Antibiotics in Infancy Linked to Childhood Atopic Asthma

Emma Goksor, MD, PhD

An association between antibiotic treatment in the first week of life and atopic asthma in childhood found in a long-term study suggests an immune-mediated effect, possibly from early disturbance of gastrointestinal microbiota, according to researchers.

Emma Goksor, MD, PhD, University of Paediatrics, University of Gothenburg, Gothenburg, Sweden and colleagues explained that disturbed microbiota can affect the development of the immune system, thereby beomcing a risk factor for asthma and allergies.

"Antibiotic treatment is known to affect the gastrointestinal microbiota and treatment of this kind during a vulnerable period of life could therefore have long-term effects," researchers wrote.

The researchers conducted a longitudinal cohort study of over 5000 Swedish children born in 2003. Parents answered periodic questionnaires about their children from age 6 months through 12 years, with 76% of parents responding at 12 years. Additional information about the pregnancy and delivery were obtained from medical records.

The questionnaire at 6 months elicited information on admission to a neonatal ward during first week of life and treatment with antibiotics. At 12 months, it queried such factors as duration of breastfeeding, introduction of different foods, kinds of pets and dampness (defined by damage) at home. At 12 years, questions addressed the current health of the child, airway symptoms, food and environment allergies, and presence of eczema and/or rhinitis.

Asthma was categorized depending on age of onset and duration and persistence of symptoms. The researchers considered history of allergic rhinitis at 12 years in distinguishing between atopic and non-atopic asthma.

Current asthma was reported in 6.4% of the children at 12 years of age, with 65% having atopic asthma and 35% non-atopic asthma. Current allergic rhinitis was reported in 52% of the children with current asthma and in 78% of those with atopic asthma. The cumulative prevalence of asthma to age 12 years was 14%, of which 30% had transient symptoms and 38% had late-onset symptoms. Relatively few (4%) reported persistent asthma.

Goksor and colleagues reported from mutivariate analyses of risk and protective factors that treatment with antibiotics during the first week of life was an independent risk factor for atopic asthma, but not for non-atopic asthma at 12 years of age (adjusted odds ratio[aOR] 2.2; 95% Confidence Interval [CI]; 1.2-4.2) versus 1.4 (0.5-3.4). Small gestational size was associated with an increased risk for non-atopic asthma, (3.8 aOR; 1.1-13.7). Breastfeeding for 4 months or more was associated with reducing risk, (0.5 aOR; 0.3-0.95) for atopic asthma, but did not significantly reduce risk of current asthma without allergic rhinitis at 12 years, with (1.1 aOR; 0.6-2.1).

Goksor and colleagues note that while other research groups have examined whether antibiotic treatment during the first year of life is associated with childhood asthma, there has been little study of antibiotics received in the first week of life.

"Focusing on the first week of life enabled us to avoid reverse causation by treatment of early wheezing episodes with antibiotics and to avoid confounding by indication," Goksor and colleagues indicate.

One large study, of over 136,000 infants, which evaluated potential risk factors ranging from maternal urinary tract infections (UTI) to caesarean vs vaginal delivery, also found a significant association between antibiotic use in infancy and childhood asthma.

"Infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home," wrote Pingsheng Wu, PhD, Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine and Center for Asthma and Environmental Sciences Research, Vanderbilt University School of Medicine, Nashville, TN and colleagues in their study of maternal and infant risk factors for childhood asthma.

The study, "Antibiotics in the first week of life were associated with atopic asthma at 12 years of age," was published online in Acta Paediatrica last month.