Published online April 1, 2008
PEDIATRICS Vol. 121 No. 4 April 2008, pp. 697-702 (doi:10.1542/peds.2007-1232)

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ARTICLE

Neonatal Antibiotic Treatment Is a Risk Factor for Early Wheezing

Bernt Alm, MD, PhD^a, Laslo Erdes, MD^b, Per Möllborg, MD^c, Rolf Pettersson, MD^d, S. Gunnar Norvenius, MD, PhD^a, Nils Åberg, MD, PhD^a, Göran Wennergren, MD, PhD^a

^a Department of Pediatrics, Göteborg University, Göteborg, Sweden
^b Pediatric Outpatient Clinic, Skene, Sweden
^c Central Infant Welfare Bureau, Uddevalla Hospital, Uddevalla, Sweden
^d Department of Pediatrics, Skaraborg Hospital, Skövde, Sweden

OBJECTIVE. The use of antibiotics in infancy and subsequent changes in the intestinal bacterial flora have been discussed as risk factors for the development of asthma. However, it has been difficult to exclude the possibility that antibiotics have been given in early episodes of wheezing. As a result, there has been a risk of reverse causation. To minimize the risk of reverse causation, we have focused on the effect of antibiotics that are already administered on the neonatal ward.

METHODS. In a cohort study of infants born in western Sweden in 2003, we studied the development of wheezing. The families of the infants were randomly selected and sent a questionnaire at child ages 6 and 12 months. The response rate was 68.5% to the 6-month questionnaire and 68.9% to the 12-month questionnaire.

RESULTS. At 12 months, 20.2% of infants had had 1 or more episodes of wheezing, and 5.3% had had 3 or more episodes. Inhaled corticosteroids had been taken by 4.1% of the infants. Independent risk factors for wheezing disorder treated with inhaled corticosteroids were neonatal antibiotic treatment, male gender, gestational age of <37 weeks, having a mother with asthma, having a sibling with asthma or eczema, and breastfeeding for <5 months.

CONCLUSIONS. Treatment with antibiotics in the neonatal period was an independent risk factor for wheezing that was treated with inhaled corticosteroids at 12 months of age. These results indirectly support the hypothesis that an alteration in the intestinal flora can increase the risk of subsequent wheezing.

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Key Words: antibiotics • cohort studies • infant • wheezing

Abbreviations: BPD—bronchopulmonary dysplasia • OR—odds ratio • CI—confidence interval

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