Effects of early middle ear effusion on child intelligence at three, five, and seven years of age.

OBJECTIVE: This study tested the hypothesis that children with prolonged middle ear effusion (MEE) during the first 3 years of life are at risk for cognitive delays or deficits. METHOD: A prospective study enrolled 698 children from diverse backgrounds and controlled for eight demographic and environmental factors. Participants were recruited at birth and monitored for ear status frequently in the home; 379 children were assessed for cognition with the Stanford-Binet, 4th ed., at 3 years of age, 294 at 5 years, and 198 at 7 years. RESULTS: Using the SAS General Linear Models (GLM) procedure, we found a significant direct relation between duration of bilateral MEE and Stanford-Binet Composite and Nonverbal Reasoning/Visualization Factor scores at age 3, but not at age 5 or age 7. Statistical clustering analysis revealed four groups with different temporal patterns of MEE: Low MEE, Early MEE (peaking at 0-6 months), Later MEE (peaking at 6-12 months), and High MEE. GLM analyses revealed no direct effects, but several moderated effects, of MEE cluster on cognitive development at 3 years, but none at 5 or 7 years. In general, children in the Later MEE and High MEE groups appeared to be more adversely affected by bilateral MEE at 3 years, but effects were moderated in complex ways by socioeconomic status or home stimulation. Growth curve modeling across the three assessment periods showed no effects of total duration of MEE but did indicate that children in the Later MEE cluster had low scores at age 3 but caught up at ages 5 and 7. CONCLUSIONS: Prolonged MEE, especially between 6 and 12 months, may put children at risk for cognitive delays at 3 years, but the risk effect is not strong and effects are no longer detectable at 5 or 7 years.

Role of leukotriene B4 and interleukin-8 in acute bacterial and viral otitis media.

In order to evaluate the role of polymorphonuclear leukocytes (PMNs) in acute otitis media (AOM), levels of leukotriene B4 (LTB4), a potent inflammatory product of PMNs, and interleukin-8 (IL-8), a PMN chemotactic cytokine, were measured in 271 middle ear fluid (MEF) samples from 106 children with AOM. Forty-two percent of the patients had evidence of respiratory viral infection. At the time of diagnosis, levels of both LTB4 and IL-8 were higher in the MEFs from patients with AOM associated with bacterial or bacterial and viral infection than those MEFs containing no pathogen (p < .05). Antibiotic treatment was not associated with a significant change in levels of LTB4 or IL-8 in the MEFs obtained 2 to 5 days into treatment, compared to those obtained at diagnosis. Bacteriologic failure after 2 to 5 days of treatment was associated with high LTB4 levels in the initial MEFs (p = .05). Recurrence of AOM within 1 month was associated with high IL-8 levels in the initial MEF (p = .04). Our findings suggest that LTB4 and IL-8 are produced during acute infection of the middle ear, and these PMN-related inflammatory substances may play an important role in delaying recovery or in recurrence of AOM. Effective treatment of AOM may require eradication of bacteria by antibiotics, as well as pharmacologic agents that modulate PMN functions.

Breast feeding and children's intelligence.

Breast feeding was reported in 1992 by Lucas, et al. to provide advantages for the development of intelligence in children of low birth weight, possibly through nutrients or other biological factors found in human breast milk but not cow's milk. Research on breast feeding and intelligence in children of normal birth weight has yielded mixed results, probably because measurement of environmental influences has not been thorough and the range of intelligence components measured has been limited. Our research with 204 3-year-old children of normal birth weight included control measures for the environment and maternal intelligence (Hollings-head socioeconomic status, Home Observation for the Measured Environment, Shipley) and two measures of childhood intelligence (Stanford-Binet Fourth Edition and Peabody Picture Vocabulary Test-Revised). Controlling for environmental variables and maternal intelligence, initiation of breast feeding predicted scores on intelligence tests at age three. Breast feeding was associated with 4.6-point higher mean in children's intelligence.

Use of C-reactive protein in differentiation between acute bacterial and viral otitis media.

