Oct. 4, 2005 — Amoxicillin in infancy is associated with fluorosis of permanent teeth, according to the results of a study reported in the October issue of the Archives of Pediatric & Adolescent Medicine.

“It has been speculated that amoxicillin use could be associated with dental enamel defects,” write Liang Hong, DDS, MS, PhD, from the University of Iowa in Iowa City, and colleagues. “Dental fluorosis is one of the most common developmental enamel defects, which results from exposure to excessive fluoride during enamel formation. Its histopathologic characteristic is hypomineralization of tooth enamel and the clinical signs range from barely noticeable white flecks to confluent pits and undesirable dark brown stains.”

Participants in the Iowa Fluoride Study were followed up from birth to 32 months. Questionnaires administered every three to four months were used to collect data on fluoride intake and amoxicillin use. At approximately nine years of age, 579 participants were evaluated for fluorosis of early-erupting permanent teeth using the Fluorosis Risk Index.

By 12 months, 75% of subjects reported amoxicillin use; this increased to 91% by 32 months. At nine years, 24% of subjects had fluorosis on both maxillary central incisors. Amoxicillin use from three to six months was associated with significantly increased risk of fluorosis on the maxillary central incisors (risk ratio [RR] = 2.04; 95% confidence interval [CI], 1.49 – 2.78).

After adjustment for fluoride intake and otitis media, the association between risk of fluorosis and amoxicillin use during three to six months was still statistically significant (Mantel-Haenszel RR = 1.85; 95% CI, 1.20 – 2.78; multivariable logistic regression odds ratio = 2.50; 95% CI, 1.21 – 5.15). Fluoride intake was another significant predictor of subsequent fluorosis.

“The findings from this study suggest a link between amoxicillin use during infancy and developmental enamel defects of permanent teeth; however, further research is needed,” the authors write.

Study limitations include use of a convenience sample, subjects with relatively high socioeconomic status, use of self-administered questionnaires, few complete nonusers of amoxicillin, lack of data on fevers and fever-reducing medication, missing questionnaire data for many individuals during some reporting periods, study dropout by some participants, reporting by parents on only the illnesses with antibiotic treatment, and possible underestimation of any potential association between otitis media and fluorosis.

“While the results of this one study do not warrant recommendations to cease use of amoxicillin early in life, they do further highlight the need to use antibiotics judiciously, particularly during infancy,” the authors conclude. “Antibiotic use needs special caution and justification among infants and young children because they are in the critical stages of development and growth.”

The National Institutes of Health supported this study.

In an accompanying editorial, Paul S. Casamassimo, DDS, MS, from the Ohio State University College of Dentistry and Columbus Children’s Hospital, discusses the findings and limitations and concludes that the association between amoxicillin use and fluorosis needs further research, perhaps with well-designed animal studies.

“As a clinician, I would welcome an explanation that would help parents’ guilt, exonerate both medical and dental providers, and, most importantly, help me to prevent a needless occurrence of fluorosis in my patients,” Dr. Casamassimo writes. “Until that time, the best course of action may be what both the medical and dental communities have advocated for a long time — careful, thoughtful, and appropriate use of both fluoride and antibiotics.”

Arch Pediatr Adolesc Med. 2005;159:943-948, 995-996

Reviewed by Gary D. Vogin, MD

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