title: Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial.
abstract: BACKGROUND
  Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction.
  
  
  OBJECTIVE
  We tested the hypothesis that periconceptional multiple-micronutrient supplementation (MMS) affects placental function.
  
  
  METHODS
  We conducted a double-blind, randomized, placebo-controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo. Eligible subjects were pre-randomly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation (UNIMMAP) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive. Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ratio of plasminogen-activator inhibitor (PAI) 1 to PAI-2 and mean uterine-artery resistance index (UtARI)] and placental active transport capacity at delivery [fetal to maternal measles antibody (MMA) ratio].
  
  
  RESULTS
  We recruited 1156 women who yielded 415 pregnancies, of which 376 met all of the inclusion criteria. With adjustment for gestational age at sampling, there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms, but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation (95% CI: -0.03, -0.00; P = 0.040) in women taking UNIMMAP.
  
  
  CONCLUSIONS
  Placental vascular function was modifiable by periconceptional micronutrient supplementation. However, the effect was small and supplementation did not further affect other variables of placental function. This trial was registered at www.controlled-trials.com as ISRCTN 13687662.
authors.affiliation: Children's Unit, Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom; Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom, and MRC Keneba, Fajara, The Gambia; stephen.owens@ncl.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Owens
authors.affiliation: Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom, and MRC Keneba, Fajara, The Gambia;
authors.forename: Ruchi
authors.initials: R
authors.lastname: Gulati
authors.affiliation: Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom, and MRC Keneba, Fajara, The Gambia;
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Fulford
authors.affiliation: Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom, and MRC Keneba, Fajara, The Gambia;
authors.forename: Fatou
authors.initials: F
authors.lastname: Sosseh
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, United Kingdom; and.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Denison
authors.affiliation: Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Brabin
authors.affiliation: Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom, and MRC Keneba, Fajara, The Gambia;
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003677:Deficiency Diseases / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005714:Gambia; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena; D018977:Micronutrients / Q000009:adverse effects / Q000627:therapeutic use*; D021041:Placental Circulation; D010929:Placentation; D016742:Preconception Care; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D012423:Rural Health; D014480:United Nations; D014655:Vascular Resistance; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018977:Micronutrients
keywords: Africa; birth weight; fetal growth; micronutrients; periconceptional; placenta; pregnancy