Maternal prenatal, with or without postpartum, vitamin D3 supplementation does not improve maternal iron status at delivery or infant iron status at 6 months of age: secondary analysis of a randomised controlled trial

Abstract

Background: Vitamin D may modify iron status through regulation of hepcidin and inflammatory pathways. This study aimed to investigate effects of maternal vitamin D supplementation on iron status in pregnancy and early infancy.

Methods: In a trial in Dhaka, Bangladesh, women (n=1300) were randomised to one of five vitamin D₃ regimens from 17 to 24 weeks' gestation until 26 weeks postpartum (prenatal; postpartum doses): 0;0, 4200;0, 16 800;0, 28 000;0 or 28 000;28 000 IU/week. All participants received standard iron-folic acid supplementation. In this secondary analysis (n=998), we examined effects of prenatal;postpartum vitamin D on serum ferritin and other biomarkers of maternal iron status (transferrin saturation, total iron binding capacity, soluble transferrin receptor and hepcidin) at delivery, and infant ferritin and haemoglobin at 6 months of age. Using linear regression, we estimated per cent mean differences between each intervention group and placebo with 95% CIs, with and without adjustment for baseline ferritin or inflammatory biomarkers (C reactive protein and α-1-acid glycoprotein (AGP)).

Results: At delivery, ferritin concentrations were similar between each intervention group and placebo in unadjusted (n=998) and baseline ferritin-adjusted analyses (n=992; p>0.05). Compared with placebo, AGP was lower in each intervention group (per cent difference (95% CI) = -11% (-21 to -1.0), -14% (-23 to -3.5) and -11% (-19 to -2.0) in the 4200 IU/week, 16 800 IU/week and 28 000 IU/week groups, respectively; n=779). In the subgroup of women with baseline 25-hydroxyvitamin D < 30 nmol/L, ferritin was lower in each intervention group versus placebo (-23% (-37 to -5.0), -20% (-35 to -1.9) and -20% (-33 to -4.1) in the 4200 IU/week, 16 800 IU/week and 28 000 IU/week groups, respectively; n=645); effects were slightly attenuated after adjustment for inflammation (n=510). There were no effects of vitamin D on other iron biomarkers among women at delivery or infants aged 6 months.

Conclusion: These findings do not support improvement of iron status by vitamin D. The effect of prenatal vitamin D supplementation on ferritin may reflect an anti-inflammatory mechanism.

Keywords: Nutrient deficiencies.

Figure 1

Maternal serum ferritin concentrations at delivery in participants with 25(OH)D concentrations ≥ 30 nmol/L (blue) and < 30 nmol/L (grey) at enrolment. For ease of visualisation, ferritin concentrations > 300 µg/L are excluded from the distribution but included in calculated geometric mean and 95% CI (n=2 in 0 IU/week, n=3 in 4200 IU/week and n=1 in 16 800 IU/week group). N for all participants: 0, n=203; 4200, n=202; 16800, n=205; 28000, n=388. N for participants with 25(OH)D < 30 nmol/L: 0, n=125; 4200, n=133; 16800, n=126; 28 000, n=261. N for participants with 25(OH)D ≥ 30 nmol/L: 0, n=76; 4200, n=68; 16800, n=78; 28000, n=124. Intervention group reflects the vitamin D dose provided in IU/week, represented as a prenatal supplementation regimen assigned at randomisation (17–24 weeks of gestation). 25(OH)D, 25-hydroxyvitamin D.