Both prenatal and first year of life antibiotic exposure may increase the risk for developing type 1 diabetes in childhood.
The most common chronic disease in childhood is type 1 diabetes. It is believed that early-life risk factors, which include antibiotic treatment, can influence the risk of type 1 diabetes through alterations of the gut microbiome composition and subsequent effects on the immune system’s development. Children with type 1 diabetes are reported to have a lower microbial diversity of their gut flora and a marked decrease in diversity before type 1 diabetes onset than children without type 1 diabetes.
Furthermore, antibiotic exposure in early life delays microbiota maturation. This study conducted by Wernroth et al. was done in Sweden, due to the highest type 1 diabetes incidence rates in the world and a relatively low antibiotic prescription rate. This enables a large proportion of nonexposed children, with a sibling analysis and a description of the indications underlying the prescriptions. The researchers’ goal in this study was to assess the impact of prenatal or early childhood exposure to antibiotics on the risk of type 1 diabetes (up to age ten years). The researchers explored the association regarding type and number of prescriptions and interactions by mode of delivery, sex, birth year, and genetic predisposition to type 1 diabetes.
Study participants born between July 2005 and September 2013 were identified from the Medical Birth Register (MBR). Investigators started follow-up at 15 months when studying exposure in the 1st year of life, because undiagnosed type 1 diabetes often leads to infections and sometimes increased use of antibiotics. Exclusion criteria included children with at least one dispensed prescription of insulin, children who died or emigrated before age 6 months/15 months. Children were defined as having type 1 diabetes if they had at least one dispensed prescription of insulin following the first 15 months of life. Information on all administered systemic antibiotics was obtained from the Swedish Prescribed Drug Register from July 2005 to September 2013 in mothers during the pregnancy and September 2014 in children during their 1st year.
There was a total of 797,318 children selected in the study cohort. Of the child participants, 1,297 events of type 1 diabetes were recorded at a mean age of 4.2 (SD 2.0) years. In total, 164,098 (22.5%) children were considered exposed to antibiotics in prenatal life and 189,682 (23.8%) children in the 1st year of life. Eight hundred prescriptions were dispensed in the 1st year of life; a total of 69.9% (n 5 259) were prescribed for ear infections, 11.6% (n =43) for urinary tract infections, and 8.9% (n=33) for infections in the skin and soft tissue. For b-lactamase–sensitive penicillin prescriptions (n=207), 89.9% (n=186) were prescribed for ear infections and 7.2% (n=15) for upper respiratory tract.
Type 1 diabetes incidence rate was 39.9/ 100,000 person-years among children exposed to antibiotics in prenatal life and 34.0/100,000 person-years among the nonexposed. Exposure to any antibiotics in prenatal life was associated with an increased risk of type 1 diabetes (adjusted [a]HR 1.15 [95% CI 1.00–1.32].
The type 1 diabetes incidence rate was 44.3/100,000 person-years among children exposed to antibiotics in the 1st year of life and 39.0/100,000 person-years among the nonexposed. Exposure to antibiotics in the 1st year of life was associated with an increased risk of type 1 diabetes (HR 1.19 [95% CI 1.05–1.36]). If causal, the estimated number of children needed to be exposed to antibiotics to cause one additional case of type 1 diabetes before age nine years was 1,475 (95% CI 356–2,594). The sibling analysis provided an HR of 1.36 (95% CI 0.99–1.88). The researchers found evidence supporting an interaction between antibiotic exposure and mode of delivery (P for interaction= 0.016), but not for sex (P =0.54), genetic predisposition (P= 0.56), or birth year (P = 0.91)). The HR was 1.10 (95% CI 0.96–1.28) in vaginally delivered children and 1.60 (95% CI 1.22– 2.08) in children delivered by cesarean section. Exposure to narrow-spectrum antibiotics was associated with an increased risk of type 1 diabetes in the analysis of the total cohort. Exposure to antibiotics used to treat acute otitis media and other respiratory tract infections was associated with an increased risk in both the total (HR 1.19 [95% CI 1.04–1.36]) and sibling analysis (HR 1.43 [95% CI 1.02– 2.01]). b-Lactamase–sensitive penicillin was dispensed to 72% (n =136,426) of the exposed children and was associated with an increased risk of type 1 diabetes (HR 1.23 [95% CI 1.06–1.42]).
Researchers discovered that antibiotic prescriptions in the 1st year of life were associated with an increased risk of type 1 diabetes before age 10. The observed association seems to be driven by exposure to antibiotics used for otitis media and other respiratory tract infections. This association remained statistically significant in the sibling analysis. Furthermore, antibiotics were associated with an increased risk of diabetes among children delivered by cesarean section, but the association was less clear for children delivered vaginally. In addition, the researchers found some evidence that prenatal exposure to any antibiotics and to antibiotics used to treat urinary tract or skin and soft tissue infection was associated with an increased risk of type 1 diabetes.
- Dispensed prescription of antibiotics in the 1st year of life is associated with the risk of type 1 diabetes before age 10.
- There was a distinct association by treatment used for otitis media and other respiratory tract infections.
- Children delivered by cesarean section were more prominently at an increased risk of type 1 diabetes before age 10.
Chardae Whitner, 2020 PharmD. Candidate, Lake Erie College of Osteopathic Medicine