1079
REVIEW ARTICLE
A Meta-Analytic Review of the Risk Factors for Acute Otitis Media
Matti Uhari, Kerttu Mantysaari, and Marjo Niemela
From the Department of Pediatrics, University of Oulu, Oulu, Finland
The occurrence of acute otitis media (AOM) has increased steadily during the last 15 years. The
possible environmental risks associated with AOM should be well identified to prevent any further
increase in its occurrence. A meta-analysis of the studies evaluating the risk factors for AOM was
performed. A MEDLINE search of the medical literature from 1966 to 1994 with the key words
children, risk, acute otitis media, and recurrent acute otitis media was performed, and the references
of the articles that were found served as the sources for the studies used in the meta-analysis. Sixtyone studies were identified. Twenty-two (36%) of these studies were accepted for the meta-analysis.
Depending on the risk factor, there were two to seven different studies from which risk ratios (RRs)
could be pooled. The studies were performed in six different countries. If any other member of the
family had had AOM, the risk increased (RR, 2.63; 95% confidence interval [Cll, 1.86-3.72;
P = .00001). The risk of AOM increased with day care outside the home (RR, 2.45; 95% CI, 1.513.98; P = .0003) and family day care (RR, 1.59; 95% CI, 1.19-2.13; P = .002). The risk of AOM
increased with parental smoking (RR, 1.66; 95% CI, 1.33-2.06; P < .00001). Breast-feeding for at
least 3 months reduced the risk of AOM (RR, 0.87; 95% CI, 0.79-0.95; P = .003). The use of a
pacifier increased the risk of AOM (RR, 1.24; 95% CI, 1.06-1.46; P = .008). Child care outside the
home and parental smoking were the factors that most significantly increased the occurrence
of AOM.
Acute otitis media (AOM) is one of the most common infectious diseases occurring in childhood. Prolonged and recurrent
episodes of AOM may lead to hearing impairment and delayed
speech development, which will influence the child's later performance at school [1]. The occurrence of AOM has increased
steadily in the United States during the last 15 years; during
this period, the number of office visits for AOM in the United
States increased from 9.91 million in 1975 to 24.5 million in
1990 [2, 3]. Even though similar data are not available from
elsewhere, it is justifiable to assume that a trend of the same
type has developed in other industrialized countries. Whether
this increased occurrence is due to changes in society that
increase the risk of recurrences of AOM should be analyzed.
However, this analysis is not possible because all the environmental risks associated with AOM have not been thoroughly
identified.
Several factors have been identified as risks increasing the
occurrence and recurrence of AOM [3]. However, the evidence
supporting these risk factors is conflicting. There has also been
misinterpretation of the results of studies, especially in cases
Received 11 October 1995; revised 16 January 1996.
Reprints or correspondence: Dr. Matti Uhari, Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland.
Clinical Infectious Diseases 1996;22:1079-83
© 1996 by The University of Chicago. All rights reserved.
1058--4838/96/2206-0027$02.00
where the risk has been found to be statistically insignificant.
The possibility and probability of a type II error ({3 error)
have often been ignored [4]. Meta-analysis is a method of
quantitative summary of published data that offers the chance
to reevaluate studies with small sample sizes by combining
their results, thus decreasing the probability of a type II error
and affording a better estimation of the true effect size of the
risk factor [5]. We performed a meta-analysis of the studies of
the risk factors for AOM to further clarify possible means for
preventing AOM in childhood.
Materials and Methods
A MEDLINE search of the medical literature from 1966 to
1994 with the key words children, risk, acute otitis media, and
recurrent acute otitis media was performed, and the references
of the articles that were found served as the sources for the
studies used in this meta-analysis. Studies were then evaluated
on the basis of study design and the presentation and analysis
of data. Disagreements on the interpretation of study results
were resolved in joint discussions by the investigators. If the
studies were original studies of risk factors that had adequate
control groups and reported the actual numbers of patients,
then they were included in the meta-analysis because the risk
ratios were reproducible. The diagnosis of AOM varied, but
pneumatic otoscopy was used in the diagnosis; however, there
was no restriction on inclusion according to the diagnostic
criteria used.
1080
This review focuses on the relative risk of AOM associated
with the presence of specific factors. The clinical and statistical
heterogeneity of the studies was evaluated before the results
were combined [5]. Pooled estimates of risks were derived with
the random effect (unconditional) model [6]. To obtain these
pooled estimates, we calculated a weighted average of the risks
using the inverse of the variance of the risk in each study as
the weight; 95% confidence intervals for estimates of the relative risk were calculated.
The classification of some of the risk factors varied from
one study to another. Whenever possible, analysis was done
with AOM classified as yes or no and with ADM classified as
less than three or three or more episodes during the period
studied.
Results
The risks associated with ADM were analyzed in 61 studies.
Altogether, 39 reports were rejected, most commonly because
of the lack of an adequate control or comparison group (10
studies) and because risk factors were not evaluated (10 studies)
(table 1). Twenty-two studies (36%) fulfilled the inclusion criteria of the meta-analysis. The pooled estimate of the relative
risk and the 95% confidence intervals were calculated from
data from studies that were sufficiently homogeneous (table 2).
