Infancy Antibiotic Exposure And Long-Term Risk Of Allergic Diseases Based On Cohort Studies:A Meta-Analysis

Objective:To systematically evaluate the effect of infant antibiotic exposure on the long-term risk of allergic diseases based on cohort studies.Methods:Search Chinese and English databases such as China Vip Science and Technology Journal Database(VIP),China Knowledge Network Database(CNKI),Wanfang Database,Embase,Pub Med,and Web of Science to search for cohort studies on antibiotic exposure in infancy and the risk of long-term allergic diseases.Detailed data extraction and bias risk assessment were performed on the included studies.Finally,Revman5.4 software was used for meta-analysis,Stata15.1 software was used to draw the funnel plot and Egger’s test was used to detect publication bias.Results:A total of 23 articles were included,including 17 articles on asthma,15 on atopic dermatitis,8 on allergic rhinitis,and 5 on food allergy.Antibiotic exposure in infancy increases the risk of long-term asthma(OR=1.72,95%CI:1.49～2.00,P<0.001),but the results of this study are highly heterogeneous(P=0.0001,I~2=65%).The results of subgroup analysis showed that when the frequency of antibiotic exposure in infancy was 1～2times,3～4 times,and more,the risk of long-term asthma was 1.16 times(OR=1.16,95%CI:1.01～1.33,P=0.040),1.41 times(OR=1.41,95%CI:1.19～1.68,P<0.001),and 2.73 times(OR=2.73,95%CI:2.32～3.22,P<0.001),respectively,compared to the non antibiotic exposure group.The timing of antibiotic exposure for≤6 months(OR=1.87,95%CI:1.19～2.96,P=0.007)and>6 months(OR=2.00,95%CI:1.35～2.96,P=0.041)can increase their long-term risk of asthma.The study area was Europe(OR=1.41,95%CI:1.15～1.72,P<0.001)and North America(OR=1.88,95%CI:1.81～1.96,P<0.001).Antibiotic exposure during infancy increased the risk of long-term asthma;There was no significant difference between infant antibiotic exposure and long-term asthma risk in Asia and Oceania(P>0.05).Antibiotic exposure in infancy increases the risk of long-term atopic dermatitis(OR=1.51,95%CI:1.49～1.54,P<0.001).Subgroup analysis showed that when the frequency of antibiotic exposure in infancy was 3～4 times and more,the risk of long-term atopic dermatitis was 1.33 times(OR=1.33,95%CI:1.03～1.71,P=0.030)and1.28 times(OR=1.28,95%CI:1.11～1.47,P<0.001),respectively,compared to the non antibiotic exposure group.There was no significant difference between the frequency of antibiotic exposure in infancy and the risk of long-term atopic dermatitis(P=0.470).The timing of antibiotic exposure for≤6 months(OR=1.33,95%CI:1.18～1.49,P<0.001)and>6 months(OR=1.58,95%CI:1.21～2.05,P<0.001)can increase the risk of long-term atopic dermatitis.The study area is Asia(OR=1.41,95%CI:1.11～1.79,P=0.006),Europe(OR=1.42,95%CI:1.25～1.60,P<0.001),North America(OR=1.51,95%CI:1.32～1.71,P<0.001),and Oceania(OR=1.68,95%CI:1.26～2.24,P<0.001).Antibiotic exposure during infancy can increase the risk of long-term atopic dermatitis.Antibiotic exposure in infancy increases the risk of long-term allergic rhinitis(OR=1.25,95%CI:1.14～1.36,P<0.001).Subgroup analysis based on the frequency of antibiotic exposure showed that when the frequency of antibiotic exposure in infancy was 1～2 and 3～4 times,the risk of long-term allergic rhinitis was 1.07 times(OR=1.07,95%CI:1.00～1.15,P=0.040)and 1.18 times(OR=1.18,95%CI:1.06～1.31,P<0.001),respectively,compared to the non antibiotic exposure group;There was no statistically significant difference in the risk of anaphylactic rhinitis between infants exposed to antibiotics more than 4 times and their long-term counterparts(P=0.250).A subgroup analysis of different study areas showed that infant antibiotic exposure in Asia(OR=1.23,95%CI:1.06～1.42,P=0.006)and North America(OR=1.40,95%CI:1.21～1.62,P<0.001)increased the risk of long-term allergic rhinitis;There was no significant difference in the risk of infant antibiotic exposure and long-term allergic rhinitis in Europe(P=0.440).Antibiotic exposure in infancy increases the risk of long-term food allergy(OR=1.30,95%CI:1.11～1.54,P=0.002).Conclusions:1.Antibiotic exposure in infancy increases the risk of long-term asthma,atopic dermatitis,allergic rhinitis,and food allergies.2.When the frequency of antibiotic exposure in infancy is 1～2 times,3～4times,or more than 4 times,it will increase the risk of long-term asthma;Exposure frequency of 3～4 times or more will increase the risk of long-term atopic dermatitis;Exposure frequency of 1～2 times and 3～4 times will increase the risk of long-term allergic rhinitis.3.The timing of antibiotic exposure in infancy at≤6 months and>6months can both increase the risk of long-term asthma and atopic dermatitis.However,there is heterogeneity in this study,and further research evidence and sample size are needed to confirm it.