Marijke de Cock

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.

Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Review

Aim:  To provide an overview of studies on perinatal exposure in humans to endocrine disrupting chemicals (EDCs) in relation to autism spectrum (ASD) and attention deficit hyperactivity (ADHD) disorders.

Obesogenic effects of endocrine disruptors, what do we know from animal and human studies?

BACKGROUND Hormonal actions and activation of receptors involved in adipogenesis and brain development during the prenatal period may be affected by exposure to certain chemicals. Experimental studies have shown that amongst others polychlorinated biphenyl (PCB)-153 and dichlorodiphenyltrichloroethane (DDT) may have obesogenic effects in prenatally exposed mice. OBJECTIVE To provide an overview of five classes of chemicals which have frequently been indicated as potential obesogens, and to discuss the evidence available regarding early life exposure to these compounds and overweight later in life. METHODS Pubmed was systematically searched for publications which related early life exposure to endocrine disrupting chemicals (EDCs) to growth parameters later in life. We included 19 studies, which were published from 1995 and onwards. RESULTS Both positive and negative associations are observed between early life exposure and weight or height at various ages, including as early as 14 months, as well as until 20 years of age. In none of the included studies negative associations between perinatal exposure to EDCs and body mass index (BMI) were found and in several studies a positive association was observed. Dose-response relations appear to be non-monotonic. CONCLUSION For certain EDCs, early life exposure may be associated with weight homeostasis later in life, however not necessarily in an obesogenic direction. More sensitive measures of adiposity as well as long-term follow-up are warranted for future studies.

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.

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.

Infant Sleep Duration is Related to Externalizing Behavior at the Age of 18 Months: Results from a Dutch Cohort Study

Background: Sleep is essential for children’s daytime functioning. Sleep problems have been related to several behavioral disorders. In the last few decades, growing attention has been given to externalizing problem behavior. Previous work has indicated that children and adolescents presenting externalizing problem behavior are at risk for an array of disorders in adulthood, including anxiety, disruptive behavior, mood problems and substance use. Several studies have shown that sleep problems may be related to externalizing problem behavior; research however is limited, especially among children younger than 18 months. Methods: Data from the Dutch mother-child cohort LINC (Linking Maternal Nutrition to Child Health) were used. Sleep patterns were assessed by sleep diaries, which were filled out by the parents or caretaker when the child was three, six, nine, twelve and eighteen months old. Using the sleep diaries, sleep duration, nocturnal awakenings and early awakenings were calculated for each child at each time point. Externalizing behavior was assessed by using the scale ‘Externalizing behavior’ of the Child Behavior Checklist 1.5-5. Mixed model analyses were conducted to determine whether random intercepts and/or slopes had to be included in analyses regarding the development of the sleep variables over time (0-18 months). A random intercept and random slope was included for sleep duration and nocturnal awakenings, while for early awakenings only a random intercept was added. Subsequently, linear regression analyses were carried out to study the relationship between sleep characteristics over time with externalizing behavior as continuous, dependent variable. Family history, educational level, smoking, alcohol use and illicit drug use during pregnancy were checked for possible confounding effects. In total, data from 85 to 91 mother-child pairs were included, depending on the sleep variable. Results: The intercept of sleep duration was found to be significantly related to externalizing scores on the CBCL (β=-2.35; CI=-4.31, -0.16; p=0.03). No other significant results were found. Conclusion/discussion: We found that sleep duration was significantly related to externalizing behavior at 18 months. More specifically our results indicate that children who sleep less on average show more externalizing behavior. However, results should be interpreted with caution as the sample size was limited. Future studies should make use of longitudinal designs and larger sample sizes to confirm the relationship between sleep patterns and behavioral development over time.

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.

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.