Reviews of pediatric research

August 1, 2007

Antibiotic/asthma link * Sickle cell pain * Breastfeeding benefits * Roller shoe injuries

• Early antibiotic use linked to asthma

Results of a study conducted in Manitoba, Canada suggest a good reason to minimize use of antibiotics in infancy-such use was shown to be tied to a marked increase in the risk of developing asthma. Researchers examined the association between oral antibiotic use in the first year of life and asthma at 7 years of age in a population of more than 13,000 children, using data from health care administrative records related to provision of universal health insurance to Manitoba residents. The data included all physician visits, hospitalizations, and drug prescriptions.

Most children (65%) had received at least one antibiotic prescription during the first year of life; 3% had received narrow-spectrum antibiotics and no broad-spectrum antibiotics. More than half (52%) received broad-spectrum antibiotics and no narrow-spectrum antibiotics, and 10% received both types of antibiotics.

The likelihood of developing asthma increased with the number of antibiotic courses, with children who received more than four courses being 111/42 times as more likely to have asthma at the age of 7 as children who received no antibiotics. This association was strengthened by the absence of maternal asthma, and by absence of a dog in the home at birth.

The relationship between early antibiotic use and asthma was far stronger among children in rural areas than among those in urban environments. The relationship was also far more robust for broad-spectrum than for narrow-spectrum antibiotics (Kozyrskyj AL et al: Chest 2007;131:1753).

Commentary:

The authors present this data in support of the "microflora hypothesis," a theory that development of immune tolerance by the maturing mucosal immune system is enhanced by the normal flora in the infant's gut. They contend that early antibiotic use disrupts the flora and puts the child at risk of allergic disease. I see probiotics written all over this!

• Is poor response to pain medication for SCD genetically based

Investigators designed a study to test the hypothesis that children with sickle cell disease (SCD) whose pain does not respond to outpatient codeine while taking hydroxyurea are more likely to have a reduced-functioning cytochrome P450 2D6 (CYP2D6) allele than children with mild SCD. The analgesic effect of codeine depends on metabolic activation by CYP2D6.

The study was completed in 73 children with SCD who came to an emergency department with continued pain that was unresponsive to codeine. The subjects ranged in age from 4 to 18 years. Any child who took hydroxyurea for frequent painful crises was considered to have severe SCD, as was any child who had three or more hospitalizations for vaso-occlusive crises during the preceding three years. All other children were designated as having mild disease.

Investigators analyzed subjects' blood samples for 11 CYP2D6 single nucleotide polymorphisms and CYP2D6 gene deletion and duplication. They also calculated CYP2D6 enzymatic activity. Within the entire sample, more than half the children (58%) had a reduced-functioning allele. Ten children had CYP2D6 duplications and 15 had deletions. Compared with youngsters with mild disease, children with severe disease were twice as likely to have both a reduced-functioning allele and reduced CYP2D6 activity (Brousseau DC et al: J Pediatr 2007;150:623).

Commentary:

Bit by bit, we are gaining some insight into why the same disease can present so differently in two different patients, and why what works in one patient may not work in the next. In the future, patients with chronic disease will come to seek care with personalized care plans determined by a battery of genetic tests. I look forward to that day.