{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:45:41Z","timestamp":1793677541042,"version":"4.5.1"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Pediatr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n Importance<\/jats:title>\n Dental caries is a highly prevalent yet preventable disease affecting more than 40% of US children, with severe early childhood caries (S-ECC) leading to serious health and economic consequences. This randomized clinical trial addresses critical evidence gaps by evaluating 38% silver diamine fluoride (SDF) effectiveness for caries arrest in young US children with S-ECC to inform US Food and Drug Administration (FDA) regulatory approval.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the efficacy of 38% SDF vs placebo for arresting active cavitated dentin caries lesions in the primary dentition of US children with S-ECC.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This phase III, multisite, randomized, blind, placebo-controlled clinical trial with 2 parallel arms had a data collection period from October 2018 through April 2023. Analyses were completed in 2024. Three sites recruited from and treated children in a variety of settings: medical and dental clinics, and Head Start and city\/state-subsidized preschool programs. Enrolled participants included 830 generally healthy children aged 12 to 71 months with S-ECC and active cavitated lesions.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Children were randomized to receive either 38% SDF or placebo, applied at baseline and at 6 months. Clinical examinations were conducted at baseline, 3 months, 6 months, and 8 months.<\/jats:p>\n <\/jats:sec>\n \n OUTCOMES AND MEASURES<\/jats:title>\n The primary outcome was the proportion of arrested lesions at 6 months after 1 application. Secondary outcomes included arrest efficacy at 3 months and after 2 applications (8 months), and pain at or before 6 months and 8 months<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 830 enrolled children, 584 (70%) completed the study. Of those lost to follow-up (approximately 30%), 81 (9.8%) were lost due to COVID-19. Participants included 428 females (52%) and 402 males (48%) and were aged 1 to 6 years with high caries experience (mean [SD] decayed, missing, and filled teeth [dmft] (International Caries Detection and Assessment System \u22651), 11.36 [4.56]; range, 1-23). In intent-to-treat analyses, SDF arrested 57.5%, 54.0%, and 50.2% of lesions at 3 months, 6 months, and 8 months, respectively, vs placebo (18.8%, 22.5%, 17.4%, respectively). Differences (99.9% CI) in arrest rates were 38.7% (28.7%-48.6%), 31.5% (21.5%-41.6%), and 32.8% (22.3%-43.2%). There were no differences in pain. Averse events (AEs) were reported by 196 (47.3%) participants in the SDF group and 180 (43.3%) in the placebo group. Most AEs were mild to moderate in severity; 4 AEs (0.6%) were severe. Treatment-related AEs were similar between the 2 groups (SDF\u2009=\u200922.9%; placebo\u2009=\u200922.2%), as were discontinuation rates due to AEs (7.5% for both groups).<\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n In this randomized clinical trial, 38% SDF was significantly more effective than placebo for arresting dentin caries lesions in primary teeth in young children with S-ECC, providing a noninvasive treatment for young high-risk children and supporting its consideration for FDA drug approval.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03649659<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapediatrics.2026.2567","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:30:31Z","timestamp":1785166231000},"page":"942","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of Silver Diamine Fluoride on Young Children With Severe Early Childhood Caries"],"prefix":"10.1001","volume":"180","author":[{"given":"Margherita","family":"Fontana","sequence":"first","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Moursi","sequence":"additional","affiliation":[{"name":"New York University, New York City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Gonzalez-Cabezas","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Khera","sequence":"additional","affiliation":[{"name":"New York University, New York City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Levy","sequence":"additional","affiliation":[{"name":"University of Iowa, Iowa City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Eckert","sequence":"additional","affiliation":[{"name":"Indiana University, Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry P.","family":"Katz","sequence":"additional","affiliation":[{"name":"Indiana University, Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia M. A.","family":"Tenuta","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia S.","family":"Campos","sequence":"additional","affiliation":[{"name":"University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeta","family":"Karl","sequence":"additional","affiliation":[{"name":"Maquette University, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Boynton","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Chinn","sequence":"additional","affiliation":[{"name":"New York University, New York City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Sheen","sequence":"additional","affiliation":[{"name":"New York University, New York City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Kolker","sequence":"additional","affiliation":[{"name":"University of Iowa, Iowa City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Warren","sequence":"additional","affiliation":[{"name":"University of Iowa, Iowa