Associations between prenatal and postnatal substance exposure and salivary C-reactive protein in early childhood.

backgroundExposure to tobacco and cannabis during developmental periods of enhanced vulnerability (e.g., in utero and early childhood) may have long-lasting effects on child health. One potential mechanism underlying these associations is the alteration of inflammatory pathways. Using data from a longitudinal study of mother/child dyads, we examined the adjusted and combined associations of prenatal and postnatal tobacco and cannabis exposure with inflammation in early childhood. Furthermore, we explored the relations between different measures of exposure, partly reflecting differences in timing, dose, and level of fetal exposure (e.g., self-report vs. biomarker), and inflammation. Finally, we explored child sex as a moderator of prenatal and postnatal tobacco and cannabis exposure and inflammation.

methodWomen were recruited from a local hospital during their first prenatal appointment. Repeated assessments were conducted at each trimester, at birth, and when children were 2, 9, 16, 24, 36, and 60 months old (N = 215; 112 female children). To evaluate associations with different measurement approaches, prenatal tobacco and cannabis exposure were assessed using: 1) continuous dose-response variables of maternal self-reported tobacco and cannabis use during each trimester to assess associations with timing and severity of exposure, 2) categorization of children into exposure groups based on drugs and metabolites present in infant meconium reflecting later pregnancy fetal exposure, and 3) categorization into exposure groups using a combination of maternal self-report data and biomarker data derived from maternal saliva samples and infant meconium taking advantage of multiple methods of assessment to examine group differences. Postnatal exposure to tobacco (assessed using child salivary cotinine) and cannabis (assessed using maternal self-reported average joints smoked per day) was measured at each infancy/early childhood assessment. Adjusted pre- and postnatal exposure associations with child inflammation were assessed by including both measures as predictor variables in linear regression models predicting child salivary C-reactive protein (CRP) concentrations at 60 months. Interactions between pre- and postnatal exposure variables were then modeled to investigate the combined relations between pre- and postnatal substance exposure with child salivary CRP concentrations at 60 months.

resultsAdjusting for postnatal exposure variables, there was a significant interaction between the average daily cigarettes and the average daily cannabis joints smoked during the third trimester predicting salivary CRP concentrations in early childhood. At high tobacco exposure, the effect of cannabis on CRP concentrations was negligible, whereas at low tobacco exposure, the effect of cannabis exposure on CRP concentrations was positive. Adjusting for postnatal tobacco and cannabis exposure, children for whom meconium data indicated co-exposure to tobacco and cannabis showed approximately 43% lower CRP concentrations at age 60 months compared to children with no exposure. However, when mother/child dyads were categorized based on a combination of maternal self-report data and biomarker data from saliva samples and infant meconium, there were no differences in salivary CRP concentrations at age 60 months across the three groups (no prenatal exposure, prenatal tobacco exposure only, prenatal co-exposure to tobacco and cannabis), controlling for postnatal associations. Regardless of the measurement method used to assess prenatal exposures in adjusted analyses, prenatal tobacco exposure alone did not predict CRP concentrations in early childhood, nor did postnatal tobacco exposure. Among boys, postnatal cannabis exposure was associated with higher concentrations of CRP at age 60 months, controlling for prenatal exposure relations. There were no significant combined associations of pre- and postnatal exposure with CRP concentrations.

conclusionThis study expands upon known relations between prenatal and postnatal substance exposure and immunological outcomes in early childhood, underscoring the importance of assessing cannabis exposure during gestation and early life in combination with tobacco exposure.