Developmental origins of health and disease: concepts, caveats, and consequences for public health nutrition

The purpose of this article is to define the concept of developmental origins of health and disease (DOHaD) as an emerging paradigm for relating evolutionary biology to contemporary health issues. As illustrated, several paradoxes emerge related to adaptations initiated in utero and in early life. Epigenetics is a concept that must be incorporated in order to understand plasticity adaptations, such as programming. The public health consequence of DOHaD challenges the one-size-fits-all norm and shows the need for prescreening prior to some interventions and for the eventuality of individualized, rather than collectively applied, preventive or remedial measures as the safest option.     

Blood lead and cadmium levels and relevant factors among children from an e-waste recycling town in China

Background

Primitive electronic waste (e-waste) recycling is ongoing in Guiyu, and thus toxic heavy metals may keep on threatening to the health of local children. Some related factors may contribute to the elevation of blood lead levels (BLLs) or blood cadmium levels (BCLs).

Objective

To investigate the children's BLLs and BCLs in Guiyu and Chendian as compare to discuss the effects of primitive e-waste recycling activities on children's health.

Methods

Two hundred and seventy-eight children less than 8 years who lived in Guiyu and Chendian were observed, and their BLLs and BCLs were determined by graphite atomizer absorption spectrophotometer. Questionnaire survey for risk factors was also performed and data were analyzed using spearman correlation analyses and logistic regression analyses.

Results

Children living in Guiyu had significantly higher BLLs and BCLs as compared with those living in Chendian (p<0.01). In Guiyu, 70.8% of children (109/154) had BLLs>10 μg/dL, and 20.1% of children (31/154) had BCLs>2 μg/L, compared with 38.7% of children (48/124) had BLLs>10 μg/dL and 7.3% of children (9/124) had BCLs>2 μg/L in Chendian (p<0.01, respectively). We also observed a significant increasing trend in BLLs with increasing age in Guiyu (p<0.01). Mean height of children in Guiyu was significantly lower than that in Chendian (p<0.01). The risk factors related to children's BLLs and BCLs mainly included father's engagement in the work related to e-waste, children's residence in Guiyu and the amount of time that children played outside near the road everyday.

Conclusions

There are close relationships between the BLLs, BCLs in children and the primitive e-waste recycling activities in Guiyu. Environmental pollution, especially lead pollution, has threatened the health of children living around e-waste recycling site.     

电子垃圾拆解集散地居民铅、镉、铜内暴露水平与淋巴细胞双微核率的关系

[目的]研究电子垃圾拆解集散地居民血尿铅、镉、铜的暴露水平和淋巴细胞双微核率的变化及其影响因素。[方法]选择某电子垃圾拆解集散地居民58人为暴露组（男性44人，女性14人），平均年龄为33．0岁；距离集散地50km，且无明显工业污染的农业区人群80人为对照组（男性41名，女性39名），平均年龄为43．7岁。采用石墨炉原子吸收光谱法检测血铅、血镉和尿铅、尿镉、尿铜含量，火焰原子吸收光谱法测定血清铜含量；胞质阻滞双微核实验测定淋巴细胞双微核率。[结果]暴露组居民血铅和尿铜中位数分别为0．52μmol／L和51．97μmol／mmol肌酐，均高于对照组（P〈0．05）。暴露组人群双微核率中位数（4‰）是对照组（1‰）的4倍，年龄是血镉增高的危险因素（OR=1．1，P〈0．01）；电子垃圾拆解职业暴露史是影响血铅水平及双微核率的危险因素（OR=2．9，P〈0．05；OR=6．7，P〈0．01）。[结论]电子垃圾拆解地居民血铅、尿铜水平及淋巴细胞双微核率均高于对照区居民。     

Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system

Background/objective: Polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-) or methoxylated forms have been detected in humans. Because this raises concern about adverse effects on the developing brain, we reviewed the scientific literature on these mechanisms.Data synthesis: Many rodent studies reported behavioral changes after developmental, neonatal, or adult exposure to PBDEs, and other studies documented subtle structural and functional alterations in brains of PBDE-exposed animals. Functional effects have been observed on synaptic plasticity and the glutamate–nitric oxide–cyclic guanosine monophosphate pathway. In the brain, changes have been observed in the expression of genes and proteins involved in synapse and axon formation, neuronal morphology, cell migration, synaptic plasticity, ion channels, and vesicular neurotransmitter release. Cellular and molecular mechanisms include effects on neuronal viability
(via apoptosis and oxidative stress), neuronal differentiation and migration, neurotransmitter release/uptake, neurotransmitter receptors and ion channels, calcium (Ca²⁺) homeostasis, and intracellular signaling pathways.Discussion: Bioactivation of PBDEs by hydroxylation has been observed for several endocrine end points. This has also been observed for mechanisms related to neurodevelopment, including binding to thyroid hormone receptors and transport proteins, disruption of Ca²⁺ homeostasis, and modulation of GABA and nicotinic acetylcholine receptor function.Conclusions: The increased hazard for developmental neurotoxicity by hydroxylated (OH-)PBDEs compared with their parent congeners via direct neurotoxicity and thyroid disruption clearly warrants further investigation into a) the role of oxidative metabolism in producing active metabolites of PBDEs and their impact on brain development; b) concentrations of parent and OH-PBDEs in the brain; and c) interactions between different environmental contaminants during exposure to mixtures, which may increase neurotoxicity.     

Mercury, cadmium, and lead levels in human placenta: a systematic review

Background: Placental tissue may furnish information on the exposure of both mother and fetus. Mercury (Hg), cadmium (Cd), and lead (Pb) are toxicants of interest in pregnancy because they are associated with alterations in child development.Objectives: The aim of this study was to summarize the available information regarding total Hg, Cd, and Pb levels in human placenta and possible related factors.Methods: We performed a systematic search of PubMed/MEDLINE, EMBASE, Lilacs, OSH, and Web of Science for original papers on total Hg, Cd, or Pb levels in human placenta that were published in English or Spanish (1976-2011). Data on study design, population characteristics, collection and analysis of placenta specimens, and main results were extracted using a standardized form.Results: We found a total of 79 papers (73 different studies). Hg, Cd, and Pb levels were reported in 24, 46, and 46 studies, respectively. Most studies included small convenience samples of healthy pregnant women. Studies were heterogeneous regarding populations selected, processing of specimens, and presentation of results. Hg concentrations > 50 ng/g were found in China (Shanghai), Japan, and the Faroe Islands. Cd levels ranged from 1.2 ng/g to 53 ng/g and were highest in the United States, Japan, and Eastern Europe. Pb showed the greatest variability, with levels ranging from 1.18 ng/g in China (Shanghai) to 500 ng/g in a polluted area of Poland.Conclusion: The use of the placenta as a biomarker to assess heavy metals exposure is not properly developed because of heterogeneity among the studies. International standardized protocols are needed to enhance comparability and increase the usefulness of this promising tissue in biomonitoring studies.     

Association of environmental exposure to heavy metals and eczema in US population: Analysis of blood cadmium,lead, and mercury

ABSTRACT

Objectives: We aim to explore the association between blood heavy metal concentrations of cadmium, lead, and mercury with ever-report of eczema in the US population.

Methods: We used NHANES cross-sectional data from 2005–2006. Eczema was measured among 4509 adults and 3898 non-adults. The association between eczema and tertiles of concentrations of cadmium, lead, mercury was estimated using multivariate logistic regression models adjusted for different confounding variables. The estimation was also stratified by gender.

Results: The prevalence of ever-report of eczema was 7.63% in adults and 13.42% in non-adults. None of the heavy metals was significantly associated with increased ORs of eczema after potential confounding variables were adjusted in the models. Our results remained null after stratifying for gender.

Conclusions: Blood cadmium, lead, and mercury were not associated with reports of eczema in general US population.     

Genetic Effects on Toxic and Essential Elements in Humans: Arsenic,Cadmium, Copper,Lead, Mercury,Selenium, and Zinc in Erythrocytes

Background and objectives

An excess of toxic trace elements or a deficiency of essential ones has been implicated in many common diseases or public health problems, but little is known about causes of variation between people living within similar environments. We estimated effects of personal and socioeconomic characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested for genetic effects using data from twin pairs.

