Postnatal Environmental Exposures Research Articles

Early and late onset childhood eczema: Role of preconceptional, pre-natal and post-natal environmental exposures

BackgroundDespite mounting evidence linking indoor and outdoor environments to eczema, the role of indoor and outdoor environmental pollutant(s) exposure during critical time window(s) on eczema remains unknown. ObjectiveTo investigate the correlations between childhood eczema and itchy rashes and exposure to outdoor air pollution and the home environment. MethodsA combined cross-sectional and retrospective cohort study of 8689 kindergarten students was conducted. We collected information about each child's health outcomes and home environment, as well as calculated individual exposure to air pollutants. Multiple logistic regression models were used to investigate the links between indoor and outdoor environments and childhood eczema and itchy rashes. ResultsChildhood ever doctor-diagnosed eczema (DDE) was linked to NO2, CO, PM2.5, PM2.5-10 and PM10 exposure during the preconceptional, pregnant, and postnatal periods, with ORs (95 % CI) ranging from 1.06 (1.00–1.13) to 1.21 (1.08–1.37). Ever doctor-diagnosed itchy rash (DDIR) was associated with SO2, CO, PM2.5, PM2.5-10 and PM10 exposure during preconceptional and postnatal periods, with ORs (95 % CI) ranging from 1.11 (1.02–1.20) to 1.31 (1.13–1.52). Preconceptional outdoor air pollution was associated with a higher risk of ever, early, and late DDE and DDIR. Indoor smoke, renovation, and dampness were all associated with DDE and DDIR. Postnatal exposure to plants has been linked to both ever and early DDE. There was no link between indoor environments and late DDE. Furthermore, pregnancy has been identified as a critical indoor exposure time window for DDE and DDIR. ConclusionsEarly-life exposure to outdoor air pollutants and indoor environments, particularly before birth, played important roles in childhood eczema.

Epigenetic intergenerational inheritance patterns and spermatozoal small noncoding RNAs

<p indent=0mm>Studies have shown that paternal obesity and mental stress does not only impair them but also affect the health of their offspring. This special genetic phenomenon is independent of changes in DNA sequences. Therefore, potential mechanisms, including DNA methylation, histone modification, and sperm small noncoding RNA (sncRNA) regulation, have been observed. Among these mechanisms, paternal postnatal environmental exposures lead to changes in sperm sncRNA profiles, which potentially regulate early embryonic abnormalities and mediate intergenerational inheritance. This finding is the focus of researchers presently. However, there are some obstacles. First, questions arise on how environmental exposures affect sperm sncRNAs profiles, i.e., the source of sncRNAs; second, the mechanism of how the sperm sncRNAs are transferred to oocytes and influence early embryonic development remain poorly understood; and lastly, how such low concentration of sncRNAs in a single sperm biologically influences the determination of phenotypes of an offspring is yet to be validated. Therefore, this review will systematically demonstrate the research value of sncRNAs in sperm during intergenerational inheritance processes to provide a reference for studies on the paternal intergenerational inheritance of metabolic diseases and mental illnesses.

Environmental Exposure in Lebanese Infants (EELI): A Longitudinal Birth Cohort- Pilot Study

BACKGROUND AND AIM: The Environmental Exposure in Lebanese Infants (EELI) study is a longitudinal birth cohort designed to assess a wide range of pre- and post-natal environmental exposures and genetic factors underlying the health and development of Lebanese infants in Beirut. The aim of the study is to better understand the origins of complex and often lifelong diseases like asthma, allergies, and other chronic conditions. METHODS: As part of the EELI study, a sub-cohort study was conducted with pregnant Lebanese women recruited in their third trimester from Hôtel-Dieu de France hospital in Beirut. The mothers, fathers and infants are followed up for 4 months after birth. Upon being recruited, the parents and eventually the infants are screened at critical time points for prospective exposures via standardized questionnaires, clinical tests, and biological samples. RESULTS:The assessment of early-life exposures in domains such as environmental pollutants, lifestyle habits, maternal stress help to elucidate their effect of the aforementioned exposures on growth and development in the fetal and early childhood stage. CONCLUSIONS:As a sub-cohort to a larger multi-year study that will potentially involve 500 Lebanese families, this pilot study also aims to test the interest and willingness of the Lebanese population to participate in environmental health research. KEYWORDS: Air pollution, birth outcomes, children’s environmental health, exposure assessment, pregnancy outcomes

Etiology of Acute Leukemia: A Review.

