Inrernarional
Journul
bi 1991
Elsevier
PEDOT
00708
of Pediatric
Science Publishers
Otorhinolaryngolom,
21 (1991)
201-209
201
B.V. 01655876/91/$03.50
Research Reports
What is an ‘otitis-prone’ Olli Pekka Departments
of Otolqwgolo~,
Alho,
Matti
Koivu
Public Healrh Scrrnce
and
child? Martti
and Pediatrim.
(Received 17 April 1990) (Revised version received 7 December (Accepted 15 December 1990)
Kyy words: Recurrent
acute otitis media;
Otitis-prone
child:
Sorri
Unruersi@ of Oulu, Oulu (k’mlond)
1990)
Epidemiology
Abstract
The present report concerns a random sample of 2512 children monitored for acute otitis media up to the age of two years. The criteria given by previous surveys classified from 1.8 to 41.2% of the population as ‘otitis-prone’, at a mean age varying between 13.4 and 18.8 months. A criterion of at least 4 episodes of acute otitis media during the next 9 months with a 30-day borderline between two distinct episodes yielded 273 children (10.8% of the population) with an acceptable mean age of 15 months. Early onset of acute otitis media was only a weak predictor of susceptibility in either the individual child or the whole population, the sensitivity levels and predictive values being too low for accurate prediction.
Introduction A uniform definition of a child with a problem of recurrent acute otitis media episodes requiring special treatment and surveillance is an essential for effective comparison of various treatments. The concept of an ‘otitis-prone’ child was first introduced by Howie et al. in 1975 [lo] referring to a child who had had at least 6 episodes of acute otitis media during the first 6 years of life. As most episodes of acute otitis media occur during the first two years of life [13,20,22] the above criterion by Howie et al. defines the cases as occurring rather late. A number of other criteria have therefore been put forward by various authors for clinical
Correspondence:
Oulu.
Finland.
O.P. Alho, Department
of Otolaryngology,
University
of Oulu, Kajaanintie
50, SF-90220
202
[6-8,11,12,15,16] or epidemiological [5,9] purposes to define otitis-prone children, although without achieving any uniform standard. A random sample of 2512 children were monitored for acute otitis media up to the age of two years and both the number of children and the mean age of occurrence given by previous proneness criteria were studied. An attempt was then made to find a suitable criterion for the ‘otitis-prone’ child in this material and to examine the extent to which the early onset of acute otitis media predicts proneness.
Subjects and methods A sample size of 1900 children was calculated to be large enough for the present epidemiological purpose, allowing a maximum difference of 2%units between the sample population rate and the true population rate at a 95% significance level, presuming a 60% population rate of acute otitis media during the first two years of life [12]. Accordingly, a series of 2512 children from 10 local government districts were enrolled by a two-stage random cluster sampling method from among a prospective one-year cohort of 9478 children born in Northern Finland with a predicted date of birth between July 1st 1985 and June 30th 1986 (99% of the total number of infants born in the area during that period) and studied from the antenatal period up to two years of age [l]. The data concerning infections were collected by one of the authors from all possible medical records in the area, including primary health care centres, hospitals and 3 private surgeries. Subtraction of the date of birth from potential date of moving away from the area or the time of data collection, whichever was the earlier, gave the observation time for each child. The actual observation times for 81 children (3.2%) were unknown, because they had moved away from the area at undisclosed times. These 81 children were not included in the investigation. The mean observation time was 653 days (21.8 months). The medical care system of Finland may be described briefly as follows. The area studied here has 10 primary health care centres, 3 central hospitals (KeskiPohjanmaa, Lappi and Llnsipohja) and one university central hospital (Oulu), where most of the physicians employed in the area are trained. The physicians in the health centres are general practitioners, but the specialist services are easily available at the hospitals and at private clinics. The primary medical care is free of charge, the general health insurance scheme covers part of the fees of private practitioners and the fees for hospital consultations are minimal. Medical services are therefore easily available for children in the area and widespread use is made of paediatric and otological services. All the children are seen routinely by a physician at infant clinics at 3, 6, 12 and 24 months of age. The physicians use pneumatic otoscopy as a standard method for examining children with acute symptoms and tympanocentesis is often performed, particularly, if the symptoms are severe and/or the infection is prolonged. Antibiotics are always prescribed for acute otitis media and a standard follow-up visit is scheduled for two to three weeks after the diagnosis.
