@article{fdi:010077038,
  title = {{T}hiamine dose response in human milk with supplementation among lactating women in {C}ambodia : study protocol for a double-blind, four-parallel arm randomised controlled trial},
  author = {{W}hitfield, {K}. {C}. and {K}roeun, {H}. and {G}reen, {T}. and {W}ieringa, {F}ranck and {B}orath, {M}. and {S}ophonneary, {P}. and {M}easelle, {J}. {R}. and {B}aldwin, {D}. and {Y}elland, {L}. {N}. and {L}eemaqz, {S}. and {C}han, {K}. and {G}allant, {J}.},
  editor = {},
  language = {{ENG}},
  abstract = {{I}ntroduction {T}hiamine (vitamin {B}1) deficiency remains a concern in {C}ambodia 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. {T}hiamine 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. {M}ethods and analysis {I}n this community-based randomised controlled trial, 320 lactating women from {K}ampong {T}hom, {C}ambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10 mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. {T}he primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. {A}t 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: {T}h{DP} and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). {A}ll participants and their families will consume study-provided salt ad libitum throughout the trial, and we will measure salt disappearance each fortnight. {R}epeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. {P}arameters of {E}-max dose-response curves will be estimated using non-linear least squares models with both 'intention to treat' and a secondary 'per-protocol' (capsule compliance >= 80%) analyses. {E}thics and dissemination {E}thical approval was obtained in {C}ambodia ({N}ational {E}thics {C}ommittee for {H}ealth {R}esearch 112/250{NECHR}), {C}anada ({M}ount {S}aint {V}incent {U}niversity {R}esearch {E}thics {B}oard 2017-141) and the {USA} ({U}niversity of {O}regon {I}nstitutional {R}eview {B}oard 07052018.008). {R}esults will be shared with participants' communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations.},
  keywords = {{CAMBODGE}},
  booktitle = {},
  journal = {{BMJ} {O}pen},
  volume = {9},
  numero = {7},
  pages = {e029255 [9 p.]},
  ISSN = {2044-6055},
  year = {2019},
  DOI = {10.1136/bmjopen-2019-029255},
  URL = {https://www.documentation.ird.fr/hor/fdi:010077038},
}