City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Thorpe","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"poi260037r1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022-060417","article-title":"Maintaining and improving the oral health of young children.","volume":"151","author":"Krol","year":"2023","journal-title":"Pediatrics"},{"issue":"6","key":"poi260037r3","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1111\/ipd.12783","article-title":"The global prevalence of early childhood caries: a systematic review with meta-analysis using the WHO diagnostic criteria.","volume":"31","author":"Uribe","year":"2021","journal-title":"Int J Paediatr Dent"},{"issue":"10","key":"poi260037r4","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.2105\/AJPH.2010.200915","article-title":"Impact of poor oral health on children\u2019s school attendance and performance.","volume":"101","author":"Jackson","year":"2011","journal-title":"Am J Public Health"},{"issue":"4","key":"poi260037r6","first-page":"376","article-title":"Cost-benefit analysis of the age one dental visit for the privately insured.","volume":"37","author":"Kolstad","year":"2015","journal-title":"Pediatr Dent"},{"issue":"6","key":"poi260037r7","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1542\/peds.2014-2984","article-title":"Maintaining and improving the oral health of young children.","volume":"134","author":"Section On Oral Health","year":"2014","journal-title":"Pediatrics"},{"issue":"21","key":"poi260037r8","doi-asserted-by":"publisher","first-page":"2172","DOI":"10.1001\/jama.2021.20007","article-title":"Screening and interventions to prevent dental caries in children younger than 5 years: US Preventive Services Task Force recommendation statement.","volume":"326","author":"Davidson","year":"2021","journal-title":"JAMA"},{"issue":"11","key":"poi260037r9","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1177\/0810767","article-title":"Effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting dentin caries in Chinese pre-school children.","volume":"81","author":"Chu","year":"2002","journal-title":"J Dent Res"},{"issue":"8","key":"poi260037r10","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1177\/154405910508400807","article-title":"Efficacy of silver diamine fluoride for caries reduction in primary teeth and first permanent molars of schoolchildren: 36-month clinical trial.","volume":"84","author":"Llodra","year":"2005","journal-title":"J Dent Res"},{"issue":"10","key":"poi260037r14","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.adaj.2023.07.012","article-title":"Impact of the COVID-19 pandemic on oral health care use in the United States through December 2021.","volume":"154","author":"Dill","year":"2023","journal-title":"J Am Dent Assoc"},{"issue":"2","key":"poi260037r16","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/idj.12320","article-title":"Mechanisms of silver diamine fluoride on arresting caries: a literature review.","volume":"68","author":"Zhao","year":"2018","journal-title":"Int Dent J"},{"issue":"1","key":"poi260037r17","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1177\/0022034518800014","article-title":"Nonrestorative treatments for caries: systematic review and network meta-analysis.","volume":"98","author":"Urquhart","year":"2019","journal-title":"J Dent Res"},{"issue":"10","key":"poi260037r18","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.adaj.2018.07.002","article-title":"Evidence-based clinical practice guideline on nonrestorative treatments for carious lesions: a report from the American Dental Association.","volume":"149","author":"Slayton","year":"2018","journal-title":"J Am Dent Assoc"},{"issue":"11","key":"poi260037r19","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012718.pub2","article-title":"Topical silver diamine fluoride (SDF) for preventing and managing dental caries in children and adults.","volume":"11","author":"Worthington","year":"2024","journal-title":"Cochrane Database Syst Rev"},{"issue":"Spec Iss A","key":"poi260037r20","first-page":"2886","article-title":"Silver diamine fluoride efficacy RCT: parental satisfaction and acceptability.","volume":"103","author":"Khera","year":"2024","journal-title":"J Dent Res"},{"issue":"1","key":"poi260037r22","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1600-0528.2006.00253.x","article-title":"Dental Discomfort Questionnaire: assessment of dental discomfort and\/or pain in very young children.","volume":"34","author":"Versloot","year":"2006","journal-title":"Community Dent Oral Epidemiol"},{"issue":"3","key":"poi260037r23","doi-asserted-by":"publisher","first-page":"659","DOI":"10.2307\/2336502","article-title":"Discrete sequential boundaries for clinical trials.","volume":"70","author":"Lan","year":"1983","journal-title":"Biometrika"},{"issue":"1","key":"poi260037r24","first-page":"8","article-title":"A randomized clinical trial to assess caries arrest by using silver diamine fluoride in US children: interim findings.","volume":"46","author":"Fontana","year":"2024","journal-title":"Pediatr Dent"},{"issue":"4","key":"poi260037r25","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1001\/jamapediatrics.2023.6770","article-title":"Noninferiority of silver diamine fluoride vs sealants for reducing dental caries prevalence and incidence: a randomized clinical trial.","volume":"178","author":"Ruff","year":"2024","journal-title":"JAMA Pediatr"},{"issue":"2","key":"poi260037r26","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.55458","article-title":"Effect of silver diamine fluoride on caries arrest and prevention: the CariedAway school-based randomized clinical trial.","volume":"6","author":"Ruff","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"194","key":"poi260037r27","article-title":"Anticaries drug products for