title: Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates.
abstract: BACKGROUND
  Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status.
  
  
  OBJECTIVE
  The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status.
  
  
  METHODS
  Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) <15 μg/L and body iron (BI) <0 mg/kg; 2) maternal ID anemia [ID + anemia (IDA); hemoglobin <110 g/L]; and 3) neonatal ID (cord blood ferritin <75 μg/L or zinc protoporphyrin/heme >118 μmol/mol).
  
  
  RESULTS
  A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (β per 10 capsules = 2.60, P < 0.05).
  
  
  CONCLUSIONS
  Prenatal iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752.
authors.affiliation: Peking University First Hospital, Beijing, China;
authors.forename: Gengli
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Peking University First Hospital, Beijing, China;
authors.forename: Guobin
authors.initials: G
authors.lastname: Xu
authors.affiliation: Peking University First Hospital, Beijing, China;
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Peking University First Hospital, Beijing, China;
authors.forename: Yaping
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Center for Human Growth and Development and.
authors.forename: Blair
authors.initials: B
authors.lastname: Richards
authors.affiliation: Center for Human Growth and Development and.
authors.forename: Katy M
authors.initials: KM
authors.lastname: Clark
authors.affiliation: Center for Human Growth and Development and.
authors.forename: Niko
authors.initials: N
authors.lastname: Kaciroti
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Georgieff
authors.affiliation: Peking University First Hospital, Beijing, China;
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Human Growth and Development and.
authors.forename: Twila
authors.initials: T
authors.lastname: Tardif
authors.affiliation: Peking University First Hospital, Beijing, China;
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Center for Human Growth and Development and Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI; and blozoff@umich.edu.
authors.forename: Betsy
authors.initials: B
authors.lastname: Lozoff
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology / Q000517:prevention & control*; D002681:China / Q000453:epidemiology; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007501:Iron / Q000008:administration & dosage*; D000090463:Iron Deficiencies; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D012424:Rural Population; D055815:Young Adult
chemical_list: D007501:Iron
keywords: iron deficiency; iron deficiency anemia; iron supplementation; neonates; pregnant women; randomized clinical trial