In this study a disease was regarded as acute otitis media (AOM) if it had been diagnosed as such by the primary physician. The diagnostic criteria consist of both acute symptoms (earache, fever, irritability, respiratory symptoms, restless sleep, etc.) and pneumo-otoscopic signs (distinct redness and outward bulging or reduced mobility of the eardrum). All the dates on which the children visited a physician because of acute otitis media were recorded, and consequently the borderline set for two distinct episodes could be varied. The data were analysed using both 30 days and 14 days as the borderline. The numbers of children out of the 2512 who fulfilled the criteria for otitis-proneness used in various previous surveys were calculated, together with the mean age of meeting these criteria. The accuracy of the occurrence of a first, second or third episode of acute otitis media before the 6th, 9th or 12th month of age for predicting whether a child was likely to become otitis-prone (2 4 episodes within 9 months) was assessed. The occurrence of each episode at the above ages was used as a statistic test for which sensitivity, specificity and predictive values and their 95% confidence intervals were calculated. The figures representing the numbers of episodes were assumed to follow a Poisson distribution, and the 95% confidence intervals were calculated on this assumption [3]. The confidence intervals for sensitivity and specificity figures were calculated based on a binomial distribution [4]. As the median length of the observation time for the otitis-prone children, 746 days (95% confidence interval 715-767) was significantly longer than that for the other children, 664 days (654-677) this analysis was performed on a set of 968 children who had a uniform observation period extending up to 2 years of age. Statistical software supplied by SAS Institute Inc., Cary, NC, U.S.A., was used for the analyses (FREQ, MEANS and LIFETEST procedures). Permission for this investigation was obtained from the Ministry of Health and Social Welfare as well as the Ethical Committee of the Faculty of Medicine, University of Oulu.
Results The cumulative incidence of acute otitis media up to two years of age was 71.0% (95% confidence interval, 68.9-73.1%) and the incidence rate 0.93 (0.90-0.96) episodes per child per year [2]. The previous criteria for otitis-proneness vary considerably and consequently the numbers of children meeting them and their mean ages upon doing so, assuming a 30-day borderline between two distinct episodes, are varied (Table I). Most definitions yield many children in relation to the resources required for treatment procedures, and some of the mean ages upon meeting the criteria are high, as the maximum morbidity is reached before the age of two years. The use of a 14-day borderline for two distinct episodes increased the numbers of children involved by some 10%.
204 TABLE
I
Criteria for otitis-proneness used in previous surveys considering recurrent otitis media, numbers identified in the present random sample of 2512 children and mean ages upon meeting the criteria Authors
Criteria
Buck [6] (1963) Perrin et al. [15] (1974) Howie et al. [lo] (1975) Gebhart [7] (1981) and Liston et al. [12] (1983) Persico et al. [16] (1985)
2 z r 2
Gonzalez
Finnish consensus conference [ll] (1987)
Harsten
episodes in episodes in episodes in episodes in
24 months 18 months or 2 5 first 6 years 6 months
> 1 episode/month in 3 subsequent months 2 3 episodes in 6 months or > 4 episodes in 18 months 2 3 recurrences in 6 months among adenotomized or tympanotomized 2 3 episodes in 6 months or 2 4 episodes in 12 months 2 6 episodes in 12 months
et al. [8] (1986)
Bluestone
2 3 6 3
et al. [5] (1988) et al. [9] (1989)
n
%
Mean age (months)
1036 651 159 439
41.2 25.9 6.3 17.4
13.4 15.1 18.8 14.1
188
7.5
13.7
453
17.8
14.3
46
1.8
16.9
473
18.8
14.5
93
3.7
16.5
The two parts of dual criterion overlapped almost entirely. The latter parts of the criteria laid down by Bluestone et al. [5], Gonzalez et al. [8] and Perrin et al. [15] added only 34, 14 and 0 children, respectively, to the number specified by the first part. A definition without a time interval would distinctly delay the qualification age. Criteria of 2 2, 2 3, 2 4 and 2 5 episodes of acute otitis media would classify 1036, 666, 442 and 275 children in this population as otitis-prone, with mean qualification ages of 13, 15, 17 and 18 months respectively. The risk of acute otitis media being greatest from September to May, a period of 9 months was considered reasonable for counting episodes. The results obtained using various threshold values during such a time-interval are displayed in Table II. As the number of children in this material that underwent either adenoidectomy or tympanostomy
TABLE
II
Numbers of otitis-prone children identified and mean age of identification using various thresholds (number of episodes in a period of 9 months) in a total series of 2512 children Criteria
n
B
Identification age (months)
12 >3 >4 25
965 550 273 139
38.4 21.9 10.8 5.5
13.0 14.5 15.0 15.1
705
%
N 30
too
.__ [
-
Fig. 1. Identification
CRUDE
of 273 otitis-prone
NUMBER
children
t
CUMULATIVE
( > 4 episodes
INCIDENCE
in 9 months)
in a series of 2512 children.
