Table 1 ∣.
Clinical studies evaluating antibiotic exposure and risk of diabetes and childhood obesity
| Study | Antibiotic exposure timing |
Date (location) |
Study design | Antibiotic data source |
Disease diagnosis | Key findingsa |
|---|---|---|---|---|---|---|
| Type 1 diabetes mellitus | ||||||
| Wernroth et al.50 | Prenatal to 12 months | 2020 (Sweden) | Cohort | Prescriber registry (ATC code) | Database diagnostic code for T1DM (ICD-10: E10) | Increased risk of T1DM before age of 10 years: ≤1 year: aHR 1.19 (1.05–1.36): 44.3/100,000 person-years among exposed children versus 39.0/100,000 person-years among non-exposed children: ≤6 months: aHR 1.26 (1.04 – 1.5) Modified by mode of delivery |
| Clausen et al.51 | Birth to 24 months | 2016 (Denmark) | Cohort | Prescriber registry (ATC code) | Database diagnostic code for T1DM | Increased risk after exposure to broad-spectrum antibiotics HR 1.13 (1.02–1.25) Modified by mode of delivery |
| Hviid and Svanström54 | 12 months to year 2005 | 2009 (Denmark) | Cohort | Prescriber registry (ATC code) | Database diagnostic code for T1DM (ICD-10: E10) | Differences not significant RR 1.16 (0.91–1.50) |
| Tapia et al.55 | Prenatal to 18 months | 2018 (Norway) | Cohort | Repeated questionnaires | Database diagnostic code for T1DM (ICD-10: E10) | Differences not significant Prenatal: aHR 1.09 (0.85–1.35) In early life: aHR 1.11 (0.81–1.50) |
| Childhood obesity | ||||||
| Trasande et al.90 | <6 months 6–14 months 14–23 months | 2013 (UK) | Longitudinal birth cohort | Repeated questionnaires | Measured during five study visits | Increased body mass at 10–38 months, after antibiotic exposure during first 6 months of life aOR 1.22 (P = 0.029) |
| Bailey et al.91 | 0–23 months 24–59 months | 2014 (Philadelphia, USA) | Cohort | Outpatient prescriptions and patient-reported medications | Measured during recurring study visits | Cumulative exposure to antibiotics was associated with development of obesity ≥4 courses: RR 1.11 (1.02–1.21) Stronger effect for broad-spectrum antibiotics: RR 1.16 (1.03–1.19) |
| Azad et al.92 | 0–5 years | 2014 (Canada) | Longitudinal birth cohort | Prescription records | Measured at 9 and 12 years of age | Increased risk of overweight and central adiposity in preadolescent boys, but not girls Age 9 years: aOR 2.19 (1.06–4.54) Age 12 years: aOR 5.35 (1.94–14.72) |
| Murphy et al.93 | 0–12 months | 2014 (18 countries/regions) | Cross-sectional | Repeated questionnaires | Self-reported or measured | With antibiotic exposure, increased childhood BMI in boys aged 5–8 years, but not girls: BMI + 0.107 kg/m2 (P < 0.0001) |
| Aversa et al.94 | 0–6 months 6–12 months 12–24 months | 2021 (Minnesota, USA) | Population-based cohort | Medical records linkage system | Medical records linkage system | Increased risk for overweight and obesity, depending on number, type and timing of antibiotic exposure Girls with overweight: HR 1.19 (1.09–1.30) Girls with obesity: HR 1.13 (0.99–1.29) Boys with overweight: HR 1.22 (1.12–1.34) Boys with obesity: HR 1.12 (1.08–1.39) |
| Mueller et al.48 | Prenatal | 2014 (New York, USA) | Cohort | Questionnaire | Measured at age 7 years | Exposure to antibiotics in the second or third trimester associated with higher risk of childhood obesity aRR 1.77 (1.25–2.51) |
| Mbakwa et al.95 | Birth to 10 years | 2016 (Netherlands) | Longitudinal cohort | Repeated questionnaires | Self-reported over 7 time points | Increased height and weight in children exposed to: One course during first 6 months of life; adjusted β 0.24 and 0.23 Two or more courses during second year of life; adjusted β 0.34 and 0.29 |
| Type 2 diabetes mellitus in adults | ||||||
| Mikkelsen et al.87 | Adulthood | 2015 (Denmark) | Case–control | Prescriber registry (ATC code) | First-ever prescription of a non-insulin glucose-lowering agent (ATC A10B) | Dose-dependent relationship with number of antibiotic courses: For 2–4, OR 1.21 (1.19–1.24) For ≥5, OR 1.53 (1.50–1.55) |
| Davis et al.88 | Adulthood | 2019 (USA) | Retrospective cohort | Outpatient antibiotic prescriptions >6 months prior to diabetes diagnosis | Two or more ICD-9 codes for diabetes or two or more prescriptions of diabetes medications, other than metformin | Increased risk after exposure to more than one prescription of antibiotics HR = 1.13 (1.01–1.25) |
| Boursi et al.89 | Adulthood | 2015 (UK) | Nested case–control | Antibiotic prescriptions >1 year before diabetes diagnosis | At least one Read code (general practitioners) | No significant difference after a single antibiotic course Dose-dependent relationship for number of antibiotic courses (two or more), with OR depending on antibiotic type |
aHR, adjusted hazard ratio; aOR, adjusted odds ratio; aRR, adjusted relative risk; ATC, Anatomical Therapeutic Chemical classification system; ICD, International Classification of Disease; RR, rate ratio; T1DM, type 1 diabetes mellitus.
a
Value ranges in parentheses are 95% confidence intervals; adjusted β are adjusted generalized estimating equation estimates in relation to z-scores.