Abstract
Higher risks of asthma have been observed in children with prenatal exposure to antibiotics and during early life compared with those who have not. However, the causality of such associations is unclear. To assess whether exposure to antibiotics in early life had a causal effect in increasing the risk of asthma in children diagnosed at 5-8years of life, and the impact in the target population. Data were from electronic health records and questionnaires for children and their mothers in the Born in Bradford birth cohort. Exposure variables were prescriptions of systemic antibiotics to the mother during pregnancy (prenatal) and to the children at 0-24months of life (postnatal). We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose-response; and estimated the population attributable risk. There was an association between prenatal exposure at 7-27days before the child's birth and asthma (adjusted OR=1.40; 1.05, 1.87), but no association with the negative control exposure (before pregnancy) (adjusted OR=0.99 (0.88, 1.12)). For postnatal exposure, the adjusted OR was 2.00 (1.71, 2.34), and for sibling analysis, it was 1.99 (1.00, 3.93). For postnatal exposure, the risk of asthma increased with the number of prescriptions. The observed effect of both exposures was lower among children with mothers of Pakistani ethnicity, but inconclusive (p>.25). The interaction between prenatal and postnatal exposures was also inconclusive (p=.287). The population attributable risk of postnatal exposure for asthma was 4.6% (0.1% for prenatal). We conclude that the associations between both late-pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect.
Highlights
There is evidence that children whose mothers received antibiotics during pregnancy, and children who were exposed to antibiotics in early life, are at higher risk of allergic diseases and asthma.1–4 it is not clear to what extent this association is due to bias or is a causal association
We investigated whether prenatal and postnatal exposure to antibiotics had a causal association with an increased risk of asthma in children recruited to the Born in Bradford birth cohort study in England (BiB cohort).[12]
Differences were observed between complete case analysis (CCA) and 151 children with missing data, especially in relation to lower proportion of children whose mothers were born in the UK, mothers not employed and higher maternal education
Summary
There is evidence that children whose mothers received antibiotics during pregnancy (prenatal exposure), and children who were exposed to antibiotics in early life (postnatal exposure), are at higher risk of allergic diseases and asthma.1–4 it is not clear to what extent this association is due to bias or is a causal association. We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose-response; and estimated the population attributable risk. Conclusions: We conclude that the associations between both late-pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect
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