Toddler behavior, the home environment, and flame retardant exposure.

Toddlers are at increased risk of dust ingestion and subsequently flame retardant (FR) exposure because they often play close to the floor and mouth hands and objects. Exposure to some FRs have been associated to endocrine disruption and neurodevelopmental disorders. Previous research has shown higher FR concentrations in toddlers' serum and urine, but which toddler-behaviors influence exposure levels remains to be determined. We investigated how toddler-behaviors are associated to FRs in hand wipes (HWs) and saliva. Fifty 8-18 month-old children from the Linking EDCs in maternal Nutrition to Child health study, were visited at home. The child's behavior was observed and assessed using a questionnaire. Hand-to-object behavior frequency was associated with HW tris(chloroethyl) phosphate (TCEP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), tris(phenyl) phosphate, tris(methylphenyl) phosphate, and resorcinol bis(diphenyl phosphate) levels above the detection limit. Children playing with electronics multiple times per week had higher TDCIPP HW levels compared to children playing with electronics once per month or never (p = 0.032 and p = 0.046). Frequent mouth-to-object and frequent mouthing a pacifier were associated with lower TDCIPP (p = 0.019) and tris(2-chloroisopropyl) phosphate (TCIPP) HW levels, respectively (p = 0.002-0.019). Exposure estimates based on hand-to-mouth behavior did not exceed the available reference doses. This is the first study investigating toddler-behavior in relation to FR hand loadings. Although a range of behaviors was investigated, only a few showed a relation with FR HW levels, suggesting that toddler-behavior might not alone be responsible for the elevated FR levels in children. It is therefore important to explore other pathways including dermal absorption and inhalation.

Fetal toxicology.

Toxic chemicals, either from natural sources or man-made, are ubiquitous in our environment. Many of the synthetic chemicals make life more comfortable and therefore production continues to grow. Simultaneously with the increase in production, an increase in neurodevelopmental disorders has been observed. Some chemicals are not biodegradable or have a very long half-life time and, despite the fact that production of a number of those chemicals has been severely reduced, they are still ubiquitous in the environment. Fetal exposure to toxic chemicals is dependent on maternal exposure to those chemicals and the developing stage of the fetus. Human evidence from epidemiologic studies is described with regard to the effect of prenatal exposure to various groups of neurotoxicants (alcohol, particulate fine matter, metals, and endocrine disrupting chemicals) on neurobehavior development. Data indicate that prenatal exposure to alcohol, polycyclic aromatic hydrocarbons, lead, methylmercury (MeHg), organophosphate pesticides (OPPs), and polychlorinated biphenyl ethers (PBDEs) impair cognitive development, whereas exposure to alcohol, MeHg, organochlorine pesticides and OPPs, polychlorinated biphenyls, PBDEs, and bisphenol A increases the risk of developing either attention deficit/hyperactivity and/or autism spectrum disorders. Psychomotor development appears to be less affected. However, data are not conclusive, which may depend on the assessment of exposure and the exposure level, among other factors.

Electronics, interior decoration and cleaning patterns affect flame retardant levels in the dust from Dutch residences.

Consumer products such as furniture foam and electronic device casings are treated with flame retardant chemicals (FRs) to prevent the spread of fire. Many FRs are able to leach out of a product and end up in house dust. FRs in house dust can be taken up by humans through inhalation, ingestion or dermal adsorption. This study aims to identify factors in the home environment that are associated with FR levels in house dust. House dust and a wide range of data on characteristics of electronics, including age and use, interior decoration, domestic house and cleaning patterns, were collected from 50 households in the Netherlands. Decabromodiphenyl ether (BDE209) and several organophosphate flame retardants were measured in dust at detection percentages ranging from 58 to 94%, with median concentrations ranging from 32 ng/g (resorcinol-bis(diphenyl)phosphate (PBDPP)) to 825 ng/g (tris(chloropropyl)phosphate (TCIPP)). For the first time, age, hours of operation and use of the standby function of electronic devices were found to affect FR levels in dust. We found that if the total number of electronic devices purchased before 2008 increased by 1 device, BDE209 levels in house dust significantly increased by 66%. In addition, house dust from homes with carpeted floors was significantly associated with a 70-80% lower concentration of several FRs compared to homes with smooth floors (e.g., laminate). Less frequent vacuum cleaning and dusting were significantly associated with 41 to 88% higher concentrations of several FRs in dust. These associations suggest that actions such as frequent vacuum cleaning and dusting as well as different FR regulations for electronic devices affect indoor exposure levels.

Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts.

BACKGROUND AND AIMS: There is evidence that endocrine disrupting chemicals (EDCs) have developmental effects at environmental concentrations. We investigated whether some EDCs are associated with the adverse birth outcome Small for Gestational Age (SGA). METHODS: We used PCB 153, p,p'-DDE, HCB, PFOS and PFOA measured in maternal, cord blood or breast milk samples of 5446 mother-child pairs (subset of 693 for the perfluorinated compounds) from seven European birth cohorts (1997-2012). SGA infants were those with birth weight below the 10th percentile for the norms defined by gestational age, country and infant's sex. We modelled the association between measured or estimated cord serum EDC concentrations and SGA using multiple logistic regression analyses. We explored effect modification by child's sex and maternal smoking during pregnancy. RESULTS: Among the 5446 newborns, 570 (10.5%) were SGA. An interquartile range (IQR) increase in PCB 153 was associated with a modestly increased risk of SGA (odds ratio (OR) of 1.05 [95% CI: 1.04-1.07]) that was stronger in girls (OR of 1.09 [95% CI: 1.04-1.14]) than in boys (OR of 1.03 [95% CI: 1.03-1.04]) (p-interaction = 0.025). For HCB, we found a modestly increased odds of SGA in girls (OR of 1.04 [95% CI: 1.01-1.07] per IQR increase), and an inverse association in boys (OR of 0.90 [95% CI: 0.85-0.95]) (p-interaction = 0.0003). Assessment of the HCB-sex-smoking interaction suggested that the increased odds of SGA associated with HCB exposure was only in girls of smoking mothers (OR of 1.18 [95% CI: 1.11-1.25]) (p-interaction = 0.055). Higher concentrations of PFOA were associated with greater risk of SGA (OR of 1.64 [95% CI: 0.97-2.76]). Elevated PFOS levels were associated with increased odds of SGA in newborns of mothers who smoked during pregnancy (OR of 1.63 [95% CI: 1.02-2.59]), while an inverse association was found in those of non-smoking mothers (OR of 0.66 [95% CI: 0.61-0.72]) (p-interaction = 0.0004). No significant associations were found for p,p'-DDE. CONCLUSIONS: Prenatal environmental exposure to organochlorine and perfluorinated compounds with endocrine disrupting properties may contribute to the prevalence of SGA. We found indication of effect modification by child's sex and smoking during pregnancy. The direction of the associations differed by chemical and these effect modifiers, suggesting diverse mechanisms of action and biological pathways.

