Perspectives on the design and methodology of periconceptional nutrient supplementation trials.
Gies , Sabine
- Publisher: Springer Nature
Medicine (miscellaneous) | Adherence | Pregnancy | wa_310 | Periconceptional | Review | Placenta | Iron | Micronutrients | qu_145.5 | Folic acid | wq_175 | Pharmacology (medical)
Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved,\ud but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy\ud supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also\ud because they generate subsidiary information on participants who remain non-pregnant. The methodological\ud challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent\ud hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines\ud the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the\ud periconceptional trial design — two of which are non-pregnant and two are pregnant — and this structure\ud provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the\ud initial decision for single or micronutrient intervention is central — as is the choice of dosage and content — in\ud order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of\ud mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline\ud and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to\ud duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced\ud by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource\ud settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate\ud safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial.