{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:12:07Z","timestamp":1765609927302,"version":"build-2065373602"},"reference-count":52,"publisher":"BMJ","issue":"7","funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,6,13]]},"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potentially low-cost, passive means of combating thiamine deficiency; however, both the dose of thiamine required to optimise milk thiamine concentrations as well as usual salt intake of lactating women are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>In this community-based randomised controlled trial, 320 lactating women from Kampong Thom, Cambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10\u2009mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. The primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. At 2, 12 and 24 weeks, we will collect sociodemographic, nutrition and health information, a battery of cognitive assessments, maternal (2 and 24 weeks) and infant (24 weeks only) venous blood samples (biomarkers: ThDP and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). All participants and their families will consume study-provided salt <jats:italic>ad libitum<\/jats:italic> throughout the trial, and we will measure salt disappearance each fortnight. Repeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. Parameters of E<jats:sub>max<\/jats:sub> dose\u2013response curves will be estimated using non-linear least squares models with both \u2018intention to treat\u2019 and a secondary \u2018per-protocol\u2019 (capsule compliance \u226580%) analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Ethical approval was obtained in Cambodia (National Ethics Committee for Health Research 112\/250NECHR), Canada (Mount Saint Vincent University Research Ethics Board 2017\u2013141) and the USA (University of Oregon Institutional Review Board 07052018.008). Results will be shared with participants\u2019 communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT03616288\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial results\">NCT03616288<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-029255","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T06:25:46Z","timestamp":1562739946000},"page":"e029255","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct03616288","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"nct03616288","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03616288","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03616288","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8315-8927","authenticated-orcid":false,"given":"Kyly C","family":"Whitfield","sequence":"first","affiliation":[{"name":"Mount Saint Vincent University, Halifax, Nova Scotia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hou","family":"Kroeun","sequence":"additional","affiliation":[{"name":"Helen Keller International Cambodia, Phnom Penh, Cambodia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Green","sequence":"additional","affiliation":[{"name":"South Australian Health & Medical Research Institute, Adelaide, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank T","family":"Wieringa","sequence":"additional","affiliation":[{"name":"UMR-204 Nutripass, Institut de Recherche pour le D\u00e9veloppement, UM\/IRD\/Supagro, Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mam","family":"Borath","sequence":"additional","affiliation":[{"name":"National Sub-Committee for Food Fortification, Cambodia Ministry of Planning, Phnom Penh, Cambodia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prak","family":"Sophonneary","sequence":"additional","affiliation":[{"name":"National Nutrition Programme, Maternal and Child Health Centre, Cambodia Ministry of Health, Phnom Penh, Cambodia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey R","family":"Measelle","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Oregon, Eugene, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dare","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Oregon, Eugene, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa N","family":"Yelland","sequence":"additional","affiliation":[{"name":"South Australian Health & Medical Research Institute, Adelaide, Australia"},{"name":"School of Public Health, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalem","family":"Leemaqz","sequence":"additional","affiliation":[{"name":"South Australian Health & Medical Research Institute, Adelaide, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Chan","sequence":"additional","affiliation":[{"name":"Mount Saint Vincent University, Halifax, Nova Scotia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelisa","family":"Gallant","sequence":"additional","affiliation":[{"name":"Mount Saint Vincent University, Halifax, Nova Scotia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"2025101811401401000_9.7.e029255.1","unstructured":"Bemeur C , Butterworth RF , et al . 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