International Journal of Infectious Diseases 17 (2013) e317e320

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International Journal of Infectious Diseases

jo u r nal h o mep ag e: w ww .elsevier .c o m /lo c
ate/ijid

Clinical features and outcome of acute otitis media in early infancy

Stavroula Ilia, Emmanouil Galanakis *
Department of Paediatrics, University of Crete, POB 2208, 71003 Heraklion, Greece

A R T I C L E

I N F O

Article history:
Received 10 February 2012
Received in revised form 5 November 2012
Accepted 9 November 2012
Corresponding Editor: Eskild Petersen,
Skejby, Denmark
Keywords:
Acute otitis media
Early onset otitis media
Infants
Outcome
Risk factors

S U M M A R Y

Objectives: Acute otitis media (AOM) is common in childhood, but little is known on its course very
early in infancy. In this study we investigated predisposing factors, clinical characteristics, and longterm outcomes of AOM in very young infants.
Methods: One hundred sixty infants aged less than 12 months with AOM hospitalized in two general
hospitals during 20052006 were included in the study and followed-up for 3 years. Demographics,
history, clinical manifestations, and further AOM episodes were studied in two infant groups dened by
age at the rst AOM episode: the very young infants, aged less than 60 days, and the older infants
aged
61365 days.
Results: Of the 147/160 infants successfully followed-up, 48 (32.7%) were aged less than 60 days and 99
(67.3%) were aged 61365 days. The very young infants with AOM had more siblings (1.25 vs. 0.87;
p = 0.047) and used paciers less often (45.8% vs. 75.8%; RR 0.61, 95% CI 0.440.84; p = 0.0007).
Purulent otorrhea and irritability were more common in the early AOM onset group (52.1% vs. 32.3%;
risk ratio (RR) 1.61, 95% condence interval (CI) 1.092.39; p = 0.03, and 60.4% vs. 38.4%; RR 1.57, 95%
CI 1.12
2.21; p = 0.01, respectively). AOM was complicated with meningitis in two infants, both in the very
young group, and with mastoiditis in a further two infants, one in each group. No difference in further
AOM episodes, use of ventilation tubes, or hearing impairment was observed between the two infant
groups.
Conclusions: AOM in the rst 2 months of life may have different predisposing factors and clinical
presentations, but not different recurrence rates or long-term outcomes.
2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

1. Introduction
Acute otitis media (AOM) is one of the most common
infections in childhood, and represents a substantial burden
with regard to doctor visits, consumption of antibiotics, absence
from day care or school, surgical procedures, and long-term
sequelae such as hearing impairment and speech disorders.
AOM can occur at all ages, but is principally a disease of young
children. Immature immunity, declining maternal antibodies,
and a dysfunctional Eustachian tube contribute to an increased
prevalence in infan- cy.1,2 The pathogenesis of otitis media is
multifactorial, implicating interactions between the pathogen,
environment, local anatomy, and host. Several risk factors have
been identied, including day care, siblings, bottle-feeding,
environmental tobacco smoke exposure, season of the year, and
respiratory tract infections, as well as individual susceptibility
affecting the hosts immune response to infections in the
35
middle ear.
AOM in childhood has been adequately investigated, however
not many studies have focused on infants aged less than 2
months,

* Corresponding author. Tel.: +30 2810 392 012; fax: +30 2810 392 827.
E-mail address: emmgalan@med.uoc.gr (E. Galanakis).

who are often excluded from studies. As a result, prevalence is yet

uncertain in this population group and clear guidelines for
68
diagnosis and treatment seem not to exist.
The initial clinical
presentation of AOM in this age group is often vague and
diagnosis is difcult.911 Most studies have suggested that the
causative pathogens are similar to those reported in older
children, but data concerning outcomes are still scarce and often
6,1014
controversial.
Furthermore, little is known of the risk factors, prevalence, and
long-term outcomes of AOM in the very rst months of life. This
prospective, longitudinal study analyzed the risk factors, clinical
characteristics, complications, and long-term outcomes associated
with a rst episode of AOM in infants aged less than 12 months
and focused on potential differences between infants with AOM
onset before 2 months of age and infants with AOM onset at 212
months of age.
2. Methods
2.1. Population
The study population consisted of infants up to 12 months of
age hospitalized for AOM in the two paediatric departments of the
University General Hospital and Venizelion General Hospital, both

1201-9712/$36.00 see front matter

2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijid.2012.11.012

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S. Ilia, E. Galanakis / International Journal of Infectious Diseases 17 (2013) e317e320

in Heraklion, Crete, Greece during the 2-year period 20052006.

