Associations of prenatal tobacco and insecticide co-exposures with neurobehavioral responses among children born to pregnant women exposed to cannabis.

BACKGROUND

Cannabis and tobacco are contaminated with insecticides and used during pregnancy in the U.S., raising concerns for co-exposures and compounded neurodevelopmental effects. However, these cumulative effects remain unexplored. We examine the associations of prenatal cannabis, tobacco, pyrethroid, and organophosphate insecticides co-exposures with early childhood neurobehaviors.

METHODS

Among 197 mother-child pairs from a birth cohort in Atlanta, Georgia, cannabis (THCCOOH), tobacco (COT and 3OH-COT), pyrethroids (3PBA), and organophosphates (TCPY) metabolite levels were quantified in maternal urine sampled at 8-14 and 24-30 weeks' gestation. Infant arousal and attention were evaluated 2 weeks postnatally using the NICU Network Neurobehavioral Assessment Scale. Externalizing and internalizing behaviors were assessed annually using the Child Behavior Checklist and averaged across ages 2-5 years. We examined individual associations using linear regression; cumulative associations using quantile g-computation and Bayesian kernel machine regression (BKMR); and whether THCCOOH modified the cumulative effect of tobacco and insecticides.

RESULTS

Of the prenatal exposures, only insecticides were associated with child neurobehavior. For example, a doubling in 3PBA was positively related to internalizing behaviors (β = 18.1 %; 95 % confidence interval [CI] = 0.0 %, 39.5 %), and TCPY was negatively associated with externalizing behaviors (β = -12.9 %; 95 % CI = -27.8 %, 5.0 %). These were modified by THCCOOH and sex. The prenatal 3PBA, TCPY, COT, and 3OH-COT mixture was associated with lower externalizing behaviors among females with detectable THCCOOH (quantile g-computation β = -46.8 %; 95 % CI = -70.4 %, -4.1 %). BKMR showed no interactions and dose-responses.

DISCUSSION

Prenatally, 3PBA and TCPY were associated with child neurobehaviors, and effects differed by THCCOOH and sex. Further studies on the neurodevelopmental burden of cannabis, tobacco, and insecticide co-exposures are needed.