In this exploratory analysis, we assessed whether nutrition modified the association between prenatal exposure to tobacco and childhood cognition/behavior among 366 Colorado-based mothers and their offspring (born ≥ 37 weeks with birthweights ≥ 2500 g). Interaction by folate (<
/≥ 1074 µg/day) and breastfeeding (<
/≥ 5 months) was assessed by including a product term with cotinine (<
/≥ limit of detection [LOD]) in regression models for NIH Toolbox and Child Behavior Checklist T-scores. Main effects were observed between cotinine ≥ LOD and inhibitory control (- 3.2
95% CI: - 6.8, 0.3), folate <
1074 µg/day and anxious/depressed symptoms (1.1
95% CI: 0.1, 2.1), and breastfeeding <
5 months and receptive language (- 4.3
95% CI: - 8.5, - 0.02), though these findings would not survive Bonferroni correction. Breastfeeding modified the tobacco-behavior associations. Sleep (3.8
95% CI: 0.5, 7.1
interaction p-value = 0.02), depressive (4.6
95% CI: 1.0, 8.2
interaction p-value = 0.01) and total problems (5.8
95% CI: - 0.7, 12.4
interaction p-value = 0.09) were observed among tobacco-exposed offspring who breastfed >
5 months, but not for shorter durations. Our findings support the need for smoking cessation campaigns throughout pregnancy and throughout the postpartum period breastfeeding to reduce neurobehavioral risks in the offspring.