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Philippe Grandjean

Publications and source records attributed to Philippe Grandjean.

15 recordsLinked to original sources
PubMed2003

Consequences of exposure measurement error for confounder identification in environmental epidemiology.

Non-differential measurement error in the exposure variable is known to attenuate the dose-response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse health effects of prenatal mercury exposure.

Bias↗
PubMed2003

Attenuated growth of breast-fed children exposed to increased concentrations of methylmercury and polychlorinated biphenyls.

Breast-feeding has been linked to slowed postnatal growth. Although the basis for this "weanling's dilemma" is unclear, environmental contaminants in human milk may be of relevance. We studied a Faroese birth cohort of 182 singleton children, born at term in 1994-95. Concentrations of mercury in cord blood and of polychlorinated biphenyls in maternal milk were measured, and duration of breast-feeding was recorded. At 18 months, children who had been exclusively breast-fed for at least 6 months weighed 0.59 kg less [95% confidence interval (CI) = 0.03, 1.16 kg] and were 1.50 cm [95% CI = 0.52, 2.47 cm] shorter than those not breast-fed. However, calculated transfer of contaminants from human milk fully explained the attenuated growth. Irrespective of duration of breast-feeding, a doubling of the mercury concentration in cord blood was associated with a decrease in weight at 18 months by 0.19 kg (95% CI = 0.03, 0.35 kg) and in height by 0.26 cm (95% CI = -0.02, 0.55 cm). Weight and height at 42 months showed the same tendencies, but the main effect occurred before 18 months of age. Thus, in communities with increased contaminant exposures, risks associated with lactational transfer of toxicants to the infant must be considered when judging the benefits of prolonged breast-feeding.

Body Height↗
PubMed2003

[Environmental epidemiology research leads to a decrease of the exposure limit for mercury].

The central nervous system is particularly vulnerable to prenatal exposure to methylmercury. Due to the widespread exposure to methylmercury from fish, several prospective environmental epidemiology studies have been initiated, in which the maternal exposure during the pregnancy is related to the neurobehavioural development of the children. We have studied a Faroese birth cohort prenatally exposed to methylmercury from maternal intake of contaminated pilot whale meat. At seven years of age, clear dose-response relationships were observed for deficits in attention, language, and memory. An increase in blood pressure was also associated with the prenatal exposure level. The exposure limit for mercury has therefore been decreased.

Animals↗
PubMed2003

Arachidonic acid status during pregnancy is associated with polychlorinated biphenyl exposure.

BACKGROUND: Seafood is an important source of long-chain polyunsaturated fatty acids (LCPs), which are essential for normal growth and development. However, the nutritional benefits could be limited by polychlorinated biphenyl (PCB) contamination. In particular, inhibition of desaturase activities by PCBs may affect the maintenance of arachidonic acid (AA) status during development. OBJECTIVE: The aim was to evaluate AA status in a birth cohort from a fishing community with a high seafood intake and a wide range of PCB exposures. DESIGN: We measured LCP concentrations in paired mother and umbilical cord serum samples obtained from 182 consecutive births in the Faroe Islands, where PCB-contaminated whale blubber forms part of the diet. PCB exposure was determined from maternal concentrations. RESULTS: Serum phospholipid AA concentrations averaged 9.14% and 16.5% (by wt) in maternal and cord serum, respectively. After adjustment for gestational age and concentrations of linoleic, alpha-linolenic, and eicosapentaenoic acids, a decrease in AA concentrations of 0.17% (by wt) (95% CI: 0.03%, 0.31%) and 0.31% (by wt) (95% CI: 0.10%, 0.52%) was seen in maternal and cord serum, respectively, for each doubling of PCB exposure. CONCLUSIONS: Increased PCB exposure was associated with a modest decrease in serum AA concentrations, which is in accordance with the experimental evidence of desaturase inhibition by PCBs. Such interference with LCP utilization could attenuate the beneficial effects of the essential lipids contained in seafood. Because AA is of key importance for growth and development, these results suggest that this possible mechanism for PCB toxicity deserves to be explored.

Animals↗
PubMed2003

Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment.

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies.

Chromatography, Gas↗
PubMed2002

Estimation of health effects of prenatal methylmercury exposure using structural equation models.

BACKGROUND: Observational studies in epidemiology always involve concerns regarding validity, especially measurement error, confounding, missing data, and other problems that may affect the study outcomes. Widely used standard statistical techniques, such as multiple regression analysis, may to some extent adjust for these shortcomings. However, structural equations may incorporate most of these considerations, thereby providing overall adjusted estimations of associations. This approach was used in a large epidemiological data set from a prospective study of developmental methyl-mercury toxicity. RESULTS: Structural equation models were developed for assessment of the association between biomarkers of prenatal mercury exposure and neuropsychological test scores in 7 year old children. Eleven neurobehavioral outcomes were grouped into motor function and verbally mediated function. Adjustment for local dependence and item bias was necessary for a satisfactory fit of the model, but had little impact on the estimated mercury effects. The mercury effect on the two latent neurobehavioral functions was similar to the strongest effects seen for individual test scores of motor function and verbal skills. Adjustment for contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates only marginally, but the mercury effect could be reduced to non-significance by assuming a large measurement error for the PCB biomarker. CONCLUSIONS: The structural equation analysis allows correction for measurement error in exposure variables, incorporation of multiple outcomes and incomplete cases. This approach therefore deserves to be applied more frequently in the analysis of complex epidemiological data sets.

Biomarkers↗
PubMed2002

Benchmark dose calculations for methylmercury-associated delays on evoked potential latencies in two cohorts of children.

Delays in evoked potential latencies were observed at increased exposures to methylmercury from seafood in two cohorts of children. Because this outcome parameter appeared to be virtually independent of confounders, including cultural differences, a joint analysis of benchmark doses was carried out. Comparable cohort members included 382 Faroese and 113 Madeiran children without middle ear infection or neurological disease at age seven years. Maternal hair-mercury concentrations at parturition in the Faroese cohort ranged from 0.6 to 39.1 microg/g (geometric average, 4.49 microg/g). In Madeira, mothers who had not changed their diet since pregnancy had current hair-mercury concentrations ranging from 1.1 to 54.4 microg/g (geometric average 10.14 microg/g). The mercury-associated delay in peak III latencies at two frequencies (20 and 40 Hz) showed similar regression equations in the two groups of children, and benchmark dose calculations were therefore carried out for the two groups separately and jointly. For a doubling of a 5% prevalence of abnormal results of the peak III latencies at 40 Hz in a linear dose-response model, the benchmark dose for the maternal hair-mercury concentration was 8.79 microg/g for the Faroese children; 8.04 microg/g for the Madeiran children; and 9.46 microg/g for both groups. Results were similar for the 20 Hz condition. Benchmark dose results were substantially lower using a logarithmic or square root curve function, although the difference in fit between the curves was far from statistically significant. The benchmark results using evoked potential latencies are in close agreement with results based on neuropsychological test performance.

Adult↗
PubMed2002

Hydroxylated PCB metabolites and PCBs in serum from pregnant Faroese women.

In the Faroe Islands in the North Atlantic, the traditional diet includes pilot whale meat and blubber and other marine food. Fatty fish and blubber of mammals may contain high concentrations of organohalogen substances (OHSs). Elevated levels of OHSs have been reported from the Faroe Islands, first documented in breast milk samples obtained in 1987. The aim of this study was to determine the concentrations of hydroxylated polychlorinated biphenyls (OH-PCBs) and polychlorinated biphenyls (PCBs) in serum samples from pregnant Faroese women known to differ in their dietary habits. High concentrations of OH-PCBs and PCBs were found in part of the human serum samples analyzed, and the relative OH-PCB and PCB congener distributions were similar to those observed elsewhere. There was a wide span between the lowest and highest OH-PCB and PCB concentrations in the serum samples analyzed, with ranges of 19-1,800 ng/g lipid weight (lw) and 150-22,000 ng/g lw, respectively. The ratio of sigmaOH-PCB/sigmaPCB averaged about 10% and varied little. 4-Hydroxy-2,2,3,4,5,5,6-heptachlorobiphenyl was the most abundant OH-PCB metabolite in all samples analyzed, with four other OH-PCB congeners as dominating metabolites in the serum. More than 25 additional OH-PCBs were indicated. This study confirms the presence of high concentrations of organohalogen substances in populations or areas far removed from their sources.

