Numerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, ...evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD.
We used a birth cohort of 2606 Norwegian mother–child pairs enrolled 2002–2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures.
Breast milk concentrations of perfluorooctane sulfonate (PFOS) and β‑hexachlorocyclohexane (β-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p′‑Dichlorodiphenyltrichloroethane (p,p′-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise.
In a multi-pollutant analysis of four classes of chemicals, early-life exposure to β-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p′-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.
•We assessed associations between early-life exposure to 27 contaminants and doctor-diagnosed ADHD in school-age children•Odds of ADHD increased 75% per interquartile range increase in β-HCH levels•Odds of ADHD increased 77% per interquartile range increase in PFOS levels, with higher odds in girls than boys•p,p′-DDT was associated with lower odds of ADHD while HCB had a non-linear exposure–response
Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling ...the effects of mixtures.
We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight.
We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002-2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72-100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models.
Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log-transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: -87 g (95% CI: -137, -340 per 1.70 ng/mL), -43 g (95% CI: -108, 23 per 1.18 ng/mL), and -135 g (95% CI: -192, -78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: -5, 97 per 2.22 ng/mL).
This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.
Background: Commuters are exposed to high concentrations of air pollutants, but little quantitative information is currently available on differences in exposure between different modes of transport, ...routes, and fuel types. Objectives: The aim of our study was to assess differences in commuters' exposure to traffic-related air pollution related to transport mode, route, and fuel type. Methods: We measured particle number counts (PNCs) and concentrations of PM₂.₅ (particulate matter ≤ 2.5 um in aerodynamic diameter), PM₁₀, and soot between June 2007 and June 2008 on 47 weekdays, from 0800 to 1000 hours, in diesel and electric buses, gasoline-and diesel-fueled cars, and along two bicycle routes with different traffic intensities in Arnhem, the Netherlands. In addition, each-day measurements were taken at an urban background location. Results: We found that median PNC exposures were highest in diesel buses (38,500 particles/cm³) and for cyclists along the high-traffic intensity route (46,600 particles/cm 3 ) and lowest in electric buses (29,200 particles/cm³). Median PM₁₀ exposure was highest from diesel buses (47 μg/m³) and lowest along the high-and low-traffic bicycle routes (39 and 37 μg/m³). The median soot exposure was highest in gasoline-fueled cars (9.0 х 10⁻⁵/m), diesel cars (7.9 х 10⁻⁵/m), and diesel buses (7.4 х 10⁻⁵/m) and lowest along the low-traffic bicycle route (4.9 х 10⁻⁵/m). Because the minute ventilation (volume of air per minute) of cyclists, which we estimated from measured heart rates, was twice the minute ventilation of car and bus passengers, we calculated that the inhaled air pollution doses were highest for cyclists. With the exception of PM₁₀, we found that inhaled air pollution doses were lowest for electric bus passengers. Conclusions: Commuters' rush hour exposures were significantly influenced by mode of transport, route, and fuel type.
Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We ...investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1 month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups.
PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative "high" (> 80th percentile) vs. "low" (< 20th percentile) toxicant exposure in this cohort. Moreover, breast milk toxicants were associated with microbiome functionality, explaining up to 34% of variance in acetic and propionic SCFAs, essential signaling molecules. Per one standard deviation of exposure, PBDE-28 was associated with less propionic acid (- 24% 95% CI - 35% to - 14% relative to the mean), and PCB-209 with less acetic acid (- 15% 95% CI - 29% to - 0.4%). Conversely, PFOA and dioxin-like PCB-167 were associated with 61% (95% CI 35% to 87%) and 22% (95% CI 8% to 35%) more propionic and acetic acid, respectively.
Environmental toxicant exposure may influence infant gut microbial function during a critical developmental window. Future studies are needed to replicate these novel findings and investigate whether this has any impact on child health.
The purposes of this study were to assess whether mental well-being has changed after introduction of the lockdown measures compared with that before, whether this change differs between boys and ...girls, and whether this change is associated with COVID-19–related concerns.
This is a two-wave prospective study among Dutch adolescents using data collected up to one year before the COVID-19 pandemic (n = 224) and 5–8 weeks after the first introduction of lockdown measures (n = 158). Mental well-being was assessed by three indicators: life satisfaction, internalizing symptoms, and psychosomatic health. General linear model repeated-measures analysis of variance was used to assess whether mental well-being has changed and if this differed by sex. Univariate linear regressions were used to assess associations between COVID-19–related concerns and a change in mental well-being.
Life satisfaction decreased (η2p = .079, p < .001), but no change in internalizing symptoms was observed (η2p = .014, p = .14), and psychosomatic health increased (η2p = .194, p < .001) after the introduction of lockdown measures. Boys scored significantly better on all mental health indicators compared with girls at baseline and follow-up. However, boys' life satisfaction significantly decreased at the follow-up (η2p = .038, p = .015), whereas girls' life satisfaction did not change. Concerns about COVID-19 were significantly associated with a lower life satisfaction and more internalizing symptoms.
Adolescents', especially boys', life satisfaction decreased during the lockdown. They reported no change in internalizing symptoms and an improved psychosomatic health. Adolescents' mental well-being is expected to vary during the COVID-19 pandemic and should continue to be monitored.
