Urinary concentrations of bisphenols and parabens and their association with attention, hyperactivity and impulsivity at adolescence.

BACKGROUND: Neurobehavioural disorder diagnoses have been increasing over the last decades, leading to heightened interest in the aetiological factors involved. Endocrine disrupting chemicals, such as parabens and bisphenols, have been suggested as one of those factors. It is unknown whether exposure during adolescence may affect neurobehavioural development. OBJECTIVE: To determine whether urinary concentrations of parabens and bisphenols are associated with attention and concentration in adolescents, in general and sex-specific. METHODS: We invited 188 adolescents (13-15 years old) for the follow-up birth cohort-study. Concentrations of five parabens and three bisphenols (BPA; BPF; BPS) were measured in morning urine after overnight fasting, using a validated LC-MS/MS method. Attention and concentration were assessed at the clinic with subtests of the Test of Everyday Attention in Children and the Dutch Attention Deficit Hyperactivity Disorder questionnaire (AVL), the latter being filled in by parents. Linear regression analyses were performed, adjusting for urine creatinine concentrations and potential confounding factors. RESULTS: 101 (54%) adolescents participated (46 girls; 55 boys). Urinary paraben concentrations were higher in girls than in boys. Methylparaben was positively associated with attention in girls (p ≤ .05; B= -2.836; 95%CI= -5.175;-.497), ethylparaben negatively with hyperactivity (p ≤ .05; B= -1.864; 95%CI= -3.587;-.141). Butylparaben was associated with more optimal scores on parent reported attention. Propylparaben was negatively associated with scores on sustained auditory attention in girls (p ≤ .10; B=.444; 95%CI= -.009;.896). Bisphenol concentrations were not associated with scores on attention and concentration after adjusting for confounders. CONCLUSION: In 13-15-year-old Dutch adolescents, urinary concentrations of methylparaben and ethylparaben were associated with better attention and less hyperactivity, whereas a trend toward significance was found between higher urinary propylparaben concentrations and poorer attention. Bisphenol concentrations were not associated with attention and concentration after adjusting for confounders.

Prenatal Environmental Exposure to Persistent Organic Pollutants and Reproductive Hormone Profile and Pubertal Development in Dutch Adolescents.

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), may interfere with hormonal processes. Knowledge about the effects of prenatal exposure to PCBs and their hydroxylated metabolites (OH-PCBs) on pubertal development is limited. Therefore, the aim of the current study was to determine whether prenatal environmental PCB and OH-PCB exposure are associated with reproductive hormone levels and pubertal characteristics in 13- to 15-year-old children. In this Dutch observational cohort study, 194 mother-infant pairs were included (1998-2002). Maternal pregnancy serum levels of PCBs, OH-PCBs, and other POPs were measured. At follow-up (2014-2016), we measured serum or plasma levels of reproductive hormones in their children. We assessed Tanner stages and testicular volume (by clinician or standardized self-assessment), and participants completed questionnaires on pubertal onset. In total, 101 adolescents (14.4 ± 0.8 years; 53.7% of invited) participated, and 55 were boys. In boys, higher prenatal PCB levels were associated with higher testosterone levels, higher pubic hair stage, larger testicular volume, and younger age at onset of growth spurt and voice break. In girls, higher prenatal PCB levels were associated with higher stages for breast development. In conclusion, higher prenatal PCB exposure could be associated with more advanced pubertal development in 13- to 15-year-old children.

Prenatal Environmental Exposure to Persistent Organic Pollutants and Indices of Overweight and Cardiovascular Risk in Dutch Adolescents.

Persistent organic pollutants (POPs) may have obesogenic effects. Knowledge about the effects of prenatal exposure to POPs on anthropometric measurements and metabolic parameters into adolescence is limited. Therefore, the aim of the current study was to determine whether prenatal environmental exposure to several POPs is associated with indices of overweight and cardiovascular risk in 13-15-year-old children. In this Dutch observational cohort study, 194 mother-infant pairs were included (1998-2002). Maternal pregnancy serum levels of PCBs, OH-PCBs, PBDEs, and other POPs were measured. At follow-up (2014-2016), levels of cholesterol, HDL-C, LDL-C, triglycerides, fasting insulin, fasting glucose, leptin, and adiponectin were measured in their children. The children's height, weight, waist circumference, hip circumference, and blood pressure were measured. In total, 101 adolescents (14.4 ± 0.8 years; 53.7% of invited) participated of which 55 were boys. Mean BMI was 19.1 ± 3.6 kg/m2 and mean BMI z-score 0.13 ± 1.14. Higher prenatal levels of PCBs were associated with lower levels of HDL-C and adiponectin in boys and higher levels of PBDEs with higher triglycerides in girls. We found significant differences by sex in the associations with OH-PCBs, with lower HDL-C and adiponectin, higher LDL-C/HDL-C ratio, fasting glucose, HOMA2-IR, height, and weight for boys. Our study indicates that higher prenatal exposure to PCBs, OH-PCBs, and PBDEs was associated with adolescent levels of some metabolic cardiovascular risk markers and hormones associated with the development of obesity and cardiovascular disease.