OBJECTIVES: The objectives of this investigation were: (1) to determine degree of elevation of serum C-reactive protein (CRP) in uncomplicated acute otitis media (AOM); (2) to compare serum CRP levels in bacterial and viral otitis media; and (3) to determine whether a single serum CRP level, obtained early in the course of AOM, could be used to differentiate between viral and bacterial otitis media. DESIGN AND METHODS: Sera were obtained from otherwise healthy infants and children with AOM who were 3 months to 7 years of age between 1989 and 1991. Tympanocentesis, bacterial and viral studies of the middle ear fluids, virologic studies of nasal wash specimens, measurements of serum antibody titers to respiratory viruses, blood counts, and quantitation of serum CRP concentrations were performed. After the initial tympanocentesis, an oral antibiotic was given for the next 10 days. The patients were clinically reevaluated over next 4 weeks. OUTCOME MEASURES: Serum CRP concentrations were compared among subjects with AOM who were divided into four groups based on the results of bacteriologic and virologic studies: group I, Bacterial infection (n = 82); group II, bacterial and viral infections (n = 69); group III, viral infection (n = 12); and group IV, no identifiable pathogen (n = 22). RESULTS: There was no statistical difference in serum CRP values among the four groups. The ranges of CRP were less than 0.6 to 22.8, less than 0.6 to 17.8, less than 0.6 to 2.0, and less than 0.6 to 6.8 mg/dL in groups I through IV, respectively. However, when CRP values in bacteria-positive cases were compared with CRP concentrations in bacteria-negative cases (1.58 +/- 3.16 vs 0.64 +/- 1.24 mg/dL), the difference was statistically significant. Furthermore, a significantly higher proportion of bacteria-positive cases had serum CRP concentrations greater than 2 mg/dL, compared with those in bacteria-negative cases. There was no correlation between initial CRP values and clinical findings and/or the clearance of bacteria from the middle ear. After 10 days of antibiotic treatment, CRP values returned to normal (< 0.6 mg/dL) in all cases. CONCLUSION: In AOM, the range of serum CRP varied from less than 0.6 to 22.8 mg/dL. High CRP values (> 2.0 mg/dL) were associated with 22% of cases of bacterial AOM but only with 6% of nonbacterial AOM. High levels of serum CRP were found to be very specific in detecting bacterial AOM, and no cases of viral AOM without a concurrent bacterial infection were found to exhibit high serum levels of CRP.

Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media.

Histamine levels were measured in 677 middle ear fluid (MEF) samples from 248 children (aged 2 months to 7 years) with acute otitis media (AOM); of these, 116 (47%) had documented viral infection. Histamine content was higher in bacteria-positive than in bacteria-negative MEF samples (P = .007) and higher in samples from patients with viral infection than in those from patients with no viral infection (P = .002). Bacteria and viruses together had an additive effect on histamine content in MEF. Histamine concentration in the initial MEF sample tended to be higher in patients with persistent otitis than in those with good response to treatment (P = .14). Results suggest that viruses, bacteria, or both induce histamine production, which leads to increased inflammation in the middle ear. Antihistaminic drugs may be beneficial. Large, prospective, controlled trials of the effects of antihistamine as an adjunct therapy in bacterial and viral AOM are required before recommendations can be made.

Relation of infant feeding practices, cigarette smoke exposure, and group child care to the onset and duration of otitis media with effusion in the first two years of life.

The relation of infant feeding practices, cigarette smoke exposure, and group child care to the onset and duration of otitis media with effusion (OME) was evaluated in a cohort of 698 healthy infants prospectively monitored by tympanometry in the home every 2 to 4 weeks until 2 years of age. Except for an experimental group of children who were offered early tube placement, the study children received conventional care from their personal physician or clinic. We used LISREL, a structural equation modeling procedure (computer software), to explore associations between environmental variables and OME onset and duration while controlling for interrelations among the variables. Supine feeding position and early initiation of group child care were associated with earlier onset of OME. Shorter duration of breast-feeding, increased packs of cigarettes smoked per day in the home, and increased hours per week in group child care were associated with an increase in the amount of time with OME during one or more of the age blocks studied (birth to 6, 6 to 12, 12 to 18, and 12 to 24 months). For a decrease in the amount of time with OME during the first 2 years of life, prolonged breast-feeding and upright feeding position should be encouraged, and cigarette smoke exposure should be minimized. Limiting early child care in large groups might also be advisable.

