Vitamin D metabolic profiling across pregnancy

Radhika Susarla; Carl Jenkinson; Jennifer Tamblyn; Brian Keevil; Shiao-Yng Chan; Mark Kilby; Martin Hewison

doi:10.1530/endoabs.38.P362

Vitamin D-deficiency during pregnancy has been associated with increased complications of pregnancy including a high risk of pre-eclampsia (PET). Current analysis of vitamin D ‘status’ is based exclusively on analysis of maternal serum 25-hydroxyvitamin D₃ (25(OH)D₃), the circulating precursor form of vitamin D. We hypothesised that comprehensive profiling of vitamin D metabolites may provide a more accurate determination of vitamin D function in pregnancy. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate multiple vitamin D metabolites from serum samples obtained from: normal pregnant women (NP) at 1st trimester (n=22) and 3^rd trimester (n=21); women with PET (n=21); non-pregnant female controls (n=20). Data (see table, Mean±S.E.M.) demonstrated that active (1α,25(OH)₂D₃, P<0.001), catabolic (24,25(OH)₂D₃, P<0.05) and inactive (Epi-25(OH)D₃, P<0.01) are increased in serum from 3rd trimester and PET pregnancies relative to NP women. Epi-25(OH)D₃ was elevated in all women across trimesters (P<0.01). By contrast, conventionally measured 25(OH)D₃ showed no significant change in any of the groups. Ratio of 24,25(OH)₂D₃/1α,25(OH)₂D₃ was 100.8±2 in normal 3rd trimester, and 258.9±39 in PET (P<0.05). Ratio of Epi-25(OH)D₃/1α,25(OH)₂D₃ was 77.4±7 in normal 3rd trimester, and 172.3±29 in PET (P<0.01). These data, suggests a shift towards catabolic pathway of vitamin D metabolism in PET. The albumin (decreases) and DBP (increases) levels inversely correlated with gestation (Table 1).

Table 1
	25(OH)D₃ (nM)	Epi-25(OH)D₃ (nM)	lα,25(OH)₂D₃ (pM)	24,25(OH)D₃ (nM)	DBP (μm)	Albumin (μm)
Non-pregnant	35.18±3.8	5.04±0.4	42.04±4.1	4.66±0.95	1.69±0.21	557.04±28.86
1st trimester	34.7±4.34	7.98±0.37	52.36±5.17	2.84±0.65	2.32±0.25	554.43±25.85
3rd Trimester	44.61±5.04	7.64±0.41	108.34±6.67	10.6±2.12	2.48±0.31	330.06±21.07
PET	38.45±5.94	9.49±0.76	77.84±9.27	15.96±2.56	2.38±0.31	409.26±20.15

Measurement of multiple vitamin D metabolites and metabolites ratios may improve the interpretation of vitamin D status in pregnancy, possibly as an additional marker of adverse pregnancy events such as PET.

Endocrine Abstracts

P362