was 206 (8.2%), one reasonable criterion for otitis-proneness would be all those children who have 2 4 episodes of atute otitis media in 9 months. This definition identifies a series of 273 children (10.8%) with a mean age of 451 days (362-540). i.e. 15 months. The crude numbers of cases and their cumulative incidence are shown in Fig. 1. The early onset of acute otitis media turns out to carry rather low predictive values and sensitivity levels. Only the 1st episode occurring before the age of 12
TABLE
III
Sensitivity, specificity and predictive values of early episodes of acute otitls media with respect to whether the child wrll become &k-prone ( 2 4 episodes in 9 months), tested in u series of 968 children with uniform observation time of 2 years SE = sensitivity,
SP = specificity,
PR = predictive
Episode 2
Episode I
I 6 Months 5 9 Months 5 12 Months
value. Values are given as percentages. Episode 3
SE
SP
PR
SE
SP
PR
SE
SP
PR
47 68 85
86 73 60
35 28 25
15 44 66
98 93 87
57 48 44
3 28 51
100 98 95
80 80 69
206
months had an acceptable sensitivity level, 0.85 (0.79-0.91) but with low specificity, 0.60 (0.57-0.63) (Table III). As the age of the child at each episode increases, the sensitivity of this criterion increases as well, but its specificity decreases. Conversely, as the number of episodes increases, the specificity increases, but the sensitivity of the criterion decreases.
Discussion A uniform definition of the otitis-prone child is essential for effective comparison of the various treatments available. If the group of children with the most problems regarding otitis media is identified as early as possible and uniformly in the whole population, the treatment resources can be used most effectively. Preventive measures, like adjustment of the form of day care, which was found to be the most important risk factor [l], may be taken, antimicrobial prophylaxis prescribed or operative measures (adenoidectomy or tympanostomy) planned for the otitis-prone children as early as possible. The number of children defined by the criterion and considered for intervention should not be too large and the qualification age should not be too late in view of the fact that the majority of acute otitis media episodes occur before the age of two years. A dual criterion obviously entails no advantage, as the groups of children specified by the two criteria overlap. Previous definitions introduced in studies of both the epidemiology of recurrent otitis media and the effect of various forms of treatment are variable. Bluestone et al. [5] recommended either an operation or antimicrobial prophylaxis for all children with 3 or more episodes in 6 months or 4 or more in 12 months, a criterion that was met by a large number of children, 473 (18.8%) in this population. On the other hand, the criterion of Harsten et al. [9], 6 or more episodes in one year, yielded only 93 children (3.7%). The criteria for antimicrobial prophylaxis for recurrent acute otitis media set by the Finnish consensus conference [ll] and by Persico et al. [16] identify only a few children in this population (1.8 and 7.5% respectively), whereas the definitions used by Liston et al. [12], Gonzalez et al. [8] and Perrin et al. [15], also for prophylaxis, are quite loose, with large numbers of children fulfilling them (from 17.4 to 25.9%). The surveys of Buck [6] and Gebhart [7], examining the influence of operative treatment on recurrent acute otitis media, both employ loose definitions and consequently identify a large proportion of the children (17.4 to 41.2%). Only a few earlier studies on the epidemiology of acute otitis media determine the borderline to be used for two distinct episodes. Teele et al. [22] used a borderline of 21 days and Sipila et al. [19] 13 days. As previous surveys suggest that 50-70s of children with acute otitis media treated only with antimicrobials have middle-ear effusion l-2 weeks later, and as many as 20-40s 4 weeks later [17,18,21], a 30-day borderline was regarded here as biologically reasonable. None of the above authors defines the borderline used to separate two distinct episodes, but since some authors obviously included a shorter borderline in their criteria, the numbers given by
207