Assessment of three-year-olds with the Stanford-Binet Fourth Edition.

The Stanford-Binet, Fourth Edition was normed for children 30 months of age and older, but its usefulness with young children (e.g., 36 months) has received little attention. This study of 121 three-year-old children examined possible administration problems, provided correlations with three environmental measures, and compared scores with those of the Peabody Picture Vocabulary Test--Revised. Problems of administration did arise on some subtests, correlations with environmental measures were moderate, and scores on the Stanford-Binet IV and PPVT-R were moderately correlated. The Stanford-Binet IV is a useful test in assessment of a broad range of intellectual abilities.

Association of rhinovirus infection with poor bacteriologic outcome of bacterial-viral otitis media.

Viruses--both alone and in combination with bacteria--have been shown to be a cause of acute otitis media (AOM). Moreover, the presence of virus in middle ear fluid (MEF) interferes with the bacteriologic response to antibiotic treatment in AOM. We studied various factors related to the eradication of bacteria from the MEF of infants and children who had AOM associated with a combination of bacteria and viruses. Of 622 cases of AOM diagnosed and treated between 1985 and 1991, 71 were due to such a combination. Bacteria were eradicated from MEF by 2-4 days of antibiotic treatment in 50 (70%) of these 71 cases; in the remaining 21 cases, the originally identified bacteria persisted or a new pathogenic bacterial species was detected after such treatment. These two groups of cases were compared with respect to the patients' age, sex, race, history of recurrent AOM, duration of respiratory symptoms, and compliance; the type of antibiotic treatment administered; the type of pathogenic bacteria and viruses identified in MEF; the presence of single or multiple pathogens; and the laterality of the disease. The only difference noted was in the type(s) of virus found in MEF. The presence of rhinovirus was associated with a higher rate of bacteriologic failure than was that of respiratory syncytial virus, parainfluenza virus, influenza virus, or other viruses. Our data suggest that the bacteriologic response to antibiotic treatment in bacterial-viral AOM may depend in part on the type(s) of virus present in MEF.

Does HOME add to the prediction of child intelligence over and above SES?

The most frequently used measure of the educational stimulation provided by the child's home environment is socioeconomic status (SES). Because SES is a global measure, researchers have developed measures that provide more detailed information. One of these is the Home Observation for Measurement of the Environment (HOME), (Caldwell & Bradley, 1984). Our research examined whether HOME adds to the predictability of child intelligence beyond that provided by SES. Subjects were 121 3-year-olds, Black and White, who were administered the fourth edition of the Stanford-Binet and the Peabody Picture Vocabulary Test-Revised. HOME and Hollingshead SES scores were obtained at age 2. HOME added to the predictability of intelligence over and above that provided by SES for the total group of children and for White children but not for Black children. The predictive utility of HOME also depended on the type of intelligence test being used.

Brainstem auditory evoked potentials in young children before and after tympanostomy tube placement.

To evaluate the effect of tympanostomy tube placement upon the hearing function of infants and young children, brainstem auditory evoked potentials (BAEP) were recorded in a group of young children (mean age 22 mos) receiving this treatment for otitis media with effusion (OME). For comparison, a group of healthy infants with normal behavioral audiometry were also tested with BAEP. Hearing loss was estimated for each ear using peak V latency-intensity curves. To evaluate the immediate effect of tube placement, 98 ears in 52 children were tested immediately before and after tube insertion. The 63 ears with effusion had prolonged peak latencies that decreased significantly (P < 0.001) immediately after tube placement and a mean hearing loss estimate of 22 dB that improved significantly (P < 0.0001) to 11 dB immediately after tube insertion. The 35 ears without effusion at myringotomy had a mean hearing loss estimate of 8 dB that did not change significantly after tube insertion. To evaluate the short-term effect of tube presence, 39 ears in 25 children were tested 3 weeks to 18 months after tube insertion. The 28 ears with dry tubes had a mean hearing loss estimate of 3 dB, and the 11 ears with otorrhea had a mean hearing loss estimate of 31 dB. The magnitude of mean hearing loss estimates in these young children with OME and the improvement in hearing function with tube placement is similar to that reported in older children studied with BAEP and audiometry. The study groups with a history of otitis media that had resolved by the time of testing had isolated prolongation of mean III-V interpeak latencies compared to normals (P < 0.01). These studies show that BAEP techniques are useful in estimating hearing loss in children with OME who are difficult to test by behavioral audiometry and show changes in rostral brainstem transmission in very young children with a history of OME.

