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Selections from Journal Watch Pediatrics and Adolescent Medicine Copyright © 2005 Massachusetts Medical Society. All rights reserved.

Azithromycin for recurrent respiratory tract infections? Not yet! ▸

Recurrent respiratory tract infections (RRTIs) are a common pediatric problem and often result in additional physician visits and time lost from school or work. Viruses most often cause these infections, but some infections may be due to the atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae. Researchers investigated the presence of these “atypicals” and examined the role of azithromycin in treatment for RRTIs.

To determine the presence of atypical bacteria, 352 patients aged 1 to 14 years with an acute respiratory infection and a history of RRTIs were compared with 208 age- and sex-matched healthy controls. Recurrent RRTI was defined as eight or more episodes per year in children younger than 3 years and six or more per year in older children. Atypical bacteria were identified in 54% of patients and only 4% of controls.

The patient group was randomized to receive azithromycin (10 mg/kg/day 3 times weekly for 3 weeks) plus supportive care, or supportive care alone. At the 1-month follow-up exam, the azithromycin-treated group had a clinical success rate—defined as complete resolution of the acute symptoms present at enrollment and no reappearance of any clinical RRTI symptoms—of 96.6%, compared with 82.3% in the group not given antibiotics. The difference in success rates was significant only in azithromycin-treated patients who had proven atypical bacterial infections. At 6 months, however, all azithromycin-treated patients, regardless of bacterial infection status, had a significantly better success rate (defined as no more than two respiratory relapses) than did supportive-care patients (63.5% vs. 52.1%).

Comment ▸

These authors should be applauded for investigating a possible new RRTI therapy that challenges existing dogma. However, this trial, which was sponsored by the maker of azithromycin, had serious methodologic problems (no placebo, unclear blinding methodology, no exclusion or stratification of children with asthma) and may have overstated the value of therapy. Widespread use of antibiotics for children with recurring infections could increase the growing number of antibiotic-resistant organisms. Therefore, the use of azithromycin in atypical respiratory infections should be reserved for documented infection caused by the offending agents.

Peggy Sue Weintrub, MD

Published in Journal Watch Pediatrics and Adolescent Medicine July 25, 2005

Now approved: tetanus-diphtheria-pertussis booster for adolescents and adults ▸

Pertussis infection is an ongoing problem in the U.S. despite widespread vaccination of infants and young children. These infections often affect adolescents and adults with waning immunity. Such individuals may have protracted cough, emesis, and weight loss; they can also transmit the disease to young, incompletely immunized children, who are at greater risk for morbidity and mortality. This manufacturer-supported, randomized, double-blind trial evaluated the immunogenicity and safety of a new combination booster vaccine containing tetanus, diphtheria, and five components of acellular pertussis (Tdap) for adolescents and adults.

More than 4000 healthy adolescents and adults aged 11 to 64 were randomized at 39 U.S. clinical centers to receive Tdap or the standard tetanus-diphtheria (Td) booster vaccine. Antibody responses to tetanus and diphtheria were similarly excellent in both groups. In both adults and adolescents, response to the pertussis component was two to five times that seen in a previous efficacy trial of infants immunized with diphtheria-tetanus-acellular pertussis vaccine (the only well-studied pertussis-vaccinated comparison group available). Adolescents in the Tdap group reported post-vaccination pain slightly more often than those in the Td group, but other adverse events were similar.

Comment ▸

Two combination Tdap booster vaccines were licensed recently: the vaccine tested in this study, for people aged 11 to 64, and another targeted for those aged 10 to 18. The Advisory Committee on Immunization Practice has recommended that one of these newly licensed vaccines replace Td for 11- and 12-year-olds and those 13- to 18-year-olds who have not yet received a Td booster. The new Tdap vaccine can be given at the same visit with the conjugated meningococcal vaccine. For additional information that supports this strategy, the June 2005 supplement of Pediatric Infectious Disease Journal is devoted to this subject.

Peggy Sue Weintrub, MD

Published in Journal Watch Pediatrics and Adolescent Medicine July 25, 2005

Early gluten exposure and risk for celiac disease ▸

To assess whether the timing of introduction of gluten to infants’ diets influences subsequent onset of celiac disease autoimmunity (CDA), investigators in Colorado prospectively followed 1560 high-risk children (mean follow-up, 4.8 years). Children at high risk for CD had either human leukocyte antigen (HLA)-DR3 or -DR4 alleles or a first-degree relative with type 1 diabetes (because these same alleles confer an increased risk for type 1 diabetes). Onset of CDA was defined as two or more consecutive tests that showed positive antibodies for tissue transglutaminase (tTG). Children were tested at birth, 9, 15, and 24 months, and annually thereafter. Clinical evaluation was conducted after two positive tTG tests. No dietary advice was provided to families.

