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Table 1. 
Univariate Analyses of Potentially Prognostic Factors for Persistent Otitis Media With Effusion (OME)*
Univariate Analyses of Potentially Prognostic Factors for Persistent Otitis Media With Effusion (OME)*
Table 2. 
Multivariate Analysis of Prognostic Factors Associated With Otitis Media With Effusion*
Multivariate Analysis of Prognostic Factors Associated With Otitis Media With Effusion*
Table 3. 
Estimated Prevalences Using the Case-Referent Design*
Estimated Prevalences Using the Case-Referent Design*
1.
Paradise  JL Otitis media in infants and children. Pediatrics. 1980;65917- 943
2.
Teele  DWKlein  JO Epidemiology of otitis media during the first seven years of life in children in Greater Boston: a prospective, cohort study. J Infect Dis. 1989;16083- 94Article
3.
Haggard  MHughes  E Objectives, Values and Methods of Screening Children's Hearing: a Review of the Literature. IHR Internal Report. Series A No. 41991;33- 52
4.
Alho  OOja  HKoivu  MSorri  M Risk factors for chronic otitis media with effusion in infancy. Arch Otolaryngol Head Neck Surg. 1995;121839- 843Article
5.
Tos  MPoulsen  GBorch  J Etiologic factors in secretory otitis. Arch Otolaryngol. 1979;105582- 588Article
6.
Kraemer  MJRichardson  MAWeiss  NS  et al.  Risk factors for persistent middle ear effusions. JAMA. 1983;2491022- 1025Article
7.
Nieto  CSCalvo  JRMGarcia  PB Climatic and racial factors related to the aetiology of secretory otitis media. ORL J Otorhinolaryngol Relat Spec. 1984;46318- 326Article
8.
Takasaka  T Incidence, prevalence, and natural history of otitis media in different geographic areas and populations. Ann Otol Rhinol Laryngol. 1990;9913- 14
9.
Sorensen  CHHolm-Jensen  STos  M Middle ear effusion and risk factors. J Otolaryngol. 1982;1146- 51
10.
Sassen  MLBrand  RGrote  JJ Risk factors for otitis media with effusion in children 0 to 2 years of age. Am J Otolaryngol. 1997;18324- 330Article
11.
Tos  M Sequelae of otitis media with and without treatment. Ann Otol Rhinol Laryngol Suppl. 1987;14618- 21
12.
Zielhuis  GAHeuvelmans-Heinen  EWRach  GHvan den Broek  P Environmental risk factors for otitis media with effusion in preschool children. Scand J Prim Health Care. 1989;733- 38Article
13.
Rasmussen  F Protracted secretory otitis media: the impact of familial factors and day-care center attendance. Int J Pediatr Otorhinolaryngol. 1993;2629- 37Article
14.
Otten  FWAGrote  JJ Otitis media with effusion and chronic upper respiratory tract infection in children: a randomized, placebo-controlled clinical study. Laryngoscope. 1990;100627- 633Article
15.
Bylander  A Upper respiratory tract infection and eustachian tube function in children. Acta Otolaryngol Suppl. 1984;97343- 349Article
16.
Yaginuma  YKobayashi  TTakasaka  T The habit of sniffing in nasal diseases as a cause of secretory otitis media. Am J Otol. 1996;17108- 110
17.
Downs  MP Identification of children at risk for middle ear effusion problems. Ann Otol Rhinol Laryngol. 1990;99168- 171
18.
Harsten  GPrellner  KHeldrup  JKalm  OKornfalt  R Recurrent acute otitis media: a prospective study of children during the first three years of life. Acta Otolaryngol. 1989;107111- 119Article
19.
Sipila  MKarma  PPukander  JTimonen  MKataja  M The Bayesian approach to the evaluation of risk factors in acute and recurrent acute otitis media. Acta Otolaryngol. 1988;10694- 101Article
20.
Casselbrant  MLBrostoff  LMFlatherty  MR  et al.  Otitis media with effusion in preschool children. Laryngoscope. 1985;95428- 435Article
21.
Birch  LElbrond  O Prospective epidemiological investigation of secretory otitis media in children attending day-care centers. ORL J Otorhinolaryngol Relat Spec. 1984;46229- 234Article
22.
Stahlberg  MRRuuskanen  OVirolainen  E Risk factors for recurrent otitis media. Pediatr Infect Dis J. 1986;530- 32Article
23.
Reed  BDLutz  LJ Household smoking exposure: association with middle ear effusions. Fam Med. 1988;20426- 430
24.
Agius  AMWake  MPahor  ALSmallman  LA Smoking and middle ear ciliary beat frequency in otitis media with effusion. Acta Otolaryngol. 1995;11544- 49Article
25.
Kero  PPiekkala  P Factors affecting the occurrence of acute otitis media during the first year of life. Acta Paediatr Scand. 1987;76618- 623Article
26.
Salamy  AEldredge  LTooley  WH Neonatal status and hearing loss in high-risk infants. J Pediatr. 1989;5847- 852Article
27.
Gannon  MMJagger  CHaggard  MP Maternal blood group in otitis media with effusion. Clin Otolaryngol. 1994;19327- 331Article
28.
Daly  KGiebink  CSLe  CT  et al.  Determining risk for chronic otitis media with effusion. Pediatr Infect Dis J. 1988;7471- 475Article
29.
Freemantle  NLong  AMason  J  et al.  The treatment of persistent glue ear in children. Effective Health Care. 1992;41- 16
30.
Hsu  GSLevine  SCGiebink  GS Management of otitis media using Agency for Health Care Policy and Research guidelines. Otolaryngol Head Neck Surg. 1998;118437- 443
31.
Schouten  EGDekker  JMKok  FJ  et al.  Risk ratio and rate ratio estimation in case-cohort designs: hypertension and cardiovascular mortality. Stat Med. 1993;121733- 1745Article
32.
Hanley  JAMcNeil  BJ The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;14329- 36Article
33.
Collet  JPBurtin  PGillet  JBossard  NDucruet  TDurr  F Risk of infectious diseases in children attending different types of day-care setting. Respiration. 1994;6116- 19Article
34.
Rovers  MMHofstad  EAHFranken-van den Brand  KIM  et al.  Prognostic factors for otitis media with effusion in infants. Clin Otolaryngol. 1998;23543- 546Article
Original Article
November 1999