various criteria with a 14-day borderline were also studied, but this did not alter the results significantly. Since the time during which the children are exposed to the increased risk of upper respiratory tract infections (a period which all children experience in its entirety only once between the ages of 6 and 24 months and during which the risk of acute otitis media is greatest [13,14,19]) lasts 9 months (from September to May), a time interval of 9 months for counting episodes was considered reasonable. A criterion of at least 4 episodes during such an interval picks out a suitable number of children (regarding limited resources for extra measures). 273 (10.8%) with an acceptable mean qualification age of 15 months. A prospective cohort-based design with random enrollment was used to minimize selection bias in this study. The data regarding infections were collected retrospectively, but since all possible sources of medical aid were visited by one of the authors, it may be assumed that virtually all the episodes were covered. The study design, data collection and basing of the definition of acute otitis media on diagnoses made by primary physicians allow the results to be carefully generalized at the population level. Howie et al. [lo] were the first to demonstrate that recurrent episodes of acute otitis media are related to early onset, a matter confirmed later by others [9,13]. There are basically two ways of approaching the problem of an early episode of acute otitis media, either at the population level, as a screening test for otitis-proneness, or at the individual level, when considering extra surveillance or measures for a child experiencing an early epis.& de of acute otitis media. The present results suggest that the occurrence of early episodes of acute otitis media is not a suitable criterion for a screening method, as its sensitivity rates are too low. Only the occurrence of the first episode before the age of 12 months achieves an acceptable sensitivity level, 0.85 (95% confidence interval, 0.79-0.91) but the specificity then is too low, 0.60 (0.57-0.63). In addition, the logic of predicting otitis-proneness from early episodes diminishes considerably once a time interval is contained in the criteria and when mean qualification ages are just slightly over one year. For example, 36% of the children in this series that were to become otitis-prone before the age of 2 years had already been identified by 12 months of age (Fig. 1). The predictive usefulness of an early episode is similarly low in the case of the individual child, as only the occurrence of a third episode before the age of 9 months involves an outstanding risk of becoming otitis-prone (predictive value 0.80). The results clearly display the problems involved in the previous criteria for otitis-proneness. In this material one proper criterion for an otitis-prone child proved to be at least 4 episodes in 9 months with a 30-day borderline to define two distinct episodes, Early first episodes of acute otitis media were found to be of little predictive value regarding both the proneness of an individual child to otitis media or the occurrence of proneness in the whole population, both the sensitivity figures and predictive values being too low for accurate prediction.
208
Acknowledgements This work was supported financially by the Oulu Medical Research Foundation, the Oulu University Scholarship Foundation and the Alma and K.A. Snellman Foundation. Collection of the cohort data was supported by the Medical Research Council of the Finnish Academy.
References 1 Alho, O.P., Koivu, M., Sorri, M. and Rantakallio, P., Risk factors for recurrent acute otitis media and respiratory infection, Int. J. Pediatr. Otorhinolaryngol., 19 (1990) 151-161. 2 Alho, O.P., Koivu, M., Sorri, M. and Rantakallio, P., The occurrence of acute otitis media in infants-a life-table analysis, Int. J. Pediatr. Otorhinolaryngol., 21 (1991) 7-14. 3 Bailar, J.C., Significance factors for true ratio of a Poisson variable to its expectation, Biometrics, 20 (1964) 639-643. 4 Bland, M., An Introduction to Medical Statistics, 2nd edn., Oxford Medical Publications, Oxford, 1987, pp. 101-104. 5 Bluestone, C.D. and Klein, J.O., Otitis Media in Infants and Children, 1st edn., W.B. Saunders, Philadelphia, 1988, pp. 163-188. of recurrent otitis media: removal of tonsils and adenoids, Clin. Pediatr., 2 6 Buck, C., Treatment (1963) 179-181. D.E., Tympanostomy tubes in the otitis media prone child, Laryngoscope, 91 (1981) 7 Gebhart, 849-866. 8 Gonzalez, C., Arnold, J.E., Woody, E.A., Erhardt, J.B., Pratt, S.R., Getts, A., Kueser, T.J., Kolmer, J.W. and Sachs, M., Prevention of recurrent acute otitis media: chemoprophylaxis versus tympanostomy tubes, Laryngoscope, 96 (1986) 1330-1334. 9 Harsten, G., Prellner, K., Heldrup, J., Kalm, 0. and Kornfalt, F., Recurrent acute otitis media, Acta Otolaryngol., 107 (1989) 111-119. J.H. and Sloyer, J., The ‘otitis-prone’ condition, Am. J. Dis. Child, 129 10 Howie, V.M., Ploussard, (1975) 676-678. 