Urinary cotinine cut-offs for tobacco smoke exposure in pregnancy and associations with child intelligence quotient: A multi-cohort analysis

BACKGROUND: Prenatal exposure to tobacco smoke may impair neurodevelopment in children. However, accurately characterizing this exposure remains challenging. METHODS: We pursued two objectives in this large population study. First, in 1708 pregnant women from the Environmental Influences on Child Health Outcomes (ECHO) cohort, we constructed Receiver Operating Characteristic (ROC) curves to determine urinary cotinine cut-offs to classify firsthand (FHS), environmental (ETS), and no exposure, and further distinguished secondhand (SHS) from thirdhand smoke (THS) exposure within ETS. Second, among 1593 participants in three pregnancy cohorts nested in ECHO, we fit multivariable linear regressions to examine the association between the newly defined smoke exposures and child full-scale intelligence quotient (IQ) at age 4-6 years, and to assess potential effect modification by maternal education or neighborhood deprivation. RESULTS: Optimal cotinine cut-offs were 17.74 ng/mL and 0.44 ng/mL to discriminate FHS and no exposure, respectively. Among the ETS group, a cut-off of 5.69 ng/mL differentiated SHS from THS. Applying these optimal cut-offs, we estimated a 0.93-point (95 %CI: 3.44, 1.59) and a 1.03-point (95 %CI: 2.84, 0.79) lower child IQ in the FHS and ETS categories, respectively, compared to no exposure. The inverse association between prenatal ETS and child IQ was mainly driven by SHS. Stronger associations were suggested in subgroups with higher education attainment or those living in less deprived neighborhoods. CONCLUSIONS: This study provides a novel classification of prenatal tobacco smoke exposures. Although the associations with child IQ were statistically insignificant, the study carries important implications for future research on developmental origins of diseases.