Non-Cochrane · intervention · PM42650369
Risk of Permanent Dental Staining Following Exposure to Newer-Generation Tetracycline Derivatives in Children: A Systematic Review and Meta-Analysis.
Machuca-Portillo Carmen, Suárez-Marchena Cira, Chandler-Gutiérrez Lucy, et al. · Children (Basel, Switzerland) · 2026 · PubMed · doi:10.3390/children13081029
Findings
Population Children younger than 8 years
4 findings
| Newer-generation tetracycline derivatives (doxycycline, minocycline, tigecycline) | Children not exposed to tetracycline derivatives | Permanent dental staining Dental examination at mean age 9.8 to 11.6 years · Leave-one-out sensitivity analysis: Todd et al. excluded | RD 0.01 [-0.038, 0.057] GRADE not reported 2 studies · 184 participants |
| Newer-generation tetracycline derivatives (doxycycline, minocycline, tigecycline) | Children not exposed to tetracycline derivatives | Permanent dental staining Dental examination at mean age 9.8 to 11.6 years | RD 0.007 [-0.015, 0.028] Low Downgraded: imprecision 3 studies · 455 participants |
| Newer-generation tetracycline derivatives (doxycycline, minocycline, tigecycline) | Children not exposed to tetracycline derivatives | Permanent dental staining Dental examination at mean age 9.8 to 11.6 years · Leave-one-out sensitivity analysis: Cascio et al. excluded | RD 0.005 [-0.017, 0.028] GRADE not reported 2 studies · 332 participants |
| Newer-generation tetracycline derivatives (doxycycline, minocycline, tigecycline) | Children not exposed to tetracycline derivatives | Permanent dental staining Dental examination at mean age 9.8 to 11.6 years · Leave-one-out sensitivity analysis: Volovitz et al. excluded | RD 0.008 [-0.015, 0.031] GRADE not reported 2 studies · 394 participants |
Included primary studies 6
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Brown 2023 Doxycycline for the Treatment of Lyme Disease in Young Children. PMID:37820258 | 2023 | this review only | not stated | not extracted yet |
| Cascio 2004 No findings of dental defects in children treated with minocycline. PMID:15215140 | 2004 | this review only | Permanent dental staining | not extracted yet |
| Poyhonen 2017 Dental staining after doxycycline use in children. PMID:29091225 | 2017 | this review only | not stated | not extracted yet |
| Todd 2015 No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. PMID:25794784 | 2015 | this review only | Permanent dental staining | not extracted yet |
| Volovitz 2007 Absence of tooth staining with doxycycline treatment in young children. PMID:17325084 | 2007 | this review only | Permanent dental staining | not extracted yet |
| Zhu 2021 Tigecycline-Induced Tooth Discoloration in Children Younger than Eight Years. PMID:34228549 | 2021 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Children younger than 8 years of age | Children younger than 8 years at exposure (n=6 studies; 130 exposed and 325 controls in the meta-analysis) |
| Intervention | Exposure to newer-generation tetracycline derivatives: doxycycline, minocycline, tigecycline | Doxycycline (n=4 studies), minocycline (n=1), tigecycline (n=1) |
| Comparison | Children not exposed to tetracycline derivatives, when a comparison group was available | Unexposed controls in 3 studies; 3 studies without a comparison group |
| Outcomes | Permanent dental discoloration or other clinically detectable developmental dental alterations (e.g., enamel hypoplasia) | Permanent dental staining (clinical examination; parent report in 1 study); enamel hypoplasia assessed in 1 study |
| Study designs | Observational studies (retrospective or prospective cohort, case-control, cross-sectional, follow-up, case series); English; from January 2000; at least 10 participants | 4 retrospective cohort studies and 2 retrospective follow-up studies without controls |
| Timing | Not specified | Dental follow-up at mean age 7.2 to 14.2 years |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | No | no |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | Yes | Yes | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: Yes | RCT: N/A · NRSI: Partial Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: N/A · NRSI: Yes | RCT: N/A · NRSI: Yes | yes |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Critically Low | no |