over-the-counter human use; final monograph.","volume":"60","author":"US Food and Drug Administration","year":"1995","journal-title":"Fed Regist"},{"key":"poi260037r29","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jdent.2015.05.006","article-title":"A randomized clinical trial on arresting dentine caries in preschool children by topical fluorides\u201318 month results.","volume":"44","author":"Duangthip","year":"2016","journal-title":"J Dent"},{"key":"poi260037r30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2020.103375","article-title":"A randomized clinical trial to arrest dentin caries in young children using silver diamine fluoride.","volume":"99","author":"Mabangkhru","year":"2020","journal-title":"J Dent"},{"issue":"3","key":"poi260037r31","doi-asserted-by":"publisher","first-page":"54","DOI":"10.22514\/jocpd.2023.015","article-title":"Emergency dental treatment among patients waitlisted for the operating room.","volume":"47","author":"Ashok","year":"2023","journal-title":"J Clin Pediatr Dent"},{"key":"poi260037r32","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jdent.2017.08.015","article-title":"Topical silver diamine fluoride for dental caries arrest in preschool children: a randomized controlled trial and microbiological analysis of caries associated microbes and resistance gene expression.","volume":"68","author":"Milgrom","year":"2018","journal-title":"J Dent"},{"issue":"2","key":"poi260037r33","first-page":"114","article-title":"Pharmacokinetics of 38 percent silver diamine fluoride in children.","volume":"44","author":"Ellenikiotis","year":"2022","journal-title":"Pediatr Dent"},{"issue":"3","key":"poi260037r34","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1177\/2380084416661474","article-title":"Clinical trials of silver diamine fluoride in arresting caries among children: a systematic review.","volume":"1","author":"Gao","year":"2016","journal-title":"JDR Clin Trans Res"},{"issue":"1","key":"poi260037r35","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1186\/s12903-024-04791-9","article-title":"An open-label, parallel-group, randomized clinical trial of different silver diamine fluoride application intervals to arrest dental caries.","volume":"24","author":"Schroth","year":"2024","journal-title":"BMC Oral Health"},{"issue":"6","key":"poi260037r36","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1159\/000477855","article-title":"Alternative caries management options for primary molars: 2.5-year outcomes of a randomised clinical trial.","volume":"51","author":"Santamar\u00eda","year":"2017","journal-title":"Caries Res"},{"issue":"4","key":"poi260037r37","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1159\/000508899","article-title":"How to intervene in the caries process: dentin caries in primary teeth.","volume":"54","author":"Santamar\u00eda","year":"2020","journal-title":"Caries Res"},{"issue":"11","key":"poi260037r38","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.jdent.2012.08.002","article-title":"Randomized clinical trial on effectiveness of silver diamine fluoride and glass ionomer in arresting dentine caries in preschool children.","volume":"40","author":"Zhi","year":"2012","journal-title":"J Dent"},{"key":"poi260037r5","first-page":"90","volume-title":"Policy on Early Childhood Caries (ECC): Consequences, and preventive strategies. The Reference Manual of Pediatric Dentistry","author":"American Academy of Pediatric Dentistry","year":"2021"},{"key":"poi260037r28","first-page":"38","volume-title":"Guide to Paediatric Clinical Research","author":"Neubauer","year":"2007"},{"key":"poi260037r2","unstructured":"US Department of Health and Human Services; National Institute of Dental and Craniofacial Research. Oral health in America: advances and challenges. Accessed May 29, 2026. https:\/\/www.nidcr.nih.gov\/research\/oralhealthinamerica"},{"key":"poi260037r11","unstructured":"World Health Organization. Executive summary. The selection and use of essential medicines 2021. Accessed May 29, 2026. https:\/\/iris.who.int\/server\/api\/core\/bitstreams\/5992aa26-a83a-4b49-a540-c09ce4c9889a\/content"},{"key":"poi260037r12","unstructured":"American Academy of Pediatric Dentistry. Policy on the use of silver diamine fluoride for pediatric dental patients. Accessed May 29, 2026. https:\/\/www.aapd.org\/media\/Policies_Guidelines\/P_SilverDiamine.pdf"},{"key":"poi260037r13","unstructured":"American Academy of Pediatrics. Guidance on the application of silver diamine fluoride (SDF) in the pediatric medical setting. Accessed May 29, 2026. https:\/\/www.aap.org\/en\/patient-care\/silver-diamine-fluoride-application-in-the-pediatric-medical-setting\/?srsltid=AfmBOopSm5WXYPjc99hps70K3cZjgS_0Iok1Ux8aV7ICkuOwz4bKWOq9"},{"key":"poi260037r15","unstructured":"Smiles for Life. Silver diamine fluoride. Accessed May 29, 2026. https:\/\/www.smilesforlifeoralhealth.org\/courses\/silver-diamine-fluoride\/"},{"key":"poi260037r21","unstructured":"International Caries Detection and Assessment System (ICDAS) Coordinating Committee. Criteria manual: International Caries Detection and Assessment System (ICDAS II). Accessed May 29, 2026. https:\/\/www.iccms-web.com\/uploads\/asset\/5ccb149905404942610729.pdf"}],"container-title":["JAMA Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/articlepdf\/2851913\/jamapediatrics_fontana_2026_oi_260037_1787759711.89084.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:01:10Z","timestamp":1788879670000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/fullarticle\/2851913"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapediatrics.2026.2567","relation":{},"ISSN":["2168-6203"],"issn-type":[{"value":"2168-6203","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}