The influence of maternal dietary exposure to dioxins and PCBs during pregnancy on ADHD symptoms and cognitive functions in Norwegian preschool children.

BACKGROUND: Polychlorinated dibenzo-p-dioxins/dibenzofurans (dioxins) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with potentially adverse impact on child neurodevelopment. Whether the potential detrimental effects of dioxins and PCBs on neurodevelopment are of specific or unspecific character is not clear. OBJECTIVES: The purpose of the current study was to examine the influence of maternal dietary exposure to dioxins and PCBs on ADHD symptoms and cognitive functioning in preschoolers. We aimed to investigate a range of functions, in particular IQ, expressive language, and executive functions. MATERIAL AND METHODS: This study includes n=1024 children enrolled in a longitudinal prospective study of ADHD (the ADHD Study), with participants recruited from The Norwegian Mother and Child Cohort Study (MoBa). Boys and girls aged 3.5years participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview (PAPA), Stanford-Binet 5th revision (SB-5), Child Development Inventory (CDI), and Behavior Rating Inventory of Executive Function, Preschool version (BRIEF-P). Maternal dietary exposure to dioxins and PCBs was estimated based on a validated food frequency questionnaire (FFQ) answered mid-pregnancy and a database of dioxin and PCB concentrations in Norwegian foods. Exposure to dioxins and dioxin-like PCBs (dl-compounds) was expressed in total toxic equivalents (TEQ), and PCB-153 was used as marker for non-dioxin-like PCBs (ndl-PCBs). Generalized linear and additive models adjusted for confounders were used to examine exposure-outcome associations. RESULTS: Exposure to PCB-153 or dl-compound was not significantly associated with any of the outcome measures when analyses were performed for boys and girls together. After stratifying by sex, adjusted analyses indicated a small inverse association with language in girls. An increase in the exposure variables of 1 SD was associated with a reduction in language score of -0.2 [CI -0.4, -0.1] for PCB-153 and -0.2 [CI -0.5, -0.1] for dl-compounds in girls. For boys, exposure to PCB-153 or dl-compounds was not associated with language skills. The difference between sex-specific associations was not statistically significant (p-value=0.13). No sex-specific effects were observed for ADHD-symptoms, IQ scores, or executive functions. CONCLUSIONS: We found no indications that variation in current low-level exposure to PCB-153 or dl-compounds in Norway is associated with variation ADHD-symptoms, verbal/non-verbal IQ, or executive functions including working memory in preschoolers. However, our findings indicated that maternal dietary exposure to PCB-153 or dl-compounds during pregnancy was significantly associated with poorer expressive language skills in preschool girls, although the sex-specific associations were not significantly different.

Prenatal methylmercury exposure and language delay at three years of age in the Norwegian Mother and Child Cohort Study.

Prenatal methylmercury (MeHg) exposure and its possible neurodevelopmental effects in susceptible children are of concern. Studies of MeHg exposure and negative health outcomes have shown conflicting results and it has been suggested that co-exposure to other contaminants and/or nutrients in fish may confound the effect of MeHg. Our objective was to examine the association between prenatal exposure to MeHg and language and communication development at three years, adjusting for intake of fish, n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) and co-exposure to dioxins and dioxin like polychlorinated biphenyls (dl-PCBs). We used data from the Norwegian Mother and Child Cohort Study (MoBa) collected between 2002 and 2008. The study sample consisted of 46,750 mother-child pairs. MeHg exposure was calculated from reported fish intake during pregnancy by a FFQ in mid-pregnancy. Children's language and communication skills were measured by maternal report on the Dale and Bishop grammar rating and the Ages and Stages communication scale (ASQ). We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regressions. Median MeHg exposure was 1.3µg/day, corresponding to 0.14µg/kgbw/week. An exposure level above the 90th percentile (>2.6µg/day, >0.29µg/kgbw/week) was defined as the high MeHg exposure. Results indicated an association between high MeHg exposure and unintelligible speech with an adjusted OR 2.22 (1.31, 3.72). High MeHg exposure was also associated with weaker communication skills adjusted OR 1.33 (1.03, 1.70). Additional adjustment for fish intake strengthened the associations, while adjusting for PCBs and n-3 LCPUFA from diet or from supplements had minor impact. In conclusion, significant associations were found between prenatal MeHg exposure above the 90th percentile and delayed language and communication skills in a generally low exposed population.

Determinants of plasma PCB, brominated flame retardants, and organochlorine pesticides in pregnant women and 3 year old children in The Norwegian Mother and Child Cohort Study.

