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
Introduction Fetal exposure to Pb through placentaAPILS and human subjects
Specific aimsPlacenta sample preparation and analysisDistribution of Pb in placental tissuesCorrelations between BPb and placenta PbConclusionsFuture Work
Introduction
The placental barrier does not protect the fetus from excess Pb exposure
Excess Pb exposure to the fetus may result in adverse health effectsUnderdeveloped 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?
Albany Pregnancy Infancy Lead Study (APILS)
Human subjectsSocioeconomically disadvantaged pregnant
womenAt risk for Pb exposureLink between low socioeconomic status and Pb
levels in children
Funded by NIEHS 1992-1998
Introduction to APILS
Longitudinal studyDetermine changes in Pb body burden
throughout pregnancy and infancyExplore interactions between Pb and nutrientsDemographic variables collected for
epidemiological studies
Pb measured in:Maternal blood during each trimester of
pregnancy and at deliveryUmbilical cord bloodInfant blood at 6 and 12 months
APILS Results
BPb levels change during pregnancyDecrease from 1st to 2nd trimesterIncrease from 2nd trimester to delivery
Schell et al. (2000)
Arch Environ Health
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
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
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?
HomogenizeFreeze-dry
Homogenize
Divide
Membrane
Body
Umbilical cord
Sample Preparation and Analysis
Analyze
HomogenizeFreeze-dry
Homogenize
Divide
Membrane
Body
Umbilical cord
Sample Preparation and Analysis
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)
Pb Distribution in Human Placenta
Placenta Bodies
Placenta Membranes
Umbilical Cords
(n = 152) (n = 157) (n = 154)
93% Detectable
100% Detectable
81% Detectable
48 ng/g 55 ng/g 14 ng/g
Preliminary Correlations
a* = 0.01<P<0.05; ** = 0.001<P<0.01; *** = P<0.001; ns = not significant (P>0.05)
Preliminary Correlations
a* = 0.01<P<0.05; ** = 0.001<P<0.01; *** = P<0.001; ns = not significant (P>0.05)
Preliminary Correlations
1st Tri 2nd Tri 3rd Tri Maternal Delivery
Cord Infant 6 mo
Infant 12 mo
ConclusionsPlacenta Pb can 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
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?
Acknowledgements
Partial funding from NIEHS grant #R01-ES 05280
Albany Medical Center HospitalDepartment of Pathology
Clinical Trace Elements Laboratory