Adult↗
PubMed2002

Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls.

OBJECTIVE: To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty. DESIGN: Following analysis for PCB in their umbilical cords, 196 boys from a Faroese birth cohort were examined for the development of puberty at 14 years of age. METHODS: Physical examination included determination of Tanner stages and testicular size. A morning urine sample was centrifuged and examined for the presence of sperm. Serum was analyzed for sex hormones. RESULTS: twenty boys (10.2%) had abnormalities in testicular development, mainly cryptorchidism. only three of them had a positive spermaturia test, but the level of exposure to pcbs in this group had not been increased. occurrence of spermaturia in 58 of the remaining 176 boys was also not associated with pcb exposure but showed highly significant associations with tanner stages and testicular size. serum concentrations of testosterone, fsh and lh were higher in boys with spermaturia, while sex hormone-binding globulin was lower and no difference occurred in inhibin b. serum hormone parameters showed only weak associations with the level of prenatal pcb exposure. CONCLUSIONS: These findings support the validity of spermaturia as a useful indicator of puberty, although a substantial rate of false negatives must be taken into account. Despite the wide range of exposure to PCB, the findings did not reveal any definite associations with the development of puberty. However, because of the limited size of the cohort, small effects cannot be excluded.

Adolescent↗
PubMed2002

Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury.

Exposure to methylmercury from marine mammals and other seafood may affect the development of the central nervous system. In a traditional Inuit community in Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have been examined in connection with all births. We examined 43 children at age 7-12 years with a battery of neurobehavioral tests. The average mercury concentration in hair was 5.0 microg/g and 1.5 microg/g in children and mothers, respectively. Clinical neurological examination did not reveal any obvious deficits. However, neuropsychological tests showed possible exposure-associated deficits, though only in a few cases reaching statistical significance. In conjunction with data from other studies, peak latencies on brainstem auditory evoked potentials tended to be prolonged at increased exposure levels. The data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.

Brain Stem↗
PubMedDate not supplied

Neurotoxic risk caused by stable and variable exposure to methylmercury from seafood.

OBJECTIVES: To examine whether the dose-effect relationship for developmental mercury neurotoxicity is affected by variable mercury exposure during pregnancy. METHODS: The study was based on a birth cohort of 1022 children born in the Faroe Islands between March 1986 and December 1987. Neurobehavioral performance of 917 children (90%) was assessed at age 7. Intrauterine methylmercury exposure was determined from mercury concentrations in cord blood and 2 sets of maternal hair. Complete exposure information was available for 614 children (67%). RESULTS: In children with complete exposure data, 8 of 16 neuropsychological tests showed deficits significantly associated with the cord-blood mercury concentration after confounder adjustment. Variable intrauterine exposure was suggested by disagreement between mercury concentrations in the 2 maternal hair samples. Removal of the 61 children (10%) with the greatest degree of variable exposure had a minimal effect on most exposure-effect relationships. However, the effect of the cord-blood concentration on verbal learning and memory was greater after this exclusion. CONCLUSION: The study supports previous findings from this cohort study that maternal mercury exposure during pregnancy is associated with neuropsychological deficits detectable at age 7 years and that this association is evident in women with stable exposures throughout pregnancy. Thus the association is not the result of variable exposures.

Child↗