Antibiotic Use in Infants Boosts Asthma Risk

WINNIPEG, Manitoba, June 11-- Children who are given antibiotics during the first year of life may be at significantly greater risk of developing asthma, researchers here found.

In a longitudinal cohort study, the odds of developing asthma by age 7 was 1.86 (95% confidence interval 1.02 to 3.37) for children who received antibiotics for nonrespiratory infections in their first year, said Anita Kozyrskyj, Ph.D., of the University of Manitoba, and colleagues.

Risk was also significantly elevated for those given multiple antibiotic courses and broad-spectrum antibiotics, particularly cephalosporins, they reported in the June issue of CHEST.

Previous epidemiologic studies have had conflicting findings on an association between early antibiotic use and asthma, the researchers said. But, they were unable to eliminate potential confounding from the use of antibiotics for wheeze-related respiratory illnesses that precede asthma.

To control for reverse causation and selection bias, the researchers studied a birth cohort of 13,116 children born in 1995 in Manitoba, using the province's health care and prescription databases.

Those who were diagnosed with asthma within the first year of life were excluded.

A little more than half of the cohort lived in urban areas, one-quarter came from low-income families, 5% had a mother with asthma, and nearly all had siblings (90%). Six percent had asthma at age 7.

Sixty-five percent of children had received at least one antibiotic prescription in their first year of life: 3% had received narrow-spectrum antibiotics only, 52% had received broad-spectrum antibiotics only, and 10% of children had received both.

The antibiotic indication was otitis media for 40% of the children, upper respiratory tract infection for 28%, and lower respiratory tract infection for 19%. Only 7% had received antibiotics for non-respiratory tract infections.

Among the findings controlled for asthma risk factors, the researchers reported:

• Asthma was significantly more likely at age 7 in children who had received antibiotics in the first year of life for non-respiratory tract infections than in those who had not received antibiotics at all (OR 1.86, 95% CI 1.02 to 3.37).
• The likelihood of developing asthma increased in a dose-dependent manner and was significant for every number of antibiotic courses (OR 1.21 for one or two, 1.30 for three or four, and 1.46 for more than four).
• The asthma risk for children who received more than four courses of antibiotics in the first year was even greater for those without a dog in the home at birth (OR 2.02, 95% CI 1.20 to 3.38), no maternal history of asthma (OR 1.57, 95% CI 1.20 to 2.04), or who lived in a rural area (OR 1.88, 95% CI 1.23 to 2.88).
• Broad-spectrum antibiotics were significantly associated with the development of asthma by age 7 (OR 1.50, 95% CI 1.16 to 1.93).
• Narrow-spectrum antibiotics tended to increase asthma risk as well, but the association was not significant (OR 1.35, 95% CI 0.29 to 6.23).

The link between nonrespiratory infections and asthma may have been at least partially because of misdiagnosed atopic dermatitis, which is a major risk factor for the development of asthma, the researchers noted.

Most of the nonrespiratory infections for which children received antibiotics were skin infections (115 of 148), they said.

"It is plausible that skin infections early in life are manifestations of an impaired barrier function of the epithelium," they wrote, "including the gastrointestinal epithelium, which leads to allergen penetration and subsequent inflammation."

Interestingly, the researchers said, the subgroups at the highest risk with antibiotic use-those living in a rural area, without maternal history of asthma, and no dog exposure-were also most likely to have received a broad-spectrum cephalosporin antibiotic.

The researchers said the study could not confirm a causal role of antibiotics in children developing asthma. But they postulated that the subgroup results may have been a result of broad-spectrum cephalosporin use or "increased sensitivity to the antibiotic effect among children with a genetic predisposition to impaired barrier function of the epithelium."

Large-scale studies are needed to further examine these associations, Dr. Kozyrskyj wrote.

"In the interim, it would be prudent to avoid the unnecessary use of broad-spectrum antibiotics in the first year of life when other antibiotics are available," they concluded.