Grantee Research Project Results
2005 Progress Report: Neurobehavioral Effects of Prevalent Toxicants in Children
EPA Grant Number: R829389C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R829389
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of Cincinnati Center for the Study of Prevalent Neurotoxicants in Children
Center Director: Lanphear, Bruce
Title: Neurobehavioral Effects of Prevalent Toxicants in Children
Investigators: Lanphear, Bruce , Bearer, Cynthia , Ris, Douglas , Khoury, Jane , Dietrich, Kim , Yolton, Kimberly , Hornung, Richard
Current Investigators: Lanphear, Bruce , Dietrich, Kim
Institution: Children Hospital of Cincinnati , University of Cincinnati
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2001 through October 31, 2006
Project Period Covered by this Report: November 1, 2004 through October 31, 2005
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The objective of this research project is to test the efficacy of an intervention for the primary prevention of lead toxicity, as measured by lead concentration and neurobehavioral functioning at 36 months of age.
Progress Summary:
Recruitment, Enrollment, and Study Progress
As of June 30, 2005, we had 6,919 pregnant women who were seen by one of the prenatal practices involved in our study. Of these, 4,265 (61%) were 18 years or older, lived in a home built after 1978 in a five-county area, were at 13 to 19 weeks gestation, and were sent a letter inviting them to participate in the study. Of these women, 3,915 (92%) completed the screening process; 965 (25%) of 3,915 women were eligible for the study. Of the 965 eligible women, 379 (40%) initially agreed to participate and completed the study consent; 45 declined before randomization. Thus, 334 women have been enrolled and have completed the baseline home visit. Of the 334 women, there have been 271 live births. Only 15 women (4.5%) dropped out after randomization. Eighty-two families have completed the 12-month home visits and clinic visits.
Quarterly phone questionnaires, starting when the child is 3 months of age, to assess injuries to the index child and any siblings, maternal supervision, and infant feeding and sleep patterns continued this year. To date, we administer quarterly phone questionnaires up to 21 months of age. The 27-month phone questionnaires are scheduled to begin November 2005.
The figures in Table 1 represent live births that have completed the 4-week visit. The number of women enrolled thus differs from this table. We do not collect information about race and ethnic characteristics until the children are 4 weeks of age.
Prevalent Neurotoxins in Children
American Indian |
Asian or Pacific Islander |
Black, not of Hispanic Origin |
Hispanic |
White, not of |
Other or |
TOTAL |
|
Female |
1 |
3 |
44 |
0 |
80 |
1 |
129 |
Male |
1 |
4 |
19 |
5 |
73 |
0 |
102 |
Unknown |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
TOTAL |
2 |
7 |
63 |
5 |
153 |
1 |
231 |
Increasing Enrollment
The changes in eligibility (dropping the moving criterion) and recruitment (addition of prenatal practices/clinics) made in 2004 have increased our enrollment rate from an average of 11 per month to an average of 14 per month. At this rate, we expect to complete enrollment by December 2005. The addition of the Good Samaritan Hospital Obstetrics (OB) Clinic also has contributed to the increased enrollment of African American women. To date, 27 percent of participants (pregnant women) are African American.
Infrastructure
IRB/HIPAA. Institutional Review Board and Health Insurance and Portability Accountability Act (IRB/HIPAA) approvals have been maintained for Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Christ Hospital, TriHealth (Good Samaritan Hospital), and the Centers for Disease Control and Prevention (CDC).
Collaborations
In the past year, the study has maintained its collaborations with all of the prenatal practices originally approached for recruiting and with four of the five prenatal practices/clinics approached in 2004. We have discontinued enrollment from the Neighborhood Health Centers, which were three OB clinic sites in the greater Cincinnati area, because of their very low numbers of new OB patients. The three participants recruited from these clinic sites continued to be followed by the study.
We have maintained our collaboration with the National Institute of Child Health and Human Development (NICHD)-funded Neonatal Research Network nurses. They currently work on recruitment and enrollment through the University Hospital OB Clinic, attend to births at all participating hospitals, and will be assisting with recruitment, enrollment, and births at Good Samaritan Hospital starting in July 2004.