Prenatal exposure to persistent organic pollutants and child overweight/obesity at 5-year follow-up: a prospective cohort study.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), may influence offspring weight gain. More prospective epidemiological studies are needed to compliment the growing body of evidence from animal studies. METHODS: Serum from 412 pregnant Norwegian and Swedish women participating in a Scandinavian prospective cohort study were collected in 1986-88, and analyses of two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) were conducted. We used linear and logistic regression models with 95% confidence intervals (CIs) to evaluate the associations between maternal serum POP concentrations at 17-20 weeks of gestation and child overweight/obesity (body mass index (BMI) ≥ 85th percentile) at 5-year follow-up. Results were further stratified by country after testing for effect modification. We also assessed potential non-monotonic dose-response (NMDR) relationships. RESULTS: In adjusted linear models, we observed increased BMI-for-age-and-sex z-score (ß = 0.18, 95% CI: 0.01-0.35), and increased triceps skinfold z-score (ß = 0.15, 95% CI: 0.02-0.27) in children at 5-year follow-up per ln-unit increase in maternal serum perfluorooctane sulfonate (PFOS) concentrations. We observed increased odds for child overweight/obesity (BMI ≥ 85th percentile) for each ln-unit increase in maternal serum PFOS levels (adjusted OR: 2.04, 95% CI: 1.11-3.74), with stronger odds among Norwegian children (OR: 2.96, 95% CI: 1.42-6.15). We found similar associations between maternal serum perfluorooctanoate (PFOA) concentrations and child overweight/obesity. We found indications of NMDR relationships between PFOS and polychlorinated biphenyl (PCB) 153 and child overweight/obesity among Swedish children. CONCLUSION: We found positive associations between maternal serum PFAS concentrations and child overweight/obesity at 5-year follow-up, particularly among Norwegian participants. We observed some evidence for NMDR relationships among Swedish participants.

Maternal obesity and attention-related symptoms in the preterm offspring.

BACKGROUND: Maternal pre-pregnancy obesity, in term-born children, is associated with an increased risk of attention problems, however this relationship has not been explored among children born extremely preterm. AIM: To estimate the risk of attention problems at age 10years in children born very preterm to overweight (i.e., body mass index (BMI) 25-29kg/m2) and obese (i.e., BMI≥30kg/m2) women relative to the risk among children born to women who were neither overweight nor obese (i.e. BMI<25kg/m2). STUDY DESIGN: Multi-center prospective cohort study. METHODS: A total of 764 children born before the 28th week of gestation and whose mother's pre-pregnancy height and pre-pregnancy weight were obtained at birth had an IQ≥70 at age 10years when parents and teachers completed Child Symptom Inventory-4 questionnaires that included items about the presence of ADHD. RESULTS: Compared to children whose mother's pre-pregnancy weight was in the normal range (BMI<25kg/m2), children were at increased risk of parent-identified ADHD behaviors if their mother was overweight (odds ratio (OR)=1.9; 95% confidence interval (CI): 1.1, 3.3), or obese (OR=2.3; 95% CI: 1.4, 3.9). They were not at increased risk of teacher-identified ADHD characteristics if their mother was overweight before her pregnancy (OR=1.0; 95% CI: 0.6, 1.8), or obese (OR=1.0; 95% CI: 0.6, 1.6). CONCLUSION: Maternal overweight and obesity are associated with increased risk of parent-identified ADHD characteristics at 10years of age in children born extremely preterm.

Legacy and alternative halogenated flame retardants in human milk in Europe: Implications for children's health.

In this study, 10 polybrominated diphenyl ethers (PBDEs) and 19 alternative halogenated flame retardants (AFRs) were determined in >450 human milk samples across three European countries, representing northern, western and eastern Europe. This study provides first insights into the occurrence of selected AFRs in mother milk samples and compares them among three European countries. Sums of median concentrations of the most frequently detected PBDEs were 2.16, 0.88 and 0.45ngg-1 lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngg-1lw in all countries, which was 2 to 15 times less compared to Σ7PBDEs. The Penta-BDE replacement, bis(2-ethylhexyl) tetrabromophthalate, BEH-TEBP, was present at the greatest concentrations of any of the AFRs and in some samples exceeded concentrations of BDE 47 and BDE 153. Four AFRs including bromobenzenes (hexabromobenzene, pentabromobenzene, pentabromotoluene) and another Penta-BDE replacement (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB) were detected in >42% of all human milk samples. Because of the potential developmental neurotoxicity of the halogenated flame retardants, infant dietary intakes via breastfeeding were estimated; in four cases the intakes of BDE 47 exceeded the reference dose indicating that the present concentrations may pose a risk for children.

Brominated and organophosphorus flame retardants in body wipes and house dust, and an estimation of house dust hand-loadings in Dutch toddlers.