A comparison of the early motor repertoire of very preterm infants and term infants.

OBJECTIVE: To obtain reference data on the early motor repertoire of very preterm infants compared with healthy term infants at three months' post-term age. STUDY DESIGN: In this observational study, using Prechtl's method on the assessment of the early motor repertoire, we compared the quality of fidgety movements and the concurrent motor optimality score - revised of infants with a gestational age <30 weeks and/or a birth weight <1000 g with healthy infants with a gestational age of 37-42 weeks. RESULTS: One hundred eighty very preterm and 180 healthy term infants participated. The median motor optimality scores - revised of very preterm infants were significantly lower in comparison to those of term infants, with scores of 24 (25th-75th percentiles: 23-26) and 26 (25th-75th percentiles: 26-28), respectively. Fidgety movements were aberrant (abnormal or absent) more often in very preterm infants than in term infants. The odds ratio was 4.59 (95% CI, 1.51-13.92). Compared with term infants, very preterm infants had poorer scores on the subscales age-adequate movement repertoire, observed postural patterns, and movement character with odds ratios ≥2.97. We found no differences regarding observed movement patterns. CONCLUSION: This study provides reference data on the early motor repertoire of very preterm and healthy term infants. It demonstrates that the early motor repertoire of very preterm infants is poorer than that of term infants, a finding consistent with existing knowledge that prematurity increases the risk of poor neurodevelopment.

Prenatal exposure to persistent organic pollutants and cognition and motor performance in adolescence.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), was found to be associated with poorer neurological development in children. Knowledge about the effects on outcomes until adolescence is limited. OBJECTIVES: To determine whether prenatal exposure to POPs, particularly hydroxylated PCBs (OH-PCBs), is associated with cognitive and motor development in 13- to 15-year-old children. METHODS: This prospective observational cohort study is part of the Development at Adolescence and Chemical Exposure (DACE)-study, a follow-up of two Dutch birth cohorts. Maternal pregnancy serum levels of PCB-153 and three OH-PCBs were measured, in part of the cohort also nine other PCBs and three OH-PCBs, and in another part five polybrominated diphenyl ethers (PBDEs), dichloroethene (DDE), pentachlorophenol (PCP) and hexabroomcyclododecane (HBCDD). Of the 188 invited adolescents, 101 (53.7%) participated, 55 were boys. Cognition (intelligence, attention, verbal memory) and motor performance (fine motor, ball skills, balance) were assessed. Scores were classified into 'normal' (IQ > 85; scores > P15) and '(sub)clinical' (IQ ≤ 85; scores ≤ P15). We used linear and logistic regression analyses, and adjusted for maternal education, maternal smoking, maternal alcohol use, breast feeding, and age at examination. RESULTS: Several OH-PCBs were associated with more optimal sustained attention and balance. PCB-183 was associated with lower total intelligence (OR: 1.29; 95%CI:0.99-1.68; P = .060), and HBCDD with lower performance intelligence (OR: 3.62; 95%CI:0.97-13.49; P = .056). PCBs, OH-PCBs and PBDEs were negatively associated with verbal memory. CONCLUSIONS: Prenatal background exposure to several POPs can influence neuropsychological outcomes in 13- to 15-year-old Dutch adolescents, although exposure to most compounds does not have clinically relevant consequences at adolescence.

Polychlorinated biphenyl exposure and deiodinase activity in young infants.

BACKGROUND: Several studies have shown effects of polychlorinated biphenyls (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while other studies did not find such effects. How PCBs might affect thyroid hormone metabolism, is still unclear. Potential mechanisms are direct influence on the thyroid gland, binding to thyroid binding proteins, increased excretion or metabolism of thyroid hormones by deiodinases or sulfatases. It is also not well known whether the effect on thyroid hormone levels is caused by PCBs themselves, or by their hydroxylated metabolites (OH-PCBs). OBJECTIVE: To determine the effects of perinatal exposure to PCBs and OH-PCBs on thyroid hormone levels in cord blood and in serum of newborn infants. METHODS: In a Dutch cohort of 100 mother-infant pairs, exposed to background PCB levels, correlations were assessed between 10 PCBs and 6 OH-PCBs in maternal blood during pregnancy and serum thyroxine (T4), T4 sulfate (T4S), triiodothyronine (T3), reverse T3 (rT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) levels in cord blood and in serum of three- and 18-month-old infants. We corrected for age of the mother, gestational age, gender and type of feeding. RESULTS: After correction, prenatal levels of three of 10 measured PCBs showed a positive correlation with cord serum T3, and four PCBs showed a negative correlation with cord serum rT3. After correction, two PCBs and the sum of the 10 measured PCBs were positively correlated with the cord serum T3/rT3 ratio, an indicator of deiodinase 3 activity. No correlations were found between PCBs and T4, TSH and TBG in cord blood. 4-OH-PCB-107 was correlated with T4 at 3months and T4, T4S and T3 at 18months. CONCLUSION: Our results suggest that PCBs have a negative effect on deiodinase type 3 activity, as reflected by a positive correlation with the T3/rT3 ratio. We identified a potential mechanism by which PCBs may affect thyroid hormone metabolism during human development.

