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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.

Background Endocrine disrupting chemicals (EDCs) present in the environment may disrupt thyroid hormones, which in early life are essential for brain development. Observational studies regarding this topic are still limited, however as the presence of chemicals in the environment is ubiquitous, further research is warranted. The objective of the current study was to assess the association between exposure markers of various EDCs and thyroxine (T4) levels in newborns in a mother-child cohort in the Netherlands. Methods Exposure to dichlorodiphenyldichloroethylene (DDE), three di-2-ethylhexyl phthalate (DEHP) metabolites, hexachlorobenzene (HCB), polychlorinated biphenyl (PCB)-153, perfluorooctanesulfonic acid (PFOS), and perfluorooctanoic acid (PFOA) was determined in cord plasma or breast milk, and information on T4 levels in heel prick blood spots was obtained through the neonatal screening programme in the Netherlands. Linear regression models were composed to determine associations between each of the compounds and T4, which were stratified for gender and adjusted for a priori defined covariates. Results Mean T4 level was 86.9 nmol/L (n = 83). Girls in the highest quartile of DDE and PFOA exposure showed an increased T4 level compared to the lowest quartile with both crude and fully adjusted models (DDE > 107.50 ng/L, +24.8 nmol/L, 95% CI 0.79, 48.75; PFOA > 1200 ng/L, +38.6 nmol/L, 95% CI 13.34, 63.83). In boys a lower T4 level was seen in the second quartile of exposure for both PFOS and PFOA, however after fully adjusting the models these associations were attenuated. No effects were observed for the other compounds. Conclusion DDE and perfluorinated alkyl acids may be associated with T4 in a sex-specific manner. These results should however be interpreted with caution, due to the relatively small study population. More research is warranted, as studies on the role of environmental contaminants in this area are still limited.

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

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.

Growth in the first year of life may already be predictive of obesity later in childhood. The objective was to assess the association between prenatal exposure to various endocrine disrupting chemicals (EDCs) and child growth during the first year. Dichloro-diphenyldichloroethylene (DDE), mono(2-ethyl-5-carboxypentyl)phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP), mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), polychlorinated biphenyl-153, perfluorooctanesulfonic acid, and perfluoro-octanoic acid were measured in cord plasma or breast milk. Data on weight, length, and head circumference (HC) until 11 months after birth was obtained from 89 mother-child pairs. Mixed models were composed for each health outcome and exposure in quartiles. For MEOHP, boys in quartile 1 had a higher BMI than higher exposed boys (p = 0.029). High DDE exposure was associated with low BMI over time in boys (0.8 kg/m2 difference at 11 m). Boys with high MECPP exposure had a greater HC (1.0 cm difference at 11 m) than other boys (p = 0.047), as did girls in the second quartile of MEHHP (p = 0.018) and DDE (p < 0.001) exposure. In conclusion, exposure to phthalates and DDE was associated with BMI as well as with HC during the first year after birth. These results should be interpreted with caution though, due to the limited sample size.

Background Various 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. Methods Three 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. Results Median 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. Conclusion Early life exposure to PCB-153 and p,p′-DDE impacts newborn TSH levels. Higher exposure levels were associated with 12–15% lower TSH levels.

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. 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. 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.