Strengths and Limitations
The major strengths of this study were its large sample size, long follow-up period, and its population-based sample, which was representative of Taiwanese residents. The diagnosis of AD in our study was given by board-certified pediatricians or dermatologists, and therefore recall bias and detection bias was likely minimal. In addition, we were able to adjust for some covariates, including gestational infections and maternal acetaminophen use during pregnancy, which were not addressed in previous studies. Our analysis of the effect of prenatal antibiotic exposure on AD diagnosed after 1 year of age and its relationship with infant antibiotic/acetaminophen use may have partly taken confounding by indication (increased infection or fever that led to increases in both AD and antibiotic/acetaminophen exposure) into account in our study, which has not been mentioned previously.
The major limitation of our study is that some covariates, which may influence the risk of AD due to maternal antibiotic use during pregnancy, such as maternal smoking, patients’ consulting behavior or healthcare utilization patterns, dietary habits, environment exposures (e.g., climate conditions, air pollution, etc.) and some unmeasured factors shared by families,2,24,32 were not adjusted for in our analysis. It is also possible that mild cases of AD who did not seek medical help were not identified in our analysis. However, the Taiwan NHI is an easily accessible, low-cost medical insurance system. Finally, we were not able to analyze the effect of prenatal antibiotics on AD by types of antibiotic use, which may have influenced the risk in patients with asthma.10,11 However, to our knowledge, this effect did not exist when investigating the influence of antibiotic exposure during pregnancy on offspring AD.9,20,24,33
In conclusion, this cohort study revealed that maternal antibiotic use during pregnancy was associated with a slightly increased risk of childhood AD. This association was similar among trimesters during pregnancy and an apparent dose-response pattern was observed, although the association may have been partly confounded by postnatal acetaminophen use in AD diagnosed after 1 year of age. Further research should be conducted to investigate this confounder in a prospectively designed study and to explore the timing before or after pregnancy in order to elucidate whether or not this association was specific to during pregnancy. Nevertheless, we believe that antibiotics should be used prudently during pregnancy and that this potential effect should be taken into account.