Non-linear and non-additive associations between the pregnancy metabolome and birthweight

Untargeted and Targeted Blood Lipidomic Signature Profile of Gestational Alcohol Exposure

“…In the uterine endometrium of guinea pigs, PC, PE, and TG are the main sources of arachidonic acid during prostaglandin synthesis, and there is a significant increase in arachidonic acid during late pregnancy. Further, there was a strong correlation reported between PE, PC, and DG and birth weights [ 36 ]; this suggests that decreases in PA, PC, PE, PI, and PS following alcohol exposure may negatively impact fetal development.…”

Associations of a Prenatal Serum Per- and Polyfluoroalkyl Substance Mixture with the Cord Serum Metabolome in the HOME Study

“…51−55 For example, Collicino et al found 35 prenatal serum metabolites related to lipid metabolism (∼30 weeks' gestation) were associated with lower birthweight z-scores in 410 mother− child dyads from Boston or New York City. 51 Conversely, a study by Yeum et al did not find that prenatal plasma metabolites (24 to 28 weeks' gestation) were associated with birth anthropometry, including birthweight z-scores. 53 However, when evaluating cord plasma rather than maternal plasma, this study did observe associations between metabolic lipid pathways and birthweight and length z-scores in 413 pregnant people and 787 infants in rural New Hampshire.…”

“…As our study demonstrates an association between PFAS and these metabolic pathways, this may help explain potential mechanisms between PFAS and these outcomes like liver disease. ,, Therefore, future studies could investigate these pathways as potential mediators between PFAS and these health outcomes. Prior studies have also observed associations of the prenatal and infant metabolome with adverse birth outcomes, such as birthweight. − For example, Collicino et al found 35 prenatal serum metabolites related to lipid metabolism (∼30 weeks’ gestation) were associated with lower birthweight z-scores in 410 mother–child dyads from Boston or New York City . Conversely, a study by Yeum et al did not find that prenatal plasma metabolites (24 to 28 weeks’ gestation) were associated with birth anthropometry, including birthweight z-scores .…”

Machine Learning Assisted Discovery of Interactions between Pesticides, Phthalates, Phenols, and Trace Elements in Child Neurodevelopment

“…Through the collective activities of the chemicals, (1) one can identify the mechanism of synergistic or antagonistic behavior that might arise beyond the concentration thresholds (and not just the regression coefficient of multiplicative associations), and (2) the use of concentration thresholds reflect the toxicological underpinning of classical threshold based on chemical dose–response studies. − Moreover, as the number of chemical exposures increases, searching for multiordered interactions gets computationally intensive. Most current methods, therefore, “hard code” or prespecify interaction terms in models, but such strategies are limited due to restrictions on sample size and are usually underpowered. , In comparison, Kernel Machine Regression or Bayesian factorization-inspired methods discover interactions with certain functional forms that do not represent any collective activity or concentration threshold. ,, The lack of similarity with toxicological threshold-based dose–response studies makes it difficult to find biologically relevant interpretations of the recovered interactions. It is also possible that such interactions can only be present in a subset of the population since not every sample will have chemical concentrations beyond certain thresholds.…”