Randomized controlled trial of prenatal zinc supplementation and fetal bone growth

Am J Clin Nutr. 2004 May;79(5):826-30. doi: 10.1093/ajcn/79.5.826.


Background: Maternal zinc deficiency is relatively common in developing countries, but its consequences for fetal growth are not established.

Objective: The goal was to examine whether improvement in maternal gestational zinc status is positively associated with fetal growth as assessed by ultrasonography.

Design: We conducted a double-masked, randomized trial among 242 pregnant Peruvian women in an impoverished shantytown in Lima, Peru. At 10-16 wk of gestation, the women were randomly assigned to receive daily supplements containing 60 mg Fe and 250 microg folic acid, with or without 25 mg Zn. We measured fetal head circumference, biparietal diameter, abdominal circumference, and femur diaphysis length at 20, 24, 28, 32, 36, and 38 wk of gestation. Fetal measures were analyzed longitudinally to evaluate differences in trends of fetal growth by supplement type, and within-subject correlations were taken into account.

Results: Femur diaphysis length was greater in fetuses whose mothers received zinc supplements (P < 0.05), and the difference tended to increase with gestational age. No significant differences by supplement type were observed for the other anatomical sites measured.

Conclusions: The observed positive effect of prenatal zinc on fetal femur diaphysis length is consistent with the results of experimental studies in animals and in vitro. The supplementation effect represents an upward shift in mean femur diaphysis length at term of about one-quarter of the reference SD. These findings suggest the potential importance of maternal zinc status for fetal bone growth in humans and illustrate the value of ultrasonography for evaluating the effect of prenatal nutritional interventions on components of fetal growth.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anemia, Iron-Deficiency / prevention & control
  • Bone Development / drug effects*
  • Bone Development / physiology
  • Bone and Bones / embryology
  • Bone and Bones / metabolism
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Femur / diagnostic imaging
  • Femur / embryology*
  • Folic Acid / administration & dosage
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Iron, Dietary / administration & dosage
  • Male
  • Peru
  • Pregnancy
  • Prenatal Nutritional Physiological Phenomena*
  • Ultrasonography, Prenatal
  • Zinc / administration & dosage*
  • Zinc / deficiency*


  • Iron, Dietary
  • Folic Acid
  • Zinc