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Comparison of Studies for Use in Risk Assessment
Pages 250-270

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From page 250...
... and the Faroe islands studies—reached different conclusions. A range of adverse neuropsychological and neurophysiolog~cal outcomes were found to be associated with prenatal Hg exposure in the Faroe islands study, whereas adverse effects were not found in the main Seychelles study.
From page 251...
... , and it wouIct reduce the likelihood of detecting associations between MeHg exposure and neurobehavioral test scores. Data from the peer-reviewed pilot SCDS of 217 children assessed at 5.5 years (Myers et al.
From page 252...
... There is, therefore, no reason to expect a confounding of exposure with lower socioeconomic status, and low socioeconomic status is not likely to explain the association of Hg exposure with adverse development outcomes in the Seychelles pilot study. ASSESSMENT OF PRENATAL Hg EXPOSURE: CORD BLOOD VERSUS MATERNAL HAIR AND TIMING OF EXPOSURE The principal measure of prenatal exposure in the Faroe study was Hg in cord blood; in the Seychelles, it was Hg in maternal hair.
From page 253...
... ~Neurobehavioral Evaluation System.
From page 254...
... In summary, it does not appear that the failure of the SCDS to collect cord-blood Hg samples can account for the discrepancies between their findings and those in the Faroe study because, in the latter study, associations were found between neurobehavioral test scores and both cord-blood Hg and maternal-hair Hg concentrations (Table 6-~. Moreover, the findings reported in New Zealand and the pilot SCDS were based solely on maternal-hair-sample data averaged across the entire pregnancy.
From page 255...
... , which yield global scores that integrate performance over many separate neuropsychological domains. In contrast, because the Faroe investigators hypothesized multifocal domain-specific neuropsychological effects, their test battery largely consisted of highly focused tests selected from those commonly used in clinical neuropsychology (e.g., California Verbal Learning Test—Children and Boston Naming Test)
From page 256...
... Similarly, although the Boston Naming Test, which was included in the Faroe Islands test battery, and the preschool language scale and the verbal scale of the McCarthy verbal scale which were incluclecI in the SCDS 66-month test battery of the SCDS can be considered tests of language skills, the specific skills they assess are quite different. The Boston Naming Test specifically assesses confrontational naming skills, consisting of line drawings of common objects that a child has to name under time pressure (20 seconcis)
From page 257...
... To help determine the degree to which the discrepant results from the Faroe study and SCDS are attributable to differences in the neurobehavioral tests used, the Seychelles group administered several of the more domain-specific tests from the Faroe battery in their S-year followup. The results of those assessments, however, are not yet available.
From page 258...
... Although differences in end points assessed and age of assessment might explain the failure of the SCDS to detect the associations found in the Faroe Islands study, findings from the New Zealand study and the Seychelles pilot study suggest that the discrepancies between the Farce Islands and the main Seychelles studies are probably not due to differences in the assessments. The New Zealand stucly found associations between MeHg exposure and scores on the McCarthy Scales of Children's Abilities (the primary outcome measure used in the SCDS)
From page 259...
... Because random assignment to predetermined exposure levels cannot be used to control for confounding in human exposure studies, it is important to assess whether a broad range of control variables confound any associations observed between exposure and outcome. Table 6-2 lists the control variables examined in the Faroe and Seychelles studies.
From page 260...
... were assessed in one study but not in the other (e.g., maternal age and birth order in the Seychelles study; obstetrical care in the Faroe study)
From page 261...
... At a workshop sponsored by the White House Office of Science and Technology Policy in November 199S, the Faroe investigators noted that, apparently due to social-class differences, the maternal Ravens scores and the child verbal-test scores were generally higher among families residing in one of the three Faroe towns than among those living in the countryside. Because more fish and whale meat are consumed by rural residents, the associations of Hg exposure with chilcI verbal-test scores could be spurious, reflecting those social-cIass differences.
From page 262...