Children generally have higher Flame Retardant (FR) concentrations in serum compared to other age groups. Toddler behavior enhances direct contact with house dust since their frequent presence proximate to the floor, and their mouthing behavior. This study aimed to thoroughly investigate FR levels in body wipes of toddlers 8-18 months old) and in indoor dust using a noninvasive sampling technique. In this cross-sectional study, body wipes from hands, mouth and back, and indoor household dust samples were collected in twenty-one families and analyzed for one brominated- and seven organophosphorus FRs (polybrominated diphenyl ether 209 (BDE209), tris(2-chloroisopropyl) phosphate (TCIPP), tris(chloroethyl) phosphate (TCEP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), tris(phenyl) phosphate (TPHP), tris(methylphenyl) phosphate (TMPP), resorcinol bis(diphenyl phosphate) and bisphenol A bis(diphenyl phosphate)). Accelerated solvent extraction was used for extraction and the extract was measured with liquid chromatography combined with mass spectrometry. Non-parametric correlation analyses were performed to assess associations. All FRs were detected in body- and indoor dust samples (median range: 1.0ng/hand wipe (BDE209) to 65ng/hand wipe (TCIPP)) and were mostly correlated with each other. We estimated that approximately 260mg dust (range 50-880mg) accumulated on toddler's hands per day. Hand-to-mouth frequency was negatively associated with FR levels in wipes (τ = -0.38, p = 0.04). With increasing age FR concentrations (BDE209, TCEP, TDCIPP, TPHP and TMPP) on hands decreased significantly (p = 0.01-0.03). Girls had significantly less FRs (TCEP, TCIPP, TPHP and TMPP) on the hands (p = 0.01-0.03) than boys. This is to the best of the authors' knowledge the first study in Europe that measured brominated- as well as organophosphorus FRs in several types of body wipes from toddlers and that estimated the amount of house dust that accumulates on toddler's hands.

Toddler exposure to flame retardant chemicals: Magnitude, health concern and potential risk- or protective factors of exposure: Observational studies summarized in a systematic review.

Endocrine disrupting flame retardant (FR) chemicals form a human health concern, that is investigated mostly from the perspective of adult- and early life exposure. No overview of studies on toddler exposure and health effects exist. However, toddlerhood is a critical developmental period and toddlers are at increased risk for exposure because of their age-specific behavior. This systematic review encompasses toddler FR exposure studies in three countries, associated health effects and potential environmental, demographic, or behavioral risk- or protective factors for toddler exposure. A systematic literature search in four databases (PubMed, Embase.com, The Cochrane Library (via Wiley) and Web of Science Core collection) resulted in the identification of ten publications representing seven unique studies that measured brominated and/or phosphorylated FRs in toddlers' (8-24 month-old) serum, urine, hand wipes and feces. This review showed that toddlers are exposed to a range of FRs, that thyroid hormone disruption is associated with FR exposure and that factors in the indoor environment, including products such as plastic toys, might increase FR exposure. Considering the limited amount of studies, and the variety of biological matrices, FRs, and risk- and protective factors, this review did not reveal a uniform pattern of toddler exposure across the different cohorts studied. More evidence is necessary and considering the feasibility of invasive sampling in young children, we suggest to emphasize research on non-invasive matrices.

Thyroid-stimulating hormone levels in newborns and early life exposure to endocrine-disrupting chemicals: analysis of three European mother-child cohorts.