Simple SummaryAcute leukemias are some of the most common cancers affecting all age groups. Despite a significant improvement made in the treatment of acute leukemias, their cause remains unknown. A number of genetic and environmental factors for the development of acute leukemias have been proposed, but none have been proven. Undoubtedly, genetics have a major role in the development of these diseases. The effects of a variety of environmental factors, occupations and hobbies have been explored. A recent “two-hit” theory” for the development of acute lymphoblastic leukemia has been proposed. This combines genetic factors and exposure to infections for the development of this disease. Several genetic factors are suggested. Most recently, for the infection portion, exposure to a virus containing Aspergillus Flavus has been proposed. This review summarizes what is currently known about the factors that are proposed for the development of acute leukemias.Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during preconception, pregnancy and throughout life, have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments, and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing but remain unexplained. Advances in genomic profiling, including genome-wide gene expression, DNA copy number and single nucleotide polymorphism (SNP) genotype, may shed some light on the role of genetics in these disparities. Separate two-hit hypotheses for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in the occurrence of leukemia requires further investigations. This review summarizes some of the above factors in acute lymphoblastic and myeloblastic leukemias and the direction for future research on the etiology of these disorders.

Characterisation of Early Microbial Colonisers within the Spiral Colon of Pre- and Post-Natal Piglets

Initial enteric microbial colonisation influences animal health and disease, hence an understanding of the first microbial colonisers within the piglet is important. The spiral colon of piglets that were stillborn (n = 20), born-alive (n = 10), and born alive and had sucked (n = 9) were collected from 28 sows to investigate whether initial microbial colonisation occurs pre- or post-partum and how it develops during the first 24 h post-partum. To examine this, DNA was extracted and 16S rRNA amplicon analysis was performed to allow analysis of microbial communities. The results indicate that microbial colonisation of the spiral colon had occurred in stillborn pigs, suggesting microbial exposure prior to birth. Alpha diversity metrics indicated that the number of taxa and community richness were higher in piglets that sucked (p < 0.001) and community evenness was lower in stillborns in comparison to born-alive (p < 0.001) but was not affected by colostrum consumption (p < 0.001). Additionally, when compared with stillborn piglets, the bacteria colonising the spiral colon during the first 24 h post-partum included the potentially pathogenic bacteria Escherichia coli, Clostridium perfringens and Clostridium celatum, and potentially beneficial bacteria Lactobacillus reutueri and Faecalibacterium prausnitzii. The relative presence of Archaea was high in stillborn piglets but decreased with post-natal environmental exposure. It is evident that stillborn piglets have bacteria present within their spiral colon, however further studies are needed in order to determine the time at which colonisation is initiated and the mechanisms determining how colonisation occurs. Additionally, as expected, the immediate post-natal environment largely influences the microorganisms colonising, while colostrum consumption further contributes to the microbial community enrichment.

Early-life environmental exposure determinants of child behavior in Europe: A longitudinal, population-based study

BackgroundEnvironmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior. Methods and findingsWe used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6–11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner’s Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent’s reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides. ConclusionsOur systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk.

Understanding Asthma and Allergies by the Lens of Biodiversity and Epigenetic Changes.

Exposure to different organisms (bacteria, mold, virus, protozoan, helminths, among others) can induce epigenetic changes affecting the modulation of immune responses and consequently increasing the susceptibility to inflammatory diseases. Epigenomic regulatory features are highly affected during embryonic development and are responsible for the expression or repression of different genes associated with cell development and targeting/conducting immune responses. The well-known, “window of opportunity” that includes maternal and post-natal environmental exposures, which include maternal infections, microbiota, diet, drugs, and pollutant exposures are of fundamental importance to immune modulation and these events are almost always accompanied by epigenetic changes. Recently, it has been shown that these alterations could be involved in both risk and protection of allergic diseases through mechanisms, such as DNA methylation and histone modifications, which can enhance Th2 responses and maintain memory Th2 cells or decrease Treg cells differentiation. In addition, epigenetic changes may differ according to the microbial agent involved and may even influence different asthma or allergy phenotypes. In this review, we discuss how exposure to different organisms, including bacteria, viruses, and helminths can lead to epigenetic modulations and how this correlates with allergic diseases considering different genetic backgrounds of several ancestral populations.

