Prenatal antibiotic exposure and childhood asthma: a population-based study

Abstract

Antibiotic use during infancy alters gut microbiota and immune development and is associated with an increased risk of childhood asthma. The impact of prenatal antibiotic exposure is unclear. We sought to characterise the association between prenatal antibiotic exposure and childhood asthma.We performed a population-based cohort study using prescription records, hospitalisation records and physician billing claims from 213 661 mother-child dyads born in Manitoba, Canada between 1996 and 2012. Associations were determined using Cox regression, adjusting for maternal asthma, postnatal antibiotics and other potential confounders. Sensitivity analyses evaluated maternal antibiotic use before and after pregnancy.36.8% of children were exposed prenatally to antibiotics and 10.1% developed asthma. Prenatal antibiotic exposure was associated with an increased risk of asthma (adjusted hazard ratio (aHR) 1.23, 95% CI 1.20-1.27). There was an apparent dose response (aHR 1.15, 95% CI 1.11-1.18 for one course; aHR 1.26, 95% CI 1.21-1.32 for two courses; and aHR 1.51, 95% CI 1.44-1.59 for three or more courses). Maternal antibiotic use during 9 months before pregnancy (aHR 1.27, 95% CI 1.24-1.31) and 9 months postpartum (aHR 1.32, 95% CI 1.28-1.36) were similarly associated with asthma.Prenatal antibiotic exposure was associated with a dose-dependent increase in asthma risk. However, similar associations were observed for maternal antibiotic use before and after pregnancy, suggesting the association is either not directly causal, or not specific to pregnancy.

Maternal antibiotic use and child asthma: is the association causal?

“…There are alternative explanations for the findings of LOEWEN et al [25]. Antibiotics substantially alter the composition of microbiota and their metabolite production.…”

“…LOEWEN et al [25] interpreted their finding, that maternal antibiotic use in the periods before, during and after pregnancy was associated with childhood asthma, as evidence that antibiotics taken in pregnancy, specifically, may not be causally associated with childhood asthma. They offered alternative hypotheses for their findings.…”

“…In this issue of the European Respiratory Journal, LOEWEN et al [25] provide fresh evidence that maternal antibiotic exposure is associated with a dose-dependent increase in child asthma risk. They examined data from a population-based cohort study of 213 661 mother-child dyads in Manitoba, Canada, from 1996 to 2012.…”

“…In conclusion, LOEWEN et al [25] should be commended for their rigorous examination of the association between maternal antibiotics and risk of childhood asthma in a large population-based study. Although the authors observed evidence for a biological gradient (dose-response association), they did not identify a particular window of susceptibility; thus, limiting their causal inference about the pregnancy-specific effects of antibiotics.…”

Influence of maternal microbiota during pregnancy on infant immunity

“…However, in a Swedish study by Örtqvist et al [59] antibiotic exposure in fetal life was associated with increased risk for asthma in a cohort analyses but not sibling analyses, suggesting that the link between antibiotic use and atopy may be confounded by shared familial risk factors. Furthermore, a recent study showed that maternal antibiotic exposure during pregnancy is associated with a dose-dependent increase in child asthma risk [60], but so was maternal antibiotic use before pregnancy and in the 9 months postpartum. However, in a well-designed sibling-control study, Mulder et al [61] found prenatal antibiotic use to be predictive of childhood asthma even compared to sibling controls.…”