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

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.