterial effects of human
milk. The immunologic properties of human milk
and other components that interfere with the attachment of bacterial pathogens to nasopharyngeal epithelial cells warrant additional study. Special emphasis needs to be given to age effects relative to
duration of breastfeeding and onset of OM disease.
The results confirm the frequent nature of AOM
and de novo OME and stress the necessity for clear,
consistent definitions of the criteria for differentiating AOM and OME in epidemiologic research. Risk
of AOM and OME was reduced significantly in infants exclusively breastfed until 6 months of age,
after which breast milk was supplemented with
other nutrients or discontinued. With the decline of
exclusive breastfeeding and with increasing months
of environmental exposures (day care, parental
smoking), feeding group differences between 6 and
12 months were reduced. Nevertheless, increased
risk for AOM and OME episodes during the first 2
years of life was identified with early pathogen colonization, day care outside the home, and not being
breastfed.
The results clearly identify modifiable postnatal
risk factors for AOM and OME in infancy. Reduction in colonization with middle-ear pathogens in
infants #3 months of age requires closer examination. Encouraging home day care and breastfeeding for at least 3 months appear to be modifiable
risk factors that significantly impact onset and duration of OM.
ACKNOWLEDGMENTS
This research was supported by National Institute of Child
Health and Human Development Grant 19679.
We thank Elizabeth Griffiths, PhD, and Allen Leavens, MSc, for
assistance in preparing the manuscript.
http://www.pediatrics.org/cgi/content/full/100/4/e7
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BREASTFEEDING AND OTITIS MEDIA
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Exclusive Breastfeeding Protects Against Bacterial Colonization and Day Care
Exposure to Otitis Media
Linda C. Duffy, Howard Faden, Raymond Wasielewski, Judy Wolf, Debra Krystofik
and Tonawanda/Williamsville Pediatrics
Pediatrics 1997;100;e7
DOI: 10.1542/peds.100.4.e7
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and
trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove
Village, Illinois, 60007. Copyright © 1997 by the American Academy of Pediatrics. All rights
reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Exclusive Breastfeeding Protects Against Bacterial Colonization and Day Care
Exposure to Otitis Media
Linda C. Duffy, Howard Faden, Raymond Wasielewski, Judy Wolf, Debra Krystofik
and Tonawanda/Williamsville Pediatrics
Pediatrics 1997;100;e7
DOI: 10.1542/peds.100.4.e7
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/100/4/e7.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 1997 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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