NIEHS - National Institute of Environmental Health Sciences
Preterm birth (PTB) affects 10% of pregnancies globally, with rates rising 12% between 2014-2022, incurring healthcare costs exceeding $25 billion annually in the US alone. While inflammation is a known trigger of PTB, the environmental factors driving this inflammatory response remain poorly understood. A critical knowledge gap exists in understanding how emerging environmental contaminants, particularly micro- and nanoplastic (MNP) particles, associate with PTB and alter placental immune function. Our preliminary data provide compelling evidence that MNPs bioaccumulate in human placentae at concentrations 23.9 times higher than in blood. Using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), we found significantly elevated MNP levels in preterm versus term placentae (224.7 vs 175.5 µg/g tissue; p=0.0032), with specific polymers showing 17-157% higher concentrations in preterm cases. The long-term objective of this research is to establish how environmental MNP exposure correlates with adverse pregnancy outcomes and identify modifiable risk factors for PTB prevention. Leveraging our completed longitudinal pregnancy cohort study (the Bacteria and Birth Study; BaBs Trial, n=585; PTB=103, term=367) with comprehensive maternal-infant biospecimens collected from first trimester through 6 weeks postpartum (>93,000 samples), we will: Aim 1) Define temporal patterns of MNP accumulation by quantifying 12 environmentally relevant polymers in maternal blood, urine, placental tissue, and cord blood (n=3,500 specimens) using Py- GC/MS, while integrating data on other environmental toxicants to establish exposure signatures that predict PTB risk; and Aim 2) Characterize the pathophysiology of MNP-associated placental dysfunction through systematic analysis of inflammatory markers (n=1,200 samples), histopathological changes (n=351 placentae), and immune cell distributions mapped by spatial transcriptomics (n=30 placentae). This comprehensive molecular and cellular characterization will establish the foundation for future mechanistic studies using animal models and in vitro systems. This research is innovative in challenging current paradigms of PTB etiology while introducing state-of-the- art methods to track environmental exposures during pregnancy. Our unique approach combines advanced analytical capabilities (Py-GC/MS- submicron plastics detection) with high-resolution spatial profiling to reveal how MNP exposure correlates with altered maternal-fetal immune balance. Success will establish: 1) The first longitudinal assessment of MNP accumulation patterns during pregnancy; 2) Novel biomarkers for identifying at- risk pregnancies; and 3) Key molecular and cellular changes associated with MNP accumulation in human placentae. These findings will directly inform the design of future mechanistic studies while directly providing evidence-based guidance for reducing harmful exposures during pregnancy, particularly benefiting vulnerable populations disproportionately affected by PTB.
Up to $640K
2031-01-31
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