Methods

We used blood samples from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30–92 years of age) and determined element concentrations in erythrocytes by inductively coupled plasma-mass spectrometry. We assessed associations between element concentrations and personal and socioeconomic characteristics, as well as the sources of genetic and environmental variation and covariation in element concentrations. We evaluated the chromosomal locations of genes affecting these characteristics by linkage analysis in 501 dizygotic twin pairs.

Results

Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial correlations, concentrations of As and Hg due mainly to common genetic effects. Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters)]}.

Conclusions

Although environmental exposure is a precondition for accumulation of toxic elements, individual characteristics and genetic factors are also important. Identification of the contributory genetic polymorphisms will improve our understanding of trace and toxic element uptake and distribution mechanisms.     

German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population

The German Environmental Survey was conducted for the third time in 1998 (GerES III). The probability sample of about 4800 subjects was selected to be representative for the German population with regard to region (East-/West-Germany), community size, age (18 to 69 years) and gender. Blood samples were taken from each study participant and questionnaires were used to get exposure-related information. Cadmium, lead, mercury, hexachlorobenzene (HCB), hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p, p'-DDE) and polychlorinated biphenyls (PCB-138, PCB-153, PCB-180) were analysed in whole blood to document the extent, distribution, and determinants of exposure of the general population to these substances. The geometric means of Cd, Pb, and Hg in blood amounted to 0.44, 31, and 0.58 microgram/l, respectively. Smokers showed a Cadmium level of 1.1 micrograms/l and non-smokers a level of 0.28 microgram/l. The geometric mean of lead was higher in the blood of males than of females (36 micrograms/l vs. 26 micrograms/l). The concentration of mercury in blood depends on fish consumption and the number of teeth with amalgam fillings. The mean concentrations of HCB and p, p'-DDE in blood were 0.44 microgram/l and 1.6 micrograms/l, respectively. In East-Germany (the former GDR) the DDE concentration in blood was more than twice as high as in West-Germany. Geometric means for PCB were 0.42, 0.68 and 0.44 microgram/l for PCB-138, PCB-153, and PCB-180, respectively. A marked increase of HCB, DDE and PCB levels with age could be observed. alpha-HCH and gamma-HCH could be detected in 1.7% and 5.2% of the samples only. beta-HCH was quantified in 34% of the samples with a 95th percentile of 0.5 microgram/l.     

Human-biomonitoring and individual soil measurements for children and mothers in an area with recently detected mercury-contaminations and public health concerns: a cross-sectional study

In this study, we assessed intracorporal mercury concentrations in subjects living on partially mercury-contaminated soils in a defined area in Switzerland. We assessed 64 mothers and 107 children who resided in a defined area for at least 3 months. Mercury in biological samples (urine and hair) was measured, a detailed questionnaire was administered for each individual, and individual mercury soil values were obtained. Human biomonitoring results were compared with health-related and reference values. Mothers and children in our study had geometric means (GMs) of 0.22 µg Hg/g creatinine in urine (95th percentile (P95) = 0.85 µg Hg/g) and 0.16 µg Hg/g (P95 = 0.56 µg Hg/g), respectively. In hair, mothers and children had GMs of 0.21 µg Hg/g (P95 = 0.94 µg/g) and 0.18 µg/g (P95 = 0.60 µg/g), respectively. We found no evidence for an association between mercury values in soil and those in human specimens nor for a health threat in residential mothers and children.     

