Meat Consumption During Pregnancy and Substance Misuse Among Adolescent Offspring: Stratification of TCN2 Genetic Variants

Abstract

Background: Reducing meat consumption is often advised; however, inadvertent nutritional deficiencies during pregnancy may result in residual neurodevelopmental harms to offspring. This study assessed possible effects of maternal diets in pregnancy on adverse substance use among adolescent offspring.

Methods: Pregnant women and their 13-year-old offspring taking part in a prospective birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), provided Food Frequency Questionnaire data from which dietary patterns were derived using principal components analysis. Multivariable logistic regression models including potential confounders evaluated adverse alcohol, cannabis, and tobacco use of the children at 15 years of age.

Results: Lower maternal meat consumption was associated with greater problematic substance use among 15-year-old offspring in dose-response patterns. Comparing never to daily meat consumption after adjustment, risks were greater for all categories of problem substance use: alcohol, odds ratio OR = 1.75, 95% CI = (1.23, 2.56), p < 0.001; tobacco use OR = 1.85, 95% CI = (1.28, 2.63), p < 0.001; and cannabis OR = 2.70, 95% CI = (1.89, 4.00), p < 0.001. Given the likelihood of residual confounding, potential causality was evaluated using stratification for maternal allelic variants that impact biological activity of cobalamin (vitamin B12) and iron. Lower meat consumption disproportionally increased the risks of offspring substance misuse among mothers with optimally functional (homozygous) variants (rs1801198) of the gene transcobalamin 2 gene (TCN2) which encodes the vitamin B12 transport protein transcobalamin 2 implicating a causal role for cobalamin deficits. Functional maternal variants in iron metabolism were unrelated to the adverse substance use. Risks potentially attributable to cobalamin deficits during pregnancy include adverse adolescent alcohol, cannabis, and tobacco use (14, 37, and 23, respectively).

Conclusions: Lower prenatal meat consumption was associated with increased risks of adolescent substance misuse. Interactions between TCN2 variant status and meat intake implicate cobalamin deficiencies.

Keywords: Avon Longitudinal Study of Parents and Children (ALSPAC); Cobalamin; Meat; Single Nucleotide Polymorphism (SNP); Transcobalamin Gene (TCN2).