Maternal vitamin D status modifies the effects of early life tobacco exposure on child lung function
J.of Allergy and Clinical Immunology V151, #2, Feb 2023, pg 556-564 https://doi.org/10.1016/j.jaci.2022.10.030
Hanna M. Knihtilä MD, PhD a b, Mengna Huang PhD a, Nicole Prince PhD a, Benjamin J. Stubbs BA a, Vincent J. Carey PhD a, Nancy Laranjo BA a, Hooman Mirzakhani MD, MMSc, PhD a, Robert S. Zeiger MD, PhD c d, Leonard B. Bacharier MD e, George T. O’Connor MD, MS f, Augusto A. Litonjua MD, MPH g, Scott T. Weiss MD, MS a, Jessica Lasky-Su ScD a
Background
Prior studies suggest that vitamin D may modify the effects of environmental exposures; however, none have investigated gestational vitamin D and cumulative tobacco smoke exposure (TSE) throughout pregnancy and early life.
Objectives
This study investigated the effects of early life TSE on child lung function and the modulatory effects of gestational vitamin D on this association.
Methods
The VDAART (Vitamin D Antenatal Asthma Reduction Trial) recruited nonsmoking pregnant women and followed the mother-child pairs to age 6 years. TSE was assessed with questionnaires and plasma cotinine measurements in the mothers (10-18 and 32-38 gestational weeks) and children (1, 3, and 6 years). Cumulative TSE was calculated from the repeated cotinine measurements. 25-hydroxyvitamin D (25OHD) levels were measured at 10-18 and 32-38 gestational weeks. Lung function was assessed at 6 years with spirometry and impulse oscillometry.
Results
Of the 476 mother-child pairs, 205 (43%) had increased cotinine levels at ≥1 time point. Cumulative TSE was associated with decreased FEV1 (β = −0.043 L, P = .018) and increased respiratory resistance at 5 Hz (R5; β = 0.060 kPa/L/s, P = .002). This association persisted in subjects with insufficient (<30 ng/mL) 25(OH)D levels throughout pregnancy (β = 0.077 kPa/L/s, P = .016 for R5) but not among those with sufficient levels throughout pregnancy.
Conclusions
Cumulative TSE from pregnancy to childhood is associated with dose- and duration-dependent decreases in child lung function at 6 years even in the absence of reported maternal smoking. Gestational vitamin D may modulate this effect and have therapeutic potential for minimizing the adverse effect of TSE on lung throughout early life.
Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART); clinicaltrials.gov identifier: NCT00920621.
Section snippets
Study populations
The VDAART (NCT00920621) is a double-blinded multicenter trial that randomized nonsmoking pregnant women at 10-18 gestational weeks (GW) for high-dose vitamin D3 supplementation (4000 IU/d) or placebo.25 All enrolled women and/or the biological fathers of the children had a history of asthma, eczema, or allergic rhinitis. Written informed consent was obtained from the mothers, and the study was approved by the Institutional Review Boards at the 3 clinical centers (Boston, St Louis, and San . . . .
Baseline characteristics
Of the 806 mother-child pairs in VDAART, 805 subjects had data on ≥1cotinine measurement and of these subjects, 476 had successful lung function data at age 6 years and were included in the present post hoc study (Fig 1). No differences were observed between the baseline characteristics of included and excluded VDAART mother-child pairs apart from study site distribution (P = .019) (see Table E1 in this article’s Online Repository at www.jacionline.org). The number of subjects with plasma . . . .
Discussion
Our study indicates that cumulative TSE, reflected by increased plasma cotinine levels at multiple time points during pregnancy and childhood, is associated with dose- and duration-dependent decreases in child lung function at age 6 years. Recent global health reports reiterate the enormous public health burden of tobacco use,1 and our study demonstrates the negative implications of TSE in a vulnerable population. The majority of reported TSE in this study were secondhand, indicating that . . . .
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