Prognostic Factors for Persistent Otitis Media With Effusion in Infants

Author Affiliations

From the Departments of Otorhinolaryngology (Ms Rovers and Drs Ingels and van den Broek), Epidemiology (Dr Zielhuis and Mr Straatman), and Medical Technology Assessment (Dr van der Wilt), University of Nijmegen, Nijmegen, the Netherlands.

Arch Otolaryngol Head Neck Surg. 1999;125(11):1203-1207. doi:10.1001/archotol.125.11.1203
Abstract

Objective  To study prognostic factors for persistent otitis media with effusion (OME) in a birth cohort of 30,099 children born in the eastern part of the Netherlands between January 1, 1996, and April 1, 1997.

Design  Case-referent study.

Subjects  Children who failed a triple hearing test before their first birthday and were subsequently diagnosed with bilateral OME during 3 of the 4 bimonthly visits to an ear, nose, and throat (ENT) department (n=372). The persistent cases were compared with 3 referent groups: (1) all the children who attended the first of 3 hearing tests; (2) all the children of the birth cohort who were referred to an ENT department after the third hearing test; and (3) all the children who were diagnosed with bilateral OME during the first visit to an ENT department.

Results  When all the children who participated in the first hearing test were taken as referents, persistent OME was associated with upper respiratory tract infections, attending a day-care center, having older siblings, and a family history of otitis media. When all the children who were referred to an ENT department were taken as referents, only attending a day-care center was associated with persistent OME. When the children diagnosed with bilateral OME during the first visit to an ENT department were taken as referents, no prognostic factors were found for OME persistence.

Conclusion  When a child is referred early, an otolaryngologist can ask the parent about the presence of prognostic factors to decide which policy to follow.