11 Karma, P., Palva, T., Kouvalainen, K., Klrjl, J., Makehi, P.H., Prinssi, V.P., Ruuskanen, 0. and Launiala, K., Finnish approach to the treatment of acute otitis media, Ann. Otol. Rhinol. Laryngol., 96, Suppl. 129 (1987) l-19. for frequent otitis 12 Liston, T.E., Foshee, C.W.S. and Pierson, M.W.D., Sulfisoxazole chemoprophylaxis media, Pediatrics, 71 (1983) 524-530. K. and Ingvarsson, L., Epidemiology of acute otitis media in children, Stand. J. Infect. 13 Lundgren, Dis., Suppl. 39 (1983) 19-25. 14 Medical Research Council, Acute otitis media in general practice, Lancet, 2 (1957) 510-514. Jr., J.B., McInemy, T.K., Miller, R.L. and Nazarian, L.F., 15 Perrin, J.M., Charney, E., MacWhinney Sulfisoxazole as chemoprophylaxis for recurrent otitis media, New EngI. J. Med., 291 (1974) 664-667. 16 Persico, M., Podoshin, L., Fradis, M., Grushka, M., Golan, D., Foltin, V., Wellisch, G., Cahana, Z., Kolin, A. and Winter, S., Recurrent acute otitis media-prophylactic penicillin treatment: a prospective study. Part I, Int. J. Pediatr. Otorhinolaryngol., 10 (1985) 37-46. P., Eskola, J. and Ruuskanen, O., Myringotomy 17 Puhakka, H., Virolainen, E., Aantaa, E., Tuohimaa, in the treatment of acute otitis media in children, Acta Otolaryngol., 88 (1979) 122-126. for acute otitis media: its 18 Schwartz, R.H., Rodriguez, W.J. and Schwartz, D.M., Office myringotomy value in preventing middle ear effusion, Laryngoscope, 91 (1981) 616-619. 19 Sipill, M., Pukander, J. and Karma, P., Incidence of acute otitis media up to the age of 1: years in urban infants, Acta Otolaryngol., 104 (1987) 138-145. 20 Stangerup, S.E. and Tos, M., Epidemiology of acute suppurative otitis media, Am. J. Otolaryngol., 7 (1986) 47-54.
21 Teele, D.W.. Klein, J.O. and Rosner, B.A.. Epidemiology of otitis media in children, Ann Otol. Rhinol. Laryngol.. 89, Suppl. 68 (1980) 5-6. 22 Teele, D.W., Klein, J.O. and Rosner. B., Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective. cohort study. J. Infect. Dis., 160 (1989) X3-94.
Journul
bi 1991
Elsevier
PEDOT
00708
of Pediatric
Science Publishers
Otorhinolaryngolom,
21 (1991)
201-209
201
B.V. 01655876/91/$03.50
Research Reports
What is an ‘otitis-prone’ Olli Pekka Departments
of Otolqwgolo~,
Alho,
Matti
Koivu
Public Healrh Scrrnce
and
child? Martti
and Pediatrim.
(Received 17 April 1990) (Revised version received 7 December (Accepted 15 December 1990)
Kyy words: Recurrent
acute otitis media;
Otitis-prone
child:
Sorri
Unruersi@ of Oulu, Oulu (k’mlond)
1990)
Epidemiology
Abstract
The present report concerns a random sample of 2512 children monitored for acute otitis media up to the age of two years. The criteria given by previous surveys classified from 1.8 to 41.2% of the population as ‘otitis-prone’, at a mean age varying between 13.4 and 18.8 months. A criterion of at least 4 episodes of acute otitis media during the next 9 months with a 30-day borderline between two distinct episodes yielded 273 children (10.8% of the population) with an acceptable mean age of 15 months. Early onset of acute otitis media was only a weak predictor of susceptibility in either the individual child or the whole population, the sensitivity levels and predictive values being too low for accurate prediction.
Introduction A uniform definition of a child with a problem of recurrent acute otitis media episodes requiring special treatment and surveillance is an essential for effective comparison of various treatments. The concept of an ‘otitis-prone’ child was first introduced by Howie et al. in 1975 [lo] referring to a child who had had at least 6 episodes of acute otitis media during the first 6 years of life. As most episodes of acute otitis media occur during the first two years of life [13,20,22] the above criterion by Howie et al. defines the cases as occurring rather late. A number of other criteria have therefore been put forward by various authors for clinical
Correspondence:
Oulu.
Finland.
O.P. Alho, Department
of Otolaryngology,
University
of Oulu, Kajaanintie
50, SF-90220
202
[6-8,11,12,15,16] or epidemiological [5,9] purposes to define otitis-prone children, although without achieving any uniform standard. A random sample of 2512 children were monitored for acute otitis media up to the age of two years and both the number of children and the mean age of occurrence given by previous proneness criteria were studied. An attempt was then made to find a suitable criterion for the ‘otitis-prone’ child in this material and to examine the extent to which the early onset of acute otitis media predicts proneness.
