4-Nonylphenol (NP) and bisphenol A (BPA) are phenolic substances used in high volumes by the industry. Studies on cells and in experimental animals have shown that both these compounds can be classified as estrogenic hormone disrupters. Information about the exposure of humans to NP and BPA is still scarce, especially regarding levels in human blood. The first aim of this study was to investigate possible sources of NP and BPA exposure from food, by analyzing the levels of NP and BPA from a Swedish food market basket, based on the Swedish per capita food consumption. A second aim was to investigate blood serum levels of NP and BPA, as well as NP-ethoxylates, among young women in Sweden (n=100). Moreover, associations between food consumption and blood NP and BPA levels were studied. In food, NP was to some extent found at levels above limit of quantification (LOQ 20 ng/g fresh weight) in fruits, cereal products, vegetables, and potatoes. BPA levels above LOQ (2 ng/g fresh weight) were found in fish, meats, potatoes, and dairy products. The estimated mean intakes per capita were (medium bound) 27 µg NP/day and 3.9 µg BPA/day, showing that food is a source of BPA and NP in the general Swedish population. In blood serum, free NP above limit of detection (LOD 0.5 ng/g) was detected in 46% of the study participants while detectable levels of total NP (LOD 0.8 ng/g) were observed in 43%. The corresponding percentages for BPA were 25% and 22%, respectively. The results indicate that there is a continuous source of exposure to NP and BPA that is high enough for free NP and BPA to be detected in some consumers. Among the participants with quantifiable levels of free and total NP (n=38), 85% (median, range: 38-112%) of the NP was present as free NP. For BPA 76% (49-109%) was detected as free BPA (n=15). All women had levels of ethoxylates of NP below LOD (0.1-0.7 ng/g). A significantly higher total consumption of fruits and vegetables was reported in questionnaires by participants with NP levels at or above LOD than among women with levels below LOD. This result is supporting the market basket results of relatively high NP levels in these types of food.
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.
We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.
We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).
We found differential DNA methylation at epigenome-wide statistical significance (p-value
After identifying an association between maternal Epstein-Barr virus (EBV) reactivation and acute lymphoblastic leukemia (ALL), the authors analyzed a nested case-control study within Finnish and Icelandic maternity cohorts with 7 million years of follow-up to confirm EBV's role in ALL. Offspring of 550,000 mothers were followed up to age 15 years during 1975-1997 by national cancer registries to identify leukemia cases. Mothers of cases and three quarters of matched mothers of controls were identified by national population registers. First-trimester sera from mothers of 304 ALL cases and 39 non-ALL cases and from 943 mothers of controls were analyzed for antibodies to viral capsid antigen, early antigen, and EBV transactivator protein ZEBRA. Relative risk, estimated as odds ratio (95% confidence interval), was adjusted for birth order and sibship size. Combining early antigen and/or ZEBRA immunoglobulin G antibodies with the presence of viral capsid antigen immunoglobulin M antibodies did not increase the estimate for ALL risk for viral capsid antigen immunoglobulin M alone (odds ratio = 1.9, 95% confidence interval: 1.2, 3.0). Both ZEBRA immunoglobulin G antibodies and viral capsid antigen immunoglobulin M antibodies were associated with an increased risk of non-ALL in the offspring (odds ratio = 4.5, 95% confidence interval: 1.3, 16; odds ratio = 5.6, 95% confidence interval: 1.1, 29, respectively), suggesting EBV reactivation in the mothers of non-ALL cases. EBV reactivation may be associated with a proportion of childhood leukemia.
During 1992-1995, 430 Danish couples were recruited after a nationwide mailing of a letter to 52,255 trade union members who were 20-35 years old, lived with a partner, and had no children. The couples were enrolled into the study when they discontinued birth control, and they were followed for six menstrual cycles or until a clinically recognized pregnancy. At enrollment and each month throughout the follow-up, both partners completed a questionnaire that asked them about their smoking, alcohol consumption, and intake of caffeinated beverages. The effect of current smoking and smoking exposure in utero was evaluated by using a logistic regression model with pregnancy outcome of each cycle in a Cox discrete model calculating the fecundability odds ratio. After adjustment for female body mass index and alcohol intake, diseases in female reproductive organs, semen quality, and duration of menstrual cycle, the fecundability odds ratio for smoking women exposed in utero was 0.53 (95% confidence interval (CI) 0.31-0.91) compared with unexposed nonsmokers. Fecundability odds ratio for nonsmoking women exposed in utero was 0.70 (95% CI 0.48-1.03) and that for female smokers not exposed in utero was 0.67 (95% CI 0.42-1.06). Exposure in utero was also associated with a decreased fecundability odds ratio in males (0.68, 95% CI 0.48-0.97), whereas present smoking did not reduce fecundability significantly. It seems advisable to encourage smoking cessation prior to the attempt to conceive as well as during pregnancy.
