ABSTRACT: Maternal smoking has been associated with elevated risk of type 2 diabetes among the offspring in adulthood. The mechanisms underlying this fetal "programming" effect remain unclear. The present study sought to explore whether maternal smoking affects metabolic health biomarkers in fetuses/newborns.In a prospective singleton pregnancy cohort (n = 248), we compared metabolic health biomarkers in the newborns of smoking and non-smoking mothers. Outcomes included cord plasma insulin, proinsulin, insulin-like growth factor I (IGF-I), IGF-II, leptin and adiponectin concentrations, glucose-to-insulin ratio (an indicator of insulin sensitivity) and proinsulin-to-insulin ratio (an indicator of ?-cell function).Independent of maternal (glucose tolerance, age, ethnicity, parity, education, body mass index, alcohol use) and infant (sex, gestational age, birth weight z score, mode of delivery, cord blood glucose concentration) characteristics, the newborns of smoking mothers had lower IGF-I concentrations (mean: 6.7 vs. 8.4 nmol/L, adjusted p = 0.006), and marginally higher proinsulin-to-insulin ratios (0.94 vs. 0.72, adjusted p = 0.06) than the newborns of non-smoking mothers. Cord plasma insulin, proinsulin, IGF-II, leptin and adiponectin concentrations and glucose-to-insulin ratios were similar in the newborns of smoking and non-smoking mothers.Maternal smoking was associated with decreased fetal IGF-I levels, and borderline lower fetal ?-cell function. Larger cohort studies are required to confirm the latter finding. The preliminary findings prompt the hypothesis that these early life metabolic changes may be involved in the impact of maternal smoking on future risk of metabolic syndrome related disorders in the offspring.