MULTICLASS ENVIRONMENTAL TOXICANTS FOUND IN CEREBROSPINAL FLUID (CSF) AND PLASMA SAMPLES FROM PREGNANT WOMEN: POTENTIAL ASSOCIATIONS WITH POSTPARTUM DEPRESSIVE SYMPTOMS

Background

Humans are exposed to a wide range of potentially neurotoxic environmental chemicals. However, assessing their overall impact on the central nervous system (CNS) remains challenging due to the difficulty in quantifying multi-class chemicals at low concentrations and the lack of direct access to the CNS. Our study leverages a unique collection of paired plasma and cerebrospinal fluid (CSF) samples from pregnant women in an urban pregnancy cohort. We aimed to comprehensively profile environmental toxicant exposures in CSF and plasma, and explore their potential associations with postpartum depression symptoms.

Methods

We curated a list of 143 environmental chemicals from 16 distinct classes with potential toxicity to the central nervous system (CNS) via a thorough literature review. We developed and validated an automated, low-volume, high-sensitivity targeted multiclass assay. The limits of detection (LOD) ranged from 0.001-1.0 ng/mL using only 0.2 mL of plasma or CSF. We quantified and characterized the distribution of these 143 potential neurotoxic chemicals in 25 paired CSF-plasma samples, collected from pregnant women prior to delivery. We assessed postpartum depression symptom severity at 6 weeks postpartum using the 10-item self-report Edinburgh Postnatal Depression Scale (EPDS), which is a widely used, validated measure considered the gold-standard for screening for postpartum depression. We first conducted univariate descriptive statistics (e.g., percentiles, median, means, range, etc.) for all analytes in plasma and CSF and other study variables of study participants. We then focused subsequent analyses on those analytes detected ( > LOD) in at least 50% of samples in each biofluid. We conducted exploratory analyses of prospective associations between chemicals levels in CSF and plasma in pregnancy with EPDS scores at 6 weeks postpartum. Due to the small sample size, we only explored the mixture effect of these chemicals using Weighted Quantile Sum (WQS) regression adjusting for maternal age and race.

Results

We found wide detection of environmental chemicals not only in plasma but also in CSF, with 16 and 18 toxicants detected in all CSF and plasma samples, respectively. 11 analytes were found in both body fluids in all individuals. Additionally, 51 analytes in CSF and 57 analytes in plasma were detected in > 50% of samples, including 31 commonly detected in both matrices. 17 analytes, mainly phthalates and pesticides, showed higher concentrations in CSF than in plasma. Weighted Quantile Sum (WQS) regression suggested a potential prospective association between the exposure mixture and EPDS scores at 6 weeks postpartum. In CSF, 33 of 50 beta estimates were positive (mean=1.9, SE=7.5, 95% CI: [12.7, 16.5]), whereas in plasma only 15 of 50 beta estimates were positive (mean=-0.64, SE=8.5, CI: [-2.4, 4.0]). Although these estimates were not statistically significant, as expected given the small sample size, these pattern suggests that associations between environmental exposures and EPDS may differ by biological matrix, with stronger signals observed in CSF.

Conclusion

Our exploratory “exposome-scale” study is among the first to report a prevalent detection of numerous multi-class environmental chemicals with potential neurotoxicity in CSF, suggesting their ability to cross the blood-CSF barrier. Their collective presence in CNS may play a role in maternal postpartum mental health and warrants further investigation.