Only hospitalized infants were included in the study, the reason
for admission being severe clinical presentation, issues with
regard to compliance to
oral
antibiotics, and parental
concern. The diagnostic criteria for AOM were in line with
those of
the guidelines of the American Academy of
Pediatrics,15 and were based on history of acute onset of signs
and symptoms of middle ear inammation and the presence of
middle ear uid. In both hospital settings, infants were routinely
examined by a paediatri- cian
and subsequently by an
otolaryngologist
using
a
microscope
and
performing
tympanocentesis in selected cases. Middle ear uid cultures
were not routinely obtained. Infants at a gestational age of less
than 35 weeks or who had undergone mechanical ventilation
in their neonatal life, and those with a known immunological
disorder or craniofacial or other major congenital abnormality
were excluded. Informed consent was obtained from the parents
and the study was approved by the Institutional Committee
of the Faculty of Medicine, University of Crete.
2.2. Study variables
A pre-constructed questionnaire was used to record demographic data and symptoms such as fever, pain, irritability,
rhinitis, and cough. Inquiries were made about potential risk
factors, including history of breast- or bottle-feeding, use of
paciers, environmental tobacco smoke exposure, respiratory
tract infec- tions, history of atopy, number of siblings, and day
care attendance. An infant was characterized as breastfed when
breastfeeding was the principal feeding mode. Atopic
manifestations included recurrent wheezing, asthma, allergic
rhinitis, and atopic dermati- tis. A family history of atopy and
episodes of otitis media in rst- degree relatives were recorded.
Two infant groups were formed as dened by the age at the rst
AOM episode: the early AOM group, aged less than 60 days, and
the late AOM group, aged 61365 days.
2.3. Follow-up
Follow-up was conducted at 6-monthly intervals for the next 3
consecutive years and included telephone contact between the
same investigator and parents regarding further AOM episodes,
chronic otitis media with effusion, insertion of ventilation tubes,
hearing impairment, and speech disorders. Every reported episode
of AOM that was conrmed by a physician was considered a
further AOM episode.
2.4. Statistics
Data were analyzed by descriptive statistics, including
frequen- cies, percentages, means, and medians. Unadjusted
associations between early vs. late onset otitis media and
recurrence rates with study variables were evaluated by twotailed Fishers exact test and t-test, and risk ratios (RR) and 95%
condence intervals
(CI) were calculated. Multiple linear
regression analysis was further performed in order to conrm
signicant relationships that were observed in the univariate
analysis. In all cases, p values <0.05 were considered to be
signicant.
3. Results
3.1. Population
A total of 160 infants were enrolled, of whom 13 (8.1%) were
lost to follow-up. Of the 147 who successfully completed the 3year follow-up period, 48 (32.7%) belonged to the early AOM
group and 99 (67.3%) to the late AOM group. The mean age at
inclusion was 0.36 years (0.13 and 0.48 years for the early and

late AOM

groups, respectively). Three infants were aged less than 1 month.