IN THE LITERATURE, many prognostic and risk factors have been described for otitis media with effusion (OME) in children. The main factors considered responsible for the development of OME are infections and eustachian tube dysfunction. Other factors that may influence the occurrence of OME are race,13 sex,14 acute otitis media,410 the presence of siblings,3,1012 family history of otitis media,2,3,7,10,12,13 respiratory tract infections,3,7,10,1416 Down syndrome,17 cleft palate,2 allergies,18 season,7,12,19,20 bottle feeding,3 attending a day-care center,35,9,12,13,21,22 passive smoking,3,6,2224 low birth weight,25,26 blood group A Rh+,27 and socioeconomic status.2,22,25

Some studies have investigated the risk factors specific for persistent OME such as male sex,2,4 sibling history of ear infection,2,27 bottle feeding,2 blood group A Rh+,27 day-care attendance,28 and season.4 The results of these studies have been contradictory, probably owing to differences in methods and study populations. In addition, the definition of persistent OME varies between studies. In most studies, persistent OME was defined as a minimum of 2 months of effusion, while the present guidelines for treatment with ventilation tubes recommend waiting 4 to 6 months.29,30

The aim of this study was to analyze prognostic factors for persistent OME of at least 4 months' duration in a large population. Children with these factors might benefit from early detection, more frequent checkups, and/or early intervention.

PATIENTS AND METHODS
PATIENTS AND REFERENTS

The population in this study comprised all the infants born in the eastern part of the Netherlands between January 1, 1996, and April 1, 1997 (N=30,099). These children were screened for hearing impairment (Ewing method) at age 9 months. Those who failed 3 screening tests were referred to an ear, nose, and throat (ENT) outpatient clinic for diagnosis with tympanometry and otoscopy. During this visit the parents were asked to complete a questionnaire with a number of items about prognostic factors. Infants with bilateral OME (determined by a type-B tympanogram and/or fluid found during the otoscopy procedure) were recalled 2 months later, while the children with unilateral or no OME were not further observed. Otitis media with effusion was considered to be persistent when the diagnosis was made during 3 of the 4 bimonthly visits (over the subsequent 6 months). Those infants with persistent OME composed the cases in this study (n=372).

To make a valid estimate of the relative risk, we performed a case-referent study.31 This meant that controls needed to be selected from the source population. As a consequence, it was possible for a child in the referent group to be a case as well as a control.

Our study had 3 possible source populations: (1) the children who participated in the first of 3 hearing tests (a random sample of 450 children [366 respondents] born between March and July 1996 was taken from this population to serve as controls, and the parents of these control children completed the same questionnaire on prognostic factors); (2) the children who were referred to an ENT department after failing the third hearing test (n=1083); and (3) the children who were diagnosed with bilateral OME during their first visit to the ENT department (n=757). Comparing the persistent cases with these 3 referent populations enabled us to study the effect of the prognostic factors over time.

PROGNOSTIC FACTORS

Day-care attendance, breastfeeding, prematurity, and passive smoking were all studied as dichotomous variables (yes/no) and as continuous variables (days per week, number of weeks, and number of cigarettes). An infant was considered to have a history of acute otitis media if the child ever had an earache with fever or if a general practitioner had prescribed treatment for earache in the past 3 months. An infant was considered to have a family history of otitis media if a sibling or parent had acute otitis media or OME once. There was a history of respiratory illness if upper respiratory tract infections (URTIs) had occurred more than 4 times in the first year of life.

STATISTICAL PROCEDURES

For each prognostic factor, the risk ratio for persistent OME was estimated by means of an odds ratio (OR) with a 95% confidence interval (CI). Multiple logistic regression was used to examine prognostic factors simultaneously. Only prognostic factors that showed an association with OME in univariate analysis were selected for the multivariate models.

The prognostic value of the models was evaluated using the c-index. This c-index is equal to the area under a receiver operating characteristic curve32 and has a range of 0.5 (no prognostic value) to 1.0 (maximum prognostic value).

Because ORs do not show the absolute difference in risk of OME in children with and without the prognostic factors, we estimated the baseline prevalence of persistent OME in the referents who participated in the first screening, using the method described by Schouten et al31: corrected β00*+log (f), where f represents the probability that a subject in the cohort was selected from the random sample (assuming that sampling was independent of the outcome). All analyses were performed using the statistical package SAS (SAS Institute, Cary, NC, version 6.12, 1996).