BackgroundVarious studies have reported interactions between thyroid hormones and early life chemical exposure. Our objective was to analyze the associations between markers of endocrine-disrupting chemical exposure and thyroid function in newborns, determined through heel prick blood spots.MethodsThree European mother-child cohorts (FLEHSI-Belgium, HUMIS-Norway, and the PCB cohort-Slovakia. Total n=1,784) were pooled for the purpose of this study. Data on thyroid-stimulating hormone (TSH) were obtained from national neonatal screening registries, and samples of cord plasma and/or breast milk were collected to determine exposure to various chemicals. Multiple regression models were composed with exposure and cohort as fixed factors, and adjustments were made for a priori defined covariates.ResultsMedian TSH concentrations were 1, 1.10, and 2.76 mU/l for the Belgian, Norwegian, and Slovak cohorts, respectively. For polychlorinated biphenyl (PCB)-153 and dichlorodiphenyldichloroethylene (p,p'-DDE), children in the third exposure quartile had a 12-15% lower TSH at birth. Results remained unchanged after additional adjustment for birth weight and gestational weight gain. No effect on TSH was observed for the other compounds.ConclusionEarly life exposure to PCB-153 and p,p'-DDE impacts newborn TSH levels. Higher exposure levels were associated with 12-15% lower TSH levels.

An effective clean-up technique for GC/EI-HRMS determination of developmental neurotoxicants in human breast milk.

The increasing number of children suffering from developmental disorders has raised questions regarding their association with the presence of environmental contaminants in mothers and children. We therefore developed a new method for the determination of 78 proven and potential developmental neurotoxicants, including polychlorinated biphenyls, legacy pesticides, pyrethroids, and old and new halogenated flame retardants in breast milk. The essential part of sample preparation was dialysis as a non-destructive clean-up step which was newly used at 10 °C and showed more efficient lipid removal (up to 96%) than the conventional methods such as gel permeation chromatography or freezing-lipid filtration and thus ensured low limits of detection (LOD) by reducing the sample volume prior to injection. Next advantages were significant solvent reduction and no risk of sample cross-contamination. Gas chromatography coupled with high resolution mass spectrometry (GC-HRMS) was subsequently used for the separation and compound quantification. The method was validated using breast milk samples fortified with the analyzed compounds. Recoveries for most of the compounds ranged from 63 to 121% with a relative standard deviation of 2-25%, and LODs ranged between 0.001 and 0.87 ng g-1 lipid weight. The method was applied to breast milk samples from a Dutch birth cohort where 35 out of the 78 compounds were quantified in more than 60% of the samples. For novel flame retardants, the method provides unique results regarding their occurrence in human matrices in Europe. Overall, the analysis of a complex mixture of developmental neurotoxicants could be useful for the assessment of the influence of the studied compounds to child health and development. Graphical abstract Flow diagram of the method and levels of the developmental neurotoxicants in Dutch human milk samples.

Developmental neurotoxicants in human milk: Comparison of levels and intakes in three European countries.

Developmental neurotoxicants (DNTs), such as methylmercury (MeHg), polychlorinated biphenyls (PCBs) and selected organochlorine pesticides (OCPs), have gained increasing interest recently due to their possible relation to developmental disorders in children, which are increasing worldwide. We analyzed levels of 14 developmental neurotoxicants in human milk samples from Slovakia (n=37), the Netherlands (n=120) and Norway (n=388). Positive identification for most target analytes was >95% in all samples. In all three countries MeHg was measured for the first time in mother milk. The highest MeHg levels were observed in Norway (39pgg-1 ww) with the highest fish consumption. Levels of indicator PCBs (iPCBs, sum of PCB 28, 52, 101, 138, 153 and 180), HCB and DDE+DDT were 2-4 times higher in Slovakia compared to the Netherlands or Norway. The levels of MeHg and organochlorine compounds were used for calculations of weekly or daily intakes (top-down approach) by means of pharmacokinetic modeling. The intakes ranged from 0.014 to 0.142µgkgbw-1week-1 for MeHg and from 0.043 to 17.4ngkgbw-1day-1 for organochlorine compounds in all three countries. Intakes of iPCBs exceeded a tolerable daily intake of 10ngkgbw-1day-1 in 16% of the Slovak participants. The top-down estimates were compared with bottom-up intakes based on national dietary estimates and the results showed good consistency between both approaches, with the bottom-up intakes exceeding the top-down by a factor of maximum 3.8 for iPCBs in the Netherlands and 3.9 for HCB in Slovakia. This confirms that food consumption in all three countries represents the dominant pathway of exposure to these developmental neurotoxicants.

Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case-cohort study.

BACKGROUND: The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the literature. METHODS: This case-cohort study included 424 mother-child pairs who participated in a prospective, multi-center study of parous women in Norway (Trondheim and Bergen) and Sweden (Uppsala). We used linear and logistic regression with 95% confidence intervals (CIs) to analyze the associations between two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) from early second trimester and indices of fetal growth. RESULTS: Among Swedish women, prenatal exposure to perfluorooctanoate (PFOA), polychlorinated biphenyl (PCB) 153 and hexachlorobenzene (HCB) were associated with higher odds for SGA birth. We found stronger associations among Swedish male offspring. In the Norwegian cohort, we found no significant associations between EDC exposure and indices of fetal growth. CONCLUSIONS: Some populations may be more vulnerable to EDCs, possibly due to differences in exposure levels, exposure sources and/or modifiable lifestyle factors. Male offspring may be more vulnerable to endocrine disruption.

Factors Associated with Maternal Serum Levels of Perfluoroalkyl Substances and Organochlorines: A Descriptive Study of Parous Women in Norway and Sweden.

INTRODUCTION: Perfluoroalkyl substances (PFASs) and organochlorines (OCs) are ubiquitous and persistent in the environment and proposed endocrine disrupting chemicals (EDCs). They can be transferred across the placenta during pregnancy, and studies suggest that the prenatal period may be particularly sensitive for influences on fetal growth and development. Several studies have investigated socio-demographic and pregnancy related factors associated with maternal serum PFAS and OC levels, but few studies have been conducted in time periods with increasing emissions of PFASs and recent emissions of OCs. METHODS: Serum from 424 pregnant women participating in the NICHD Scandinavian Successive Small-for-gestational Age (SGA) births study was collected in 1986-1988, and analyses of two PFASs and six OCs were conducted. Associations between EDCs and geographic, time dependent, socio-demographic and pregnancy related variables were evaluated by using multivariable linear regression models. RESULTS: Previous breastfeeding duration, time since last breastfeeding period, sampling date and country of residence were important factors associated with serum levels of PFOS and PFOA. Smoking status and pre-pregnancy BMI were negatively associated with PFOS, and maternal height was borderline negatively associated with PFOS and PFOA. Glomerular filtration rate (GFR) was negatively associated with PFOS in a sub-sample. Maternal serum levels of OCs were positively associated with maternal age, and negatively associated with previous breastfeeding duration and sampling date. Smoking had a consistently negative association with PCB 118 in a dose-dependent manner. Education level, pre-pregnancy BMI and alcohol consumption varied in importance according to the compound under study. CONCLUSIONS: Several maternal factors, including potentially modifiable factors, markers of pregnancy physiology and factors also related to perinatal outcomes were associated with EDC levels. Results from this study are relevant to populations with still high PFAS and OC levels, i.e. developing countries. Moreover, we can use this knowledge about associated factors on emerging EDCs with similar properties.

Species-Specific Associations Between Soil-Transmitted Helminths and Micronutrients in Vietnamese Schoolchildren.

Soil-transmitted helminth (STH) infections and micronutrient deficiencies are closely related and often coexist among low-income populations. We studied the association between infections with specific STH species and micronutrient status in rural Vietnamese schoolchildren. Children (N = 510) aged 6-9 years were recruited from two primary schools. STH infections were determined in stool samples. Hemoglobin, ferritin, retinol, and zinc were measured in blood samples, as well as C-reactive protein to control for inflammation. Iodine excretion was measured in urine. Associations of single and multiple infections with Ascaris lumbricoides, Trichuris trichiura, and hookworm with micronutrient status (hemoglobin, plasma ferritin, retinol, zinc, and urinary iodine) were estimated by multiple regression analysis. Ascaris infections showed a specific and intensity-dependent negative association with vitamin A. Trichuris and hookworm infections were associated with lower hemoglobin concentration, but not with plasma ferritin. Trichuris-infected children had zinc deficiency less often than uninfected children. In conclusion, our study shows species-specific associations between STH infections and micronutrient status in children. The different life cycles of STH species might have specific effects on the absorption or loss of specific micronutrients. Tailor-made combinations of deworming and nutritional interventions may be needed to improve child health and nutrition.

