Published: May 13, 2014 | Updated: May 14, 2014
By Michael Smith, North American Correspondent, MedPage Today
Click Here For Story Source and VIDEO

Action Points

• Note that this study of administrative data suggests a link between early antibiotic use and subsequent asthma in children.
• Be aware that causality can not be determined here; it is conceivable that children who are more prone to diseases that require antibiotic treatment are also more prone to developing asthma.

Kids treated with antibiotics before their first birthday have increased risk of asthma, researchers reported.

And the risk increases the more often antibiotics are prescribed, according toKenneth Mandl, MD, of Harvard Medical School, and colleagues.

The finding supports the so-called hygiene and microbiota hypotheses put forward to explain the increasing prevalence of asthma, Mandl and colleagues concludedonline in Annals of Allergy, Asthma, and Immunology.

The association doesn’t prove that antibiotic use causes asthma, they cautioned, since it could also be true that some other factor causes both asthma and the need for antibiotics.

But the finding is sufficiently strong that doctors should be careful when prescribing antibiotics for infants, they argued.

Indeed, that’s the take-home message of the study, commented Martha Hartz, MD, of the Mayo Clinic in Rochester, Minn. It “reinforces to pediatricians and family practitioners that overuse of antibiotics has its downsides,” she told MedPage Today. “Unless a child needs an antibiotic, if there’s some way around it that’s not harmful or life-threatening to the child, they should be avoided.”

The study had a large number of patients and relied on objective measures of antibiotic use and asthma incidence, Hartz said. But she cautioned that the results might not apply to all children.

“This was largely an urban population,” she noted, but children in rural areas tend to have less risk of asthma, perhaps because they are exposed to a wider range of pathogens, such as the endotoxin from animal stool.

She also noted that the researchers did not control for several important possible confounders, such as family smoking and whether a child’s birth was vaginal or by C-section.

The hygiene hypothesis has been around for several years as a possible explanation for the increase in asthma seen in Western countries, Mandl and colleagues noted.

Indeed, the idea has also been suggested as an explanation for the increase in allergies such as peanut allergy, which tripled over a decade, according to a recent study.

The hypothesis is that reduced exposure to microbes during childhood leads to an increased risk of atopic disease in childhood. But the researchers noted the evidence also supports the idea that perturbation of the gut biota — perhaps by antibiotics — leads to a disturbed immune system.

The antibiotic link has some animal evidence to support it, Mandl and colleagues noted, but previous studies of antibiotic exposure and childhood asthma have had inconsistent results. In particular, lower respiratory tract illness in infancy has tended to confound any observations, they noted.

To try to clarify the issue, they conducted a population-based retrospective cohort study of children enrolled in a nationwide health insurance plan in the U.S.

In all, the data included medical insurance claims for some 1.6 million children from Jan. 1, 1999, through Dec. 31, 2006, and the study population was the 62,576 children continuously enrolled in the plan from birth through at least age 5.

The main objective was to examine the association between antibiotic use in the first year of life and the development of transient wheezing (defined as asthma that did not persist beyond age 3), late-onset asthma (beginning after age 3), and persistent asthma (beginning in the first 3 years of life and persisting through one or more years after age 3).

The researchers also investigated the effect of early-life respiratory infections on the three asthma phenotypes.

Nearly one in five children — 18.5% — developed wheezing or asthma between infancy and age 7, they reported, and the prevalence of the three types was roughly similar: 5,460 cases (or 8.7%) were transient, 6,418 (or 10.3%) were late-onset, and 5,946 (or 9.5%) were persistent.

In addition, some 26,693 children (or 42.7% of the study population) had at least one course of antibiotic in the first year of life, with a mean of 1.1 courses.

And 12,131 (or 19.4%) and 27,537 (or 44%) had at least one episode of lower or upper respiratory tract infection, respectively.

The researchers found that use of antimicrobials in the first year of life was associated with transient wheezing (odds ratio [OR] 2.0, 95% CI 1.9-2.2, P<0.001). Antibiotic use was also linked with an increased risk of persistent asthma (OR 1.6, 95% CI 1.5-1.7, P<0.001).

On the other hand, there was no association with late-onset asthma, Mandl and colleagues reported.

The associations remained after excluding children who had asthma or respiratory tract infections in the first year of life, premature infants, and those with cystic fibrosis.

Moreover, in that population, Mandl and colleagues observed a significant dose-response for both transient and persistent asthma, although the odds of late-onset disease remained insignificant.

For instance, when children got five or more antibiotic courses, the odds ratio for persistent asthma rose to 1.9 (95% CI 1.5-2.6, P<0.001), compared with a per-course odds ratio of 1.1.

For all three asthma types, the risk was higher in children who had lower or upper respiratory tract infection in the first year of life, Mandl and colleagues found.

Lower respiratory tract infection in particular led to markedly higher risks: the odds ratios for transient and persistent asthma were 6.1 and 5.1, respectively. The risk of late-onset asthma was also significant but lower, with an odds ratio of 1.4.

There were also “significant but modest” associations between upper respiratory tract infections and all three asthma types, Mandl and colleagues reported.