Ninety-nine (67.3%) infants had siblings, 50 (34.0%) had atopic
manifestations, 55 (37.4%) were never breastfed, and 86 (58.5%)
had at least one smoking parent. At enrolment, no infant in the
early AOM group was vaccinated, and 87% and 74% of infants in
the late AOM group were properly vaccinated for age against
Haemophilus inuenzae and Streptococcus pneumoniae, respectively. In the early AOM group, two infants developed meningitis and
one developed mastoiditis; in the late AOM group, one 3-monthold infant presented with mastoiditis. A total of 37 (25.2%) middle
ear uid cultures yielded a pathogen, 19 (39.6%) of them in the
early AOM group and 18 (18.2%) in the late AOM group. Isolated
pathogens included S. pneumoniae (9; 24.3%), Staphylococcus
aureus (3, 8.1%), Haemophilus spp (2; 5.4%), and enteric Gramnegative Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (28; 75.7%).
3.2. Characteristics of infants by age at onset of AOM
Study variables in the early and late AOM groups are depicted
in Table 1. As compared to their older peers, the very young
infants had more siblings (mean 1.25 vs. 0.87; p = 0.047)
and used paciers less often (45.8% vs. 75.8%; RR 0.61, 95% CI
0.440.84; p = 0.0007). No signicant differences were found
in terms of ethnicity, gender, delivery mode, birth weight,
season of birth, feeding mode, environmental
tobacco
exposure, and family history of atopy or AOM. Fever of
38
8C was the presenting symptom in 82 (55.8%) infants, with no
signicant difference between the two age groups. Purulent
otorrhea and irritability were signicantly more common in the
early AOM onset group (52% vs. 32%; RR 1.61, 95% CI 1.092.39;
p = 0.03, and 60% vs. 38%; RR 1.57, 95% CI 1.122.21; p = 0.01,
respectively). No differences were observed regarding white
blood cells, erythrocyte sedimen- tation rate, or C-reactive
protein values. Concomitant reported diagnoses, i.e., upper
respiratory tract infection (26%), bronchiol- itis
(20%),
conjunctivitis (5%), and vomiting and diarrhea (13%), were
comparable in the two groups.
3.3. Further AOM episodes
One hundred twenty-two of 147 children had more than one
episode of AOM (a total of 451 episodes, mean 3.7 episodes per
child) during the follow-up period. No differences were observed
regarding further AOM episodes and the insertion of ventilation
tubes in the early and late AOM groups (Table 1). Hearing
impairment was reported in six children, all of them in the late
AOM group, but this difference was not signicant (RR 1.06, 95%
CI
1.011.12; p = 0.178).
In the whole study population, infants using a pacier (70.5% vs.
44%; RR 1.60, 95% CI 1.012.53; p = 0.019), attending day care
(36.9% vs. 12%; RR 3.07, 95% CI 1.049.11; p = 0.018), having a
positive family history of atopy and AOM (26% vs. 4%; RR 6.56, 95%
CI 0.9445.8; p = 0.016, and 55.7% vs. 24.0%; RR 2.32, 95% CI 1.13
4.75; p = 0.004, respectively), and belonging to a Greek rather
than an immigrant family (74.6% vs. 40%; RR 1.86, 95% CI 1.14
3.05; p = 0.0015) were more prone to multiple AOM episodes.
Multiple AOM episodes were further more common in children
with a hearing impairment (9.5
vs. 4.44
episodes; p =
0.0001) and insertion
of
ventilation
tubes
(7.36
vs.
3.57
episodes; p = 0.0001). No signicant differences were
found regarding gender, birth weight, parental smoking habits,
and number of siblings. Multiple linear regression analysis
conrmed the signi- cant relationship between multiple AOM
episodes and family history of AOM (p = 0.045), family history
of atopy (p = 0.027), hearing impairment (p = 0.001), and need
for ventilation tubes (p < 0.0001).

S. Ilia, E. Galanakis / International Journal of Infectious Diseases 17 (2013) e317e320

e319

Table 1
Acute otitis media in infants with rst episode in the rst 2 months of life as compared to infants with rst episode in months 212 of life
Total, N = 147, n (%)
Gender
Boys
Girls
Birth weight
Mean (g)
Season of birth
Springsummer
Fallwinter
Breastfeeding
Mean (months)
Delivery
Vaginal
Caesarean section
Use of pacier
Yes
No
Smoking mother
Yes
No
Smoking father
Yes
No
Family history of atopy
Yes
No
Family history of AOM
Yes
No
Number of siblings
Mean (range)
Ethnicity
Greek
Immigrant
Complications
Yes
No
Further AOM episodes
Yes
No
Further AOM episodes
Number (mean)
Ventilation tubes
Yes
No
Hearing impairment
Yes
No

Early AOM, n = 48, n (%)

Late AOM, n = 99, n (%)

p-Value
NS

92 (62.6)
55 (37.4)

30 (62.5)
18 (37.5)

62 (62.6)
37 (37.4)
NS

3159

3234

3123
NS

69 (46.9)
78 (53.1)

18 (37.5)
30 (62.5)

51 (51.5)
48 (48.5)
NS

4.86

5.5

4.53
NS

93 (63.3)
54 (36.7)

31 (64.6)
17 (35.4)

62 (62.6)
37 (37.4)

97 (66.0)
50 (34.0)

22 (45.8)
26 (54.2)

75 (75.8)
24 (24.2)

45 (30.6)
102 (69.4)

16 (33.3)
32 (66.7)

29 (29.3)
70 (70.7)

74 (50.3)
73 (49.7)

28 (58.3)
20 (41.7)

46 (46.5)
53 (53.5)

33 (22.4)
114 (77.6)

9 (18.7)
39 (81.3)

24 (24.2)
75 (75.8)

74 (50.3)
73 (49.7)

26 (54.2)
22 (45.8)

48 (48.5)
51 (51.5)

0.0007

NS

NS

NS

NS

0.047
0.99 (07)

1.25 (07)

0.87 (04)
NS

101 (68.7)
46 (31.3)

28 (58.3)
20 (41.7)

73 (73.7)
26 (26.3)

4 (2.7)
143 (97.3)

3 (6.3)
45 (93.7)

1 (1.0)
98 (99.0)

122 (83.0)
25 (17.0)

38 (79.2)
10 (20.8)

84 (84.8)
15 (15.2)

NS

NS

NS
451 (3.7)

177 (3.68)

274 (3.8)
NS

19 (12.9)
128 (87.0)

4 (8.3)
44 (91.7)

15 (15.2)
84 (84.8)

6 (4.1)
141 (95.9)

0 (0)
48 (100)

6 (6.1)
93 (93.9)

NS

AOM, acute otitis media; NS, not signicant.

