Longitudinal changes in vitamin D and its metabolites in pregnant South Africans

Vitamin D deficiency (VDD) has been associated with adverse maternal and foetal outcomes and is determined by measuring 25 hydroxyvitamin D (25(OH)D). The 25(OH)D is catabolized to 24, 25-(OH) ₂D and the ratio of 25(OH) D to 24, 25-(OH)₂D, the vitamin D metabolite ratio (VMR), is thought to be a superior marker of VDD, being elevated in such states. The aims of this study were to assess the longitudinal vitamin D status of pregnant women by measuring cholecalciferol, 25(OH)D, 24, 25-(OH)₂D and VMR at two time points and also to determine any association of vitamin D and metabolites with gestational age at birth, birth length and weight.

We recruited 400 pregnant black African women in their first trimester (V1) and measured weights and heights. Ultrasound scans were performed for gestational age. Blood was drawn at V1 and at about 26 weeks (V2) of gestation for cholecalciferol, 25(OH)D, 24, 25-(OH)₂D, VMR and parathyroid hormone (PTH). An OGTT was performed at V2 where fasting glucose, insulin and 30-minute glucose were measured. At birth, we measured birth weight, length and gestational age. Maternal insulin, PTH and vitamin D binding protein (VDBP) were measured by immunoassay. Maternal albumin was measured colorimetrically. Maternal cholecalciferol, 25(OH)D and 24, 25-(OH)₂D, were measured by mass spectrometry and free and bioavailable vitamin D were calculated. Initial gestation was determined by ultrasound. We compared analytes by visit as well as by 25(OH)D status. Vitamin D deficiency (<30 nmol/L) was defined according to the National Academy of Medicine guidelines. Linear regression analysis was used to determine associations of vitamin D molecules with maternal blood pressure, fasting and 30-minute insulin and blood glucose and neonatal parameters.

Results are presented for participants for whom we had complete data (n = 330-346 depending on variable). The prevalence of vitamin D deficiency (VDD) was 35.8 % at V1 and 32.4 % at V2. Levels of 25(OH)D did not change significantly between visits. Levels of 24, 25(OH)₂D dropped from the first to the second visit (17.64 ± 12.64 to 9.39 ± 9.07 nmol/L; p < 0.0001) while VMR increased ((3.15 (1.31; 7.67) to 7.90 (2.44; 25.98); p < 0.0001). The proportion of women with the lowest cholecalciferol concentrations increased at V2 compared to the V1 (36.1-42.8 %; p = 0.02). In multivariable regression models 25(OH)D was negatively associated with 30-minute glucose concentrations (p = 0.038) whilst 24, 25-(OH)₂D was positively associated with fasting insulin (p = 0.017) and HOM A-I R (p = 0.023). There was no correlation of 25(OH)D or metabolites with infant birth weight, birth length or gestational age.

Maternal VDD is common in pregnant black South African women. Decreased VMR suggest that catabolism of 25(OH)D is reduced in pregnancy to maintain adequate free vitamin D levels.