Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to ...assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects.
We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity).
We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure.
We found a significant increase in growth associated with p,p'-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = -0.10; 95% CI: -0.19, -0.01).
To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p'-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels.
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).
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.
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.
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.
•The association between prenatal EDC exposure and SGA was assessed.•Pooled statistical analysis in 7 European birth cohorts•PCB 153 and PFOA were associated with SGA.•HCB associated with SGA, depending on child's sex and smoking status of the mother•PFOS was associated with SGA depending on the smoking status of the mother.
Our previous gene expression studies in a PCB-exposed cohort of young children in Slovakia revealed that early-life exposures to PCBs and other organochlorine compounds were associated with ...significant alterations across several pathogenetic pathways. The present study was undertaken to further explore the high-throughput qRT-PCR-based gene expression effects by using TaqMan low-density array (TLDA) for selected genes in a sample of 55 children from the cohort. We analyzed the transcriptional changes of 11 genes in relation to PCB and organochlorine pesticide exposure levels (including DDT, DDE, HCH, and HCB), and to BMI and ethnicity in this cohort. The results indicated an overall downregulation of expression of these genes. Maximum downregulation (in fold change) was observed in the
ENTPD3
gene, and the minimum level of downregulation was in
CYP2D6
. As per our multinomial regression model study, downregulation of
LEPR
gene was significantly directly correlated with all the exposure variables. Downregulation of
APC
,
ARNT
,
CYP2D6
,
LEPR
,
LRP12
, and MYC genes was directly correlated with BMI (kg/m
2
) of the individuals. Gender-specific differences in gene expression were observed in
CYP2D6
(
p
-value 0.0001) and
LEPR
(
p
-value 0.028), while downregulation of
CYP2D6
(
p
-value 0.01),
LEPR
(
p
-value 0.02),
LRP12
(
p
-value 0.04), and
MYC
(
p
-value 0.02) genes was consistently observed in Roma children compared to Caucasians. The investigation of such health disparities must be emphasized in future research, together with interventions to reduce the health consequences of PCB exposures. In this context, we emphasize the importance of biomarker-based approaches to future research on genetic susceptibility to the effects of these compounds.
Allergic diseases have increased in developed countries during the past decades. A cohort of Slovak children was followed from birth to track allergic symptoms dynamics in early childhood. ...Information on allergic symptoms (atopic dermatitis = AD, rhino conjunctivitis = RC, wheezing = Wh, urticaria = Ur) and food allergies among children was based on clinical evaluation of children by allergists at three developmental stages (infant, toddler, preschool). Out of 320 cases of allergies, 64 infants, 145 toddlers, and 195 preschool children suffered from AD, RC, Wh, Ur, or their combinations (i.e., significant increase with age,
p
< 0.001). AD first appeared in infants, Wh and/or RC rose mainly in toddlers, and Ur among preschool children. AD in infants or toddlers disappeared in the subsequent developmental stage in approximately one third of all cases. Single AD persistence without remission or extension was not common and accounted only for 6.9% of AD infants’ allergic manifestations. In addition to single-symptom allergic diseases, this study also identified several combinations of atopic symptoms.
Conclusions
: The proportion of multi-symptom allergies increased while single-symptom forms decreased. The observed temporal trends of allergic symptoms correspond to the atopic march.
What is Known:
• The observed temporal trends of allergic symptoms correspond to the atopic march.
What is New:
• Allergic diseases in children were first manifested as single forms, with atopic dermatitis (AD) commonly functioning as the “entry point” to allergies.
• The overall proportion of single-symptom allergic disorders decreased over time while the proportion of multi-symptom allergies increased.
The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and ...disorder pathways, viz.,
endocrine disruption
,
metabolic disorder & diabetes
, and
cancer
, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention.
Microarray studies of global gene expression were conducted from the 45-month-old children on the Affymetrix platform followed by Ingenuity Pathway Analysis (IPA®) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR TaqMan low-density array (TLDA) was performed to further validate the selected genes on the whole blood cells of the most highly exposed children from the study cohort (
n
= 71).
TP53
,
MYC
,
BCL2
, and
LRP12
differential gene expressions suggested strong relationships between potential future tumor promotion and PCB exposure in Slovak children. The IPA analysis further detected the most important signaling pathways, including molecular mechanism of cancers, prostate cancer signaling, ovarian cancer signaling, P53 signaling, oncostatin M signaling, and their respective functions (viz., prostate cancer, breast cancer, progression of tumor, growth of tumor, and non-Hodgkin’s disease). The results suggest that PCB exposures, even at the early age of these children, may have lifelong consequences for the future development of chronic diseases.
