Maternal fat-soluble vitamin trajectories and infant birth weight in individuals with overweight or obesity

Background: Birth weight is a strong determinant of long-term metabolic health, with both low birth weight and macrosomia linked to increased cardiometabolic risk. Fat-soluble vitamins A, D, and E modulate pathways relevant to fetal growth, however, their trajectories and potential associations with birth weight in pregnant individuals with overweight or obesity remain scarcely characterized. Objective: To examine maternal vitamins A (retinol), D (25(OH)D), and E (α-tocopherol) concentrations during the second and third trimesters of pregnancy and their associations with birth weight, in individuals with pre-pregnancy overweight or obesity. Methods: This secondary analysis of the Exercise Training in Pregnancy Trial (ETIP) study included 57 mother-infant pairs with available vitamin measurements in the second and third trimesters. Plasma retinol and α-tocopherol were measured by high performance liquid chromatography, and serum 25(OH)D by liquid chromatography-tandem mass spectrometry. Birth weight was classified as normal (2500 - < 4000 g) or macrosomic (≥ 4000 g). Circulating vitamin concentrations between trimesters were compared using the Wilcoxon signed-rank test and associations between vitamins and birth weight were examined using multivariate linear regression models. Results: From the second to the third trimester, mean maternal retinol and 25(OH)D concentrations declined significantly (retinol: 1.52 (SD = 0.37) to 1.32 (SD = 0.33) µmol/L; 25(OH)D: 73.7 (SD = 30.0) to 63.3 (SD = 25.0) nmol/L), whereas α-tocopherol increased from 34.6 (SD = 7.1) to 46.3 (SD = 10.0) µmol/L. In the third trimester, 19.3% had vitamin A insufficiency, while vitamin D deficiency and insufficiency affected 31.6% and 33.3%, respectively. Macrosomia occurred in 43.9% of infants and 56.1% had birth weight within the normal range. Maternal vitamins A, D, and E were not associated with birth weight, and no vitamin A and D interaction was observed. Conclusion: In pregnant individuals with overweight or obesity, maternal vitamin A and D concentrations declined across pregnancy, while vitamin E increased. Vitamin A insufficiency, vitamin D deficiency/insufficiency, and macrosomia were common. Maternal fat-soluble vitamin levels were not independently associated with birth weight, suggesting that vitamin status during mid- to late pregnancy may not be a major determinant of fetal growth in this metabolically high-risk population.