The rising use of pesticides in modern agriculture has led to a shift in disease burden in which exposure to these chemicals plays an increasingly important role. The human gut microbiome, which is ...partially responsible for the biotransformation of xenobiotics, is also known to promote biotransformation of environmental pollutants. Understanding the effects of occupational pesticide exposure on the gut microbiome can thus provide valuable insights into the mechanisms underlying the impact of pesticide exposure on health. Here we investigate the impact of occupational pesticide exposure on human gut microbiome composition in 7198 participants from the Dutch Microbiome Project of the Lifelines Study. We used job-exposure matrices in combination with occupational codes to retrieve categorical and cumulative estimates of occupational exposures to general pesticides, herbicides, insecticides and fungicides. Approximately 4% of our cohort was occupationally exposed to at least one class of pesticides, with predominant exposure to multiple pesticide classes. Most participants reported long-term employment, suggesting a cumulative profile of exposure. We demonstrate that contact with insecticides, fungicides and a general “all pesticides” class was consistently associated with changes in the gut microbiome, showing significant associations with decreased alpha diversity and a differing beta diversity. We also report changes in the abundance of 39 different bacterial taxa upon exposure to the different pesticide classes included in this study. Together, the extent of statistically relevant associations between gut microbial changes and pesticide exposure in our findings highlights the impact of these compounds on the human gut microbiome.
•We investigated the associations between perinatal exposure to 27 persistent chemicals and autism in school-aged children.•The organochlorine pesticide residue β-HCH is associated with an increased ...risk of autism among Norwegian children.•The estimated daily intake of β-HCH for a child via breast milk was calculated to be 0.03 µg/kg of body weight per day.•A follow-up in vivo experiment with zebrafish embryos and larvae confirmed the neurotoxicity effect of β-HCH.•Perturbation of dopaminergic neuron development is suggested as a potential underlying mechanism for β-HCH neurotoxicity.
The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs).
To evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae.
1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002–2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect.
A total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother–child pairs in this study. β-Hexachlorocyclohexane (β-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of β-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed β-HCH concentration). The median concentration of β-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92–6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of β-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with β-HCH.
Prenatal exposure to β-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm β-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.
Triglyceride-bound fatty acids constitute the majority of lipids in human milk and may affect infant growth. We describe the composition of fatty acids in human milk, identify predictors, and ...investigate associations between fatty acids and infant growth using data from the Norwegian Human Milk Study birth cohort. In a subset of participants (n = 789, 30% of cohort), oversampled for overweight and obesity, we analyzed milk concentrations of detectable fatty acids. We modelled percent composition of fatty acids in relation to maternal body mass index, pregnancy weight gain, parity, smoking, delivery mode, gestational age, fish intake, and cod liver oil intake. We assessed the relation between fatty acids and infant growth from 0 to 6 months. Of the factors tested, excess pregnancy weight gain was positively associated with monounsaturated fatty acids and inversely associated with stearic acid. Multiparity was negatively associated with monounsaturated fatty acids and n-3 fatty acids while positively associated with stearic acid. Gestational age was inversely associated with myristic acid. Medium-chain saturated fatty acids were inversely associated with infant growth, and mono-unsaturated fatty acids, particularly oleic acid, were associated with an increased odds of rapid growth. Notably, excessive maternal weight gain was associated with cis-vaccenic acid, which was further associated with a threefold increased risk of rapid infant growth (OR = 2.9, 95% CI 1.2–6.6), suggesting that monounsaturated fatty acids in milk may play a role in the intergenerational transmission of obesity.
Prenatal exposure to metabolism-disrupting chemicals (MDCs) has been linked to birth weight, but the molecular mechanisms remain largely unknown. In this study, we investigated gene expressions and ...biological pathways underlying the associations between MDCs and birth weight, using microarray transcriptomics, in a Belgian birth cohort. Whole cord blood measurements of dichlorodiphenyldichloroethylene (
-DDE), polychlorinated biphenyls 153 (PCB-153), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and transcriptome profiling were conducted in 192 mother-child pairs. A workflow including a transcriptome-wide association study, pathway enrichment analysis with a meet-in-the-middle approach, and mediation analysis was performed to characterize the biological pathways and intermediate gene expressions of the MDC-birth weight relationship. Among 26,170 transcriptomic features, we successfully annotated five overlapping metabolism-related gene expressions associated with both an MDC and birth weight, comprising
,
,
,
, and
. We found 11 overlapping pathways, and they are mostly related to genetic information processing. We found no evidence of any significant mediating effect. In conclusion, this exploratory study provides insights into transcriptome perturbations that may be involved in MDC-induced altered birth weight.
Adolescents might be susceptible to the effects of the COVID-19 lockdown. We assessed changes in mental wellbeing throughout the first year of the pandemic and compared these with prepandemic levels.
...This five-wave prospective study among Dutch adolescents aged 12–17 years used data collected before the pandemic (n = 224) (T0), in May (T1), July (T2), and October 2020 (T3), and in February 2021 (T4). Generalized estimating equations were used to assess the association between stringency of the lockdown with mental wellbeing.
Adolescents had a lower life satisfaction during the first full lockdown (T1) adjusted β: −0.36, 95% confidence interval (CI): −0.58 to −0.13, during the partial lockdown (T3) (adjusted β: −0.37, 95% CI: −0.63 to −0.12), and during the second full lockdown (T4) (adjusted β: −0.79, 95% CI: −1.07 to −0.52) compared to before the pandemic (T0). Adolescents reported more internalizing symptoms during only the second full lockdown (T4) (adjusted β: 2.58, 95% CI: 0.41–4.75). During the pandemic at T1 (adjusted β: 0.29, 95% CI: 0.20–0.38), T2 (adjusted β: 0.36, 95% CI: 0.26–0.46), T3 (adjusted β: 0.33, 95% CI: 0.22–0.45), and T4 (adjusted β: 0.20, 95% CI: 0.07–0.34), adolescents reported a better psychosomatic health, partly attributable to less trouble falling asleep (p < .01).
The COVID-19 lockdown measures have had both a negative and positive impact on mental wellbeing of Dutch adolescents. However, mental wellbeing was most impacted during the second full lockdown compared to before the pandemic.
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