Association of infant antibiotic exposure and risk of childhood asthma: A meta-analysis.
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ABSTRACT: Background
Infant antibiotic exposure may be associated with childhood asthma development.Objective
To examine and detail this association considering potential confounders.Study design
PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for publications from January 2011 to March 2021. Eligible studies were independently reviewed to extract data and assess quality. Random effect model was used to pool odds ratio (OR) and corresponding 95% confidence intervals (CIs).Results
A total of 52 studies were included. The association of infant antibiotic exposure and childhood asthma was statistically significant for overall analysis (OR, 1.37; 95% CI, 1.29-1.45) and for studies that addressed reverse causation (RC) and confounding by indication (CbI) (1.19; 95% CI, 1.11-1.28). Significance remained after stratification by adjustment for maternal antibiotic exposure, medical consultation, sex, smoke exposure, parental allergy, birth weight, and delivery mode. In detailed analyses, macrolides (OR, 1.56; 95% CI, 1.31-1.86), antibiotic course≥5 (OR, 1.79; 95% CI, 1.36-2.36), exposure within 1 week of birth (OR, 1.82; 95% CI, 1.34-2.47), asthma developed among 1-3 years (OR, 1.84; 95% CI, 1.63-2.08), short time lag between exposure and asthma onset (OR, 2.05; 95% CI, 1.91-2.20), persistent asthma (OR, 2.61; 95% CI, 1.49-4.59), and atopic asthma (OR, 2.14; 95% CI, 1.58-2.90) showed higher pooled estimates.Conclusion
Infant antibiotic exposure is associated with increased risk of childhood asthma considering confounding, and the association varied with different settings of exposure and outcomes. This highlights the need for prevention of asthma after early antibiotic exposure. Heterogeneity among studies called for caution when interpretation.
SUBMITTER: Zhang Z
PROVIDER: S-EPMC8661061 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity.MethodsInfant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score?>?95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps?+?subscapular (SST)) measurements] determined from ages 15-60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n?=?392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n?=?1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models.ResultsAntibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15-60 months of age was observed for any antibiotic exposure [OR(95% CI)?=?1.45(1.001, 2.14)] and exposure to ?3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [??=?0.15(0.01, 0.28)] but not girls [??=?-0.04(-0.19, 0.11)] (P interaction?=?0.026). Similarly, exposure to ?3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26)?cm] but not girls [0.57(-1.32, 2.45)?cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values?<?0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity.ConclusionsInfant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.
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Project description:This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.
| S-EPMC5579965 | biostudies-literature
Project description:BACKGROUND:Early antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the relationship between early life antibiotic exposure and childhood asthma, eczema and hay fever. METHODS:Pubmed and Embase were searched for studies published between 01-01-2008 and 01-08-2018, examining the effects of (1) prenatal antibiotic exposure and (2) infant antibiotic administration (during the first 2 years of life) on childhood asthma, eczema and hay fever from 0 to 18?years of age. These publications were assessed using the Newcastle Ottawa Scale (NOS) and analysed narratively. RESULTS:(1) Prenatal antibiotics: Asthma (12 studies): The majority of studies (9/12) reported significant relationships (range OR 1.13 (1.02-1.24) to OR 3.19 (1.52-6.67)). Three studies reported inconsistent findings. Eczema (3 studies): An overall significant effect was reported in one study and in two other studies only when prenatal antibiotic exposure was prolonged. (2) Infant antibiotics: Asthma (27 studies): 17/27 studies reported overall significant findings (range HR 1.12 (1.08-1.16) to OR 3.21 (1.89-5.45)). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. 10/27 studies reported inconsistent findings depending on certain conditions and types of analyses. Of 19 studies addressing reverse causation or confounding by indication at least somewhat, 11 reported overall significant effects. Eczema (15 studies): 6/15 studies reported overall significant effects; 9 studies had either insignificant or inconsistent findings. Hay fever (9 studies): 6/9 reported significant effects, and the other three insignificant or inconsistent findings. General: Multiple and broad-spectrum antibiotics were more strongly associated with allergies. The majority of studies scored a 6 or 7 out of 9 based on the NOS, indicating they generally had a medium risk of bias. Although most studies showed significant findings between early antibiotic exposure and asthma, the actual effects are still unclear as intrapartum antibiotic administration, familial factors and confounding by maternal and child infections were often not addressed. CONCLUSIONS:This review points to a moderate amount of evidence for a relationship between early life antibiotics (especially prenatal) and childhood asthma, some evidence for a relationship with hay fever and less convincing evidence for a relationship with eczema. More studies are still needed addressing intra-partum antibiotics, familial factors, and possible confounding by maternal and childhood infections. Children exposed to multiple, broad-spectrum antibiotics early in life appear to have a greater risk of allergies, especially asthma; these effects should be investigated further.
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