High Maternal Circulating Cotinine During Pregnancy is Associated With Persistently Shorter Stature From Birth to Five Years in an Asian Cohort

Abstract

Background: Self-reported maternal active smoking has been associated with reduced offspring birth length and shorter stature in early and late childhood. Objective: To use circulating cotinine as an objective biomarker to investigate the association between smoking and environmental tobacco smoke (ETS) exposure in pregnancy and longitudinal measures of offspring length/height from birth to 60 months. Methods: In 969 maternal-offspring dyads from the GUSTO cohort, maternal plasma cotinine at 26-28 weeks' gestation was measured by LC/MS/MS and categorized into four groups: Group 1: Cotinine <0.17 ng/mL (the assay's detection limit) and no ETS exposure; Group 2: Cotinine <0.17 ng/mL but self-reported ETS; Group 3: Cotinine 0.17-13.99 ng/mL (ETS or light smoking); Group 4: Cotinine ≥14 ng/mL (active smoking). Results: Adjusting for infant sex, gestational age at birth, ethnicity, maternal age, education, parity, BMI, and height, Group 4 offspring were shorter at birth [z-score β =-0.42 SD units (SDs) (95% CI =-0.77 to-0.06)] than Group 1 offspring. Group 4 offspring continued to be shorter at older ages, with similar effect sizes at 3 months [-0.57 SDs (-0.95 to-0.20)], 36 months [-0.53 SDs (-0.92 to-0.15)], 48 months [-0.43 SDs (-0.81 to-0.04)], and 60 months [-0.57 SDs (-0.96 to-0.17)]. Associations were particularly marked in boys. No significant differences in stature were observed in Groups 2 or 3 compared with Group 1. Conclusions: This Asian longitudinal study associated high prenatal cotinine with persistently shorter stature in offspring from birth and into early childhood, whilst low prenatal cotinine levels and ETS exposure showed no such association. Implications: Little is known about the long-term effects of prenatal tobacco exposure on offspring stature in Asia where passive smoking is common. This study has used an objective biomarker to reveal that the association of prenatal tobacco exposure with offspring length/height mainly occurs at a high maternal cotinine level of greater than 14 ng/mL in pregnancy, consistent with active smoking, but no significant associations were found with lower cotinine levels, consistent with passive smoking. Encouraging women to quit smoking prior to or during pregnancy may avert the long-term negative impact on their child's height despite appreciable prenatal ETS exposure.