Higher Maternal Body Mass Index Attenuates the Response to High-Dose Vitamin D Supplementation During Pregnancy: A...

Vitamin D supplementation during pregnancy is recommended to optimize maternal vitamin D status, yet biochemical response is highly variable, potentially limiting attainment of adequate 25-hydroxyvitamin D [25(OH)D] concentrations. Maternal body mass index (BMI) may modify vitamin D response, but this relationship has not been comprehensively examined in randomized trials conducted during pregnancy.

This study examines whether maternal BMI modifies the biochemical response to high-dose vitamin D supplementation during pregnancy.

Using data from the vitamin D antenatal asthma reduction trial, a randomized, double-blind trial of pregnant participants, we examined whether maternal BMI modifies response to high-dose (110 μg/d) compared with standard-dose (10 μg/d) vitamin D supplementation. Maternal serum 25(OH)D was measured at enrollment (10‒18 wk) and in the third trimester (32‒38 wk). Linear mixed-effects models examined the interaction between treatment group and BMI (categories <25, 25‒29.9, and ≥30; continuous; and ordinal), adjusting for baseline 25(OH)D and demographic and clinical covariates.

Among 816 participants in the intention-to-treat analysis, high-dose supplementation increased maternal 25(OH)D by 22.43 nmol/L [95% confidence interval (CI): 17.16, 27.70 nmol/L; P < 0.001] versus standard-dose supplementation among those with BMI <25 kg/m². This treatment effect was attenuated with higher BMI: by 8.39 nmol/L (95% CI: -16.46, -0.32 nmol/L; P = 0.041) in the overweight group (BMI 25‒29.9 kg/m²) and 8.63 nmol/L (95% CI: -16.06, -1.20 nmol/L; P = 0.023) in the obese group (BMI ≥30 kg/m²), representing 37% and 38% reductions in treatment effect, respectively. Modeled continuously, each 1 kg/m² increase was associated with a 0.45 nmol/L reduction in treatment effect (95% CI: -0.86, -0.03 nmol/L; P = 0.035). Sensitivity analyses using change-score models and prepregnancy BMI yielded consistent results.

Maternal BMI attenuates the biochemical response to vitamin D supplementation during pregnancy in a graded, BMI-dependent manner. Although most participants receiving 110 μg/d achieved 25(OH)D concentrations ≥50 nmol/L, higher BMI was associated with a smaller increase in 25(OH)D and a greater likelihood of remaining below the higher 75 nmol/L target. These findings suggest that uniform prenatal supplementation strategies may not fully account for BMI-related differences in vitamin D response. Future studies should determine whether BMI-stratified dosing improves achieved vitamin D status and translates into better maternal or offspring outcomes. This trial was registered at clinicaltrials.gov as NCT00920621.