Objective To investigate the association of maternal urinary cotinine levels during pregnancy with children's neurocognitive development at 2 yearsold, and to explore the sensitive window period of maternal urinary cotinine levels on the neurocognitive development of children.

Methods Based on a birth cohort from Wuhan, China, Bayley Scales of Infant Development (Chinese version) was performed to assess the neurocognitive development of children at 2 years old. The assessment result were expressed by the mental development index (MDI) and psychomotor development index (PDI), and the MDI score or PDI score less than 80 was defined as abnormal. Generalized estimating equations were used to analyze the association of urinary cotinine levels in the first, second, and third trimesters of pregnancy with the status of neurocognitive development of 2-year-old children.

Results A total of 989 mother-child pairs were included in this study. After adjusting for specific gravity, the medians (P₂₅, P₇₅) of urinary cotinine concentrations in the first, second, and third trimesters were 3.49 (2.14, 6.33), 3.48 (1.99, 6.30), and 2.61 (1.45, 4.80) ng/mL, respectively. After adjusting for potential confounding factors, MDI score decreased by 1.66 (95% confidence interval, CI: -2.97, -0.35) points with each ln-unit increase in urinary cotinine concentration during the first pregnancy. After adjusting for confounding factors, the concentrations of cotinine in urine during the first and second trimesters of pregnancy were positively associated with the risk of abnormal MDI scores in children, with OR (95%CI) values of 1.25 (1.03, 1.51) and 1.26 (1.04, 1.53), respectively. There were no significant associations of maternal urinary cotinine concentrations in three trimesters with children's PDI scores or risk of PDI abnormalities (P>0.05).

Conclusion There were significant negative associations of nicotine exposure in the first and second trimesters of pregnancy with the neurocognitive development status of children at 2 years old. Cotinine is a major metabolite of nicotine. Thus, pregnant women should avoid nicotine exposure in the first and second trimesters to reduce the risk of childhood neurocognitive developmental disorders.