Maternal smoking and newborn cytokine and immunoglobulin levels

Introduction:: Prenatal smoking exposure may lead to permanent changes in neonatal inflammation and immune response that have lifelong implications, including increased risks for atopy and respiratory disorders. Methods:: The effect of maternal smoking on neonatal biomarkers of inflammation and immune response was assessed among 3459 singletons and twins in the Upstate KIDS Study. The following inflammatory biomarkers were measured using newborn dried blood spots (DBSs): interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, C-reactive protein, and tumor necrosis factor alpha. Immunoglobulins (IgE, IgA, IgM, and IgG subclasses) were also assessed. We used generalized estimating equations to calculate mean differences (β) in biomarker levels by timing of pregnancy smoking, cigarette load, and secondhand smoke exposure after adjusting for sociodemographic and lifestyle factors including maternal body mass index. Results:: Of the 344 (12%) women reporting smoking during pregnancy, about 40% continued throughout pregnancy and 13% reported smoking more than 1 pack per day. After covariate adjustment and Bonferroni correction for multiple comparisons, maternal smoking throughout pregnancy remained significantly associated with increased levels of IL-8 (β = 0.20, 95% confidence interval: 0.07, 0.32; p <.003). No significant associations were found with cigarette load or secondhand smoke exposure. Higher IgG3 levels were also associated with maternal smoking throughout pregnancy, although the association became nominally significant after adjustment for covariates (β = 0.09; 95% confidence interval: 0.0007, 0.17; p <.05). Conclusions:: Maternal smoking throughout pregnancy was independently associated with increased IL-8 levels in newborns. Importantly, neonates of women who stopped smoking anytime in pregnancy did not have increased IL-8 levels. Implications:: This study evaluated a range of inflammatory biomarkers and immunoglobulins in association with maternal smoking and timing/duration of smoking along with secondhand smoke exposure. By using DBSs, we present data from a large cohort of children born in Upstate New York. Our findings suggest that early differences in immunoregulation of neonates exposed to maternal smoking for full duration in utero may already be detected at birth.