Based on data from the most valid of the studies, the researchers concluded that antibiotic exposure in utero or in the first year of life increased the odds of childhood asthma by about 13%. However, they emphasise that the evidence is still weak and in need of additional rigorous research.
The study, scheduled for publication in Paediatrics, "provides evidence for some caution in interpreting this purported association", lead researcher Dr Michael B. Bracken, an epidemiologist at Yale University said.
A popular explanation for the increasing rate of asthma in developed countries is the hygiene hypothesis, which suggests that a reduction in microbial exposure - a result of antibiotic use - could trigger atopic immune responses and the risk of asthma.
Dr Bracken and colleagues surveyed the medical literature and identified 22 studies that investigated the effect of antibiotic exposure during pregnancy or the first year of life on the risk of an asthma diagnosis up to age 18.
Overall, children exposed to antibiotics between birth and their first birthday had a 52% greater chance of developing asthma compared to those not exposed. Among the three studies that included children exposed during pregnancy, the relative odds rose by an average of 24%.
However, the researchers acknowledge potential biases that could have inflated the effects and might account for the wide variability in estimates between studies. Parents of children with asthma may be more likely to recall early life exposures, for example. Early symptoms of asthma may also have been mistaken for a respiratory infection and treated with antibiotics, resulting in the potential for reverse causality.
To get a better idea of the true influence of antibiotics on asthma risk, the researchers conducted separate analyses stratified by factors such as study design.
As expected, retrospective studies reported the highest associations, combining for an estimate of more than double the odds of asthma with antibiotic exposure.
Studies that didn't adjust for early respiratory infections also resulted in higher relative odds.
The most valid evidence, the researchers conclude, came from database and prospective studies that had adjusted for respiratory infections. Pooling this subset of data pointed to a 13% increased odds of developing asthma for children exposed to antibiotics in utero or during the first year of life.
They say an estimated 87 children would need to be exposed for each additional antibiotics-related case of childhood asthma. Given the large number of children who are exposed to antibiotics, the researchers suggest the findings could link a large number of asthma cases to the drugs.
While their selective approach likely eliminated many of the potential confounders, Dr Bracken said there was still a possibility that some "sources of bias from reverse causation" had persisted.
"If we have managed to control for bias, then the association is smaller than previously thought," he added.
Until further large, prospective studies address the relationship, the researchers offer the "tentative" conclusion that early antibiotic exposure does slightly increase the risk of developing childhood asthma.
"Antibiotics are well known to be over-prescribed, often for viral diseases for which they are ineffective," Dr Bracken said. "This research adds to the message that antibiotics should only be prescribed when indicated.” (Reuters Health/ May 2011)