Developmental neurotoxicity of persistent organic pollutants: an update on childhood outcome.

Organohalogens are persistent organic pollutants that have a wide range of chemical application. There is growing evidence that several of these chemical compounds interfere with human development in various ways. The aim of this review is to provide an update on the relationship between various persistent organic pollutants and childhood neurodevelopmental outcome from studies from the past 10 years. This review focuses on exposure to polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs) and dichlorodiphenyldichloroethylene (DDE), and in addition on exposure to phthalates, bisphenol A, and perfluorinated compounds and their associations with neurodevelopmental outcome in childhood, up to 18 years of age. This review shows that exposure to environmental chemicals affects neurodevelopmental outcome in children. Regarding exposure to PCBs and OH-PCBs, most studies report no or inverse associations with neurodevelopmental outcomes. Regarding exposure to PBDEs, lower mental development, psychomotor development and IQ were found at preschool age, and poorer attention at school age. Regarding exposure to DDE, most studies reported inverse associations with outcome, while others found no associations. Significant relations were particularly found at early infancy on psychomotor development, on attention and ADHD, whereas at school age, no adverse relationships were described. Additionally, several studies report gender-related vulnerability. Future research should focus on the long-term effects of prenatal and childhood exposure to these environmental chemicals, on sex-specific and combined exposure effects of environmental chemicals, and on possible mechanisms by which these chemicals have their effects on neurodevelopmental and behavioral outcomes.

Prenatal exposure to polychlorinated biphenyls and their hydroxylated metabolites is associated with neurological functioning in 3-month-old infants.

Polychlorinated biphenyls (PCBs) are environmental chemicals which are potentially toxic to the developing brain. Their hydroxylated metabolites (OH-PCBs) are suggested to be even more toxic. Knowledge about the health effects of prenatal OH-PCB exposure is limited. We aimed to determine whether prenatal background exposure to PCBs and OH-PCBs is associated with neurological functioning in 3-month-old boys and girls. In a Dutch observational cohort study, we measured 10 PCBs and 6 OH-PCBs in maternal blood samples of 98 pregnant women. We assessed their infants neurologically with Touwen examination at 3 months and calculated an Optimality Score (OS, range 0-53, low-high optimality). We calculated correlation coefficients between compound levels and OS. Subsequently, we tested whether levels were associated with specific clusters and whether levels differed between infants with "normal" (dysfunction on ≤1 cluster) and "non-optimal" development (dysfunction on ≥2 clusters). The mean OS was 48 (range 44-52). Higher exposure to PCB-146 correlated significantly with higher OS (r = 0.209; p = 0.039). In boys, higher exposure to 4-OH-PCB-107 correlated with lower OS (r = -0.305; p = 0.030). Higher exposure to 9 PCBs and the sum of all PCBs was associated with better visuomotor and/or better sensorimotor function. Infants classified as "non-optimal" (n = 36) had significantly lower prenatal exposure to 6 PCBs and the sum of all PCBs (p < 0.05) compared with infants classified as "normal" (n = 62). In conclusion, higher prenatal exposure to Dutch background PCB levels is associated with better neurological functioning in 3-month-old infants. Prenatal exposure to 4-OH-PCB-107 is associated with less optimal neurological functioning in boys.

Prenatal exposure to polychlorinated biphenyls and their hydroxylated metabolites is associated with motor development of three-month-old infants.

BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that are potentially toxic to the developing brain. Hydroxylated metabolites of PCBs (OH-PCBs) are suggested to be even more toxic. Little is known about their short-term effects on human health. OBJECTIVES: To determine whether prenatal background exposure to PCBs and OH-PCBs was associated with the motor development of three-month-old infants. METHODS: Ninety-seven mother-infant pairs participated in this Dutch, observational cohort study. We determined the concentrations of PCBs and OH-PCBs in cord blood samples. When the infants were three months old we evaluated their motor development by assessing the presence and performance of spontaneous movement patterns from video recordings. We calculated a Motor Optimality Score (MOS). The score could range from low (5) to high (28) optimality. We explored the correlations between PCB and OH-PCB levels and MOS. Subsequently, we tested whether the levels differed between infants with a low (<26) or high (≥26) MOS and whether the levels associated with detailed aspects of their motor repertoires. RESULTS: We found several associations between PCB and OH-PCB levels and MOS, including detailed aspects of the early motor development. High 4-OH-PCB-107 levels were associated with a low MOS (P=.013). High PCB-187 levels were associated with reduced midline arm and leg movements (P=.047 and P=.043, respectively). High 4'-OH-PCB-172 levels were associated with more manipulation (P=.033). CONCLUSIONS: Prenatal exposure to high background levels of most PCBs and 4-OH-PCB-107 seems to impair early motor development, whereas only 4'-OH-PCB-172 showed the opposite.