RESULTS

The results of the univariate analyses are given in Table 1. In the analysis with the referent children who participated in the first screening, 5 factors were associated with persistent OME: sex (OR=1.4 [95% CI, 1.0-1.8]), URTIs (OR=2.6 [95% CI, 2.0-3.6]), older siblings (OR=3.2 [95% CI, 2.3-4.4]), attending a day-care center (OR=1.9 [95% CI, 1.3-2.6]), and a family history of otitis media (OR=1.9 [95% CI, 1.4-2.5]). Other variables such as prematurity, number of days in day care, breastfeeding, duration of breastfeeding, atopy, educational level of the parents, AOM, and passive smoking and number of cigarettes did not show an association with persistent OME. When all the infants who were referred to an ENT department were selected as referents, only day-care attendance was associated with persistent OME (OR=1.5 [95% CI, 1.1-1.9]). When the children diagnosed with bilateral OME during the first visit to an ENT department were selected as referents, none of the factors was associated with persistent OME.

The OR for children with both older siblings and URTIs was 1.8 (95% CI, 1.3-2.6), while the OR for children with URTIs but without older siblings was 5.5 (95% CI, 3.1-9.6). Similarly, children with older siblings and attending day care had an OR of 1.6 (95% CI, 1.0-2.4), while children without older siblings and attending day care had an OR of 4.2 (95% CI, 2.4-7.3). The OR also differed within the strata of day care. Children attending day care who had older siblings showed an increased risk of 1.85 (95% CI, 1.05-3.28), while children not attending day care but who had older siblings had an OR of 5.0 (95% CI, 3.3-7.5).

When the children referred to the ENT department served as referents, such effect modification was also found, but the confidence intervals overlapped. The OR for children with both older siblings and URTIs was 1.1 (95% CI, 0.8-1.4), while the OR for children with URTIs but without older siblings was 1.7 (95% CI, 1.0-2.9). The OR for children attending day care and who had older siblings was 1.4 (95% CI, 1.0-1.9), while the odds for children attending day care but who did not have older siblings was 2.0 (95% CI, 1.2-3.3). Children attending day care who had older siblings had an OR of 1.0 (95% CI, 0.7-1.6), while children not attending day care who had older siblings had an OR of 1.5 (95% CI, 1.0-2.2). When the children diagnosed with bilateral OME during the first visit to an ENT department served as referents, the effect modification was even smaller.

Multiple logistic regression was used to investigate the association between sex, URTIs, the presence of older siblings, day-care attendance, and family history. In this model only URTIs, older siblings, attending a day-care center, and a family history were associated with persistent OME (Table 2). The final logistic model can therefore be described by:

P(Persistent OME)=1/[1+ e−(−1.5 + 0.7 URTIs + 1.1 Older Siblings + 0.6 Day Care + 0.4 Family History)].

The c-index of this model was 0.70. When we adjusted for the above effect modification by adding 2 interaction factors (day care×URTIs and older siblings×URTIs) the c-index did not improve.

Table 2 indicates that after correction for URTIs, day-care attendance, and a family history of otitis media, a child with older siblings was 3 times more likely to develop persistent OME than one without. After correction for the other factors, a child with URTIs was 2.1 times more likely to develop persistent OME. Children attending day care and children with a family history of otitis media were 1.9 and 1.5 times more likely to develop persistent OME than children not attending day care or children without a family history, respectively. Inclusion of the other possible prognostic factors in the multivariate model did not increase the c-index.

Prevalences of OME, calculated using the method described by Schouten et al,31 are given in Table 3. In the sample of 352 referents who could be used in the multivariate analysis, 5 children were both case and referent. If we assume that the 360 cases without missing values also represent all the children who participated in the first screening, the total cohort can be calculated by (360 cases/5)×352 referents=25,344 infants. In this case, f=352/25,344=0.0139, and β0=1.48+log(0.0139)=−5.75. The prevalence is given by exp (β0+0.7 URTIs+1.1 older siblings+0.6 day care+0.4 family history). The prevalence of persistent OME in children without URTIs, older siblings, a family history of otitis media, or attendance at day care was 0.3%, while the prevalence was 5.5% when all these factors were present.

COMMENT

In accordance with other studies, we found that a history of URTIs, day-care attendance, having older siblings, and a family history of otitis media were prognostic factors for persistent OME.2,27,28 However, this was only the case when a sample of the original screening population served as referents. When the children with persistent OME were compared with the children referred to an ENT department after the third screening, only day-care attendance was associated with persistent OME. When the children diagnosed with bilateral OME during the first visit to an ENT department served as referents, no factors were associated with persistent OME.