The postnatal window is critical for the development of sex-specific metabolic and gut microbiota outcomes in offspring

ABSTRACT The Developmental Origins of Health and Disease (DOHaD) concept has been proposed to explain the influence of environmental conditions during critical developmental stages on the risk of diseases in adulthood. The aim of this study was to compare the impact of the prenatal vs. postnatal environment on the gut microbiota in dams during the preconception, gestation and lactation periods and their consequences on metabolic outcomes in offspring. Here we used the cross-fostering technique, e.g. the exchange of pups following birth to a foster dam, to decipher the metabolic effects of the intrauterine versus postnatal environmental exposures to a polyphenol-rich cranberry extract (CE). CE administration to high-fat high-sucrose (HFHS)-fed dams improved glucose homeostasis and reduced liver steatosis in association with a shift in the maternal gut microbiota composition. Unexpectedly, we observed that the postnatal environment contributed to metabolic outcomes in female offspring, as revealed by adverse effects on adiposity and glucose metabolism, while no effect was observed in male offspring. In addition to the strong sexual dimorphism, we found a significant influence of the nursing mother on the community structure of the gut microbiota based on α-diversity and β-diversity indices in offspring. Gut microbiota transplantation (GMT) experiments partly reproduced the observed phenotype in female offspring. Our data support the concept that the postnatal environment represents a critical window to influence future sex-dependent metabolic outcomes in offspring that are causally but partly linked with gut microbiome alterations.

Symptom burden of atopic dermatitis in early childhood assessed from daily monitoring of symptoms and topical steroid use

To our knowledge, diseaseburden of atopic dermatitis (AD) as number of days with symptoms and medical treatment has never been studied as measure of severity. To investigate risk factors for AD burden in the first 3years of life. The Copenhagen Prospective Studies on Asthma in Childhood2010 included 700 children. AD burden was assessed by daily diary entries with information on AD and steroid days measuring 18 possible heritable, prenatal, and postnatal environmental exposures. The children with AD had a median (interquartile range) of 136 symptom days (61-294days) and 72 steroid days (27-145days) during the first 3years of life, with the highest disease burden in the second year of life. The multivariable risk factor analysis showed that maternal AD and childhood allergic sensitization were associated with a higher number of AD days and maternal AD, filaggrin mutation, and allergic sensitization were associated with a higher number of steroid days. Participants with a personal interest in atopic diseases could be more likely to participate. Children's burden of AD, assessed quantitatively as AD and steroid days, demonstrated positive associations with maternal AD, filaggrin mutation, and early-life allergic sensitization, with the highest disease burden in the second year of life.

Abstract 2440: The epigenetic influence of maternal diet on prevention of high-fat diet induced obesity and breast cancer in later life

Abstract Breast cancer is one of the most lethal diseases in women. Individual epigenetic profiles that are initially established in utero and postnatal environmental exposures contribute to later-life breast cancer incidence. Intervention on environmental factors such as diets during these sensitive periods provides excellent opportunities to re-program epigenetic profiles leading to cancer prevention. The bioactive dietary compound, genistein (GE) enriched in soybean products such as soymilk, soy protein and tofu, has been widely accepted as a potent anticancer reagent through regulation of epigenetic mechanisms. Our pilot study indicates that maternal dietary GE exposure effectively prevents later-life breast cancer development through epigenetic reprogramming in transgenic breast cancer mouse models. More importantly, we found that maternal GE significantly inhibited a postnatal overnutrition stimulus such as high-fat diet (HFD)-induced breast cancer promotion and metabolic disorders in mouse offspring. Diets with high saturated fat such as the Western diet and its related obesity are considered major risk factors for breast cancer. Importantly, we found that maternal dietary GE reversed HFD-induced lipid panel abnormalities, reduced obesity-related biomarkers and influences gut microbiome profiles through epigenetic regulations. Overnutrition-induced metabolic disorders such as overweight and obesity are a global epidemic that impair human life quality and increases risk of development of many human diseases including breast cancer. Elucidation of the key mechanisms and interactions between nutrition stress and breast cancer and exploration of a novel in utero preventive strategy through natural bioactive products will have global impact. Citation Format: Yuanyuan Li, Min Chen, Trygve Tollefsbol. The epigenetic influence of maternal diet on prevention of high-fat diet induced obesity and breast cancer in later life [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2440.

Environmental factors associated with allergy in urban and rural children from the South African Food Allergy (SAFFA) cohort

