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ETIOLOGY/OTHER ARTICLE ANALYSIS &EVALUATION ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION Associations between fluorosis of permanent incisors and fluoride intake from infant formula, other dietary sources and dentifrice during early childhood. Levy SM, Broffitt B, Marshall TA, Eichenberger-Gilmore JM, Warren JJ. J Am Dent Assoc 2010;141(10):1190-1201. REVIEWER Jayanth Kumar, DDS, MPH PURPOSE/QUESTION To describe associations between dental fluorosis and fluoride intakes, with an emphasis on intake from fluoride in infant formula SOURCE OF FUNDING National Institute for Dental and Craniofacial Research grants RO1- DE09551 and RO1-DE12101 and National Center for Research Resources grant M01-RR00059 TYPE OF STUDY/DESIGN Cohort study LEVEL OF EVIDENCE Level 2: Limited-quality, patient- oriented evidence STRENGTH OF RECOMMENDATION GRADE Not applicable J Evid Base Dent Pract 2012;12:119-120 1532-3382/$36.00 Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jebdp.2012.03.014 Higher Fluoride Intakes in Early Childhood May Increase the Risk of Milder Forms of Dental Fluorosis SUMMARY Subjects This analysis is based on 560 children examined when the participants of the Iowa Fluoride Study were about 9 years of age (range, 7.7-12.0 years). Fluoride intake history gathered through questionnaires when the partici- pants were aged 3 to 9 months and 16 to 36 months was compared among 178 children who had 2 or more maxillary incisors affected with dental fluorosis and 382 who had no maxillary incisor fluorosis. Using the Fluoro- sis Risk Index (FRI) to assess for dental fluorosis, most fluorosis detected was mild (FRI score = 2, n = 173, 97%); only 5 participants had more in- volved fluorosis (FRI score = 3). Key Risk/Study Factor Higher fluoride intake from infant formula, beverages, and toothpaste in- gestion was identified as a risk factor for dental fluorosis. Main Outcome Measure Dental fluorosis on maxillary incisor teeth. Main Results The overall relative risk (RR) associated with being in the upper quartile of 3- to 9-month-olds’ Area Under the Curve fluoride intake from powdered formula was 1.40 (P = .02, 95% confidence interval [CI] = 1.06-1.84). Higher intake from infant formula alone among children with lower fluo- ride intake from beverages and toothpaste resulted in a higher prevalence (34.7% vs 20.7%, RR = 1.68, 95% CI = 1.11-2.54); however, this effect ap- pears to be masked when there is higher fluoride intake from beverages and toothpaste (33.3% vs 35.3%, RR 0.94 [95% CI, 0.31-2.91]). Conclusions Data support the hypothesis that high fluoride intakes from reconstituted powdered formula, beverages, and toothpaste ingestion are associated with milder forms of dental fluorosis of permanent maxillary incisors. COMMENTARY AND ANALYSIS Dental fluorosis prevalence in children in the United States has increased, as evidenced by a higher prevalence in the 1999 to 2004 survey than that in 1986 to 1987. The prevalence of dental fluorosis was 22.6% and 40.7% among adolescents aged 12 to 15 years examined in the 1986 to 1987 and 1999 to 2004 surveys, respectively. 1 This increase in the occurrence of dental fluorosis suggests that the potential for exposure to excessive amounts of fluoride has increased. Since the introduction of water fluoridation, other sources of fluoride, such as supplements, fluoride dentifrices, rinses, gels, and carbonated beverages are available. Because fluoridated water is

Higher Fluoride Intakes in Early Childhood May Increase the Risk of Milder Forms of Dental Fluorosis

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ETIOLOGY/OTHER

ARTICLE ANALYSIS & EVALUATION

ARTICLE TITLE ANDBIBLIOGRAPHICINFORMATION

Associations between fluorosis ofpermanent incisors and fluorideintake from infant formula, otherdietary sources and dentifrice duringearly childhood.

Levy SM, Broffitt B, Marshall TA,Eichenberger-Gilmore JM, Warren JJ.

J Am Dent Assoc 2010;141(10):1190-1201.

