Early-life antibiotic
use ups asthma risk |
Giving young children antibiotics
can put them at greater risk of asthma, according to
a study published online ahead of print in the journal
Chest. Kids in rural areas who are given multiple
antibiotic treatments in their first year run more risk
of developing childhood asthma than children who don't
get antibiotics. The large study's findings have left
the researchers scratching their heads since asthma
is usually more of an urban problem.
The team at the University of Manitoba
analysed antibiotic prescription and other data during
the first year of birth for the entire population of
13,116 children born in Manitoba in 1995. They assessed
any potential association with the development of asthma
by age seven and found that, independent of other risk
factors, the odds of developing asthma by age seven
was one-and-a-half times greater for children prescribed
more than four courses of antibiotics than those prescribed
none in their first year of life.
For the recipients of more than
four courses of antibiotics, the adjusted risk of developing
asthma was greater for rural than urban children (OR
= 1.88 vs. 1.22), among those with no maternal history
of asthma than those with maternal history (OR = 1.57
vs. 0.95) and among those with no exposure to a dog
than those with exposure (OR = 2.02 vs. 0.72).
TURNING
THE TABLES
"We were particularly surprised that asthma risk was
higher for rural than urban children. In Manitoba, as
elsewhere, this population normally has a lower risk
of developing the illness. The results for urban kids
showed virtually no association between antibiotic use
and asthma, which is in keeping with the finding of
other studies," says Anita Kozyrskyj, PhD in community
health sciences and BScPhm, an associate professor in
the faculties of medicine and pharmacy at the University
of Manitoba.
The study was funded by the Canadian
Institute for Health Research and data was collected
from Manitoba's healthcare databases, which include
information on all hospital and doctor visits, as well
as all prescription records, which are recorded electronically.
"This provided us with a unique opportunity to link
data from a large population that's 57% urban and 43%
rural, and study questions related to antibiotic use
outcomes in both settings," says Dr Kozyrskyj.
She offers a couple of possibilities
as to why antibiotic use alters asthma risk in rural
children. "Firstly, there might not be an increased
risk in urban kids because their gastrointestinal microflora
is already altered due to their environment, thus their
heightened risk of developing asthma is relatively unaffected
by whether they were prescribed antibiotics early in
life. Secondly, rural children are more likely to be
prescribed broad-spectrum cephalosporins. Rural parents
tend to access health services less regularly, so physicians
are inclined to prescribe broad-spectrum antibiotics,
which are more likely to wipe out beneficial gastrointestinal
flora."
MICROFLORAL
CLEARCUTTING
Her study bolsters the microfloral hypothesis of asthma
causation, which argues that a lack of microbial flora
in the gastrointestinal tract due to antibiotic overuse
prevents the maturation of the mucosal immune system
during infancy.
Dr. Tom Kovesi, a pediatric respirologist
at the Children's Hospital of Eastern Ontario, in Ottawa,
sees this study as fitting within a growing body of
research that points to the young immune system's role
in childhood asthma. "The cleaner your environment when
you're a little kid — including your internal environment
— the less robust and more allergy-prone your immune
system is, and the higher the likelihood of developing
asthma," said Dr. Kovesi.
"We all know that antibiotics are
over-prescribed in Canada, but parents and physicians
often err on the cautious side and administer antibiotics,
whether or not they're necessary. I think this sort
of research is telling us that if a child is really
not that sick, and there isn't clear evidence that there's
a bacterial infection, there are sometimes some real
advantages to not giving the antibiotics," he said.
Nevertheless, he cautioned that "If a child has a serious
infection and needs antibiotics, you should absolutely
prescribe them."
Kozyrskyj noted that her study
doesn't discount the hygiene hypothesis of asthma causation
— that children require exposure to some pathogenic
bacteria for the proper development of their immune
system. Therefore, the next stage of her research will
involve looking at a subset of 700 children on which
they have collected information on endotoxin exposure
in early-life. "Exposure to endotoxins, a component
of gram-negative bacteria found in the environment,
is thought to be protective against asthma, which supports
the hygiene hypothesis of asthma etiology. We hope to
determine these factors' effect on asthma risk. I'm
also interested in pursuing further information on childhood
infections, especially skin infections because we noticed
that children with skin infections were more likely
to develop asthma."
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