Reduced Dietary Calcium and Vitamin D Results in Preterm Birth and Altered Placental Morphogenesis in Mice During Pregnancy

Rebecca L. Wilson, Jessica A. Phillips, Tina Bianco-Miotto, Dale McAninch, Zona Goh, Paul H. Anderson, Claire T. Roberts

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Vitamin D and calcium are essential micronutrients for reproductive success. Vitamin D deficiency during pregnancy is associated with increased risk of pregnancy complications including pre-eclampsia and preterm birth (PTB). However, inconsistencies in the literature reflect uncertainties regarding the true biological importance of vitamin D but may be explained by maternal calcium intakes. We aimed to determine whether low dietary consumption of calcium along with vitamin D deficiency had an additive effect on adverse pregnancy outcome by investigating placental morphogenesis and foetal growth in a mouse model. Female mice were randomly assigned to one of four diets: control-fed (+Ca+VD), reduced vitamin D only (+Ca−VD), reduced calcium only (−Ca+VD) and reduced calcium and vitamin D (−Ca−VD), and sacrificed at gestational day (GD) 18.5. Maternal serum 25-hydroxyvitamin D (25(OH)D3) levels were lower in each reduced diet group when compared with levels in +Ca+VD-fed mice. While the pregnancy rate did not differ between groups, in the −Ca−VD-fed group, 55% (5 out of 9 pregnant of known gestational age) gave birth preterm (<GD18.5). Of the −Ca−VD animals that gave birth at GD18.5, mean foetal weight increased by 8% when compared with +Ca+VD (P < 0.05) which was associated with increased placental efficiency (P = 0.05) as a result of changes to the placental labyrinth microstructure. In conclusion, we observed an interactive effect of low calcium and vitamin D intake that may impact offspring phenotype and preterm birth rate supporting the hypothesis that both calcium and vitamin D status are important for a successful pregnancy.

Original languageEnglish
Pages (from-to)1330-1339
Number of pages10
JournalReproductive Sciences
Issue number6
Early online date1 Jan 2020
Publication statusPublished - 1 Jun 2020
Externally publishedYes


  • Calcium
  • Mouse
  • Placenta
  • Pregnancy
  • Vitamin D


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