title: Perspectives on the design and methodology of periconceptional nutrient supplementation trials.
abstract: Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved, but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also because they generate subsidiary information on participants who remain non-pregnant. The methodological challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the periconceptional trial design--two of which are non-pregnant and two are pregnant--and this structure provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the initial decision for single or micronutrient intervention is central--as is the choice of dosage and content--in order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial.
authors.affiliation: Clinical Division, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L35QA, UK. b.j.brabin@liverpool.ac.uk.|Global Child Health Group, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. b.j.brabin@liverpool.ac.uk.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Brabin
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. s.gies@itg.be.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gies
authors.affiliation: Northumbria Healthcare NHS Foundation Trust, North Shields, NE29 8NH, UK. sowens@3mac.com.
authors.forename: Stephen
authors.initials: S
authors.lastname: Owens
authors.affiliation: Clinical Sciences Department, Institute of Tropical Medicine, Antwerp, Belgium. yclaeys@itg.be.
authors.forename: Yves
authors.initials: Y
authors.lastname: Claeys
authors.affiliation: Medical Research Council Unit (MRC), Fajara, The Gambia. udalessandro@mrc.gm.|London School of Hygiene and Tropical Medicine, London, UK. udalessandro@mrc.gm.|Institute of Tropical Medicine, Antwerp, Belgium. udalessandro@mrc.gm.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.affiliation: Clinical Research Unit of Nanoro (URCN/IRSS), Nanoro, Burkina Faso. tintohalidou@yahoo.fr.
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK. loretta.Brabin@manchester.ac.uk.
authors.forename: Loretta
authors.initials: L
authors.lastname: Brabin
mesh_terms: D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018977:Micronutrients / Q000008:administration & dosage; D017063:Outcome Assessment, Health Care; D011247:Pregnancy; D011295:Prenatal Care; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D018977:Micronutrients
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