Subjects and methods A sample size of 1900 children was calculated to be large enough for the present epidemiological purpose, allowing a maximum difference of 2%units between the sample population rate and the true population rate at a 95% significance level, presuming a 60% population rate of acute otitis media during the first two years of life [12]. Accordingly, a series of 2512 children from 10 local government districts were enrolled by a two-stage random cluster sampling method from among a prospective one-year cohort of 9478 children born in Northern Finland with a predicted date of birth between July 1st 1985 and June 30th 1986 (99% of the total number of infants born in the area during that period) and studied from the antenatal period up to two years of age [l]. The data concerning infections were collected by one of the authors from all possible medical records in the area, including primary health care centres, hospitals and 3 private surgeries. Subtraction of the date of birth from potential date of moving away from the area or the time of data collection, whichever was the earlier, gave the observation time for each child. The actual observation times for 81 children (3.2%) were unknown, because they had moved away from the area at undisclosed times. These 81 children were not included in the investigation. The mean observation time was 653 days (21.8 months). The medical care system of Finland may be described briefly as follows. The area studied here has 10 primary health care centres, 3 central hospitals (KeskiPohjanmaa, Lappi and Llnsipohja) and one university central hospital (Oulu), where most of the physicians employed in the area are trained. The physicians in the health centres are general practitioners, but the specialist services are easily available at the hospitals and at private clinics. The primary medical care is free of charge, the general health insurance scheme covers part of the fees of private practitioners and the fees for hospital consultations are minimal. Medical services are therefore easily available for children in the area and widespread use is made of paediatric and otological services. All the children are seen routinely by a physician at infant clinics at 3, 6, 12 and 24 months of age. The physicians use pneumatic otoscopy as a standard method for examining children with acute symptoms and tympanocentesis is often performed, particularly, if the symptoms are severe and/or the infection is prolonged. Antibiotics are always prescribed for acute otitis media and a standard follow-up visit is scheduled for two to three weeks after the diagnosis.
In this study a disease was regarded as acute otitis media (AOM) if it had been diagnosed as such by the primary physician. The diagnostic criteria consist of both acute symptoms (earache, fever, irritability, respiratory symptoms, restless sleep, etc.) and pneumo-otoscopic signs (distinct redness and outward bulging or reduced mobility of the eardrum). All the dates on which the children visited a physician because of acute otitis media were recorded, and consequently the borderline set for two distinct episodes could be varied. The data were analysed using both 30 days and 14 days as the borderline. The numbers of children out of the 2512 who fulfilled the criteria for otitis-proneness used in various previous surveys were calculated, together with the mean age of meeting these criteria. The accuracy of the occurrence of a first, second or third episode of acute otitis media before the 6th, 9th or 12th month of age for predicting whether a child was likely to become otitis-prone (2 4 episodes within 9 months) was assessed. The occurrence of each episode at the above ages was used as a statistic test for which sensitivity, specificity and predictive values and their 95% confidence intervals were calculated. The figures representing the numbers of episodes were assumed to follow a Poisson distribution, and the 95% confidence intervals were calculated on this assumption [3]. The confidence intervals for sensitivity and specificity figures were calculated based on a binomial distribution [4]. As the median length of the observation time for the otitis-prone children, 746 days (95% confidence interval 715-767) was significantly longer than that for the other children, 664 days (654-677) this analysis was performed on a set of 968 children who had a uniform observation period extending up to 2 years of age. Statistical software supplied by SAS Institute Inc., Cary, NC, U.S.A., was used for the analyses (FREQ, MEANS and LIFETEST procedures). Permission for this investigation was obtained from the Ministry of Health and Social Welfare as well as the Ethical Committee of the Faculty of Medicine, University of Oulu.
Results The cumulative incidence of acute otitis media up to two years of age was 71.0% (95% confidence interval, 68.9-73.1%) and the incidence rate 0.93 (0.90-0.96) episodes per child per year [2]. The previous criteria for otitis-proneness vary considerably and consequently the numbers of children meeting them and their mean ages upon doing so, assuming a 30-day borderline between two distinct episodes, are varied (Table I). Most definitions yield many children in relation to the resources required for treatment procedures, and some of the mean ages upon meeting the criteria are high, as the maximum morbidity is reached before the age of two years. The use of a 14-day borderline for two distinct episodes increased the numbers of children involved by some 10%.