The studies were performed in six different countries.
If any other member of the family had had ADM, the risk
increased (RR, 2.63; 95% CI, 1.86-3.72; P = .00001) (figure
1). When classifying AOM as yes or no, day care outside the
home appeared to be a significant risk (RR, 2.45; 95% CI,
1.51-3.98; P = .0003) (figure 1). Family day care appeared
to significantly increase the risk of ADM (RR, 1.59; 95% CI,
1.19-2.13; P = .002) when compared with care at home (figure
1). Parental smoking increased the risk of ADM (RR, 1.66;
95% CI, 1.33-2.06; P < .00001). Breast feeding for at least
3 months reduced the risk of ADM (RR, 0.87; 95% CI, 0.790.95; P = .003). The risk factor associated with the use of a
pacifier was analyzed in two studies on ADM [8, 28], and the
pooled estimate of the risk ratio was significant (RR, 1.24;
95% CI, 1.06-1.46; P = .008). The effect of giving a child a
Table 1. Reasons that studies of acute otitis media were rejected
from the meta-analysis and pooling of the risk ratios.
Reason for rejection
Lack of an adequate control or comparison group
No evaluation of risk factors for acute otitis media
Episodes counted, no numbers of patients
No numbers of patients, only risk ratios
Review article, not an original study
Only preterm babies included
Total
cm
Uhari, Mantysaari, and Niemela
No. of studies
10
10
7
6
4
2
39
Table 2.
analysis.
Studies ofthe risk ofAOM that were included in the meta-
Study type
Total no.
of
subjects
1971
1975
1976
1976
Case-control
Follow-up
Follow-up
Case-control
233
3,349
39
250
[11] 1976
[12] 1982
Follow-up
Case-control
207
200
[13]
[14]
[15]
[16]
[17]
1982
1982
1984
1985
1985
Follow-up
Follow-up
Follow-up
Follow-up
Case-control
237
681
20
279
471
[18]
[19]
[20]
[21]
[22]
1986
1987
1988
1989
1989
Case-control
Follow-up
Follow-up
Follow-up
Follow-up
438
575
1,294
113
877
[23]
[24]
[:'5]
[26]
[27]
[28]
1990
1992
1993
1993
1994
1994
Follow-up
Follow-up
Follow-up
Case-control
Follow-up
Follow-up
674
2,304
1,220
170
400
938
[Reference] year
of publication
[7]
[8]
[9]
[10]
NOTE.
1996;22 (June)
Risk factors evaluated
Baby bottle in bed
Pacifier
Day care type
Atopy, day care type, family
history of AOM
Day care type
Atopy, breast-feeding, day
care type
Breast-feeding
Day care type
Breast-feeding
Breast-feeding
Breast-feeding, day care
type, siblings, smoking
Day care type, smoking
Day care type
Breast-feeding
Family history
Breast-feeding, family
history, siblings, smoking,
baby bottle in bed
Breast-feeding
Atopy
Breast-feeding
Smoking
Breast-feeding
Allergy, pacifier
AOM = acute otitis media.
baby bottle in bed was analyzed in two studies [7, 22], but the
risks obtained were too heterogeneous to be pooled [5].
Child care outside the home, parental smoking, and having
at least one sibling significantly increased the risk of having
less than three or three or more episodes of ADM (table 3).
G.hild care at day care centers significantly increased the risk
of ADM, but the differences between family day care vs. home
care and care at day care centers vs. family day care were not
significant (table 3).
Discussion
Child care outside the home was an important risk factor
for ADM in our meta-analysis. The risk of recurrent ADM
increases with the number of contacts with other children; these
contacts increase as children shift from home care to family
day care and child care at day care centers (the child care
associated with the most contacts). When analyzing a continuously increasing risk in insufficient increments, one may find
insignificant differences; this circumstance may be the reason
why an insignificant risk ratio was found when family day care
em
Positive family history of ADM
Studies
included
[references]
[10,21,22]
Day care outside home
[9,11,12,14,17,18]
1,972
Parental smoking
[17,18,22]
1,784
Family day care vs. home care
[9,11,12,17,18]
1,030
At least one sibling
[17,22]
1,344
Day care center vs. family care
[9,11,12,17,18]
Day care center (yes/no)
[9,11,12,17,18,19]
1,918
I-H
Use of a pacifier
[8,28]
4,110
:H-i
Breast-feeding >3 mo
[12,13,17,22,23,27]
2,548
Breast-feeding >6 mo
[12,13,17,20,22,25,27] 3,384
Breast-feeding (yes/no)
[15,16,17,22,23]
Risk factor
Figure 1. Pooled risk ratios
from 18 studies analyzed in a
meta-analysis ofthe risk factors for
acute otitis media (ADM). ADM
was classified as yes or no.
