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1.  Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother–Child Study (NewGeneris) 
Environmental Health Perspectives  2013;121(10):1200-1206.
Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs.
Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy.
Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires.
Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g)
Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.
Citation: Pedersen M, Schoket B, Godschalk RW, Wright J, von Stedingk H, Törnqvist M, Sunyer J, Nielsen JK, Merlo DF, Mendez MA, Meltzer HM, Lukács V, Landström A, Kyrtopoulos SA, Kovács K, Knudsen LE, Haugen M, Hardie LJ, Gützkow KB, Fleming S, Fthenou E, Farmer PB, Espinosa A, Chatzi L, Brunborg G, Brady NJ, Botsivali M, Arab K, Anna L, Alexander J, Agramunt S, Kleinjans JC, Segerbäck D, Kogevinas M. 2013. Bulky DNA adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother–child study (NewGeneris). Environ Health Perspect 121:1200–1206; http://dx.doi.org/10.1289/ehp.1206333
doi:10.1289/ehp.1206333
PMCID: PMC3801201  PMID: 23906905
2.  Dietary Acrylamide Intake during Pregnancy and Fetal Growth—Results from the Norwegian Mother and Child Cohort Study (MoBa) 
Environmental Health Perspectives  2012;121(3):374-379.
Background: Acrylamide has shown developmental and reproductive toxicity in animals, as well as neurotoxic effects in humans with occupational exposures. Because it is widespread in food and can pass through the human placenta, concerns have been raised about potential developmental effects of dietary exposures in humans.
Objectives: We assessed associations of prenatal exposure to dietary acrylamide with small for gestational age (SGA) and birth weight.
Methods: This study included 50,651 women in the Norwegian Mother and Child Cohort Study (MoBa). Acrylamide exposure assessment was based on intake estimates obtained from a food frequency questionnaire (FFQ), which were compared with hemoglobin (Hb) adduct measurements reflecting acrylamide exposure in a subset of samples (n = 79). Data on infant birth weight and gestational age were obtained from the Medical Birth Registry of Norway. Multivariable regression was used to estimate associations between prenatal acrylamide and birth outcomes.
Results: Acrylamide intake during pregnancy was negatively associated with fetal growth. When women in the highest quartile of acrylamide intake were compared with women in the lowest quartile, the multivariable-adjusted odds ratio (OR) for SGA was 1.11 (95% CI: 1.02, 1.21) and the coefficient for birth weight was –25.7 g (95% CI: –35.9, –15.4). Results were similar after excluding mothers who smoked during pregnancy. Maternal acrylamide– and glycidamide–Hb adduct levels were correlated with estimated dietary acrylamide intakes (Spearman correlations = 0.24; 95% CI: 0.02, 0.44; and 0.48; 95% CI: 0.29, 0.63, respectively).
Conclusions: Lowering dietary acrylamide intake during pregnancy may improve fetal growth.
doi:10.1289/ehp.1205396
PMCID: PMC3621181  PMID: 23204292
acrylamide; birth weight; diet; Hb adducts; MoBa; pregnancy; small for gestational age
3.  Maternal caffeine intake during pregnancy is associated with birth weight but not with gestational length: results from a large prospective observational cohort study 
BMC Medicine  2013;11:42.
Background
Pregnant women consume caffeine daily. The aim of this study was to examine the association between maternal caffeine intake from different sources and (a) gestational length, particularly the risk for spontaneous preterm delivery (PTD), and (b) birth weight (BW) and the baby being small for gestational age (SGA).
Methods
This study is based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. A total of 59,123 women with uncomplicated pregnancies giving birth to a live singleton were identified. Caffeine intake from different sources was self-reported at gestational weeks 17, 22 and 30. Spontaneous PTD was defined as spontaneous onset of delivery between 22+0 and 36+6 weeks (n = 1,451). As there is no consensus, SGA was defined according to ultrasound-based (Marsal, n = 856), population-based (Skjaerven, n = 4,503) and customized (Gardosi, n = 4,733) growth curves.