Prenatal Exposure to Perfluoroalkyl Substances and Behavioral Development in Children.

BACKGROUND: In recent years, prevalence rates of behavioral disorders in children have increased. One factor possibly implied in the etiology of behavioral disorders is exposure to perfluoroalkyl substances (PFASs). The use of PFASs is highly integrated into everyday life, and exposure is ubiquitous. Exposure to PFASs during early life may be particularly harmful, as it represents a critical time window for brain development. However, research in the area is limited, especially among preschool children. The objective of the current study was to explore the relationship between prenatal exposure to several PFASs and behavioral development at the age of 18 months. METHODS: Data from the Dutch cohort LINC (Linking Maternal Nutrition to Child Health) were used. Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were measured in cord plasma. The total exposure of PFASs was also calculated (ΣPFASs). Behavioral development was assessed with the Child Behavior Checklist 1.5-5 (CBCL 1.5-5). The CBCL scales "Attention Deficit Hyperactivity Disorder" (ADHD) and "Externalizing problems" were used for further analysis. Separate regression models were composed for each combination, in which exposure levels were classified in tertiles. Both whole population and sex-stratified analyses were performed. A family history of ADHD, the educational level, smoking or using alcohol or illicit drugs during pregnancy were considered as confounders. In total, data from 76 mother-child pairs was included. RESULTS: No significant associations were found between prenatal PFAS exposure and ADHD scores in the whole population and in the sex-stratified analyses. With regard to externalizing behavior, a significant negative association was found between the highest levels of ΣPFAS exposure and externalizing problem behavior in the whole population, but only in the crude model. After stratifying for sex, boys in the second and third tertile of exposure to PFOA presented significantly lower scores on the Externalizing Problem Scale than boys with the lowest exposure levels in the adjusted model. Girls exposed to higher levels of ΣPFAS exposure (T2) showed significantly lower scores on the Externalizing Problem Scale, in both crude and adjusted models. No significant associations with PFOS were found. CONCLUSIONS: RESULTS from the current study show that prenatal exposure to PFOA was negatively related to externalizing behavior in boys. RESULTS were different for boys and girls, emphasizing that mechanisms at work might be sex-dependent. However, results should be interpreted with caution as the sample size was small.

LInking EDCs in maternal Nutrition to Child health (LINC study) - protocol for prospective cohort to study early life exposure to environmental chemicals and child health.

BACKGROUND: The presence of chemicals in the environment is ubiquitous. Human biomonitoring studies have shown that various chemicals can be detected in the majority of the population, including pregnant women. These compounds may pass the placenta, and reach the fetus. This early life exposure in particular may be detrimental as some chemicals may disrupt the endocrine system, which is involved in various processes during development. The LINC study is a prospective birth cohort designed to study associations between early life environmental exposures and child health, including growth and neurodevelopment. The purpose of this paper is to give an overview of this cohort. METHODS AND DESIGN: Recruitment for this cohort has started in 2011 in three Dutch areas and is still ongoing. To date over 300 mother-child pairs have been included. Women are preferably included during the first trimester of pregnancy. Major congenital anomalies and twin births are reasons for exclusion. To assess exposure to environmental chemicals, cord blood, placenta, meconium and vernix are collected. Parents collect urine of the child shortly after birth and breast milk in the second month of life. Exposure to a broad range of environmental chemicals are determined in cord plasma and breast milk. Furthermore various hormones, including leptin and cortisone, are determined in cord plasma, and in heel prick blood spots (thyroxine). Data on anthropometry of the child is collected through midwives and youth health care centres on various time points until the child is 18 months of age. Furthermore cognitive development is monitored by means of the van Wiechen scheme, and information on behavioral development is collected by means of the infant behavior questionnaire and the child behavior checklist. When the child is 12 months of age, a house visit is scheduled to assess various housing characteristics, as well as hand-to-mouth behavior of the child. At this visit exposure of the child to flame retardants (with endocrine disrupting properties) in house dust is determined by means of body wipes. They are furthermore also measured in a saliva sample of the child. Next to these measurements, women receive questionnaires each trimester regarding amongst others lifestyle of the parents, general health of the parents and the child, and mental state of the mother. DISCUSSION: This study was approved by the medical ethics committee of the VU University Medical Centre. Consent for the infant is given by the mother, who is specifically required to give consent for both herself as well as her child. Results will be published regardless of the findings of this study, and will be widely disseminated among related medical stakeholders (e.g. midwives and pediatricians), policy makers, and the general public.

