Serum Free 1,25‐dihydroxyvitamin D and the Free 1,25‐dihydroxyvitamin D Index During a Longitudinal Study of Human Pregnancy and Lactation

Abstract

The changes in three different indices of 1,25-dihydroxyvitamin D (1,25(OH)2D) biological activity were studied longitudinally in 35 women during late pregnancy and lactation and in 26 control women. Measurements were made of maternal serum total 1,25(OH)2D and free 1,25(OH)2D concentration (by centrifugal ultrafiltration) and the free 1,25(OH)2D index (the molar ratio of total 1,25(OH)2D and vitamin D binding protein (DBP]. During late pregnancy total 1,25(OH)2D concentrations were significantly elevated when compared to controls, as were free 1,25(OH)2D and DBP concentrations and the free 1,25(OH)2D index. Serum total 1,25(OH)2D, free 1,25(OH)2D and DBP concentrations all fell dramatically during the first 2 weeks of lactation with total 1,25(OH)2D and free 1,25(OH)2D concentrations falling to levels below those of controls. During the course of lactation both total 1,25(OH)2D and free 1,25(OH)2D levels rose significantly although they were not different from controls at 18 weeks of lactation. In contrast, the free 1,25(OH)2D index fell during the first 2 weeks of lactation, but remained at this level, significantly lower than controls. Neither urinary calcium excretion nor dietary calcium intake correlated with total or free 1,25(OH)2D, DBP, or the free 1,25(OH)2D index. The disagreement in the results of free 1,25(OH)2D concentration and free 1,25(OH)2D index demonstrates that these two approaches to measuring biologically active 1,25(OH)2D are not equivalent. In attempting to account for the increased calcium requirements of human reproduction we conclude that in pregnancy any of the 1,25(OH)2D measurements may be appropriate. In lactation, however, either 1,25(OH)2D is not a major factor or 1,25(OH)2D biological activity is inadequately represented by any of the currently available methods.

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…B) HUMAN DATA. Similar to the findings in the animal models, cross-sectional studies have found a doubling or tripling of serum calcitriol that begins early in the first trimester and reaches the highest levels in the third trimester (81,207,287,324,387,578,599,632,764,981,987). Longitudinal studies have confirmed a progressive increase in free and bound calcitriol that is maintained to term (33, 81,764,809,813,959,987).…”

“…B) HUMAN DATA. Free and total calcitriol falls to normal during postpartum (206,439,578,746,809,987) and remains normal throughout lactation and postweaning (156,157,206,207,348,385,470,505,632,764,805,871,987). One study found that extended lactation (Ͼ6 mo) was associated with higher calcitriol (348), another report found that calcitriol increased during the postweaning interval of bone recovery (871), and a third report found that calcitriol was 10% higher during lactation and that this persisted during the post-weaning interval (454).…”

Changes in serum markers of bone turnover during normal pregnancy

“…Despite these signi¢cant changes in the bone turnover markers, it is of note that the serum albuminadjusted calcium values did not change throughout pregnancy. Others have observed an increase in the adjusted calcium, 21 which would correlate with an increase in 1,25(OH) 2 D, 6 while a slight decrease has been observed in ionized calcium. 22 Although a trend towards an increasing total calcium was observed in our data, this was not signi¢cant, and this discrepancy may be a drawback of the limited number of sampling points in this study.…”

“…6 It has been suggested that this may be driven by parathyroid hormone (PTH); 7 however, more recent studies have shown a signi¢cant decrease in PTH during pregnancy and have suggested the possible involvement of parathyroid hormone -related protein (PTHrP). 8,9 Bone histology suggests an increase in resorption at this time, 10 and this is supported by recent studies of biochemical markers of bone turnover.…”

Vitamin D and Human Pregnancy

“…This was initially thought to be mediated by 1,25(OH) 2 D, as it is known that serum levels of 1,25(OH) 2 D increase early in pregnancy and peak at twice the non-pregnant range 33,43,[48][49][50][51][52][53] . However, free concentrations of 1,25(OH) 2 D appear to increase only during the third trimester, and the peak in intestinal calcium absorption occurs well before this 54,55 .…”