Results
The main caffeine source was coffee, but tea and chocolate were the main sources in women with low caffeine intake. Median pre-pregnancy caffeine intake was 126 mg/day (IQR 40 to 254), 44 mg/day (13 to 104) at gestational week 17 and 62 mg/day (21 to 130) at gestational week 30. Coffee caffeine, but not caffeine from other sources, was associated with prolonged gestation (8 h/100 mg/day, P <10-7). Neither total nor coffee caffeine was associated with spontaneous PTD risk. Caffeine intake from different sources, measured repeatedly during pregnancy, was associated with lower BW (Marsal-28 g, Skjaerven-25 g, Gardosi-21 g per 100 mg/day additional total caffeine for a baby with expected BW 3,600 g, P <10-25). Caffeine intake of 200 to 300 mg/day increased the odds for SGA (OR Marsal 1.62, Skjaerven 1.44, Gardosi 1.27, P <0.05), compared to 0 to 50 mg/day.
Conclusions
Coffee, but not caffeine, consumption was associated with marginally increased gestational length but not with spontaneous PTD risk. Caffeine intake was consistently associated with decreased BW and increased odds of SGA. The association was strengthened by concordant results for caffeine sources, time of survey and different SGA definitions. This might have clinical implications as even caffeine consumption below the recommended maximum (200 mg/day in the Nordic countries and USA, 300 mg/day according to the World Health Organization (WHO)) was associated with increased risk for SGA.
doi:10.1186/1741-7015-11-42
PMCID: PMC3606471  PMID: 23421532
preterm delivery; gestational length; small for gestational age; birth weight; growth curve; intrauterine growth restriction; caffeine; coffee; tea; soft drinks
4.  Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris) 
Environmental Health Perspectives  2012;120(12):1739-1745.
Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents.
Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother–child study.
Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006–2010. Maternal diet was estimated through food-frequency questionnaires.
Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was –132 g (95% CI: –207, –56); the corresponding difference for head circumference was –0.33 cm (95% CI: –0.61, –0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight.
Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.
doi:10.1289/ehp.1205327
PMCID: PMC3548277  PMID: 23092936
biomarker; children; diet; intrauterine growth restriction; in utero exposure
5.  Biomarkers of Human Exposure to Acrylamide and Relation to Polymorphisms in Metabolizing Genes 
Toxicological Sciences  2009;108(1):90-99.
Acrylamide (AA) is formed in heat treated carbohydrate rich foods in the so-called Maillard reaction. AA is readily absorbed in the body and converted to glycidamide (GA) by epoxidation by the CYP2E1 (cytochrome P450 2E) enzyme. Both AA and GA may be detoxified through direct conjunction to glutathione by glutathione-S-transferases and GA by hydrolysis to glyceramide. Recently, we reported that biomarkers of AA exposure reflect intake of major food sources of AA; there were large interindividual variations in the blood ratio of GA-Hb/AA-Hb (GA- and AA-hemoglobin adducts). In this study we investigated whether the ratio of GA-Hb/AA-Hb in subjects could be related to polymorphic differences in genes coding for metabolizing enzymes CYP2E1, EPHX1 (microsomal epoxide hydrolase), GSTM1, GSTT1, and GSTP1, all being expected to be involved in the activation and detoxification of AA-associated adducts. We found significant associations between GSTM1 and GSTT1 genotypes and the ratio of GA-Hb/AA-Hb (p = 0.039 and p = 0.006, respectively). The ratio of GA-Hb/AA-Hb in individuals with the combined GSTM1- and GSTT1-null variants was significantly (p = 0.029) higher than those with the wild-type genotypes. Although the number of subjects was small, there were also significant associations with other combinations; CYP2E1 (Val179Val) plus GSTM1-null (p = 0.022); CYP2E1 (Val/Val), GSTM1-null plus GSTT1-null (p = 0.047); and CYP2E1 (Val/Val), GSTT1 null, EPHX1 (Tyr113Tyr) plus EPHX1 (His139Arg) (p = 0.018). Individuals with these combined genotypes had significantly higher blood ratio of GA-Hb/AA-Hb than other combinations. The observed associations correspond with what would be expected from the relative roles of these enzymes in activation and detoxification of AA, except for individuals with the EPHX1 (His139Arg) variant. The internal dose of genotoxic metabolite and also the concentration of AA in blood seem to be affected by these polymorphic genes. The genotypes and their combination may constitute useful biomarkers for the assessment of individual susceptibility to AA intake, and could add to the precision of epidemiological studies of dietary cancer.