Significance of Findings
Preliminary Data on Biomarkers in Health Outcomes and Measures of the Environment (HOME) Study Participants. As of June 30, 2005, we have enrolled 334 women, 271 who have given birth. Thus far, we have partial laboratory results for the first 50 mother-infant pairs (Table 2). Our primary reason for tabulating these results was to show that the results are not below the level of detection and to compare them with national reference values using the CDC’s Second National Report on Human Exposure to Environmental Chemicals (Centers for Disease Control, 2003). We also wanted to provide preliminary results for the correlation of toxicants measured in maternal serum, maternal blood, cord serum, and cord blood with meconium.
Maternal Blood Samples During Pregnancy |
Infant Samples |
|||||
Timing of Samples |
16 week |
26 week |
Birth |
Cord Blood |
Meconium |
|
Total Mercury |
||||||
National CDC Reference |
1.02 |
1.02 |
1.02 |
NA |
NA |
|
Geometric Mean (mg/L) |
0.96 |
0.85 |
0.73 |
0.65 |
pending |
|
Range (mg/L) |
0.14 to 8.3 |
0.14 to 6.7 |
0.14 to 4.3 |
0.14 to 8.4 |
pending |
|
No. (%) Below Detection |
8% |
4% |
4% |
27% |
pending |
|
No. (%) > 3.5 (mg/L) |
8% |
6% |
6% |
11% |
pending |
|
Total Lead |
||||||
National CDC Reference |
1.37 |
1.37 |
1.37 |
NA |
NA |
|
Geometric Mean (mg/dL) |
1.79 |
1.79 |
1.81 |
2.13 |
pending |
|
Range (mg/dL) |
0.07 to 3.2 |
0.07 to 4.2 |
0.09 to 3.4 |
0.6 to 2.8 |
pending |
|
No. (%) Below Detection |
None |
None |
None |
None |
pending |
|
Blood Lead > 2.5 |
17% |
16% |
15% |
32% |
pending |
|
Total PCBs |
||||||
National CDC Reference |
NA |
NA |
NA |
NA |
NA |
|
Geometric Mean (ng/g) |
50.3 |
42.8 |
44.0 |
21.1 |
46.2 |
|
Range (ng/g) |
8.6 to 143 |
6.9 to 190 |
3.8 to 166 |
.89 to 121 |
1.1 to 563 |
|
No. (%) Below Detection |
None |
None |
None |
None |
None |
|
p’p-DDE |
|
|
||||
National CDC Reference |
68.9 |
68.9 |
68.9 |
NA |
NA |
|
Geometric Mean (ng/g) |
75.6 |
53.9 |
59.5 |
52.5 |
190.3 |
|
Range (ng/g) |
29 to 1,081 |
27 to 160 |
0.93 to 1274 |
1.82 to 1,090 |
22.9 to 1333 |
|
No. (%) Below Detection |
None |
None |
(4%) |
9% |
None |
|
DDT |
|
|
|
|
|
|
National CDC Reference |
NA |
NA |
NA |
NA |
NA |
|
Geometric Mean (ng/g) |
4.1 |
2.5 |
3.4 |
3.5 |
11.4 |
|
Range (ng/g) |
0.84 to 82.6 |
0.78 to 11.7 |
0.69 to 90.6 |
2.1 to 55.6 |
1.6 to 66.8 |
|
No. (%) Below Detection |
20% |
9.3% |
18.3% |
52.2% |
11.9% |
|
|
|
|
|
|
There were surprisingly few samples with undetectable values (Table 2). We were able to detect and quantify lead, mercury, metabolites of pyrethroid and organophosphate pesticides, polychlorinated biphenyls (PCBs), and p,p'-DDE (a metabolite of DDT) in virtually all of the maternal blood and serum samples (Table 2). Similarly, we detected DDT in more than 80 percent of all maternal serum samples. We also were able to detect lead, p,p'-DDE, and PCBs in virtually all of the infants, but the detection frequency was lower for total mercury (27%) and DDT (52%). Results for serum cotinine, hair cotinine, and meconium cotinine were not available for this update, but about 25 percent of mothers either smoke continuously or are exposed to tobacco products in their home.
