Maternal, Fetal Vitamin D Levels: No Effect on Child Bone Health

Becky McCall

March 17, 2017

Concentrations of 25-hydroxyvitamin D (25[OH]D) in the pregnant mother and newborn show no association with childhood bone health, new data from the largest prospective cohort study of its kind to date indicate.

The findings suggest 25(OH)D concentrations during childhood are more relevant for bone health than in utero levels.

"No associations were seen between maternal 25(OH)D concentrations during mid-pregnancy, or offspring 25(OH)D concentrations at birth, with offspring bone outcomes at age 6 years," conclude the investigators of the multiethnic, population-based study, led by Audry Garcia, PhD, University Medical Center Rotterdam, The Netherlands.

Published online March 1 in The Lancet Diabetes & Endocrinology, the results "do not support vitamin D supplementation as a routine antenatal care practice in pregnant women to improve bone mass or bone density in childhood or in later life," according to the authors.

In an accompanying editorial, Christopher S Kovacs, MD, Memorial University, St John's, Newfoundland, says that when taken in context with previous observational studies, "it seems likely that there is no real association between 25(OH)D measures at or before birth and childhood bone mass."

"As Dr Garcia and colleagues suggest, childhood 25(OH)D concentration is probably more relevant than cord blood 25(OH)D concentration in determining childhood bone mass," he adds.

Nearly 5000 Mother–Child Pairs Studied

Embedded within the Generation R Study, Dr Garcia and colleagues measured maternal 25(OH)D concentrations in mid-pregnancy (median 20.4 weeks gestation) and 25(OH)D concentrations at birth in the baby, to reflect fetal concentrations.

Total body bone mineral density, bone mineral content, area-adjusted bone mineral content, and bone area (using dual-energy X-ray absorptiometry [DXA]) were measured in the same children at age 6 years. In total, both mid-pregnancy maternal 25(OH)D concentrations and offspring DXA scans at age 6 years were obtained for 4815 mother–child pairs.

The results were adjusted for sociodemographic and lifestyle variables, and height (which can affect DXA scan accuracy in children). Forty-five percent of mothers were highly educated, and most children were of European descent (81%); children of these sociodemographic groups provided most of the bone data.

Initially, researchers found an inverse relationship between maternal vitamin D status and bone health in the offspring at age 6.

Severe maternal 25(OH)D deficiency (< 25 nmol/L) mid-pregnancy was associated with higher offspring bone mineral content (4.7 g; P = .011) and larger bone area (7.5 cm2; P = .001) at age 6 years, compared with maternal 25(OH)D sufficiency (≥ 50 nmol/L) mid-pregnancy.

Adjusting for maternal body mass index, maternal calcium intake, child sex, or child weight status did not affect results.

For associations between 25(OH)D concentrations at birth in the offspring and bone outcomes at age 6, the same findings were true as for maternal 25(OH)D levels.

But a further strength of the study was the availability of data on 25(OH)D concentrations at the time of bone measurements in a subset of children.

In this group (n = 3034), the associations between maternal and fetal 25(OH)D status and bone mineral content and bone area were no longer significant after adjusting for the child's 25(OH)D status.

"In this large cohort, after taking into account the child's own 25(OH)D status, no associations were seen between maternal 25(OH)D status during mid-pregnancy or offspring 25(OH)D concentrations at birth with offspring bone outcomes at age 6 years," the researchers stress.

Prior Studies Showed Mixed Results

The authors note that prior studies have yielded conflicting results regarding theassociation between maternal vitamin D status and offspring bone health, which has led to contradictory recommendations on vitamin D supplementation during pregnancy.

This motivated the current study, the findings of which are consistent with those of another large, prospective cohort study reported by Medscape Medical News in 2013. This earlier trial found no association between vitamin D levels of mothers during pregnancy and the subsequent bone-mineral content of their children at age 9 years.

The Maternal Vitamin D Osteoporosis Study (MAVIDOS) study, also previously reported by Medscape Medical News, showed that vitamin D supplements (1000 IU/day) taken during pregnancy did not improve bone mass in offspring at 14 days compared with placebo overall; however, those born in winter months did gain significant bone benefits from maternal vitamin D supplementation.

Dr Garcia and colleagues suggest that the facilitating action of vitamin D in maintaining the mineral homoeostasis necessary for bone mineralization becomes relevant only after birth.

They also highlight the fact that another study has suggested calcium intake and parathyroid hormone could be more relevant for bone development than 25(OH)D status, but note that they "did not have information on the children's dietary or calcium supplement intake, or on their parathyroid hormone concentrations to study these associations."

Summing up in the editorial, Dr Kovacs says that "overall, the bulk of available data suggest that vitamin D and calcitriol are not needed to regulate calcium homoeostasis or skeletal development before birth."

But he cautions that "vitamin D sufficiency should be maintained during pregnancy because calcitriol becomes important soon after birth when the intestines become the dominant route of calcium delivery."

Dr Garcia and Dr Kovacs have reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online March 1, 2017. Abstract

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