Maternal serum retinol, 25(OH)D and 1,25(OH)2D concentrations during pregnancy and peak bone mass and trabecular bone score in adult offspring at 26-year follow-up

Abstract

BackgroundVitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear.Method and findingsForty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986–88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) μmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 μmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS.ConclusionsThis is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD.

Maternal Diet, Nutritional Status, and Birth-Related Factors Influencing Offspring’s Bone Mineral Density: A Narrative Review of Observational, Cohort, and Randomized Controlled Trials

“…One study reported a negative association with offspring total BMD (with no difference in lumbar BMD) [ 17 ]. Six studies found no association between maternal vitamin D status and bone parameters from the neonatal period even to the age of 26 years [ 23 , 35 , 36 , 37 , 38 , 39 ]. In the four remaining studies, positive associations were found between maternal vitamin D status and offspring BMD [ 18 , 40 ], with sex-specific association in one study [ 41 ], as well as neonatal bone SOS [ 42 ].…”

“…In a study by Javaid et al [ 18 ], calcium concentrations in cord blood were positively related to offspring LS aBMD but not WB aBMD. Two studies assessed maternal vitamin A status in relation to offspring BMD [ 22 , 23 ]. When samples were taken at around weeks 33/34 of gestation, no association was found in both studies [ 22 , 23 ].…”

“…Genetic and epigenetic processes, as well as accessibility of nutrients, seems to play an important role in bone development and affect peak bone mass, whose lower levels are a crucial risk factor for osteoporosis [ 7 , 10 , 11 ]. Among dietary factors, vitamin D and calcium are the most often mentioned [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], however, the role of macronutrients [ 19 , 20 , 21 ] and other nutrients, such as vitamin A [ 22 , 23 ], folate [ 19 , 24 ] or magnesium [ 19 , 21 ] have also been raised in studies regarding bone health.…”

Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D

“…Moreover, serum 1,25-diOH-VitD is already VDR receptor saturating. Therefore, the intracellular receptor supersaturating concentration is not required, albeit, for potential VDR-independent actions 34 . We resourced 1,25-diOH-VitD since several studies reported its superiority over 25-OH-VitD as an independent clinical correlate 31 , 35 - 37 .…”

Relationships Between Vitamin D Status and Cytokine: Results from Interferon-Based Therapy in Non-Cirrhotic, Treatment-Naïve Patients with Chronic Hepatitis C Infection

“…The 25(OH)D is then transported into the blood stream to the proximal tubule of the kidney where it is 1α-hydroxylated to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3 or calcitriol), which is its only active form. 5 …”