Elsevier

Bone

Volume 124, July 2019, Pages 126-131
Bone

Full Length Article
Maternal vitamin D in pregnancy and offspring bone measures in childhood: The Vitamin D in Pregnancy study

https://doi.org/10.1016/j.bone.2019.04.013Get rights and content

Highlights

  • Maternal 25(OH)D in early pregnancy was associated with offspring bone measures at 11 years in a sexually dimorphic manner

  • Maternal 25(OH)D in early pregnancy was positively associated with bone density and content in boys, but not girls.

  • There were no clear maternal 25(OH)D cutpoints, though there appeared to be greater effect in those with 25(OH)D <28nmol/L

Abstract

Previously we have demonstrated an association between maternal serum 25-hydroxyvitamin D (25(OH)D) during pregnancy and knee-heel length in offspring at birth. However, it is unknown whether maternal serum 25(OH)D is associated with bone measures in childhood. Thus, we aimed to examine associations between 25(OH)D at two stages of pregnancy and offspring bone measures at 11 years.

Women were recruited from a single antenatal clinic in Victoria, Australia before 16 weeks gestation and provided two serum samples to determine 25(OH)D status at recruitment and 28–32 weeks gestation. Children and their mothers were followed up at 11 years of age. Children undertook dual energy X-ray absorptiometry scans at the lumbar spine and total body.

Maternal 25(OH)D at recruitment (before 16 weeks gestation) was positively associated with the children's bone mineral content and density in boys, but not girls. In boys, a 10 nmol/L (4 ng/mL) increase in maternal 25(OH)D was associated with a median 0.5 g (95% CI 0.1,0.8) and 0.009 g/cm2 (95% CI 0.001,0.017) increase in bone mineral content and density at the spine, respectively, and a median 0.006 g/cm2 (95% CI 0.001,0.011) increase in at the total body. There was no sustained associations with 25(OH)D at the later timepoint (28–32 weeks) with any outcome.

At age 11 years, maternal 25(OH)D levels during early pregnancy, but not late were positively associated with bone measures in boys, but not girls.

Introduction

It is increasingly accepted that there are developmental origins of chronic disease in adulthood [1]. Osteoporosis is no exception and indeed the risk of developing osteoporosis in later life and consequent fracture may be programmed by early life exposures [2,3].

Vitamin D, measured as the circulating level of 25(OH)D, is a key substrate for the production of 1,25 dihydroxyvitamin D, a secosteroid hormone which plays an important role in bone growth and mineralisation [4]. A substantial number of Australian women, including those of child-bearing age, have low serum 25(OH)D levels [5]. Maternal insufficiency is a cause for concern not only for the mothers, but also because it exposes offspring to insufficiency in potentially critical early phases of development [6]. Optimising vitamin D levels may thus be an affordable modifiable factor to target during pregnancy to enhance offspring bone development.

Previously we have reported that maternal serum 25(OH)D level at 28–32 weeks gestation, but not at an earlier stage of gestation, was associated with a reduced knee-heel length, a proxy measure of long bone development in utero, in the offspring at birth [7]. Other prospective studies have explored associations between maternal 25(OH)D and offspring bone measures in early life [8]. In one study, 25(OH)D levels were associated with changes in foetal bone morphology as early as 19 weeks gestation [9]. Positive associations between maternal 25(OH)D levels and offspring bone mineral content (BMC) in childhood [10] and young adulthood [11] have previously been described, although null [12] and inverse associations in childhood have also been reported [13].

An apparent difference in studies is the timing of the 25(OH)D measurements. To our knowledge, no study to-date has collected maternal vitamin D levels at two defined time points in each individual and examined whether temporality of vitamin D status plays an important role in this association. We thus aimed to determine whether vitamin D status during early and later gestation was associated with bone measures in offspring aged approximately 11 years.

Section snippets

Participants

Mothers were recruited as part of a prospective longitudinal study based in Geelong, a regional city in south-eastern Australia [7]. Mothers with a singleton pregnancy were recruited before 16 weeks gestation from the primary public maternity hospital servicing the region, University Hospital Geelong (formerly Geelong Hospital) between 2003 and 2004. From 475 women recruited, 402 infants were born to mothers who had at least one blood sample taken during pregnancy and provided some measurements

Sample characteristics

Of the original 402 mother-child pairs, 208 (51.7%) participated in the 11 year follow-up. Of these, 195 had DXA measurements for both the spine and TBLH, and 183 had complete DXA measures and maternal vitamin D measurements at both recruitment (before 16 weeks) and 28–32 weeks gestation. A further two older children were excluded from analyses as their bone measures were outliers (+5.9 SD and +4.6 SD).

Women who were included in final analyses had similar characteristics to non-responders and

Discussion

To our knowledge, this study is the first to report differential relationships between maternal 25(OH)D at two stages of pregnancy and bone outcomes in offspring. Our results suggest that maternal 25(OH)D levels during earlier pregnancy may have a greater effect on offspring bone measures at age 11 years, in boys. There have been no studies describing childhood bone measures directly and risk of osteoporotic fracture later in life; however, BMD has been shown to track in childhood [18] and thus

Funding

This work was supported by the National Health and Medical Research Council (Australia) and Bupa Health Foundation. NKH and SMH are supported by Dean's Postdoctoral Research Fellowships (Deakin University), SLB is supported by an NHMRC Career Development Fellowship (1107510).

Declaration of interests

NKH, SB-O, MM, SMH and JAP have nothing to declare. JDW received in-kind support from Swisse Wellness and is currently receiving grant support from the NHMRC both for for an unrelated project studying vitamin D and health in young women. JAP is currently recieving funding from the NHMRC for unrelated projects.

Acknowledgements

We would like to thank participants of the Vitamin D in Pregnancy study for their continued involvement. Appreciation is also extended to Dr. Ruth Morley, who initiated the study, and to Ms. Kathy Bennett and Mrs. Amelia Betson for their roles in the collecting clinical data at birth and the 11 year follow-up, respectively.

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