Maternal vitamin D status modifies the effects of early life tobacco exposure on child lung function

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 (25[OH]D) 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 (13 = -0.043 L, P = .018) and increased respiratory resistance at 5 Hz (R5; 13 = 0.060 kPa/L/s, P = .002). This association persisted in subjects with insufficient (<30 ng/ mL) 25(OH)D levels throughout pregnancy (13 = 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.