OBJECTIVES: The aim of the study was to investigate reproductive outcomes such as birthweight, preterm births, and postterrm births among women working in research laboratories while pregnant. METHODS: Female university personnel were identified from a source cohort of Swedish laboratory employees, and the database was linked to the medical birth register. The first births of the women were included in the analysis, 249 pregnancies among the women with laboratory work and 613 pregnancies among the women without laboratory tasks. Information about exposure to various laboratory agents was obtained from a previous questionnaire investigation at the research group level according to a specific definition. The ponderal index and ratio between observed and expected birthweights were calculated. Logistic regression models were used for analyses of dichotomous outcomes (preterm, postterrm and birthweight). RESULTS: Exposure to laboratory work with solvents was associated with an increased risk of preterm births, the estimated odds ratio (OR) being 3.4 (1.0
We studied the relation between birth defects and maternal agricultural work in a nationwide time- and area-matched case-referent series of 1,306 pairs of infants (581 orofacial clefts, 365 central nervous system defects, 360 skeletal defects) obtained through the Finnish Register of Congenital Malformations. We supplemented the Register data, including the mothers' latest and previous pregnancies, diseases, consumption of drugs and alcohol, smoking habits, and the like, with detailed interviews on the mothers' work conditions. When all of the birth defects were pooled and agricultural work was compared with nonagricultural work in the first trimester of pregnancy, the adjusted odds ratio was 1.4 [95% confidence interval (CI) = 0.9-2.0]. For orofacial clefts, the corresponding odds ratio was 1.9 (95% CI = 1.1-3.5). An industrial hygienist's blinded assessment indicated that seven mothers of infants with orofacial clefts and three reference mothers had been exposed to pesticides in agricultural work; the adjusted odds ratio for work with pesticide exposure, when compared with unexposed agricultural work, was 1.9 (95% CI = 0.4-8.3). Exposure to solvents did not explain the observed association.
The hypothesis that exposure to traffic-related air pollution increases the risk of developing cancer during childhood was investigated. The authors enrolled 1,989 children reported to the Danish Cancer Registry with a diagnosis of leukemia, tumor of the central nervous system, or malignant lymphoma during 1968-1991 and 5,506 control children selected at random from the entire childhood population. The residential histories of the children were traced from 9 months before birth until the time of diagnosis of the cases and a similar period for the controls. For each of the 18,440 identified addresses, information on traffic and the configuration of streets and buildings was collected. Average concentrations of benzene and nitrogen dioxide (indicators of traffic-related air pollution) were calculated for the relevant period, and exposures to air pollution during pregnancy and during childhood were calculated separately. The risks of leukemia, central nervous system tumors, and all selected cancers combined were not linked to exposure to benzene or nitrogen dioxide during either period. The risk of lymphomas increased by 25% (p for trend = 0.06) and 51% (p for trend = 0.05) for a doubling of the concentration of benzene and nitrogen dioxide, respectively, during the pregnancy. The association was restricted to Hodgkin's disease.
The incidence of allergic diseases was studied in the children living in an oil-extracting region of the Republic of Udmurtia. A hygienic assessment of the level of environmental pollution was made in the study areas. The increased atmospheric contamination was ascertained to cause an increase in the incidence of allergic diseases in children. There was a correlation between the concentration of noxious substances as part of the ambient air and the prevalence of allergic diseases in children. The studies suggest that the children living in the oil-extracting area have worse parameters of nonspecific resistance than do the control children. The findings serve as the basis for developing measure to lower environmental pollution and to reduce the incidence of allergic diseases in children.
Environmental exposure during pregnancy may have lifelong health consequences for the offspring and some studies have association between maternal exposure to air pollution during pregnancy and offspring's birth weight. However, many of these studies do not take into account small-scale variations in exposure, residential mobility, and work addresses during pregnancy. We used information from the National Birth Registry of Norway to examine associations between ambient environmental exposure such as air pollution and temperature, and offspring's birth weight taking advantage of information on migration history and work address in a large population-based cohort. A dispersion model was used to estimate ambient air pollution levels at all residential addresses and work addresses for a total of 25,229 pregnancies between 1999 and 2002 in Oslo, Norway. Ambient exposure to traffic pollution for the entire pregnancy was associated with a reduction in term birth weight in crude analyzes when comparing children of the highest and lowest exposed mothers. No evidence for an association between exposure to traffic pollution at home and work addresses and term birth weight after adjustment for covariates known to influence birth weight during pregnancy. After stratification, small statistically non-significant reductions were present but only for multiparious mothers. This group also had less residential mobility and less employment during pregnancy. The overall findings suggest no clear association between term birth weight and traffic pollution exposure during pregnancy. However, mobility patterns could introduce possible confounding when examining small-scale variations in exposure by using addresses. This could be of importance in future studies.
The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large population studies.