Of the 51 children who developed CDA, 34 underwent small-bowel biopsies (25 were CDA-positive). The mean age at first positive tTG antibody test was 4.7 years. Three CDA-positive children (6%) were exposed to wheat, barley, and rye (gluten foods) by 3 months of age; 12 (23%) were exposed at 4 to 6 months, and 36 (71%) at or after age 7 months. Among HLA-DR3-positive children, introduction of gluten foods by age 3 months was associated with a fivefold increased risk for CDA compared with exposure at age 4 to 6 months. Exposure at or after age 7 months was associated with a slightly increased risk for CDA compared with exposure at 4 to 6 months. CDA risk was not influenced by breast-feeding duration or age at exposure to oats, rice, or cows’ milk. In analyses limited to children with the highest risk for celiac disease (HLA-DR3–positive), children exposed to gluten foods during the first 3 months of life had a 40% risk for CDA by age 5.5 years.

Comment ▸

This report is the second by these investigators to show an association between early introduction of certain nutrients and subsequent autoimmunity in high-risk populations (see JW Pediatr Adolesc Med Nov 24 2003). We should caution families with a history of type 1 diabetes or celiac disease about early exposure to wheat, barley, or rye, as is recommended by the American Academy of Pediatrics. I would not specifically expose at-risk infants to gluten at age 4 to 6 months based solely on these data, but we should watch this literature carefully.

F. Bruder Stapleton, MD

Published in Journal Watch Pediatrics and Adolescent Medicine July 25, 2005

Obesity: new information, surprising findings ▸

Although numerous studies have linked various risk factors with obesity in childhood and adulthood, many were retrospective and inadequately controlled for confounding variables. Two new studies add to our understanding of factors associated with obesity.

As part of the Avon Longitudinal Study of Parents and Children, a prospective birth cohort study, U.K. investigators assessed potential risk factors for obesity (>95% BMI) in 7758 seven-year-old children. After adjustment for confounding variables, the following factors were associated with obesity: maternal BMI >30 (odds ratio, 4.25), paternal BMI >30 (OR, 2.54), and both parents BMI >30 (OR, 10.44); maternal smoking during pregnancy (⩾20 cigarettes/day; OR, 1.80); birth weight (OR, 1.05/100 g); TV viewing (>8 hours/week; OR, 1.55); and duration of nighttime sleep (<10.5 hours/night; OR, 1.45). Neither duration of breast-feeding nor timing of introduction of solid foods was protective against obesity at age 7. In a subgroup of 909 children for whom additional early-life data were available, further risk factors were identified: weight gain at 8 months and 18 months of age (ORs for highest quartile by age, 3.13 and 2.65, respectively); catch-up growth between birth and 2 years (OR, 2.60); adiposity rebound (increase in BMI after reaching its lowest point) by 43 months of age (OR, 15.00); and weight gain in the first 12 months of life (OR, 1.06/100 g).

In another study, investigators analyzed data from the 1970 British Cohort Study to examine adult outcomes of childhood obesity. Of the 8490 participants, 4% had been obese at age 10 years, and 16% were obese at 30 years. In nonobese adults, the researchers found no relation between obesity at 10 years (BMI >95%) and self-reported adult socioeconomic, educational, social, or psychological outcomes. Obesity at 30 years (BMI >28.5) had a mild effect on such outcomes, but obesity in women that persisted from childhood was associated with lack of gainful employment (OR, 1.9) and not having a current partner (OR, 2.0).

Comment ▸

Clearly, many environmental factors influence childhood obesity. Early childhood diet and nutrition, including adiposity rebound, is an important risk factor for later obesity. Also, parental obesity, which remains the single most important risk factor, is probably the most difficult to change. Surprisingly, the results from the long-term outcome study are less alarming than expected, demonstrating that childhood obesity has little effect on future economic, educational, and social well-being. However, the results might be different in the U.S. and in a contemporary cohort.

Howard Bauchner, MD

Published in Journal Watch Pediatrics and Adolescent Medicine August 4, 2005

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