When possible, we provided reference values for U.S. women of reproductive age for comparison with pregnant women in our birth cohort. In some cases, there are no national reference values. For example, there are no national reference values for toxicants in meconium. In other cases, there are U.S. reference values for some of the persistent pollutants (e.g., p,p'-DDE and DDT), but it is difficult to compare our samples with national reference values because the accuracy of the laboratory testing has improved substantially in the past 3 to 4 years (Barr, et al., 2003; Barr, et al., 2004; Sundau, et al., 2003). For example, fewer than 10 percent of women had detectable levels of DDT in their serum from the CDC’s Second National Report on Human Exposure to Environmental Chemicals, whereas about 80 percent of pregnant women in our birth cohort had detectable levels of DDT.
Heavy Metals
The total blood mercury levels in pregnant women are consistent with those from the National Health and Nutrition Examination Survey (1999-2000), indicating that the findings of this study will be relevant to the U.S. population. The correlation of maternal birth mercury levels and cord blood mercury levels was high (r = 0.91). In contrast, maternal blood lead levels were about 30 percent higher than the national average. The correlation of the three maternal blood lead levels was poor, indicating the potential for measurement error in prior studies that relied on a single maternal blood lead or cord blood concentration to measure fetal lead exposure (Table 3).
Persistent Pollutants
We have some preliminary results for persistent pollutants (Table 2). In general, the concentrations of various toxins, including PCBs, p’p-DDE, and DDT were higher in meconium compared with the same toxins measured in maternal serum, maternal urine, and cord serum. We also found that the concentrations of persistent pollutants in meconium generally were correlated with those same toxicants measured in maternal serum, cord serum, and maternal urine (Table 3). The mean maternal samples (i.e., the average of three serum samples taken during pregnancy) tended to be correlated more highly with meconium toxicant levels than any single sample. These correlations were done using lipid adjusted values.
|
Consent |
26 - week |
Birth |
Mean |
Cord |
Total PCBs |
|
|
|
|
|
26 – week |
0.73 |
|
|
|
|
Birth |
0.68 |
0.60 |
|
|
|
Mean Maternal |
0.93 |
0.89 |
0.82 |
|
|
Cord |
0.67 |
0.57 |
0.50 |
0.67 |
|
Meconium |
0.37 |
0.39 |
0.22 |
0.38 |
0.05 |
DDE |
|
|
|
|
|
26 – week |
0.79 |
|
|
|
|
Birth |
0.71 |
0.48 |
|
|
|
Mean Maternal |
0.97 |
0.92 |
0.81 |
|
|
Cord |
0.67 |
0.32 |
0.68 |
0.68 |
|
Meconium |
0.62 |
0.28 |
0.35 |
0.62 |
0.73 |
DDT |
|
|
|
|
|
26 – week |
0.34 |
|
|
|
|
Birth |
0.67 |
0.24 |
|
|
|
Mean Maternal |
0.91 |
0.54 |
0.88 |
|
|
Cord |
0.49 |
0.31 |
0.60 |
0.67 |
|
Meconium |
0.19 |
0.01 |
0.25 |
0.28 |
0.43 |
Blood Lead |
|
|
|
|
|
26 – week |
0.04 |
|
|
|
|
Birth |
-0.02 |
-0.10 |
|
|
|
Mean Maternal |
0.75 |
0.56 |
0.54 |
|
|
Cord |
0.01 |
-0.06 |
0.34 |
0.19 |
|
Meconium |
pending |
pending |
pending |
pending |
pending |
Mercury |
|
|
|
|
|
26 – week |
0.85 |
|
|
|
|
Birth |
0.84 |
0.83 |
|
|
|
Mean Maternal |
0.96 |
0.94 |
0.94 |
|
|
Cord |
0.73 |
0.81 |
0.91 |
0.88 |
|
Meconium |
pending |
pending |
pending |
pending |
pending |
Nonpersistent Pesticides
We have preliminary data for nonpersistent pesticides, organophosphate, and pyrethroid pesticide metabolites, measured in maternal urine. Results for metabolites of nonpersistent pesticides in meconium are pending. The concentrations of pesticides in maternal urine were somewhat higher than the CDC’s national reference values (Table 4). The concentrations of diethylphosphate and dimethylthiophosphate, two organophosphate pesticides metabolites, were three- to five-times higher among the women in our birth cohort than the national reference values. In contrast, there are no national reference values for 3-phenoxybenzoic acid (3PBA), a metabolite of pyrethroid pesticides. The correlation coefficients for log-transformed 3PBA for maternal urine taken at 16 weeks, 26 weeks, and at delivery ranged from 0.44 to 0.52.