The recently published South African Food Allergy (SAFFA) study, indicates a clear rural and urban difference in allergy prevalence within a single country.1,2 Various protective and promoting environmental factors have been postulated to influence food and other forms of allergy. Dietary factors, including the consumption of unpasteurized cow’s milk, fermented milk and the variety of foods introduced during infancy were investigated. The influence of fast food, fried food, and microwaved meat and vegetable consumption on allergy were also assessed. This study also investigates the role of a westernized diet, high in advanced glycation end-products (AGE’s), in allergy prevalence. 398 rural and 1185 urban children (12 months to 36 months of age) were screened for self-reported allergic symptoms, food sensitization, and challenge-proven food allergy. Additionally, a subgroup of children (535 urban and 347 rural) was screened for aeroallergen sensitization. Parents/guardians completed questionnaires on antenatal and post-natal environmental and food exposure, including unpasteurized milk and fermented milk products (‘amasi’). 535 urban and 398 rural participants completed questionnaires on fast food consumption. Overall, higher rates of allergic diseases were reported in rural, as supposed to urban children. In the urban cohort, consumption of ‘amasi’ was associated with lower rates of AR (16.8% vs. 31.3%; p<0.001), AD (21.3% vs. 28.6%; p=0.01) and self-reported asthma (5.3% vs. 11.5%; p=0.003). When compared to rural children, consumption of food containing high advanced glycation end products (AGE’s) was associated with significantly higher aeroallergen sensitization rates in urban children (13.8% vs 2.8%; p<0.01, OR 5.5; 1.6-19.1; p<.0.01). In rural children, high consumption of fried/microwaved meat was associated with food sensitization at 1mm and 3mm with odds ratios of 4.4 (CI 1.5-13.0; p=0.01) and 5.0 (CI 1.2-19.9; p=0.02) respectively. Furthermore, high consumption of fruit and vegetables by rural children were associated with significantly higher rates of self-reported asthma (5.7% vs. 3.6%; p<0.001), food sensitization at ≥3mm (8.9% vs. 2.0%; p=0.01) and food allergy (4.4% vs. 0.0%; p<0.001). Early in life, rural exposure protects against some allergies in childhood. Urbanization may hamper exposure to these modifiable, protective elements.

Identification of modifiable pre- and postnatal dietary and environmental exposures associated with owner-reported canine atopic dermatitis in Finland using a web-based questionnaire.

A cross-sectional hypothesis generating study was performed to investigate modifiable exposures such as whether feeding pattern (a non-processed meat based diet, NPMD, or an ultra-processed carbohydrate based diet, UPCD), certain environmental factors and their timing of exposure might be associated with the development of canine atopic dermatitis (CAD). Also, genetic and demographic factors were tested for associations with CAD. The data was collected from the validated internet-based DogRisk food frequency questionnaire in Finland. A total of 2236 dogs were eligible for the study (the owners reported 406 cases and 1830 controls). Our main interest was to analyze modifiable early risk factors of CAD, focusing on nutritional and environmental factors. We tested four early life periods; prenatal, neonatal, early postnatal and late postnatal periods. Twenty-two variables were tested for associations with CAD using logistic regression analysis. From the final models we identified novel dietary associations with CAD: the NPMD during the prenatal and early postnatal periods had a significant negative association with the incidence of CAD in adult dogs (age above 1 year). Oppositely, UPCD was associated with a significantly higher risk for CAD incidence. Other variables that were associated with a significantly lower risk for CAD were maternal deworming during pregnancy, sunlight exposure during early postnatal period, normal body condition score during the early postnatal period, the puppy being born within the same family that it would stay in, and spending time on a dirt or grass surface from 2 to 6 months. Also, the genetic factors regarding maternal history of CAD, allergy-prone breeds and more than 50% white-colored coat all showed a significant positive association with CAD incidence in agreement with previous findings. Although no causality can be established, feeding NPMD early in life seemed to be protective against CAD, while UPCD could be considered a risk factor. Prospective intervention studies are needed to establish the causal effects of the protective role of NPMD on prevalence of CAD during the fetal and early postnatal life.

Family-Based Designs that Disentangle Inherited Factors from Pre- and Postnatal Environmental Exposures: In Vitro Fertilization, Discordant Sibling Pairs, Maternal versus Paternal Comparisons, and Adoption Designs.

Identifying environmental risk and protective exposures that have causal effects on health is an important scientific goal. Many environmental exposures are nonrandomly allocated and influenced by dispositional factors including inherited ones. We review family-based designs that can separate the influence of environmental exposures from inherited influences shared between parent and offspring. We focus on prenatal exposures. We highlight that the family-based designs that can separate the prenatal environment from inherited confounds are different to those that are able to pull apart later-life environmental exposures from inherited confounds. We provide a brief review of the literature on maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) and conduct problems; these inconsistencies in the literature make a review useful and this illustrates that results of family-based genetically informed studies are inconsistent with a causal interpretation for this exposure and these two offspring outcomes.

Association between environmental tobacco smoke exposure across the first four years of life and manifestation of externalizing behavior problems in school-aged children.