Efficacy of cefixime in the treatment of acute otitis media in children.

OBJECTIVE: To compare the efficacy of cefixime with amoxicillin in the treatment of acute otitis media in children. DESIGN: Randomized, nonblinded study. SETTING: General pediatric clinic at a university hospital in Texas. PARTICIPANTS: A volunteer sample of 201 children, aged 2 months through 6 years. INTERVENTIONS: A 10-day oral course of cefixime (8 mg/kg per day administered once daily) or amoxicillin (40 mg/kg per day administered in three divided doses [every 8 hours]). MEASUREMENTS/MAIN RESULTS: Tympanocentesis for bacterial culture was performed on all affected ears on enrollment and after 4 to 6 days of therapy. The patients were evaluated clinically 4 to 6 days after starting therapy, at the end of therapy, and 3 to 4 weeks after therapy was completed. Using Fisher's Exact Test, no significant difference was found between the two treatment groups for rate of clinical improvement or rate of eradication of Haemophilus influenzae and Streptococcus pneumoniae. However, combining the results from this study and two previously reported studies, cefixime was found to be more effective in eradication of H influenzae and less effective in eradication of S pneumoniae.

Presence of cytomegalovirus and herpes simplex virus in middle ear fluids from children with acute otitis media.

Twenty-seven (10%) of 271 infants and children with acute otitis media (AOM) were found to be infected with cytomegalovirus (CMV) or herpes simplex virus type 1 (HSV). CMV or HSV, alone or in combination with bacteria or other viruses, was isolated from the middle ear fluid (MEF) of 10 patients. In three cases, CMV alone was isolated from the MEF, and in one case, HSV alone was isolated. One of the CMV cases involved an acute primary or reactivation of CMV infection, with CMV-bacterial otitis and conjunctivitis as major manifestations. One patient with AOM and stomatitis had purulent otitis associated with the presence of HSV in MEF, with no other bacterial or viral pathogens noted in MEF or nasal wash specimens. While most patients with CMV infection were probably asymptomatic excreters at the time of development of AOM, CMV did enter the middle ear. The presence of CMV in MEF was prolonged, and the patients continued to have clinical signs of otitis despite negative bacterial cultures. Among patients with bacterial otitis, a higher proportion of those who had CMV found only in nasal wash specimens had persistent bacteria in MEF, compared with those who were concurrently infected with other viruses (57% vs. 19%; P less than .04). This report is the first to suggest an etiologic role for CMV and HSV in AOM.

Effect of viral respiratory tract infection on outcome of acute otitis media.

We prospectively studied 271 infants and children (2 months to 7 years of age) with acute otitis media (AOM) for viral and bacterial causes, outcome at the end of therapy, and frequency of recurrence within 1 month. Comprehensive virologic methods, including viral antigen detection, cell culture, and serologic studies, were used to diagnose viral infection of the respiratory tract, middle ear, or both. Evidence of viral infection was found in 46% (124/271) of patients with AOM. Sixty-six patients (24%) had virus or viral antigen in the middle ear fluid; 50 of these patients (76%) also had bacteria in middle ear fluid, and 16 (24%) had virus alone. More patients with AOM and combined bacterial and viral infection (51%) had persistent otitis (3 to 12 days after institution of antibiotic treatment), compared with those with only bacterial otitis (35%; p = 0.05) or patients with only viral infection (19%; p less than 0.01). Of patients with only viral infection, 4 of 10 with virus in middle ear fluid had persistent otitis, compared with none of 11 patients who had virus only in nasal wash specimens or whose viral infection was diagnosed only by serologic studies. Our data suggest that viruses interact with bacteria and that concurrent viral infection can significantly worsen the clinical course of bacterial AOM. The presence of virus in middle ear fluid may contribute to the pathogenesis and outcome of bacterial AOM. The mechanism of these interactions deserve further investigation.

