Extending non-targeted exposure discovery of environmental chemical exposures during pregnancy and their association with pregnancy complications—a cross-sectional study

Abstract

Background: Non-targeted Analysis (NTA) methods can identify novel exposures in a variety of biological matrices, however, few have been assessed for relationships with pregnancy complications. Objectives: This study characterizes levels of nine exogenous and endogenous chemicals including linear and branched isomers perfluorooctane sulfonate (PFOS); perfluorohexane sulfonate (PFHxS); monoethylhexyl phthalate; 4-nitrophenol; and tetraethylene glycol; the fatty acids: tridecanedioic acid and octadecanedioic acid, and the bile acid: deoxycholic acid. These chemicals were identified, selected, and confirmed in prior NTA steps and we evaluate their relationship with pregnancy complications in a diverse pregnancy cohort in San Francisco. Methods: Matched maternal and cord serum samples were collected from 302 pregnant people at delivery from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculate distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. Among the maternal samples we used logistic regression to calculate the odds of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy associated with prenatal chemical exposures. Results: We detected linear PFOS, PFHxS, tridecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. We observed strong correlations between cord and maternal levels of PFHxS (coefficient = 0.9), linear PFOS (0.8), and branched PFOS (0.8). In maternal samples, branched PFOS was correlated with linear PFOS (0.8) and PFHxS (0.6). We found Linear PFOS and branched PFOS were positively associated with increased odds of GDM [OR (95%CI): 1.60 (0.94, 2.73) and 1.56 (1.00 , 2.44) respectively] and tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [1.71 (0.79 , 3.82 )]. Discussion: Chemicals measured in this study were identified through NTA and targeted quantification. We identified endogenous and exogenous chemicals some of which have seldom been quantified in pregnant people.

Accommodating detection limits of multiple exposures in environmental mixture analyses: an overview of statistical approaches

“…Some analytical laboratories often provide the machine readings for specimens whose observed values is declared to be below the LOD, with the understanding that the specimen's level of analyte cannot reliably distinguished from zero; these readings may involve substantial measurements errors. Machine-read values have been often used in environmental mixture studies [54][55][56]. However, we did not consider the machineread approach in our case study because it is difficult to justify the actual mechanism of the machine-raed approach given that each machine in each lab has its unique way of generating the reads, and the accuracy could vary dramatically.…”

Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns

“…Each plate was incubated either without inhibitors, or with the BChE inhibitor tetraisopropylpyrophosphoramide (iso-OMPA; final concentration 50 µM; Sigma, T1505), or the AChE inhibitor BW284c51 (final concentration 5 µM; Sigma, A9103). To enable comparison between plates, each plate included four internal controls: (1) a random maternal sample, (2) its corresponding newborn sample, (3) a recombinant AChE protein sample, and (4) a recombinant BChE protein sample. The first two served as normalizing controls and the last two as internal controls.…”

“…The womb environment plays a crucial role in determining the future physical and mental health of the fetus. Many factors influencing this environment have been shown to affect fetal development (1)(2)(3)(4)(5)(6)(7). Specifically, psychosocial stress in the form of clinical or preclinical prenatal depression or anxiety has been shown to affect 20% of all pregnancies (8)(9)(10).…”