Maternal vitamin D deficiency is associated with multisystem long-term health outcomes in offspring, according to a summative review of five published substudies.
Findings from a longitudinal, prospective study of 901 mother and offspring pairs indicate that children born to mothers with serum 25-hydroxy-vitamin D (25-OH-D) levels less than 50 nmol/L at 18 weeks' gestation were at increased risk for impaired lung development at 6 years, neurocognitive problems at 10 years, eating disorders during adolescence, and lower peak bone mass at 20 years. Prue H. Hart, PhD, from the Telethon Kids Institute at the University of Western Australia, and colleagues report their findings in an article published online December 15 in Pediatrics.
The researchers used data from the Western Australian Pregnancy Cohort (Raine) Study, an unselected, community-based cohort comprising predominantly white women, to examine the relationship between maternal vitamin D status and health outcomes over time of offspring who were born in Perth, Western Australia, from 1989 to 1991. "Of importance, the emphasis was on changes that reflect organ development (eg, lung capacity, language ability, peak bone mass) and that may predispose, in some cases, to ill health later in life," the authors write.
Of the full maternal cohort, 323 (36%) were vitamin D-deficient at 18 weeks' gestation. Twenty-nine of the pregnant women (3%) were severely deficient, with 25-OH-D levels less than 25 nmol/L.
The findings from the substudies reported in the summation demonstrate:
A significant, positive association between maternal serum 25-OH-D levels and Z scores for forced vital capacity in children at 6 years of age. The effects on lung measures titrated with levels of vitamin D after the researchers adjusted for confounders. The findings of this substudy of 260 mother–offspring pairs suggest "an association of vitamin D deficiency with respiratory disease is due to an impact on lung development," the researchers report.
A significant association with language development at ages 5 and 10 years. In this 743 mother–offspring pair substudy, multivariable regression analyses showed that the risk of having a child with clinically significant language impairment was increased by nearly twofold in women with the lowest vitamin D levels at 18 weeks' gestation compared with those in the highest quartile of the 25-OH-D distribution.
An increased risk for high scores (at least 2 standard deviations above the mean) in early adulthood on the Attention Switching subscale of the Autism-Spectrum Quotient for children of vitamin D-deficient mothers in a substudy of 406 mother-offspring pairs.
A significant predictive relationship between lower maternal vitamin D status and eating disorder risk in female offspring. Specifically, a serum 25-OH-D level in the lowest quartile was associated with a twofold increase in odds for having an eating disorder by age 20 years relative to concentrations in the highest quartile, after adjustment for multiple potential confounders.
A significant association between maternal vitamin D deficiency and lower peak bone mass in offspring at 20 years. Total body bone mineral content was reduced by 2.7% and total body bone mineral density was reduced by 1.7% (after accounting for season of sample collection and maternal and offspring factors) compared with children of vitamin D-sufficient mothers.
Taken together, the findings from the observational studies "suggest, but do not prove, that vitamin D plays an active role in fetal lung, brain, and bone development," the authors write. "The possibility remains that the reduced lung, brain, and bone development in the offspring of vitamin D-deficient mothers may not reflect vitamin D deficiency per se but some other health factor in the women that is associated with maternal vitamin D deficiency."
Although the researchers adjusted for a range of potentially relevant confounders, "it was not possible to adjust for every possible confounder," the authors note. ”What is striking with the studies reported here is the breadth of the health outcomes for which an association is reported in the collection of studies; confounding by maternal health status as the explanation for the observed associations is highly unlikely," they contend.
On the basis of the collective findings, the researchers suggest that sufficient level vitamin D in utero "is permissive for optimal development of multiple organs, not just bone as would be historically proposed."
Until definitive data from randomized controlled trials of vitamin D supplementation of pregnant women are available, the authors conclude, "maintaining a 25(OH)D level of>50 nmol/L in pregnant women must be considered a reasonable target."
Raine Study core management funding has been provided by the University of Western Australia; Telethon Kids Institute; Raine Medical Research Foundation' University of Western Australia Faculty of Medicine, Dentistry and Health Sciences; Women’s and Infant’s Research Foundation; Curtin University; and Edith Cowan University. The authors have disclosed no relevant financial relationships.
Pediatrics. Published online December 15, 2014. Abstract
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