Relation of early antibiotic use to childhood asthma: confounding by indication?

Abstract

Summary Background Findings from studies of the relation between early antibiotic use and subsequent asthma have been inconsistent, which may be attributable to methodologic issues. Objective Our objective was to assess the impact of confounding by indication on the relation of early antibiotic use to childhood asthma through age 5 in a non-selected birth cohort (n = 424). Methods Oral antibiotic use was assessed by frequent nurse interviews in the first 9 months of life. Physician-diagnosed active asthma and eczema were assessed by questionnaire at 1, 2, 3, and 5 years, and were considered as ever asthma or ever eczema if positive at any age. Allergen-specific IgE was assessed in plasma at 1, 2, 3, and 5 years. Confounding by indication was investigated by considering the relation of asthma to antibiotic use while controlling for the number of illness visits to a physician in early life. Results There was no statistically significant relation of early antibiotic use with physician-diagnosed eczema or allergen-specific IgE. A dose–response relation was evident for antibiotic use with ever asthma (odds ratio [OR] = 1.5, P = 0.047). Ever asthma also increased significantly with the number of illness visits to a physician (P<0.001). After adjustment for number of illness visits, antibiotic use showed no relation with asthma. Conclusions The relation of asthma to antibiotics in this cohort appears to be an artefact of the strong relation of number of physician visits for illness with both antibiotic use and risk for asthma.

Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis

“…Taken together, this results in two studies with doubtful results [38,39], three studies in which the association disappeared after correcting for RC [3,40,42], and eight that found a positive association that could not be explained by RC [41,[43][44][45][46][47][48][49].…”

“…Taken together, this results in four studies that did not collect data on the indication for antibiotic prescription or episodes of LRTIs [41,43,48,49], two studies in which the association disappeared after adjusting for CbI [46,50] and three studies in which a positive association remained after controlling for both RC and CbI [44,45,47].…”

“…Two studies adjusted for consultation behaviour or number of illness visits [43,48], and one of them expressly stated that this was to resolve CbI [43]; however, we contend that this method is not specific enough for the exact indication for antibiotics.…”

“…In three of these studies [3,40,42], initially positive associations between antibiotic use and wheeze or asthma disappeared after correction, whereas in the fourth study [41] the association between antibiotic use and wheeze remained after correcting for RC. RC as an explanation was unlikely in six studies that had ensured that exposure (antibiotic use) and follow-up periods took place subsequently and were not overlapping [43][44][45][46][47][48]. Furthermore, ALM et al [49] found an increased risk of wheeze in the first year of life after antibiotic use in the first days after birth.…”

“…Several of the eight studies mentioned previously (RC excluded) did not collect relevant information about the indication for antibiotic prescription or episodes of infections at the time of antibiotic exposure [41,43,48,49], whereas the other studies did [44][45][46][47]. The study by KUSEL et al [46] illustrates why CbI should be taken into account.…”