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Early Antibiotics Usage During Infancy is Associated With High Risk of Celiac Disease Autoimmunity: A
Tal Cozacov1, Michal Yackobovitch-Gavan2, Anat Guz-Mark1,3
1From the Institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Medical Center of Israel, Petach-Tikva.
Insights
Early antibiotic exposure in infants is linked to increased celiac disease autoimmunity (CDA) risk, especially with more prescriptions. This association is more pronounced in females, highlighting potential environmental triggers for this autoimmune condition.
Area of Science:
- Pediatric autoimmune disorders
- Microbiome and immunology
- Environmental health impacts
Background:
- Celiac disease (CD) arises from genetic predisposition and environmental factors.
- Early-life antibiotic use is a potential environmental influence on CD development.
Purpose of the Study:
- To investigate the association between early-life antibiotic exposure and celiac disease autoimmunity (CDA).
- To explore dose-response relationships and effect modifiers in this association.
Main Methods:
- Retrospective cohort study of over 1.8 million children born 1995-2022 in Israel.
- Antibiotic exposure assessed by type, timing, and count in the first year of life.
- CDA diagnosed via serology; Cox models adjusted for sex, ethnicity, and socioeconomic position (SEP).
Main Results:
- 56% of children received antibiotics in their first year.
- Antibiotic exposure in the first year correlated with a 9% increased CDA risk (HR 1.090).
- A dose-response was observed, with ≥10 prescriptions increasing risk significantly (HR 1.426); stronger in females and low SEP.
Conclusions:
- First-year antibiotic exposure is associated with elevated CDA risk.
- Increased prescription numbers amplify this risk, particularly in females.
- Early antibiotic use represents a significant environmental factor in CDA pathogenesis.
Background:
Celiac disease develops in genetically predisposed individuals, influenced by environmental factors. This study assessed the association between early-life antibiotic exposure and celiac disease autoimmunity (CDA).
Methods:
This retrospective cohort study used data from Clalit Health Services, the largest Israeli Health Maintenance Organization, on children born between 1995 and 2022. Antibiotic exposure was assessed by type, timing and prescription count during the first year of life. CDA was defined by 2 positive serology tests, and adjusted hazard ratios (HR) were calculated using Cox models, accounting for sex, ethnicity and socioeconomic position (SEP).
Results:
A total of 1,860,533 patient records were analyzed, with 8546 (0.5%) diagnosed with CDA [median (interquartile range): age 6.9 (4.4,10.8)]. Antibiotic exposure during the first year of life was observed in 56% of the cohort, with higher rates among males, low SEP and Arab ethnicity. Adjusted HRs for CDA were 1.090 (95% confidence interval: 1.041-1.141, P < 0.001) for the exposure to antibiotics during the first year of life, and 0.893 (95% confidence interval: 0.869-0.918, P < 0.001) for the age of first exposure. A dose-response relationship was observed as prescription numbers increased (HR = 1.076, P = 0.003 for 1-3 prescriptions, HR = 1.426, P < 0.001 for ≥10 prescriptions). Stronger associations between exposure indices to antibiotics and CDA were observed in females and low SEP.
Conclusions:
Antibiotic exposure during the first year of life is associated with a higher risk of developing CDA, particularly with increasing prescription numbers, and mainly in females.
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