doi:10.1093/toxsci/kfn269
PMCID: PMC2644397  PMID: 19131562
cytochrome P450 2E1; glutathione-S-transferase; SNPs; polymorphisms; glycidamide; acrylamide; biotransformation
6.  Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women 
Annals of Nutrition & Metabolism  2008;52(4):272-280.
Background
Use of dietary supplements during pregnancy may give an important contribution to nutrient intake, and for nutrients like folate and vitamin D supplements are recommended. Our objective was to study use and contribution of dietary supplement to nutrient intake among women participating in the Norwegian Mother and Child Cohort Study (MoBa).
Methods
This study is based on 40,108 women participating in MoBa which is conducted by the Norwegian Institute of Public Health. The women had filled inversion 2 of the food frequency questionnaire in MoBa between February 2002 and February 2005.
Results
81% reported use of one or more dietary supplements. The most commonly used category was cod liver oil/fish oil supplements (59%) followed by singular folic acid supplements (36%) and multivitamin/multimineral supplements (31%). The nutrient contribution of the dietary supplements varied from 65% for folate and vitamin D to 1% for potassium among supplement users. The dietary intake of vitamin D, folate, iodine and iron did not reach the Nordic Recommendations for pregnant women.
Conclusions
Use of supplements improved the intake of folate, iron and vitamin D, but not sufficiently to reach the recommended amounts.
doi:10.1159/000146274
PMCID: PMC2813797  PMID: 18645244
Dietary supplements; Pregnancy; Nutrient intake; Multivitamins; Minerals; Fatty acids; Vitamin D; Folate; Iodine
7.  Which health-related quality of life score? A comparison of alternative utility measures in patients with Type 2 diabetes in the ADVANCE trial 
Background
Diabetes has a high burden of illness both in life years lost and in disability through related co-morbidities. Accurate assessment of the non-mortality burden requires appropriate health-related quality of life and summary utility measures of which there are several contenders. The study aimed to measure the impact of diabetes on various health-related quality of life domains, and compare several summary utility measures.
Methods
In the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) study, 978 Australian patients with Type 2 diabetes completed two health-related quality of life questionnaires at baseline: the EQ-5D and the SF-36v2, from which nine summary utility measures were calculated, and compared. The algorithms were grouped into four classes: (i) based on the EQ-5D; (ii) using fewer items than those in the SF-12 (iii) using the items in the SF-12; and (iv) using all items of the SF-36.
Results
Overall health-related quality of life of the subjects was good (mean utility ranged from 0.68 (±0.08) to 0.85(±0.14) over the nine utility measures) and comparable to patients without diabetes. Summary indices were well correlated with each other (r = 0.76 to 0.99), and showed lower health-related quality of life in patients with major diabetes-related events such as stroke or myocardial infarction. Despite the smaller number of items used in the scoring of the EQ-5D, it generally performed at least as well as SF-36 based methods. However, all utility measures had some limitation such as limited range or ceiling effects.
Conclusion
The summary utility measures showed good agreement, and showed good discrimination between major and minor health state changes. However, EQ-5D based measures performed as well and are generally simpler to use.
doi:10.1186/1477-7525-5-21
PMCID: PMC1950473  PMID: 17462100

Results 1-7 (7)