204 TABLE
I
Criteria for otitis-proneness used in previous surveys considering recurrent otitis media, numbers identified in the present random sample of 2512 children and mean ages upon meeting the criteria Authors
Criteria
Buck [6] (1963) Perrin et al. [15] (1974) Howie et al. [lo] (1975) Gebhart [7] (1981) and Liston et al. [12] (1983) Persico et al. [16] (1985)
2 z r 2
Gonzalez
Finnish consensus conference [ll] (1987)
Harsten
episodes in episodes in episodes in episodes in
24 months 18 months or 2 5 first 6 years 6 months
> 1 episode/month in 3 subsequent months 2 3 episodes in 6 months or > 4 episodes in 18 months 2 3 recurrences in 6 months among adenotomized or tympanotomized 2 3 episodes in 6 months or 2 4 episodes in 12 months 2 6 episodes in 12 months
et al. [8] (1986)
Bluestone
2 3 6 3
et al. [5] (1988) et al. [9] (1989)
n
%
Mean age (months)
1036 651 159 439
41.2 25.9 6.3 17.4
13.4 15.1 18.8 14.1
188
7.5
13.7
453
17.8
14.3
46
1.8
16.9
473
18.8
14.5
93
3.7
16.5
The two parts of dual criterion overlapped almost entirely. The latter parts of the criteria laid down by Bluestone et al. [5], Gonzalez et al. [8] and Perrin et al. [15] added only 34, 14 and 0 children, respectively, to the number specified by the first part. A definition without a time interval would distinctly delay the qualification age. Criteria of 2 2, 2 3, 2 4 and 2 5 episodes of acute otitis media would classify 1036, 666, 442 and 275 children in this population as otitis-prone, with mean qualification ages of 13, 15, 17 and 18 months respectively. The risk of acute otitis media being greatest from September to May, a period of 9 months was considered reasonable for counting episodes. The results obtained using various threshold values during such a time-interval are displayed in Table II. As the number of children in this material that underwent either adenoidectomy or tympanostomy
TABLE
II
Numbers of otitis-prone children identified and mean age of identification using various thresholds (number of episodes in a period of 9 months) in a total series of 2512 children Criteria
n
B
Identification age (months)
12 >3 >4 25
965 550 273 139
38.4 21.9 10.8 5.5
13.0 14.5 15.0 15.1
705
%
N 30
too
.__ [
-
Fig. 1. Identification
CRUDE
of 273 otitis-prone
NUMBER
children
t
CUMULATIVE
( > 4 episodes
INCIDENCE
in 9 months)
in a series of 2512 children.
was 206 (8.2%), one reasonable criterion for otitis-proneness would be all those children who have 2 4 episodes of atute otitis media in 9 months. This definition identifies a series of 273 children (10.8%) with a mean age of 451 days (362-540). i.e. 15 months. The crude numbers of cases and their cumulative incidence are shown in Fig. 1. The early onset of acute otitis media turns out to carry rather low predictive values and sensitivity levels. Only the 1st episode occurring before the age of 12
TABLE
III
Sensitivity, specificity and predictive values of early episodes of acute otitls media with respect to whether the child wrll become &k-prone ( 2 4 episodes in 9 months), tested in u series of 968 children with uniform observation time of 2 years SE = sensitivity,
SP = specificity,
PR = predictive
Episode 2
Episode I
I 6 Months 5 9 Months 5 12 Months
value. Values are given as percentages. Episode 3
SE
SP
PR
SE
SP
PR
SE
SP
PR
47 68 85
86 73 60
35 28 25
15 44 66
98 93 87
57 48 44
3 28 51
100 98 95
80 80 69
206
months had an acceptable sensitivity level, 0.85 (0.79-0.91) but with low specificity, 0.60 (0.57-0.63) (Table III). As the age of the child at each episode increases, the sensitivity of this criterion increases as well, but its specificity decreases. Conversely, as the number of episodes increases, the specificity increases, but the sensitivity of the criterion decreases.
Discussion A uniform definition of the otitis-prone child is essential for effective comparison of the various treatments available. If the group of children with the most problems regarding otitis media is identified as early as possible and uniformly in the whole population, the treatment resources can be used most effectively. Preventive measures, like adjustment of the form of day care, which was found to be the most important risk factor [l], may be taken, antimicrobial prophylaxis prescribed or operative measures (adenoidectomy or tympanostomy) planned for the otitis-prone children as early as possible. The number of children defined by the criterion and considered for intervention should not be too large and the qualification age should not be too late in view of the fact that the majority of acute otitis media episodes occur before the age of two years. A dual criterion obviously entails no advantage, as the groups of children specified by the two criteria overlap. Previous definitions introduced in studies of both the epidemiology of recurrent otitis media and the effect of various forms of treatment are variable. Bluestone et al. [5] recommended either an operation or antimicrobial prophylaxis for all children with 3 or more episodes in 6 months or 4 or more in 12 months, a criterion that was met by a large number of children, 473 (18.8%) in this population. On the other hand, the criterion of Harsten et al. [9], 6 or more episodes in one year, yielded only 93 children (3.7%). The criteria for antimicrobial prophylaxis for recurrent acute otitis media set by the Finnish consensus conference [ll] and by Persico et al. [16] identify only a few children in this population (1.8 and 7.5% respectively), whereas the definitions used by Liston et al. [12], Gonzalez et al. [8] and Perrin et al. [15], also for prophylaxis, are quite loose, with large numbers of children fulfilling them (from 17.4 to 25.9%). The surveys of Buck [6] and Gebhart [7], examining the influence of operative treatment on recurrent acute otitis media, both employ loose definitions and consequently identify a large proportion of the children (17.4 to 41.2%). Only a few earlier studies on the epidemiology of acute otitis media determine the borderline to be used for two distinct episodes. Teele et al. [22] used a borderline of 21 days and Sipila et al. [19] 13 days. As previous surveys suggest that 50-70s of children with acute otitis media treated only with antimicrobials have middle-ear effusion l-2 weeks later, and as many as 20-40s 4 weeks later [17,18,21], a 30-day borderline was regarded here as biologically reasonable. None of the above authors defines the borderline used to separate two distinct episodes, but since some authors obviously included a shorter borderline in their criteria, the numbers given by
207
various criteria with a 14-day borderline were also studied, but this did not alter the results significantly. Since the time during which the children are exposed to the increased risk of upper respiratory tract infections (a period which all children experience in its entirety only once between the ages of 6 and 24 months and during which the risk of acute otitis media is greatest [13,14,19]) lasts 9 months (from September to May), a time interval of 9 months for counting episodes was considered reasonable. A criterion of at least 4 episodes during such an interval picks out a suitable number of children (regarding limited resources for extra measures). 273 (10.8%) with an acceptable mean qualification age of 15 months. A prospective cohort-based design with random enrollment was used to minimize selection bias in this study. The data regarding infections were collected retrospectively, but since all possible sources of medical aid were visited by one of the authors, it may be assumed that virtually all the episodes were covered. The study design, data collection and basing of the definition of acute otitis media on diagnoses made by primary physicians allow the results to be carefully generalized at the population level. Howie et al. [lo] were the first to demonstrate that recurrent episodes of acute otitis media are related to early onset, a matter confirmed later by others [9,13]. There are basically two ways of approaching the problem of an early episode of acute otitis media, either at the population level, as a screening test for otitis-proneness, or at the individual level, when considering extra surveillance or measures for a child experiencing an early epis.& de of acute otitis media. The present results suggest that the occurrence of early episodes of acute otitis media is not a suitable criterion for a screening method, as its sensitivity rates are too low. Only the occurrence of the first episode before the age of 12 months achieves an acceptable sensitivity level, 0.85 (95% confidence interval, 0.79-0.91) but the specificity then is too low, 0.60 (0.57-0.63). In addition, the logic of predicting otitis-proneness from early episodes diminishes considerably once a time interval is contained in the criteria and when mean qualification ages are just slightly over one year. For example, 36% of the children in this series that were to become otitis-prone before the age of 2 years had already been identified by 12 months of age (Fig. 1). The predictive usefulness of an early episode is similarly low in the case of the individual child, as only the occurrence of a third episode before the age of 9 months involves an outstanding risk of becoming otitis-prone (predictive value 0.80). The results clearly display the problems involved in the previous criteria for otitis-proneness. In this material one proper criterion for an otitis-prone child proved to be at least 4 episodes in 9 months with a 30-day borderline to define two distinct episodes, Early first episodes of acute otitis media were found to be of little predictive value regarding both the proneness of an individual child to otitis media or the occurrence of proneness in the whole population, both the sensitivity figures and predictive values being too low for accurate prediction.
208
Acknowledgements This work was supported financially by the Oulu Medical Research Foundation, the Oulu University Scholarship Foundation and the Alma and K.A. Snellman Foundation. Collection of the cohort data was supported by the Medical Research Council of the Finnish Academy.
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