REVIEWER

Jayanth Kumar, DDS, MPH

PURPOSE/QUESTION

To describe associations betweendental fluorosis and fluoride intakes,with an emphasis on intake fromfluoride in infant formula

SOURCE OF FUNDING

National Institute for Dental andCraniofacial Research grants RO1-DE09551 and RO1-DE12101 andNational Center for ResearchResources grant M01-RR00059

TYPE OF STUDY/DESIGN

Cohort study

LEVEL OF EVIDENCE

Level 2: Limited-quality, patient-oriented evidence

STRENGTH OFRECOMMENDATION GRADE

Not applicable

J Evid Base Dent Pract 2012;12:119-1201532-3382/$36.00� 2012 Elsevier Inc. All rights reserved.doi:10.1016/j.jebdp.2012.03.014

Higher Fluoride Intakes in Early ChildhoodMay Increase the Risk of Milder Forms ofDental Fluorosis

SUMMARY

SubjectsThis analysis is based on 560 children examined when the participants ofthe Iowa Fluoride Study were about 9 years of age (range, 7.7-12.0 years).Fluoride intake history gathered through questionnaires when the partici-pants were aged 3 to 9 months and 16 to 36 months was compared among178 children who had 2 or more maxillary incisors affected with dentalfluorosis and 382 who had no maxillary incisor fluorosis. Using the Fluoro-sis Risk Index (FRI) to assess for dental fluorosis, most fluorosis detectedwas mild (FRI score = 2, n = 173, 97%); only 5 participants had more in-volved fluorosis (FRI score = 3).

Key Risk/Study FactorHigher fluoride intake from infant formula, beverages, and toothpaste in-gestion was identified as a risk factor for dental fluorosis.

Main Outcome MeasureDental fluorosis on maxillary incisor teeth.

Main ResultsThe overall relative risk (RR) associated with being in the upper quartile of3- to 9-month-olds’ Area Under the Curve fluoride intake from powderedformula was 1.40 (P = .02, 95% confidence interval [CI] = 1.06-1.84).Higher intake from infant formula alone among children with lower fluo-ride intake from beverages and toothpaste resulted in a higher prevalence(34.7% vs 20.7%, RR = 1.68, 95% CI = 1.11-2.54); however, this effect ap-pears to be masked when there is higher fluoride intake from beveragesand toothpaste (33.3% vs 35.3%, RR 0.94 [95% CI, 0.31-2.91]).

ConclusionsData support the hypothesis that high fluoride intakes from reconstitutedpowdered formula, beverages, and toothpaste ingestion are associated withmilder forms of dental fluorosis of permanent maxillary incisors.

COMMENTARYANDANALYSIS

Dental fluorosis prevalence in children in theUnited States has increased, asevidenced by a higher prevalence in the 1999 to 2004 survey than that in1986 to 1987. The prevalence of dental fluorosis was 22.6% and 40.7%among adolescents aged 12 to 15 years examined in the 1986 to 1987 and1999 to 2004 surveys, respectively.1 This increase in the occurrence of dentalfluorosis suggests that the potential for exposure to excessive amounts offluoride has increased. Since the introduction of water fluoridation, othersources of fluoride, such as supplements, fluoride dentifrices, rinses, gels,and carbonated beverages are available. Because fluoridated water is

JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE

frequently used to prepare infant formula and because in-fants are smaller than adults, the relative fluoride intakecan be higher for infants than adults, although still verysmall. A 2006 National Research Council report estimatedthat some US infants could exceed the tolerable upper in-take levels that were established by the Institute of Medi-cine in 1997 (0.7 mg per day for infants from birth to 6months of age and 0.9 mg per day for infants aged 7 to12 months).2

Levy et al explored the risk of dental fluorosis associ-ated with the consumption of beverages and formulareconstituted with fluoridated water during infancy,and toothpaste ingested during early childhood. Chil-dren with dental fluorosis of the maxillary incisors hadhigher intake of fluoride from beverages (including in-fant formula) throughout early childhood (up to 36months) than did children without dental fluorosis.Higher fluoride intake could result from fluoride con-tent of infant formula itself and/or higher fluoride con-tent in water and beverages. Fluoride ingestion fromtoothpaste during the period of 16 to 36 months ofage also contributed to the risk of fluorosis. The typeof dental fluorosis observed in the study was primarilymild, which manifests as white striations or snow cappingof cusps and incisal edges. Only 5 participants had morepronounced fluorosis (that is, staining or pitting of theenamel).

