Perspectives on the design and methodology of periconceptional nutrient supplementation trials.

Article English OPEN
Brabin, Loretta ; Brabin, BJ ; Gies , Sabine ; Tinto, Halidou ; Owens, S ; Claeys, S ; d'Alessandro, U (2016)
  • Publisher: Springer Nature
  • Journal: volume 17 (eissn: 1745-6215)
  • Related identifiers: doi: 10.1186/s13063-015-1124-0, pmc: PMC4736099
  • Subject: 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.
  • References (120)
    120 references, page 1 of 12

    1. Smithells RW, Sheppard S, Schorah CJ, Seller MJ, Nevin NC, Harris R, et al. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet. 1980;1:339-40.

    2. De-Regil LM,Fernandez-Gaxiola AC, Dowswell T, Pena-Rosas JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database of systematic Reviews 2010, Issue 10. [DOI:10. 1002/14651858.CD007950.pub2]

    3. Pharoah POD, Buttfield IH, Hetzel BS. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet. 1971;1:308-10.

    4. Cetin I, Berti C, Calabrese S. Role of micronutrients in the periconceptional period. Hum Reproduction Update. 2010;16:80-95.

    5. Ronsmans C, Fisher DJ, Osmond C, Margetts BM. Fall CHD for the Maternal Micronutrient Supplementation Group (MMSSG). Multiple micronutrient supplementation during pregnancy in low-income countries: a metaanalysis of effects on stillbirths and on early and late neonatal mortality. Food Nutr Bull. 2009;30:S547-26.

    6. Ramakrishnan U, Grant FK, Goldenberg T, Bui V, Imdad A, Bhutta ZA. Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012;26 Suppl 1:153-67.

    7. Persson LA, Arifeen S, Ekström E-C, Rasmussen KM, Frongillo EA, Yunus M, et al. Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: the MINIMat randomized trial. JAMA. 2012;307:2050-9.

    8. West Jr KP, Shamim AA, Mehra S, Labrique AB, Ali H, Shaikh S, et al. Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial. JAMA. 2014;312:2649-58.

    9. Haider BA, Yakoob MY, Bhutta ZA. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes. BMC Public Health. 2011;13 Suppl 3:S19.

    10. Bhutta ZA, Imdad A, Ramakrishnan U, Martorell R. Is it time to replace iron folate supplements in pregnancy with multiple micronutrients? Paediatr Perinat Epidemiol. 2012;26 Suppl 1:27-35.

  • Related Research Results (2)
  • Metrics
    No metrics available