Having older siblings seemed to modify the effect of a history of URTIs on persistent OME. Children without older siblings but with a history of URTIs were at higher risk for persistent OME than children with both older siblings and a history of URTIs. Moreover, children attending day care who did not have older siblings were at higher risk for persistent OME than children attending day care who did have older siblings. This suggests an important role of immune status: children with older siblings have probably been exposed to pathogens that cause URTIs and OME, so their immune system may be stimulated to protect them against these pathogens.33

After the third hearing test, 318 children (23%) were not referred to an ENT department for a variety of reasons (mostly because the parents did not want it). This might have caused some bias if the infants lost to follow-up formed a select group. For example, if these children did not have persistent OME and did not score on the prognostic factors either, the calculated ORs would overestimate the true rates. But as it is unlikely that this was the case in a large proportion of the children lost to follow-up, the amount of bias can be considered small.

It is possible that all the children referred to an ENT department had already been suffering from OME for at least 3 months, since they failed the hearing test 3 times. This might explain the lesser effect of the prognostic factors when the children referred to an ENT department and the children diagnosed with bilateral OME at an ENT department served as referents.

Data on prognostic factors were based on questionnaires completed by the parents. Although parental recall of prognostic factors also forms the source of information in clinical practice, it should be noted that recall errors and misclassification will lead to some degree of underestimation of the ORs.

Children from the referent group who participated in the first of the 3 hearing tests were used as controls in an earlier study.34 These children were born between March and July 1996. We do not expect that the presence of prognostic factors depends on the month of birth, but we know that the prevalence of persistent OME is highest during the winter months and lowest during the summer months. The children born between March and July had their conditions first diagnosed at the ENT department at age 12 months. Therefore, fewer of the referents might have been diagnosed with OME, and the calculated ORs might be a little overestimated.

To show the absolute difference in risk of persistent OME, we estimated the prevalences. The risk of OME in children without a history of URTIs, older siblings, a family history of otitis media, or day-care attendance was 0.3%, while the estimated risk in children with a history of URTIs, older siblings, a family history of OME, and day-care attendance was 5.5%. These differences show that information on prognostic factors does not wholly discriminate between those who develop persistent OME and those who do not, but the differences seem to be substantial enough to be used.

In conclusion, this study showed that children with all 4 prognostic factors at the time of screening were at higher risk for persistent OME. However, when these children were older and had been suffering from OME for some months, these factors were no longer prognostic. So when a child is referred early to a general practitioner, pediatrician, or otorhinolaryngologist, and if these physicians must decide which policy to follow, they can ask the parents about the presence of the prognostic factors and decide accordingly.

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Article Information

Accepted for publication July 16, 1999.

Corresponding author: Maroeska M. Rovers, Department of Otorhinolaryngology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands (e-mail: m.rovers@mie.kun.nl).

