Associations of alpha and gamma-tocopherol during early life with lung function in childhood

BACKGROUND: Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE: To determine the extent to which plasma alpha (alpha-T) or gamma tocopherol (gamma-T) isoform levels in early childhood or in-utero are associated with childhood lung function. METHODS: We included 622 participants in the Project Viva cohort, who had lung function at a mid-childhood visit (age 6-10 years old). Maternal and child tocopherol isoform levels were measured by HPLC at second trimester and 3 years old, respectively. Multivariable linear regression models (adjusted for mid-childhood BMI-z-scores, and maternal education, smoking in pregnancy, and prenatal PM2.5 particulate exposure), stratified by tertiles of child gamma-T, were employed to assess the association of alpha-T levels with FEV1 and FVC percent predicted. Similarly, models stratified by child alpha-T tertile evaluated associations of gamma-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. RESULTS: The maternal second trimester alpha-T level was median;IQR: 63; 47-82 muM. The early childhood levels were median;IQR: 25; 20-33 muM. In the lowest tertile of early childhood gamma-T, children with higher alpha-T levels (per 10 muM) had higher mid-childhood FEV1 %-predicted (beta=3.09, 95%CI=0.58-5.59), and a higher FVC %-predicted (beta=2.77, 95%CI=0.47,5.06). This protective association of alpha-T was lost at higher gamma-T levels. We did not see any consistent associations of second trimester levels of either alpha-T or gamma-T with mid-childhood FEV1 or FVC. CONCLUSION: When gamma-T levels were in the lowest tertile, higher early childhood alpha-T was associated with better lung function at mid-childhood. Second trimester maternal plasma alpha-T concentration was 3-fold higher than the adult female non-pregnant population. CLINICAL IMPLICATION: alpha-Tocopherol and gamma-tocopherol isoforms are potentially modifiable exposures that have differential associations with lung function in later childhood.