Association between Circulating and Placental Vitamin D Biomarkers in Healthy Pregnant Women on a Controlled Diet with Equivalent Vitamin D Intake during the Third Trimester
Authors: Park Heyjun , Brannon Patsy M , West Allyson A , Yan Jian , Jiang Xinyin , Perry Cydne A , Malysheva Olga V , Mehta Saurabh , Caudill Marie A 
Published: November 2023

This 10‐wk feeding study sought to advance understanding of the role of the placenta in maternal vitamin D status. To achieve this aim, we assessed associations between placental vitamin D metabolites [25‐hydroxyvitamin D3 (25[OH]D3), 24,25‐dihydroxyvitamin D3 (24,25[OH]2D3)], placental expression of vitamin D‐related genes [25‐hydroxylase (CYP2R1), 1a‐hydroxylase (CYP27B1), 24‐hydroxylase (CYP24A1)] and maternal blood vitamin D metabolites [25(OH)D3, 24,25(OH)2D3, 1,25‐dihydroxyvitamin D (1,25[OH]2D)] among healthy third‐trimester pregnant women (n=26). Participants consumed equivalent and rigorously controlled vitamin D (515 IU/d) and calcium intakes (1445 mg/d) throughout the third trimester, and blood samples were obtained at study‐baseline (beginning of third trimester) and study‐end (term), while placenta tissues were collected at delivery. Blood and placental vitamin D metabolites were measured by LC‐MS/MS, and placental gene transcript abundance was quantified by qRT‐PCR with Taqman probes. In Pearson correlation analyses, 25(OH)D3 and 24,25(OH)2D3 concentrations showed a strong positive correlation in placenta [r=0.83, P<0.001], and in maternal blood [r=0.89, P<0.001 at baseline; r=0.84, P<0.001 at study‐end]. Remarkably, placental 25(OH)D3 concentrations correlated positively with maternal serum 25(OH)D3 levels [r=0.63, P<0.001 at baseline; r=0.85, P<0.001 at study‐end], and also with maternal circulating 24,25(OH)2D3 levels [r=0.63, P=0.001 at baseline; r=0.81, P<0.001 at study‐end]. Similarly, placental 24,25(OH)2D3 concentrations were positively correlated with maternal serum 25(OH)D3 [r=0.45, P=0.03 at baseline; r=0.68, P<0.001 at study‐end] and maternal blood 24,25(OH)2D3 levels [r=0.52, P=0.01 at baseline; r=0.67, P<0.001 at study‐end]. Moreover, positive associations were observed between 25(OH)D3 and 1,25(OH)2D concentrations in maternal circulation [r=0.47, P=0.02 at baseline; r=0.36, P=0.068 at study‐end], and circulating 1,25(OH)2D and 24,25(OH)2D levels were correlated only at baseline [r=0.44, P=0.02]. Of note, in multivariate‐adjusted regression models, baseline concentrations of maternal serum 25(OH)D3 correlated positively with both placental CYP27B1 [R2=0.86 ; β=0.007; P=0.04] and CYP24A1 expression [R2 = 0.70; β=0.012; P=0.01]. In addition, maternal serum 25(OH)D at study‐end and placental CYP2R1 expression showed an inverse relationship with a borderline significance [R2=0.92; β=−0.006; P=0.06], and placental CYP24A1 expression positively correlated with 1,25(OH)2D levels at both study‐time points [R2=0.70; β=0.0022; P=0.01 at baseline; R2=0.67; β=0.0017; P=0.03 at study‐end]. To the best our knowledge, this is the first study to quantify vitamin D metabolites in human placenta tissue. The strong correlations between maternal circulating vitamin D metabolites and placental metabolic and genomic readouts suggest that the placenta may modulate the vitamin D metabolite profile in the maternal compartment.Support or Funding InformationGERBER FOUNDATION 1843‐3882, NIH R03 HD080824‐01A1