from Maternal Urine During Pregnancy for the First 50 Participants in the HOME Study
|
Maternal Urine Samples During Pregnancy |
||
Timing |
16 weeks |
26 weeks |
Birth |
I. Major Metabolites of Organophosphate Pesticides |
|
||
DEP (Diethylphosphate) |
|
|
|
National CDC Reference |
1.0 |
1.0 |
1.0 |
Geometric Mean (mg/g) |
5.5 |
5.9 |
4.7 |
Range (mg/g) |
2.2 to 21.8 |
0.11 to 26.9 |
0.09 to 36.0 |
No. (%) Below Detection |
None |
2% |
8.3% |
DETP (Diethylthiophosphate) |
|
|
|
National CDC Reference |
NA |
NA |
NA |
Geometric Mean (mg/g) |
0.94 |
0.87 |
0.64 |
Range (mg/g) |
0.1 to 22.7 |
0.17 to 8.2 |
0.07 to 38.8 |
No. (%) Below Detection |
22% |
22% |
35% |
DMP (Dimethylphosphate) |
|
|
|
National CDC Reference |
NA |
NA |
NA |
Geometric Mean (mg/g) |
2.0 |
1.92 |
1.29 |
Range (mg/g) |
0.16 to 33.1 |
0.14 to 61.2 |
0.12 to 27.8 |
No. (%) Below Detection |
34% |
42% |
58% |
DMTP (Dimethylthiophosphate) |
|
|
|
National CDC Reference |
1.59 |
1.59 |
1.59 |
Geometric Mean (mg/g) |
5.36 |
4.11 |
2.91 |
Range (mg/g) |
0.59 to 86.7 |
0.53 to 167.9 |
0.27 to |
No. (%) Below Detection |
14% |
6% |
10.4% |
II. Major Metabolite of Pyrethroid Pesticides |
|
||
3PBA (3-phenoxybenzoic acid) |
|
|
|
National CDC Reference* |
NA |
NA |
NA |
Geometric Mean (mg/g) |
1.51 |
1.20 |
1.23 |
Range (mg/g) |
0.26 to 21.5 |
0.08 to 51.4 |
0.18 to 14.5 |
No. (%) Below Detection |
NA |
2% |
2% |
|
|
|
|
These preliminary results indicate that the levels of exposures to environmental toxicants and chemicals in our birth cohort, with some important exceptions, are comparable with the CDC national report. This finding is important because we are interested primarily in exploring the relationship of low-level exposure to recognized, prevalent toxicants with adverse neurobehavioral and reproductive outcomes. On the other hand, the levels of organophosphate pesticide metabolites in this birth cohort were considerably higher than the national reference population. In contrast with other environmental toxins, there is a paucity of data about the association of exposure to organophosphate and pyrethroid pesticides with neurodevelopmental and reproductive effects. Thus, we think this birth cohort is particularly well-suited to answer questions about both low-level exposures to recognized toxicants and to test for potential adverse effects of organophosphate pesticide exposure in a population with higher exposure levels.
Sample Analyses
Samples collected from the second 50 participants who delivered their babies were sent to the CDC in October 2004 to begin analyses (results are pending). Samples collected from participants who delivered their babies after October 2004 will be sent to the CDC this fall. Samples sent included maternal blood, serum, hair, and saliva; cord blood; and meconium.
Project 1: Intervention Component (Supplement)
All aims and hypotheses included in the original proposal for the lead hazard reduction intervention still guide the project.
Intervention Status. As of June 30, 2005, we have enrolled 334 women and their families in the HOME Study. Of these, we assigned 283 (84%) participants randomly to either the lead hazard control arm or the injury control arm. Of the 283 randomized families, 138 (49%) were assigned to the lead hazard control arm and 143 (51%) were assigned to the injury hazard control arm. Of the families assigned to the lead hazard controls, 106 lead hazard control interventions have been completed at an average cost of $5,457. This is $1,545 more than our original estimates. The difference in cost was caused by an expansion of the lead hazard controls. The expanded lead hazard controls, including window replacement, were determined in collaboration with the U.S. Department of Housing and Urban Development (HUD). We are examining how this added cost will require us to modify our final sample size or whether HUD would be able to augment the intervention budget. For the 143 families assigned to the injury intervention, 73 injury hazard control interventions have been completed at an average cost of $337 per housing unit. Fewer injury repairs have been completed because the injury interventions are done when the infants are 3 to 6 months of age, whereas the lead intervention is done during pregnancy.
