Neurobehavioral deficits at age 7 years associated with prenatal exposure to toxicants from maternal seafood diet
Highlights
► Detailed assessment of prenatal PCB exposure in the first Faroese birth cohort was carried out. ► Weak associations suggested the presence of PCB-related developmental neurotoxicity ► After adjustment for methylmercury exposure, the tendencies were attenuated. ► Prenatal methylmercury exposure remained a statistically significant predictor of neurobehavioral deficits.
Introduction
Environmental exposures are likely to involve more than a single neurotoxicant at a time. Because a large number of chemicals are suspected of being toxic to the developing brain (Grandjean and Landrigan, 2006), assessment of complex exposures is a prerequisite for neuroepidemiological research. We have conducted extensive studies of birth cohorts in the Faroe Islands, where we mainly focused on methylmercury (Grandjean et al., 1997, Murata et al., 1999). In the Faroes, increased exposure to this neurotoxicant originates from the traditional habit of eating pilot whales (Vestergaard and Zachariassen, 1987), the meat of which contains high mercury concentrations (Julshamn et al., 1987). In addition, lipophilic pollutants, such as polychlorinated biphenyls (PCBs), accumulate in the whale blubber (Borrell and Aguilar, 1993) and are thought to cause developmental neurotoxicity (European Food Safety Authority, 2005). We have previously found little evidence that PCB exposure in the Faroes contributes to neurobehavioral deficits, which seem to be mainly due to methylmercury (Budtz-Jorgensen et al., 2010, Grandjean et al., 2001, Steuerwald et al., 2000), but these assessments relied on incomplete estimates of the total PCB concentration in umbilical cord tissue obtained from half of the birth cohort members. We have now completed measurements of major PCB congeners and related pollutants in banked blood sampled from the umbilical cord from almost all births within the cohort, and are therefore able to update the initial findings.
As statistical analysis of several analytes in regard to their possible effects on several neurobehavioral outcomes would be difficult to interpret from large numbers of regression analyses, we have used structural equation models to identify the relative and joint effect of these potential neurotoxicants on neurodevelopment, while adjusting for methylmercury exposure. In addition, as experimental evidence has suggested a possible interaction between methylmercury and PCBs (Coccini et al., 2006, Fischer et al., 2008), we have also explored this possibility.
Section snippets
Cohort establishment and exposure assessment
A birth cohort was generated in 1986–1987 at the three hospitals in the Faroe Islands (Grandjean et al., 1992). A questionnaire completed by the midwife contained summary information on maternal diet during pregnancy, while other relevant information was retrieved from the medical records.
In connection with each singleton birth, both cord blood and cord tissue were collected and frozen for subsequent analysis. Because of the limited volume of cord blood available and difficulties in analyzing
Results
The overall characteristics for the cohort are shown in Table 1. The log transformed concentrations of the more highly chlorinated PCB congeners: CB-118, CB-138, CB-153, and CB-180 showed close correlations (r above 0.70 for log transformed values). Less chlorinated congeners (CB-28, CB-52, and CB-101) showed many results below the detection limit; they were less clearly associated with the other PCBs (r below 0.26 for log transformed values) and were therefore not considered any further.
Discussion
The results in this study support our previous conclusion that, in the Faroese population, methylmercury neurotoxicity is a greater hazard than PCB (Grandjean et al., 1997, Grandjean et al., 2001, Steuerwald et al., 2000). Also, the results show that prenatal exposures to methylmercury constitute a greater hazard than lower levels of postnatal exposures at age 7 years. Although robust, these observations need to be evaluated in the light of the validity of the study parameters and the evidence
Conclusions
The present report examines the potential developmental neurotoxicity associated with prenatal exposure to PCBs based on comprehensive data on neurotoxicant exposures in a Faroese birth cohort born in 1986-1987. Several measures of PCB exposure, including a structural equation model, showed only weak associations with test deficits at age 7 years. Adjustment for methylmercury exposure substantially weakened the PCB effects. Although a statistically significant PCB effect was observed for verbal
Conflict of interest statement
The authors have no competing interests to declare.
Acknowledgments
This research was supported by the U.S. National Institute of Environmental Health Sciences (ES09797). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH or any other funding agency.
References (44)
- et al.
Serum polychlorinated biphenyl and organochlorine insecticide concentrations in a Faroese birth cohort
Chemosphere
(2006) - et al.
Effects of developmental co-exposure to methylmercury and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) on cholinergic muscarinic receptors in rat brain
Neurotoxicology
(2006) - et al.
Feasibility and validity of three computer-assisted neurobehavioral tests in 7-year-old children
Neurotoxicol Teratol
(1996) - et al.
Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years
Neurotoxicol Teratol
(2006) - et al.
Neonatal co-exposure to low doses of an ortho-PCB (PCB 153) and methyl mercury exacerbate defective developmental neurobehavior in mice
Toxicology
(2008) - et al.
Developmental neurotoxicity of industrial chemicals
Lancet
(2006) - et al.
Relation of a seafood diet to mercury, selenium, arsenic, and polychlorinated biphenyl and other organochlorine concentrations in human milk
Environ Res
(1995) - et al.
Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury
Neurotoxicol Teratol
(1997) - et al.
Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants
Neurotoxicol Teratol
(2001) - et al.
Trace elements intake in the Faroe Islands. I. Element levels in edible parts of pilot whales (Globicephalus meleanus)
Sci Total Environ
(1987)
Evoked potentials in Faroese children prenatally exposed to methylmercury
Neurotoxicol Teratol
Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults
Toxicol Appl Pharmacol
Maternal seafood diet, methylmercury exposure, and neonatal neurologic function
J Pediatr
Issues in the interpretation of associations of PCBs and IQ
Neurotoxicol Teratol
Developmental aspects of environmental neurotoxicology: Lessons from lead and polychlorinated biphenyls
J Neurol Sci
Prenatal exposure to lead and cognitive deficit in 7- and 14-year-old children in the presence of concomitant exposure to similar molar concentration of methylmercury
Neurotoxicol Teratol
Structural equations with latent variables
Pollution by DDT and PCB in blubber and muscle of long-finned pilot whales from the Faroe Islands
Prenatal exposure to polychlorinated biphenyls: a neuropsychologic analysis
Environ Health Perspect
Methylmercury neurotoxicity independent of PCB exposure
Environ Health Perspect
Estimation of health effects of prenatal methylmercury exposure using structural equation models
Environ Health
Effects of exposure imprecision on estimation of the benchmark dose
Risk Anal
Cited by (64)
2,3′,4,4′,5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells
2023, Journal of Hazardous MaterialsNeuroendocrine effects of polychlorinated biphenyls (PCBs)
2023, Advances in NeurotoxicologyMarine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
2022, Environment InternationalToxic metals in food
2021, Handbook on the Toxicology of Metals: Fifth EditionMercury
2021, Handbook on the Toxicology of Metals: Fifth Edition