4. Discussion
AOM is very common in childhood, affecting nearly all children
at some time, but little is known on the disease in the very rst
months of life. As factors predisposing to AOM are quite well
known,3,14,16 we focused on potential differences between infants
with early as opposed to late AOM onset and found that factors
known to contribute to AOM, such as the use of paciers and the
number of siblings, seem to have a different impact in infant
groups of different ages. We also found that infants with early
AOM more often presented with otorrhea and/or irritability.
Burton et al. reported that patients aged less than 6 weeks with
AOM had a 30
50% incidence of recurrent otitis media during the rst 2 years of
life, and once in this category they had a 50% incidence of the
need for
ventilating tubes, which was not conrmed by
13,14
others.
In our study, infants using a pacier were shown to be prone
to late AOM and to multiple AOM episodes. The relationship
between pacier use and AOM has been debated for almost two
decades, with most studies concluding that pacier use is a risk
factor for AOM.1722 This association has
been attributed
either to the increase in the reux of nasopharyngeal secretions
into the middle

ear or to changes induced by the pacier on the dental structures

and the function of the Eustachian tube. Our ndings pointing
to multiple AOM episodes in infants using paciers are thus
in accordance with the aforementioned studies; however, this
relationship did not remain signicant after applying multiple
regression statistics. Having older siblings was associated with
early age of AOM onset. Infants with a positive family history of
AOM and a positive family history of atopy had more AOM
episodes, in line with previous studies,23 but were not more
susceptible to otitis onset in early infancy. The relationship
between family history of otitis media and early otitis media has
been attributed to genetic predisposition or greater awareness of
2,24
otitis media leading to increased medical care-seeking.
The vast majority of the participating subjects (83.0%) in this
study had multiple AOM episodes, probably because our cohort
comprised infants hospitalized for AOM, i.e., the more severely
affected children. These ndings should therefore not be generalized to all infants with AOM. Of note, in a study in the same area,
further AOM episodes during the rst year of life were observed
in
16
41.8% of infants with an initial episode. Our study demonstrated
that early-onset AOM infants were not more susceptible to

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S. Ilia, E. Galanakis / International Journal of Infectious Diseases 17 (2013) e317e320

recurrent episodes, conrming earlier results, while elsewhere

infants with early AOM onset have been shown to be prone to
recurrent AOM, chronic otitis media, and placement of ear
tubes.1,14,25 These conicting results may be related to differences
in study design and populations. In our study, placement of
ventilation tubes was only associated with multiple AOM
episodes, which is rather expected given that grommets are
used for the relief of children with AOM recurrences. In the
literature, the most consistent risk factor for AOM recurrence
has been day care attendance, which was not conrmed in our
study by multivariate analysis.
A limitation of our study is that the denition of AOM was
based on clinical ndings and not always conrmed by culture;
hence, differences in pathogens between the early and late AOM
onset groups could not be analyzed properly. As information on
AOM episodes during the 3-year follow-up was based on
parental reports, recall bias cannot be
excluded. Previous
studies have shown parental over-reporting of AOM episodes,
while elsewhere parents have been shown to report fairly
accurately.26 In order to diminish recall bias, we consulted
parents relatively often, and thus their reports are expected to be
credible. Information on
the long-term outcome, including
hearing, speech, and developmental impairment, could have
been validated by objective methods. Socioeconomic status
might well interfere in the long-term outcome, nevertheless
access to hospitals was rather homo- geneously feasible in the
study area. Not many infants (8.1%) were lost to follow-up, and
comparison of baseline characteristics did not reveal any
differences, therefore lost cases did not indicate selective losses.
In conclusion, our data show that factors predisposing to or
preventing AOM in infancy may act differently in early and late
infancy. The clinical presentation may be different, but
recurrences and long-term outcomes are similar in infants with
early and late AOM onset.
Acknowledgements
We thank the parents for their contribution to this longduration study.
Ethical approval: The study was approved by the Institutional
Committee of the Faculty of Medicine, University of Crete.
Conict of interest: No conict of interest to declare.

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