Collaborations. In the past year, the study has maintained its collaborations with the Ohio Department of Health and the National Center for Healthy Housing (NCHH) for the Lead Hazard Control arm of the study. The NCHH conducted a site visit in July 2004 and June 2005. During the site visits, NCHH reviews intervention records, observes ongoing interventions in participants’ homes, and provides feedback to the intervention team regarding protocol adherence, research documentation, and lead-safe work methods. The NCHH’s full report is available upon request.
For the Injury Hazard Control arm, we have continued our collaboration with a local child safety expert, Mark Movish. Mr. Movish continues to serve as a resource for updates on safety products, ordering of safety products, and monitoring injury interventions for quality assurance purposes.
Future Activities:
Upcoming Study Visits and Outcome Assessments
The first 24-month home and clinic visits began in late summer 2005. Study staff members currently are preparing for the collection of blood, urine, and hair from the 24-month-old participants at the clinic visit. Outcome assessments that will be repeated include growth measures (i.e., length, weight, and head circumference) and developmental assessments (Bayley Scales of Infant Development-II).
The 24-month home visit also will include the maternal questionnaire to assess the child’s exposure to toxins, observational assessments of lead and injury hazards, and the collection of environmental samples. The Behavior Assessment System for Children, 2nd Edition, also will be administered at the 24-month home visit.
References:
Centers for Disease Control and Prevention. Second National Report on Human Exposure to Environmental Chemicals. U.S. Public Health Service, Department of Health and Human Services, 2003.
Barr DB, Bravo R, Weerasekera G, Caltabiano LM, Whitehead RD Jr, Olsson AO, Caudill SP, Schober SE, Pirkle JL, Sampson EJ, Jackson RJ, Needham LL. Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population. Environmental Health Perspectives 2004;112:186-200.
Barr JR, Maggio VL, Barr DB, Turner WE, Sjodin A, Sandau CD, Pirkle JL, Needham LL, Patterson DG Jr. New high-resolution mass spectrometric approach for the measurement of polychlorinated biphenyls and organochlorine pesticides in human serum. Journal of Chromatography B, Analytical Technology and Biomedical Life Sciences 2003;794:137-148.
Sandau CD, Sjodin A, Davis MD, Barr JR, Maggio VL, Waterman AL, Preston KE, Preau JL Jr, Barr DB, Needham LL, Patterson DG Jr. Comprehensive solid-phase extraction method for persistent organic pollutants. Validation and application to the analysis of persistent chlorinated pesticides. Analytical Chemistry 2003;75:71-77.
Journal Articles:
No journal articles submitted with this report: View all 19 publications for this subprojectSupplemental Keywords:
toxicology, ADHD behavioral assessment, behavioral deficit, genetic susceptibility, pesticides, biomarkers, environmental agents, exposure, exposure assessment, hearing loss, lead, meconium, neurotoxicity, pesticide exposure, risk assessment, toxicants,, RFA, Scientific Discipline, Health, ENVIRONMENTAL MANAGEMENT, Toxics, Toxicology, Health Risk Assessment, Chemistry, pesticides, Risk Assessments, Children's Health, Biology, Risk Assessment, pesticide exposure, behavioral assessment, lead, neurotoxicity, children, toxicity, behavioral deficits, biological markers, exposure assessmentRelevant Websites:
http://www.healthyhomestoday.com Exit
http://www.cincinnatichildrens.org/research/project/enviro Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R829389 CECEHDPR - University of Cincinnati Center for the Study of Prevalent Neurotoxicants in Children Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829389C001 Neurobehavioral Effects of Prevalent Toxicants in Children
R829389C002 Validation of Meconium Markers of Fetal Neurotoxicant Exposures
R829389C003 Community-Based Research Project Identifying Residential Hazards Using Home Test Kits
R829389C004 Early Exposure to Lead and Adult Antisocial Outcome
R829389C005 Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
Main Center: R829389
151 publications for this center
111 journal articles for this center