Challenging gender inequity through male involvement in maternal and newborn health: critical assessment of an emerging evidence base

Men's involvement in the health of women and children is considered an important avenue for addressing gender influences on maternal and newborn health. The impact of male involvement around the time of childbirth on maternal and newborn health outcomes was examined as one part of a systematic review of maternal health intervention studies published between 2000 and 2012. Of 33,888 articles screened, 13 eligible studies relating to male involvement were identified. The interventions documented in these studies comprise an emerging evidence base for male involvement in maternal and newborn health. We conducted a secondary qualitative analysis of the 13 studies, reviewing content that had been systematically extracted. A critical assessment of this extracted content finds important gaps in the evidence base, which are likely to limit how ‘male involvement’ is understood and implemented in maternal and newborn health policy, programmes and research. Collectively, the studies point to the need for an evidence base that includes studies that clearly articulate and document the gender-transformative potential of involving men. This broader evidence base could support the use of male involvement as a strategy to improve both health and gender equity outcomes.     

Exposure to brominated flame retardants,perfluorinated compounds,phthalates and phenols in European birth cohorts: ENRIECO evaluation,first human biomonitoring results,and recommendations

There are emerging concerns about potential effects on child health and development of early-life exposure to substances such as brominated flame retardants (BFRs), perfluorinated compounds (PFCs), phthalates and phenols (including bisphenol A (BPA)); pregnancy and birth cohort studies are ideally designed to study such concerns prospectively. As part of the ENRIECO project, we evaluated existing human biomonitoring data for these substances in European birth cohorts and develop recommendations for more harmonized methods that will enable combination and comparison of cohort data in the future. The ENRIECO inventory shows that 20 European birth cohorts have measured or are measuring BFRs (N = 10), PFCs (N = 11), phthalates (N = 16) or phenols (N = 8). Generally, samples were collected prenatally or at birth and measurements involved few subjects in each cohort (a few hundred maximum). Biological matrices, timing, and analytical methods of the measurements varied between cohorts. Few cohorts have measured at multiple time points or in children. In European cohorts, levels of BFRs were very low and at least 10-fold lower than in US; levels of PFCs and phthalates have decreased over the last decade since the phasing out of certain of these compounds; concentrations of phenols are comparable to those in the US. Although there is little published data in the cohorts now, many measurements are ongoing and we recommend that cohorts start working towards combined and comparison studies. Specific recommendations for use of existing data include the development of conversion models for the different media used for measurement of persistent chemicals, and inter-laboratory comparisons and calibrations. Recommendations for further data collection include more evaluation of exposure to these chemicals in children; repeated measurements of non-persistent chemicals; validation and harmonisation of questionnaires; and the development of mechanisms for fast European birth cohort response for the detection and prioritisation of new chemicals of concern.     

Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study

Background

Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent.

Prevalence of heart attack and stroke and associated risk factors among Inuit in Canada: A comparison with the general Canadian population

Background

It is generally believed that cardiovascular disease (CVD) is rare in the Inuit population because of their traditional marine-based diet, but the evidence is inconsistent.

In utero and childhood DDT,DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: The CHAMACOS study

Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine-disrupting chemicals (EDCs) in humans and animals. The purpose of this study is to examine the relationship of in utero and childhood exposure to these purported EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS, an ongoing birth cohort in California's Salinas Valley. We measured o,p′- and p,p′-DDT, p,p′-DDE, PBDEs and PCBs in serum collected from mothers during pregnancy or at delivery and from their sons at 9 years. We measured concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) from 234 of their sons at 12 years. In adjusted models, we found that a 10-fold increase in maternal prenatal serum concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0, 47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were associated with increases in boys’ LH levels. A 10-fold increase in total prenatal ΣPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in FSH, primarily driven by non- dioxin-like congeners. Boys' hormone levels were only marginally associated with prenatal DDT or DDE in primary models, but when boys' Tanner stage at age 12 was added to models, prenatal maternal DDT levels were associated with decreases in LH (adjusted percent change per 10-fold increase = ?18.5%, 95% CI: ?29.8, ?5.4) and T (percent change = ?18.2%, 95% CI: ?30.2, ?4.2) and DDE with LH (percent change = ?18.3%, 95% CI: ?32.9, ?0.6). Exposures measured in the children's serum at 9 years also showed associations between BDE-153 and ΣPCBs. However, there is evidence that these associations appear to be mediated by child BMI. This study suggests associations on male hormones of 12 year old boys related to exposure to certain EDC exposure prenatally. The implications on future reproductive function in puberty and adulthood should be determined.