References
1.
Paradise  JL Otitis media in infants and children. Pediatrics. 1980;65917- 943
2.
Teele  DWKlein  JO Epidemiology of otitis media during the first seven years of life in children in Greater Boston: a prospective, cohort study. J Infect Dis. 1989;16083- 94Article
3.
Haggard  MHughes  E Objectives, Values and Methods of Screening Children's Hearing: a Review of the Literature. IHR Internal Report. Series A No. 41991;33- 52
4.
Alho  OOja  HKoivu  MSorri  M Risk factors for chronic otitis media with effusion in infancy. Arch Otolaryngol Head Neck Surg. 1995;121839- 843Article
5.
Tos  MPoulsen  GBorch  J Etiologic factors in secretory otitis. Arch Otolaryngol. 1979;105582- 588Article
6.
Kraemer  MJRichardson  MAWeiss  NS  et al.  Risk factors for persistent middle ear effusions. JAMA. 1983;2491022- 1025Article
7.
Nieto  CSCalvo  JRMGarcia  PB Climatic and racial factors related to the aetiology of secretory otitis media. ORL J Otorhinolaryngol Relat Spec. 1984;46318- 326Article
8.
Takasaka  T Incidence, prevalence, and natural history of otitis media in different geographic areas and populations. Ann Otol Rhinol Laryngol. 1990;9913- 14
9.
Sorensen  CHHolm-Jensen  STos  M Middle ear effusion and risk factors. J Otolaryngol. 1982;1146- 51
10.
Sassen  MLBrand  RGrote  JJ Risk factors for otitis media with effusion in children 0 to 2 years of age. Am J Otolaryngol. 1997;18324- 330Article
11.
Tos  M Sequelae of otitis media with and without treatment. Ann Otol Rhinol Laryngol Suppl. 1987;14618- 21
12.
Zielhuis  GAHeuvelmans-Heinen  EWRach  GHvan den Broek  P Environmental risk factors for otitis media with effusion in preschool children. Scand J Prim Health Care. 1989;733- 38Article
13.
Rasmussen  F Protracted secretory otitis media: the impact of familial factors and day-care center attendance. Int J Pediatr Otorhinolaryngol. 1993;2629- 37Article
14.
Otten  FWAGrote  JJ Otitis media with effusion and chronic upper respiratory tract infection in children: a randomized, placebo-controlled clinical study. Laryngoscope. 1990;100627- 633Article
15.
Bylander  A Upper respiratory tract infection and eustachian tube function in children. Acta Otolaryngol Suppl. 1984;97343- 349Article
16.
Yaginuma  YKobayashi  TTakasaka  T The habit of sniffing in nasal diseases as a cause of secretory otitis media. Am J Otol. 1996;17108- 110
17.
Downs  MP Identification of children at risk for middle ear effusion problems. Ann Otol Rhinol Laryngol. 1990;99168- 171
18.
Harsten  GPrellner  KHeldrup  JKalm  OKornfalt  R Recurrent acute otitis media: a prospective study of children during the first three years of life. Acta Otolaryngol. 1989;107111- 119Article
19.
Sipila  MKarma  PPukander  JTimonen  MKataja  M The Bayesian approach to the evaluation of risk factors in acute and recurrent acute otitis media. Acta Otolaryngol. 1988;10694- 101Article
20.
Casselbrant  MLBrostoff  LMFlatherty  MR  et al.  Otitis media with effusion in preschool children. Laryngoscope. 1985;95428- 435Article
21.
Birch  LElbrond  O Prospective epidemiological investigation of secretory otitis media in children attending day-care centers. ORL J Otorhinolaryngol Relat Spec. 1984;46229- 234Article
22.
Stahlberg  MRRuuskanen  OVirolainen  E Risk factors for recurrent otitis media. Pediatr Infect Dis J. 1986;530- 32Article
23.
Reed  BDLutz  LJ Household smoking exposure: association with middle ear effusions. Fam Med. 1988;20426- 430
24.
Agius  AMWake  MPahor  ALSmallman  LA Smoking and middle ear ciliary beat frequency in otitis media with effusion. Acta Otolaryngol. 1995;11544- 49Article
25.
Kero  PPiekkala  P Factors affecting the occurrence of acute otitis media during the first year of life. Acta Paediatr Scand. 1987;76618- 623Article
26.
Salamy  AEldredge  LTooley  WH Neonatal status and hearing loss in high-risk infants. J Pediatr. 1989;5847- 852Article
27.
Gannon  MMJagger  CHaggard  MP Maternal blood group in otitis media with effusion. Clin Otolaryngol. 1994;19327- 331Article
28.
Daly  KGiebink  CSLe  CT  et al.  Determining risk for chronic otitis media with effusion. Pediatr Infect Dis J. 1988;7471- 475Article
29.
Freemantle  NLong  AMason  J  et al.  The treatment of persistent glue ear in children. Effective Health Care. 1992;41- 16
30.
Hsu  GSLevine  SCGiebink  GS Management of otitis media using Agency for Health Care Policy and Research guidelines. Otolaryngol Head Neck Surg. 1998;118437- 443
31.
Schouten  EGDekker  JMKok  FJ  et al.  Risk ratio and rate ratio estimation in case-cohort designs: hypertension and cardiovascular mortality. Stat Med. 1993;121733- 1745Article
32.
Hanley  JAMcNeil  BJ The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;14329- 36Article
33.
Collet  JPBurtin  PGillet  JBossard  NDucruet  TDurr  F Risk of infectious diseases in children attending different types of day-care setting. Respiration. 1994;6116- 19Article
34.
Rovers  MMHofstad  EAHFranken-van den Brand  KIM  et al.  Prognostic factors for otitis media with effusion in infants. Clin Otolaryngol. 1998;23543- 546Article
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