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Low gestational vitamin D level is related to decreased offspring lung function

Published: January 21, 2021

Vitamin D (VD) insufficiency is extremely common worldwide, especially among pregnant and lactating women. VD has been linked to fetal lung and immune system development, with animal studies demonstrating structural and functional lung changes in the offspring of VD-deficient mothers. However, studies in humans have been conflicting and have generally failed to show any association between gestational VD level and offspring lung function.

In a recent original article published in The Journal of Allergy and Clinical Immunology (JACI), Knihtilä and colleagues examined the association between gestational VD level and offspring lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). VDAART is a prospective, multi-center study that randomized pregnant US women at high risk of having children with asthma to high-dose VD supplementation or placebo. Plasma VD level was measured in the mothers at recruitment (10-18 gestational weeks) and at third trimester (32-38 gestational weeks), and in the children at birth and at ages 1 and 3 years. Based on detailed questionnaires from birth to age 6 years, the children were categorized into three clinical childhood asthma phenotypes: asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Child lung function was measured with 2 different methods: impulse oscillometry at ages 4, 5, and 6 years and spirometry at ages 5 and 6 years.

A total of 570 mother-child pairs were included in the study. Lower gestational VD level quartiles were associated with decreased child lung function from age 4 to 6 years as measured by both impulse oscillometry and spirometry. At age 6 years, offspring of mothers in the highest mean gestational VD level quartile had 10.7% higher forced expiratory volume in 1 second (FEV1) than those in the lowest quartile. In contrast, the child VD level at ages 1 and 3 years was not associated with lung function from age 4 to 6 years. The authors performed a separate analysis comparing the lung function of children with mothers having deficient (<20 ng/ml), insufficient (20-29 ng/ml), or sufficient (≥30 ng/ml) VD level at both recruitment and at third trimester. Similar to the VD level quartiles, these gestational VD level groups demonstrated a significant positive association with child lung function from age 4 to 6 years. When comparing the different childhood asthma phenotypes, children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group, whereas differences between the transient early wheeze group and the asymptomatic/infrequent wheeze group were consistently smaller or nonexistent when compared with what was seen with the asthma group. The associations with lung function of both low gestational VD level and child asthma at age 6 years remained significant in a multivariable model, suggesting independent effects of these two risk factors.

These findings indicate that low gestational VD level is an important and independent risk factor for decreased childhood lung function from 4 to 6 years of age, and children who develop asthma have lung function deficits that are present in early life. Both early and late pregnancy VD levels were significantly associated with offspring lung function and suggested that gestational VD level of ≥30 ng/ml might be optimal for offspring respiratory health in subjects who are at high risk of asthma.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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