Risk of Permanent Dental Staining Following Exposure to Newer-Generation Tetracycline Derivatives in Children: A Systematic Review and Meta-Analysis

Background/Objectives: Historical concerns regarding permanent dental staining have restricted the use of tetracycline antibiotics in children younger than 8 years. However, newer-generation tetracycline derivatives, particularly doxycycline, differ pharmacologically from first-generation tetracyclines and may present a lower risk of discoloration. This systematic review and meta-analysis evaluated the risk of dental staining associated with newer-generation tetracycline derivatives. Methods: It was conducted according to the PRISMA 2020 statement and registered in PROSPERO. PubMed/MEDLINE, Scopus, and Embase were searched. Methodological quality was assessed, and the certainty of evidence using the GRADE approach. A random-effects meta-analysis of comparative studies was performed using the risk difference (RD) as the summary effect measure. Results: Six observational studies fulfilled the eligibility criteria. Three studies reported no cases of dental staining following doxycycline exposure, whereas one study identified parent-reported discoloration in 2 of 18 evaluated children (11.1%). Dental staining was reported in 2 of 41 children (4.9%) treated with minocycline and in 2 of 12 children (16.7%) with tigecycline. Meta-analysis of the three comparative studies demonstrated no significant increase in the risk of dental staining among exposed children compared with controls (RD = 0.007; 95% CI −0.015 to 0.028; I2 = 0%). Methodological quality ranged from moderate to high. According to GRADE, the certainty of evidence was low for doxycycline/minocycline and very low for tigecycline. Conclusions: Current evidence, although limited, suggests that short-course doxycycline is associated with little or no clinically relevant risk of permanent dental staining in children younger than 8 years. In contrast, the available evidence for minocycline and tigecycline remains insufficient to establish their dental safety.