Respiratory viruses interfere with bacteriologic response to antibiotic in children with acute otitis media.

Fifty-eight infants and children with acute otitis media were prospectively studied for bacterial and viral pathogenesis and response to antibiotic therapy. Tympanocentesis for bacterial and viral cultures of middle ear fluids (MEF) was done before and 2-4 days after beginning treatment. Patients were followed until the end of antibiotic course. Bacteria were cultured from the preantibiotic MEF in 43 cases (74%). Viruses were cultured from the preantibiotic MEF in 11 cases (19%); all of these MEFs also contained bacterial pathogens. A significantly higher proportion of patients with both virus and bacteria (50%) failed to respond with clearing of bacteria 2-4 days into therapy compared with the group with bacteria alone (13%). The patients with persistently positive viral cultures of the MEF seemed to have purulent otitis of longer duration. Presence of virus in the MEF may interfere with bacteriologic and clinical responses to antibiotic. The mechanism of interference deserves further investigation.

Bacteriologic and clinical efficacy of cefixime compared with amoxicillin in acute otitis media.

The ability of cefixime or amoxicillin to eradicate causative pathogens was evaluated in 140 infants and children with acute otitis media with effusion. When pretherapy and on-therapy bacteriologic cultures were used, success was defined as elimination of pathogens regardless of clinical improvement. Parent compliance with administration instructions was closely monitored. Cefixime was administered daily or twice daily and because results on the two dosage regimens did not differ, data were combined for analysis. Results suggested that cefixime was somewhat more effective than amoxicillin for acute otitis media with effusion caused by Haemophilus influenzae but less effective for infections caused by Streptococcus pneumoniae. The study agents were equally effective against Branhamella catarrhalis.

Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media.

During a 28-month period, 84 children with acute otitis media were studied by viral and bacterial cultures of middle ear fluid and viral cultures of nasal lavage fluid. Viruses were isolated from the middle ear fluid of 17 (20%) patients. Evidence of viral infection was demonstrated by positive viral cultures of middle ear fluid and/or nasal lavage fluid in 33 (39%) patients. Rhinovirus in one patient and influenza b virus in another were the only pathogens isolated. Influenza virus, enterovirus, and rhinovirus were the most common viruses found in middle ear fluids. Parainfluenza virus, adenovirus, and respiratory syncytial virus were found less often. In 82% of cases, the virus isolated from middle ear fluid was also isolated from nasal lavage fluid, but only 44% of viruses found in nasal lavage fluid were also found in middle ear fluid. Mixed bacterial and combined viral-bacterial infections were common. Only 15% of patients had no pathogen isolated from middle ear fluids. Using tissue culture techniques, we demonstrated that enterovirus and rhinovirus are also common middle ear pathogens. Our data reemphasize the significance of viruses as etiologic agents of acute otitis media and propose several questions regarding the viral-bacterial interactions and the types of viruses involved in the pathogenesis of the disease.

In vivo sensitivity test in otitis media: efficacy of antibiotics.

During a 10-year period, antibiotics were assigned in random, double-blind fashion in six combinations to treat 948 episodes of otitis media in children. Exudate from the middle ear of all patients was cultured before treatment. Three follow-up visits were conducted; the first follow-up visit was three to five days after the start of therapy, and the second and third visits were 14 and 31 days after onset of treatment. Exudates were recultured for 75% of the patients on the first follow-up visit. Comparison of treatment results showed that triple sulfonamide combined with either phenoxymethyl penicillin, or benzathine and procaine penicillin G given intramuscularly (IM) was as effective as was ampicillin or amoxicillin. Phenoxymethyl penicillin and cyclacillin alone were usually effective against pneumococci but relatively ineffective against Haemophilus influenzae. Cefaclor and trimethoprim-sulfamethoxazole produced unsatisfactory results in about half the cases caused by pneumococci or H influenzae. Although production of beta-lactamase by some otitis-causing Haemophilus and Staphylococcus species may explain the ineffectiveness of some treatments, the percentage of organisms positive for beta-lactamase was too small to be responsible for the poor results with certain drugs.