We evaluated concentrations of 15 PCB congeners in blood serum of 2047 adults, 431 8–9-year old children and 1134 mother-child pairs born in 2001–2003. These subjects were long-standing residents ...living up to 70 km (to the north) and up to 50 km (to the south) of the former Chemko Strážske PCB production facility in the Michalovce district of Slovakia. We plotted serum concentration against distance from the plant both with and without consideration of the direction of their homes from the site. The decrease in exposure with distance could be described by an exponential function which was dependent on direction and climatic parameters. By kriging we created maps depicting predicted isoconcentration contours for sex- and age-adjusted serum concentration of ∑PCBs for the same group of children, adults and mothers. The principle of our risk analysis was to relate serum concentration data, reflecting PCB body burden, using the critical concentrations established by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES 2010) as thresholds below which the probability of effects on health is regarded as negligible. We conclude that 10 years ago, around 200,000 residents were at risk in this densely populated area. Exposure has since decreased but the mechanism for this has not yet been studied.
Reasons for the highly variable and often poor protection conferred by the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine are multifaceted and poorly understood.
We aimed to determine ...whether early-life exposure to PCBs (polychlorinated biphenyls) and DDE 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene reduces 6-month infant BCG vaccine response.
Data came from families participating in a prospective birth cohort in eastern Slovakia. At birth, maternal and cord blood were collected for chemical analyses, and infants were immunized with BCG. Blood was collected from infants for chemical analyses and to determine 6-month BCG-specific immunoglobulin (Ig) G and IgA levels. Multivariable linear regression models were fit to examine chemical-BCG associations among approximately 500 mother-infant pairs, with adjustment for confounders.
The median 6-month infant concentration of the prevalent congener PCB-153 was 113 ng/g lipid interquartile range (IQR): 37-248, and 388 ng/g lipid (IQR: 115-847) for DDE. Higher 6-month infant concentrations of PCB-153 and DDE were strongly associated with lower 6-month BCG-specific antibody levels. For instance, BCG-specific IgG levels were 37% lower for infants with PCB-153 concentrations at the 75th percentile compared to the 25th percentile (95% CI: -42, -32; p < 0.001). Results were similar in magnitude and precision for DDE. There was also evidence of PCB-DDE additivity, where exposure to both compounds reduced anti-BCG levels more than exposure to either compound alone.
The associations observed in this study indicate that environmental exposures may be overlooked contributors to poorer responses to BCG vaccine. The overall association between these exposures and tuberculosis incidence is unknown.
Jusko TA, De Roos AJ, Lee SY, Thevenet-Morrison K, Schwartz SM, Verner MA, Palkovicova Murinova L, Drobná B, Kočan A, Fabišiková A, Čonka K, Trnovec T, Hertz-Picciotto I, Lawrence BP. 2016. A birth cohort study of maternal and infant serum PCB-153 and DDE concentrations and responses to infant tuberculosis vaccination. Environ Health Perspect 124:813-821; http://dx.doi.org/10.1289/ehp.1510101.
Due to their extensive usage, organophosphorus flame retardants (OPFRs) have been detected in humans and in the environment. Human are exposed to OPFRs via inhalation of indoor air, dust uptake or ...dietary uptake through contaminated food and drinking water. Only recently, few studies addressing dietary exposure to OPFRs were published. In this study, we used human biomonitoring (HBM) data of OPFRs to estimate how much the dietary intake may contribute to the total exposure. We estimated by reverse dosimetry, the daily intake of tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for children using HBM data from studies with sampling sites in Belgium, Denmark, France, Germany, Slovenia and Slovakia. For estimating the dietary exposure, a deterministic approach was chosen. The occurrence data of selected food categories were used from a published Belgium food basket study. Since the occurrence data were left-censored, the Lower bound (LB)-Upper bound (UB) approach was used. The estimated daily intake (EDI) calculated on the basis of urine metabolite concentrations ranged from 0.03 to 0.18 µg/kg bw/d for TDCIPP, from 0.05 to 0.17 µg/kg bw/d for TCIPP and from 0.02 to 0.2 µg/kg bw/d for TCEP. Based on national food consumption data and occurrence data, the estimated dietary intake for TDCIPP ranged from 0.005 to 0.09 µg/kg bw/d, for TCIPP ranged from 0.037 to 0.2 µg/kg bw/d and for TCEP ranged from 0.007 to 0.018 µg/kg bw/d (summarized for all countries). The estimated dietary intake of TDCIPP contributes 11-173% to the EDI, depending on country and LB-UB scenario. The estimated dietary uptake of TCIPP was in all calculations, except in Belgium and France, above 100%. In the case of TCEP, it is assumed that the dietary intake ranges from 6 to 57%. The EDI and the estimated dietary intake contribute less than 3% to the reference dose (RfD). Therefore, the estimated exposure to OPFRs indicates a minimal health risk based on the current knowledge of available exposure, kinetic and toxicity data. We were able to show that the dietary exposure can have an impact on the general exposure based on our underlying exposure scenarios.
Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during ...the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016–2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from −0.34 to −0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality.
As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This ...survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.
•Harmonized EU-wide HBM survey in 10,795 participants covering 11 chemical groups.•Both legacy compounds and their substitutes are ubiquitous.•Social and geographical gradients in internal exposure are observed.•Higher biomarker concentrations observed in younger age groups.•For 15 out of 20 biomarkers health risks cannot be excluded.
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