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Placenta as a biomarker for assessing in utero exposure to Pb

Placenta as a biomarker for assessing in utero exposure to Pb. Pamela C. Kruger and Patrick J. Parsons Wadsworth Center, NYS Department of Health Lawrence M. Schell State University of New York at Albany Alice D. Stark Office of Public Health, NYS Department of Health. Overview.

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Placenta as a biomarker for assessing in utero exposure to Pb

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  1. Placenta as a biomarker for assessing in utero exposure to Pb Pamela C. Kruger and Patrick J. Parsons Wadsworth Center, NYS Department of Health Lawrence M. Schell State University of New York at Albany Alice D. Stark Office of Public Health, NYS Department of Health

  2. Overview • Introduction • Fetal exposure to Pb through placenta • APILS and human subjects • Specific aims • Placenta sample preparation and analysis • Distribution of Pb in placental tissues • Correlations between BPb and placenta Pb • Conclusions • Future Work

  3. Introduction • The placental barrier does not protect the fetus from excess Pb exposure • Excess Pb exposure to the fetus may result in adverse health effects • Underdeveloped organs, blood-brain barrier, excretory pathways • What are typical Pb levels in the human placenta? • Is placenta a good indicator of fetal exposure to Pb?

  4. Albany Pregnancy Infancy Lead Study (APILS) • Human subjects • Socioeconomically disadvantaged pregnant women • At risk for Pb exposure • Link between low socioeconomic status and Pb levels in children • Funded by NIEHS 1992-1998

  5. Introduction to APILS • Longitudinal study • Determine changes in Pb body burden throughout pregnancy and infancy • Explore interactions between Pb and nutrients • Demographic variables collected for epidemiological studies • Pb measured in: • Maternal blood during each trimester of pregnancy and at delivery • Umbilical cord blood • Infant blood at 6 and 12 months

  6. APILS Results • BPb levels change during pregnancy • Decrease from 1st to 2nd trimester • Increase from 2nd trimester to delivery • Schell et al. (2000) • Arch Environ Health

  7. APILS Results • Maternal BPb strongly and positively correlated with infant BPb levels • Maternal intake of vitamin D and Fe inversely correlated with infant BPb • Schell et al. (2003) Children's Health

  8. APILS Results • Inverse relationships found between infant intake of Zn, Fe, Ca and 6 mo. BPb, and Fe and 12 mo. BPb • Schell et al. (2004) Environ Res • 2nd trimester BPb levels related to infant head circumference at 6 and 12 mos. • Schell et al. (2009) Am J Hum Biol

  9. Placenta Pb study: Specific Aims • Analyze 3 placental tissue components (body, membrane and umbilical cord) for Pb content by ICP-MS • Examine Pb distribution between the 3 placental tissue components in ~150 subjects • Explore possible correlations of placenta Pb with blood Pb for ≥70 paired subjects • Is placenta Pb a reasonable biomarker of in utero exposure? What other options are there?

  10. Divide Umbilical cord Membrane Homogenize Body Homogenize Freeze-dry Sample Preparation and Analysis

  11. Divide Umbilical cord Membrane Homogenize Body Homogenize Freeze-dry Sample Preparation and Analysis Analyze

  12. ICP-MS Method Validation • Standard reference materials (SRMs) • NIST 1577b Bovine Liver, NIST 1640 Natural Water • Certified reference materials (CRMs) • High Purity Standards Bovine Liver Solution • Reference materials (RMs) • NIST 8414 Bovine Muscle • NYS Caprine Liver • Spike recovery experiments • Method detection limit = 6.3 ng/g (ppb) • 3s of a placenta digest; n = 30 (10 reps, 3 days)

  13. Pb Distribution in Human Placenta (n = 152) (n = 157) (n = 154) 48 ng/g 55 ng/g 14 ng/g 93% Detectable 100% Detectable 81% Detectable Placenta Bodies Placenta Membranes Umbilical Cords

  14. Preliminary Correlations a* = 0.01<P<0.05; ** = 0.001<P<0.01; *** = P<0.001; ns = not significant (P>0.05)

  15. Preliminary Correlations a* = 0.01<P<0.05; ** = 0.001<P<0.01; *** = P<0.001; ns = not significant (P>0.05)

  16. Preliminary Correlations 1st Tri 2nd Tri 3rd Tri Maternal Delivery Cord Infant 6 mo Infant 12 mo

  17. Conclusions • Placenta Pbcan be measured with good accuracy and precision using ICP-MS, following digestion • Detectable Pb was found in 93% of placenta bodies, 100% of placenta membranes, and 81% of umbilical cords • Geometric mean placenta Pb levels: 55 ng/g (membrane), 48 ng/g (body), 14 ng/g (cord) • Preliminary statistical analysis: • Direct correlations between placenta Pb and BPb

  18. Future Work • Epidemiological modeling for associations between placenta Pb and various health outcomes • Improvements to the Pb biokinetic models? • Does the compartmentalization of placenta Pb fit any of the existing models?

  19. Acknowledgements • Partial funding from NIEHS grant #R01-ES 05280 • Albany Medical Center Hospital • Department of Pathology • Clinical Trace Elements Laboratory

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