Prenatal exposure to endocrine disrupting chemicals and birth weight-A prospective cohort study.

Prenatal exposure to endocrine disrupting chemicals may affect fetal development through disruption of hormonal actions and epigenetic modifications, potentially predisposing individuals to later on-set health risks, such as obesity. The objective of this study was to determine associations between biological exposure markers of various endocrine disrupting chemicals and birth weight in a newly established, prospective mother-child cohort in the Netherlands. Birth weight (n = 91) was obtained from birth records, and exposure to dichlorodiphenyldichloroethylene (DDE), three di-2-ethylhexyl phthalate (DEHP) metabolites, polychlorinated biphenyl-153, perfluorooctanesulfonic acid (PFOS), and perfluorooctanoic acid (PFOA) was determined in cord plasma. For DDE, exposure was also measured in breast milk. Linear regression analysis was used to determine associations between compounds and birth weight, which were stratified for gender and adjusted for a priori defined covariates. Increased exposure to DDE was associated with lower birth weight in boys (>95.89 ng L-1, -325.9 g, 95% CI -634.26 to -17.56), whereas in girls a tendency towards a higher birth weight was observed. Lower birth weights for boys were also observed for high exposure to MECPP, and to a certain extent also for PFOA. MEHHP and PFOS exposure on the other hand were associated with higher birth weights in boys. In girls no effects were observed for these compounds. It can be concluded that prenatal exposure to DDE, perfluorinated alkyl acids, and phthalates was associated with changes in birth weight in this population. Associations were gender specific, and appeared to be non-linear. Since the population was relatively small, results should be interpreted with caution.

Children's exposure to polybrominated diphenyl ethers (PBDEs) through mouthing toys.

Polybrominated diphenyl ethers (PBDEs) have previously been detected in children toys, yet the risk of child exposure to these chemicals through the mouthing of toys or other items is still unknown. We aimed to expand on the current knowledge by investigating the impact of infants' mouthing activities on exposure to PBDEs present in toys. This was established by a leaching model for determining the amount PBDEs that can leach from toys into saliva in simulated conditions. The PBDE migration rate was at its highest for the 15 min low-exposure scenario incubations (198 pg/cm(2) × min) with the ERM EC-591 certified reference material (CRM) (0.17% w/w PBDEs). The leaching process was congener-dependent, since the percentage of lower brominated PBDE congeners that leached out was up to 4.5 times higher than for the heavier PBDEs. To study the scenario in which a child would mouth on a toy flame retarded with BDE 209 alone, a plastic item containing 7% BDE 209 (w/w) was also tested. The BDE 209 amounts leached out in only 15 min were higher than the amounts leached from the CRM after the 16 h incubation. For the Belgian population, the exposure scenario from mouthing on toys containing PBDEs in amounts similar to the REACH threshold was found to be lower than the exposure from mother's milk, but higher than the exposure through diet or even dust.