1081
Risk Factors of Acute Otitis Media
1996;22 (June)
Number of
subjects
0.5
1.0
2.0
I
I
I
3.0
4.0
I
I
3.0
4.0
I
I
1,240
I
I
1-+-1
650
I
H-I:
I
I
I-H:
r-+-i:
I
2,193
I
I
I
..-was compared to home care and care at day care centers was
compared to family day care of children who had had less than
three or three or more episodes of ADM. The number of children in day care outside their home has increased during the
last few years, especially in day care centers. Thus, changes
occurring only in the organization of these facilities alone could
explain the observed increase in the occurrence of ADM.
The participation of mothers in work outside the home is a
reality that cannot be changed; therefore, we should focus on
organizing day care facilities so that the risk of infection is as
low as possible, which means that more effort should be directed at evaluating the epidemiology of infections in day care
centers. Because the size of the day care center is known to
be the single most important factor increasing the risk of infec-
2.0
I
Decreased risk
Increased risk
---..
tions, children should be cared for in small centers [29]. Parental smoking habits are difficult to change, but the increased
risk of ADM in children of parents who smoke is another good
reason to stop smoking.
The preventive effect of breast-feeding on gastrointestinal
infections has been well documented, but the results of the
effect of breast-feeding on other infections and ADM have
been controversial. In our meta-analysis, breast-feeding was
beneficial, and breast-feeding even for only 3 months decreased
the risk of ADM. Paradise et al. [30] reported that breast milk
rather than the position during feeding provides protection from
middle ear effusion in children with cleft palates. However,
we do not know whether the breast milk is beneficial or if
cow's milk increases the risk of ADM.
Table 3. Pooled estimates of the risk ratios of recurrent acute otitis media according to the risk factors analyzed in the meta-analysis.
Risk factor
At least one sibling
Child care outside home
Parental smoking
Family day care vs. home care
Day care center vs. family care
Day care center vs. home care
Atopy or allergy
Breast-feeding
Breast-feeding, ~3 mo vs. <3 mo
Breast-feeding, ~6 mo vs. <6 mo
NOTE.
[References]
No. of subjects
RR
95% CI
P value
[17,22]
[11, 17, 18]
[17, 18,22,26]
[11, 17, 18]
[11,17,18]
[11,17,18]
[10, 12, 28]
[16, 22]
[13,17,22]
[13, 17, 22]
1,344
1,111
1,954
822
545
1,107
1,362
1,156
1,331
1,331
1.92
1.82
1.76
1.61
1.41
1.38
1.23
0.48
0.69
0.69
1.29-2.85
1.21-2.73
1.36-2.28
0.89-2.93
0.96-2.07
1.19-1.61
0.94-1.61
0.32-0.72
0.46-1.03
0.49-0.97
.001
.004
.00002
.12
.12
.00002
.12
.0004
.07
.03
Acute otitis media was classified as less than three or three or more episodes.
1082
Uhari, Mantysaari, and Niemela
Both the treatment of AOM and the prevention of recurrent
AOM with antibiotics have been evaluated by means of metaanalysis [31, 32]. It was found that antibiotic therapy has a clinically
and statistically significant impact on the resolution of otitis media
with effusion [31]. Further antibiotic therapy has a beneficial but
limited effect on recurrent otitis [32]. The prevention of AOM
without medical treatment would be even more desirable, and at
least some of the identified risk factors can be manipulated so that
a significant proportion of recurrent AOM could be prevented.
The diagnosis of AOM is not easy; at best, pneumatic otoscopy performed by an experienced pediatrician or otologist
provides a true positive finding in about 80% of cases [33].
The diagnostic difficulties lead to an overestimation of the
occurrence of AOM. When the risk factors of AOM are evaluated, overdiagnosis causes an underestimation of the risk ratios,
which may be reflected in our meta-analysis because the diagnostic criteria for AOM varied and were not evaluated in each
study.
The pooled risk ratios found in this meta-analysis are small
compared with some other risk factors, such as etiologic factors
(e.g., the effect of smoking on lung cancer). However, all the
risks identified in our analysis are important since AOM is so
common. Even a small increment in the relative risk of a common disease markedly increases its occurrence.
Consistent results were found with all the risk factors analyzed, even though the risk ratios were not significant in all
separate studies. We performed a homogeneity test before pooling the risk ratios, and the results of all the tests were insignificant for those risk factors pooled, thus justifying the final pooling and indicating that the results are reliable.
Meta-analysis has been widely used in social science studies
where P values, correlation coefficients, and risk ratios have
been pooled [6]. In medical studies, the interest is often on the
effect size of a certain treatment, and we are not satisfied
knowing only that one therapy is better than another. Thus,
meta-analysis has been mainly done in randomized clinical
trials. The pooled estimate of a risk ratio is a valuable indicator
of a risk factor's importance to and impact on a disease. The
risk factors for AOM are heavily interrelated; therefore, the
pooled estimate of the risk ratio of a single risk factor should
be interpreted cautiously, which means that when the effect of
deletion of more than one risk factor is estimated, the result is
less than the sum of the effects of separate risk factors.
Our meta-analysis showed that there are reliably identified
risk factors for AOM, the most important of which are day
care outside the home, breast-feeding, and parental smoking.
We suggest that physicians treating children with AOM should
actively try to influence these risk factors whenever possible.
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