Prenatal Systemic and Local Immune Response in Smoking and Nonsmoking Women

Objective: Maternal tobacco use and systemic immune responsiveness are individually associated with preterm birth (PTB), and the interaction of tobacco use on systemic cytokines requires further study. Currently, there is limited evidence on the impact of prenatal smoking status on serum cytokines and stress. Our primary aim is to determine whether prenatal smoking impacts systemic cytokine distribution.

Design: This was a planned secondary analysis of a prospective, longitudinal multi-center trial
Setting: Regional prenatal clinics

Sample: Eightly-one smoking and nonsmoking pregnant women with singleton gestation

Methods: Cytokine biomarkers (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, TNFa) and CRP were measured using a multiplex beadlyte assay on a Luminex IS-100. At each timepoint, smoking status was collected via self-report (survey) and validated by preset urine cotinine limits. Cytokine data were log transformed. Statistical analysis included descriptive statistics, ANOVA, T-tests and Spearman’s rank correlation coefficient using Statistical Analysis Software (SAS) version 9.3.

Results:  Eighty-one women underwent evaluation in the first trimester, 76 in the second and 69 in the third. Thirty-nine of the participants (48%) were smokers and self-report smoking status was strongly correlated with urine cotinine (ρ = .68). Less than 10% of women who stated they were nonsmokers, were classified as smokers based on urine cotinine limtis. First trimester serum C-reactive protein (CRP) was significantly higher in women who smoked (p= .04). Furthermore, proinflammatory cytokines in the second and trimester (IL-6 and IL-1α) were also significantly different between women who smoke and do not smoke during pregnancy (p= .04; p= .02, respectively). No significant differences were observed in other serum cytokine concentrations, including anti-inflammatory IL-10.

Conclusion/Implications for nursing practice: Prenatal tobacco may impact the critical balance between pro and anti-inflammatory cytokines/molecules. Both elevated CRP and pro-inflammatory mediators can trigger oxidative stress, potentially impacting endothelial/endocervical structure. Furthermore, upregulation of pro-inflammatory cytokines in the second and third trimester may stimulate an unnecessary inflammatory response and increase the risk for preterm birth. Nurses and other healthcare professionals need to consistently screen for prenatal tobacco use and offer evidenced based-smoking cessation interventions to reduce preterm birth risk. Further research needs to investigate the role of maternal tobacco use on local and systemic immune response during pregnancy.

Keywords: preterm birth, immune response, stress, tobacco, cytokines