BACKGROUND: Exposure to persistent organic pollutants (POPs) during prenatal and postnatal life has been extensively studied in relation to adverse health effects in children. OBJECTIVES: The aim was to identify determinants of the concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (polybrominated diphenyl ethers, PBDEs; polybrominated biphenyl, PBB), and organochlorine pesticides (OCPs) in blood samples from pregnant women and children in The Norwegian Mother and Child Cohort Study (MoBa). METHODS: Blood samples were collected from two independent subsamples within MoBa; a group of women (n=96) enrolled in mid-pregnancy during the years 2002-2008 and a group of 3 year old children (n=99) participating during 2010-2011. PCB congeners (74, 99, 138, 153, 180, 170, 194, 209, 105, 114, 118, 156, 157, 167, and 189), brominated flame retardants (PBDE-28, 47, 99, 100, 153, 154, and PBB-153), as well as the OCPs hexachlorobenzene (HCB), oxychlordane, 4,4'dichlorodiphenyltrichloroethane (DDT), and 4,4'dichlorodiphenyldichloroethylene (DDE) were measured in both pregnant women and children. RESULTS: Age, low parity, and low pre-pregnant BMI were the most important determinants of increased plasma concentrations of POPs in pregnant women. In 3 year old children, prolonged breastfeeding duration was a major determinant of increased POP concentrations. Estimated dietary exposure to PCBs during pregnancy was positively associated with plasma concentrations in 3 year old children, but not in pregnant women. Plasma concentrations were approximately 40% higher in children compared to pregnant women. CONCLUSIONS: Several factors associated with exposure and toxicokinetics, i.e. accumulation, excretion and transfer via breastmilk of POPs were the main predictors of POP levels in pregnant women and children. Diet, which is the main exposure source for these compounds in the general population, was found to predict PCB levels only among children. For the PBDEs, for which non-dietary sources are more important, toxicokinetic factors appeared to have less predictive impact.

Development and validation of prediction models for blood concentrations of dioxins and PCBs using dietary intakes.

BACKGROUND: Dioxins and PCBs accumulate in the food chain and might exert toxic effects in animals and humans. In large epidemiologic studies, exposure estimates of these compounds based on analyses of biological material might not be available or affordable. OBJECTIVES: To develop and then validate models for predicting concentrations of dioxins and PCBs in blood using a comprehensive food frequency questionnaire and blood concentrations. METHODS: Prediction models were built on data from one study (n=195), and validated in an independent study group (n=66). We used linear regression to develop predictive models for dioxins and PCBs, both sums of congeners and 33 single congeners (7 and 10 polychlorinated dibenzo-p-dioxins and furans (PCDDs/PCDFs), 12 dioxin-like polychlorinated biphenyls (PCBs: 4 non-ortho and 8 mono-ortho), sum of all the 29 dioxin-like compounds (total TEQ) and sum of 4 non dioxin-like PCBs (∑ CB-101, 138, 153, 183=PCB(4)). We used the blood concentration and dietary intake of each of the above as dependent and independent variables, while sex, parity, age, place of living, smoking status, energy intake and education were covariates. We validated the models in a new study population comparing the predicted blood concentrations with the measured blood concentrations using correlation coefficients and Weighted Kappa (К(W)) as measures of agreement, considering К(W)>0.40 as successful prediction. RESULTS: The models explained 78% (sum dioxin-like compounds), 76% (PCDDs), 76% (PCDFs), 74% (no-PCBs), 69% (mo-PCBs), 68% (PCB(4)) and 63% (CB-153) of the variance. In addition to dietary intake, age and sex were the most important covariates. The predicted blood concentrations were highly correlated with the measured values, with r=0.75 for dl-compounds 0.70 for PCB(4), (p<0.001) and 0.66 (p<0.001) for CB-153. К(W) was 0.68 for sum dl-compounds 0.65 for both PCB(4) and CB-153. Out of 33 congeners 16 (13dl-compounds and 3 ndl PCBs) had К(W)>0.40. CONCLUSIONS: The models developed had high power to predict blood levels of dioxins and PCBs and to correctly rank subjects according to high or low exposure based on dietary intake and demographic information. These models underline the value of dietary intake data for use in investigations of associations between dioxin and PCB exposure and health outcomes in large epidemiological studies with limited biomaterial for chemical analysis.

Maternal seafood consumption and infant birth weight, length and head circumference in the Norwegian Mother and Child Cohort Study.

Results from previous studies on associations between maternal fish and seafood intakes and fetal growth are inconclusive. The aim of the present study was to investigate how maternal intakes of seafood, subtypes of seafood and supplementary n-3 fatty acids were associated with infant birth weight, length and head circumference in a prospective study in Norway. The study population included 62 099 participants in the Norwegian Mother and Child Cohort Study. The mothers answered an FFQ in mid pregnancy. The FFQ comprised detailed questions about intake of various seafood items and n-3 supplements. Data on infant birth weight, length and head circumference were obtained from the Medical Birth Registry. We used multivariable regression to examine how total seafood, various seafood subtypes and supplementary n-3 intakes were associated with birth size measures. Total seafood intake was positively associated with birth weight and head circumference. Lean fish was positively associated with all birth size measures; shellfish was positively associated with birth weight, while fatty fish was not associated with any birth size measures. Intake of supplementary n-3 was negatively associated with head circumference. The relative risk of giving birth to a small baby ( < 2500 g) in full-term pregnancies was significantly lower in women who consumed >60 g/d of seafood than in women who consumed ≤ 5 g/d (OR = 0·56 (95 % CI 0·35, 0·88). In conclusion, maternal seafood consumption was positively associated with birth size, driven by lean fish intake, while supplementary n-3 intake was negatively associated with infant head circumference.

Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants.

The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life.