Calcium Intake, Vitamin D Status, Placental Vitamin D Receptor (Vdr) Expression, Placental Calcium Transport, And Neonatal Outcomes In Adolescent Pregnancy

Abstract

Pregnancy and adolescence are both periods of elevated calcium (Ca) demand. Pregnancy during adolescence places both mother and fetus at risk for adverse skeletal outcomes. The overall goal of this research was to address how maternal Ca intake and vitamin D status impact calcitropic hormones and fetal bone development during pregnancy, and investigate how effects may be mediated at the level of the placental in a skeletally immature population. Maternal Ca intake,25(OH)D status calcitropic hormones (PTH and 1,25(OH)2D) and fetal biometry measures (fetal femur and humerus length and birth length) were monitored across pregnancy in 171 pregnant adolescents ([LESS-THAN OR EQUAL TO]18 yrs). Neonatal hormonal status and placental tissue were obtained at delivery. Stable Ca isotopes were administered to twelve adolescents early in labor (44Ca orally and 42Ca intravenously) to obtain a dynamic measure of maternal-to-fetal Ca transfer. Among these adolescents, 25(OH)D insufficiency ([LESS-THAN OR EQUAL TO]20 ng/mL) was prevalent (~50%) and PTH was inversely related to 25(OH)D status throughout pregnancy, and was elevated ([GREATER-THAN OR EQUAL TO]60 pg/mL) in 24% of teens at term. Maternal 25(OH)D was also negatively associated with 1,25(OH)2D concentrations. Associations with Ca intake were less evident, indicating that maternal vitamin D status is a key determinant of the calcitropic hormone response to pregnancy. iii Maternal Ca intake and 25(OH)D status interacted to influence fetal femur and humerus Zscores; sufficient status of one nutrient was associated with improved long bone Z-score when the other nutrient was limited. This interaction remained evident at delivery, and was associated with neonatal birth length. At the level of the placenta, VDR expression was positively related to neonatal 1,25(OH)2D, and was higher in neonates with low 25(OH)D status. Placental VDR was also positively related to fetal femur length. Of note, placental VDR expression was a significant predictor of maternal-to-fetal 42Ca transport which was itself significant in a model of fetal femur Z-score. Placental VDR expression was responsive to fetal endocrine signals and appeared to impact fetal skeletal growth via modulation of placental Ca transport. In a skeletally immature pregnant adolescent, achieving adequate 25(OH)D status and Ca intake may improve calcitropic hormone levels and optimize fetal skeletal accretion. iv