... and Prenatal Hg Exposure on Developmental Outcomes in the Faroe Islands Study Hg Without Controlling for Residencea Residenceb be p b p b Test NES Finger Tapping Preferred Hand Other Hand Both Hands NES Hand-Eye Coordination Error Score NES Continuous Performance Missed Responses Reaction Time WISC-R Hg Controlling for Residences p 0.03 0.95 -0.47 0.26 -1.41 0.11 0.001 0.94 -1.10 -0.39 -1.67 0.03 -0.12 0.16 -14.55 0.06 0.27 40.30 0.05 0.46 0.14 0.19 -1.14 -0.55 -2.04 0.04 0.02 0.24 <0.001 35.34 0.04 0.31 0.07 0.18 0.04 0.002 Digit Spans 0.06 0.58 -0.27 0.05 -0.26 0.07 Similarities 0.04 0.91 - 0.05 0.90 - 0.08 0.84 Block Designs 0.19 0.02 -0.17 0.11 -0.12 0.26 Bender Visual Motor Gestalt Test Error on Copying -1.03 0.005 0.67 0.15 0.45 0.35 Delayed Recall 0.35 0.004 -0.25 0.10 -0.17 0.28 Boston Naming Test No cues 1.10 0.005 -1.77 <0.001 -1.51 0.003 With cues 1.24 0.001 -1.91 c0.001 -1.60 0.001 CVLT Learning 0.89 0.16 - 1.25 0.12 - 1.10 0.18 Immediate recall 0.37 0.06 -0.57 0.02 -0.49 0.05 Delayed recall 0.02 0.92 -0.55 0.05 -0.56 0.05 Recognition 0.15 0.92 - 0.29 0.15 - 0.30 0.14 Controlling for all independent variables except Hg; 0 = country, 1 = town. bControlling for all independent variables except residence.
From page 263...
... in the Faroe study, prenatal PCB exposure was measured in umbilical cord tissue rather than cord blood or maternal blood or milk, as in most previous studies, and specimens were
From page 264...
... Regressions assessing the associations between Hg exposure and the five principal 7-year outcomes were then run separately for each of the groups. The regression coefficients for Hg in the lowest PCB fertile were no weaker than those among the infants exposed to moderate or heavy PCB doses, lending additional support to the conclusion that the associations between Hg and these outcomes are not attributable to confounding by prenatal PCB exposure.
From page 265...
... As stated above, one substantial difference between the Faroe and the Seychelles populations relates to their PCB exposure. Whereas PCB concentrations in the Seychelles population are among the lowest observed anywhere in the world, the portion of the Faroe population that eats whale blubber accumulates unusually high PCB body burdens.
From page 266...
... Thus, it seems unlikely that differences in vulnerability due to PCB exposure can explain the differences between the Faroe Islands and the Seychelles findings. The sample in the main Seychelles study appears to have been developmentally robust.
From page 267...
... Because multiple regression analysis examines associations that are averaged across the entire distribution of exposure, associations that hold only for the most highly exposed children can be difficult to detect. Thus, if adverse effects of prenatal MeHg exposure occur primarily in the upper range, the power to detect them will be limited, and it would not be surprising if associations found in one Seychelles cohort (the pilot study)
From page 268...
... For example, it is possible that slightly reduced vulnerability in the Seychelles population combined with the use in that study of a biomarker of exposure that averages across pregnancy could make it difficult to detect neurocognitive effects that might be specific to third trimester exposure. · When the two studies reporting associations between MeHg and neurobehavior are compared, the strengths of the New Zealand study include an ethnically heterogeneous sample and the use of developmental end points with greater predictive validity.
From page 269...
... · Most of the MeHg exposure standards currently in effect are based on extrapolations from the Iraqi MeHg poisoning episode, in which exposure was due to He consumption of highly contaminated grain and resulted In body burdens that greatly exceeded those found In the general population of fish consumers. Given the availability of data from three well-designed epidem~ological studies in which prenatal MeHg exposures were in the range of general-population exposures, exposure standards should be based on data from these newer studies.
From page 270...
... 1995. Neurodevelopmental outcomes of Seychellois children sixty-six months after in utero exposure to methylmercury from a maternal fish dies: Pilot study.


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