Given the complexity of calculating average exposureover a period of time from indirect periodic measure-ments of intake through questionnaires during a timewhen children are being exposed to varying sources, it isdifficult to isolate the risk associated with a single source,such as infant formula. Furthermore, caution should beexercised when generalizing the results of this study tothe population at large because not all children were avail-able for follow-up from the original cohort of Iowa Fluo-ride Study, small sample sizes in a stratified analysisresulted in wide confidence intervals indicating the poten-tial for unstable rates, and the possibility of bias arisingfrom the case-control analysis of a cohort study.

Notwithstanding the limitations, the results are largelyconsistent with a systematic review that concluded infantformula consumption was associated with a higher preva-lence of dental fluorosis in the permanent dentition (sum-mary odds ratio [OR] 1.8, 95%CI 1.4-2.3).3However, therewas significant heterogeneity among studies, and evidenceof publication bias was apparent. A meta-regression analy-sis indicated that the OR associating infant formula withdental fluorosis increased by 5% for each 0.1 mg/L in-crease in the reported levels of fluoride in the water supply(OR 1.05, 95% CI 1.02-1.09). The authors concluded thatthe evidence that the fluoride in the infant formula causeddental fluorosis was weak.

Health care providers typically advocate exclusivebreastfeeding as the optimal form of nutrition until thechild is 6 months. But for infants who are exclusively

120

fed infant formula, it is appropriate to give the followingguidance4:

� Continue use of liquid or powdered concentrate infantformulas reconstituted with optimally fluoridateddrinking water.

� If the potential risk for dental fluorosis is a concern, useready-to-feed formula or liquid or powdered concen-trate formula reconstituted with water that is eitherfluoride-free or has low concentrations of fluoride.

The policy of adding fluoride to water for the preventionof caries is intended to maintain the lowest level capable ofproducing the desired anticaries effect. Considering theavailability of fluoride from many sources, the U.S.Department of Health and Human Services has proposedthat the recommended level of fluoride in drinking waterbe set at 0.7mgoffluoride per liter of water.5 This newguid-ance once finalized would replace the current recommen-ded range of 0.7 to 1.2 mg, thus lowering the fluorideconcentration of drinking water in many communities.When combined with the recommendation to reduce fluo-ride ingestion from toothpastes by using a smear or pea-sized amount under parental supervision during the devel-opment of teeth, this should substantially lower fluoride in-take. A question remains, however, as to how this attempt tolower thefluoride intakewill affect theoccurrenceofdentalcaries, which has been in decline over the past 5 decades.

REFERENCES

1. Beltr�an-Aguilar ED, Barker L, Dye BA. Prevalence and severity of den-tal fluorosis in the United States, 1999-2004. NCHS Data Brief2010;(53):1-8.

2. National Research Council, Committee on Fluoride in DrinkingWater. Effects of fluoride on teeth. In: National Research Council,Committee on Fluoride inDrinkingWater. Fluoride in drinking water:a scientific review of EPA’s standards. Washington, DC: National Acad-emies Press; 2006. p. 103-30.

3. Hujoel PP, Zina LG, Moimaz SA, Cunha-Cruz J. Infant formula andenamel fluorosis: a systematic review. J Am Dent Assoc2009;140(7):841-54.

4. Berg J, Gerweck C, Hujoel PP, King R, Krol DM, Kumar J, et al.Evidence-based clinical recommendations regarding fluoride intakefrom reconstituted infant formula and enamel fluorosis. A report ofthe American Dental Association Council on Scientific Affairs. J AmDent Assoc 2011;142(1):79-87.

5. U.S. Department of Health and Human Services. News Release.HHS and EPA announce new scientific assessments and actionson fluoride. Agencies working together to maintain benefits of pre-venting tooth decay while preventing excessive exposure. Availableat: http://www.hhs.gov/news/press/2011pres/01/20110107a.html.Accessed February 3, 2012.

REVIEWER

Jayanth Kumar, DDS, MPHActing Director, Bureau of Dental Health, New York StateDepartment of Health, Associate Professor, School of PublicHealth, University at Albany, 542, ESP Tower,Albany, NY [email protected]

June 2012