Extensive literature in human and animal models has documented an association between maternal smoking during pregnancy and externalizing behavior in offspring. It remains unclear; however, the extent to which postnatal environmental smoke exposure is associated with behavioral development, particularly for children whose mothers did not smoke during pregnancy. The present study examined whether magnitude of exposure to environmental smoke across the first four years of life demonstrated a linear association with later externalizing symptoms. Exposure was quantified through salivary cotinine measured when children were 6, 15, 24, and 48months of age, providing a more accurate quantification of realized exposure than can be estimated from parental report of cigarettes smoked. Data were available for n=1,096 (50% male; 44% African American) children recruited for the Family Life Project, a study of child development in areas of rural poverty. Analyses indicate a linear association between cotinine and children's symptoms of hyperactivity and conduct problems. This association remained significant after controlling for family poverty level, parental education, parental history of ADHD, hostility, depression, caregiver IQ, and obstetric complications. Furthermore, this association was unchanged when excluding mothers who smoked during pregnancy from the model. Findings are consistent with animal models demonstrating an effect of environmental exposure to nicotine on ongoing brain development in regions related to hyperactivity and impulsivity, and highlight the importance of mitigating children's exposure to environmental smoke, including sources that extend beyond the parents.

Impact of Nicotine Replacement and Electronic Nicotine Delivery Systems on Fetal Brain Development.

Maternal tobacco smoking during pregnancy remains a major public health issue. The neurotoxic properties of nicotine are associated with fetal neurodevelopmental disorders and perinatal morbimortality. Recent research has demonstrated the effects of nicotine toxicity on genetic and epigenetic alterations. Smoking cessation strategies including nicotine replacement therapy (NRT) and electronic nicotine delivery systems (ENDS) show lack of clear evidence of effectiveness and safety in pregnant women. Limited trials using randomized controls concluded that the intermittent use formulation of NRT (gum, sprays, inhaler) in pregnant women is safe because the total dose of nicotine delivered to the fetus is less than continuous-use formulations (transdermal patch). Electronic nicotine delivery systems (ENDS) were hyped as a safer alternative during pregnancy. However, refill liquids of ENDS are suspected to be cytotoxic for the fetus. Animal studies revealed the impact of ENDS on neural stem cells, showing a similar risk of pre- and postnatal neurobiological and neurobehavioral disorders to that associated with the exposure to traditional tobacco smoking during early life. There is currently no clear evidence of impact on fetal brain development, but recent research suggests that the current guidelines should be reconsidered. The safety of NRT and ENDS is increasingly being called into question. In this review, we discuss the special features (pharmacodynamics, pharmacokinetics, and metabolism) of nicotine, NRT, and ENDS during pregnancy and postnatal environmental exposure. Further, we assess their impact on pre- and postnatal neurodevelopment.

Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network.

The Undiagnosed Diseases Network (UDN) aims to achieve a unifying etiologic diagnosis for patients with mysterious conditions. Although the UDN has focused on the identification of genetic determinants, environmental etiologies may be causative or modifying agents that interact with predisposing genes. We developed and implemented a screening questionnaire to assess environmental exposures in UDN patients. We hypothesized that patients with potentially adverse environmental exposures would be less likely to have a genetic basis for their undiagnosed disease. Among seven postnatal environmental exposure categories assessed in 269 UDN participants, patients with a confirmed or strong candidate genetic diagnosis were significantly less likely to report exposures to metals, dust, or chemicals (p < 0.05). A composite variable of the seven exposure categories was substantially more common (40%) in patients without a genetic diagnosis than in those with a genetic diagnosis (18.4%) (p = 0.004). In multivariable analysis adjusting for age and sex, the composite variable of any positive environmental exposure was associated with a reduced odds of finding a genetic diagnosis (OR 0.41, 95% CI 0.18-0.96, p = 0.04). These results were generally robust to exclusion of patients with early life disease onset. Our results suggest a possible approach to increase the yield of genetic etiologies for adult undiagnosed diseases by first focusing on patients without significant environmental exposures. Still, there is ample reason to expect cases in which specific environmental exposures impact the risk of clinically evident genetic disease. Our findings emphasize the importance of systematic investigations of potential environmental risk factors for undiagnosed diseases.

Exploring a potential mechanistic role of DNA methylation in the relationship between in utero and post-natal environmental exposures and risk of childhood acute lymphoblastic leukaemia.

The aetiology of childhood acute lymphoblastic leukaemia (ALL) is unclear. Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various in utero and post-natal environmental exposures have been suggested to alter risk of childhood ALL. DNA methylation patterns can be influenced by environmental exposures, and are reported to be altered in ALL, suggesting a potential mediating mechanism between environment and ALL disease risk. To investigate this, we used a 'meet in the middle' approach, investigating the overlap between exposure-associated and disease-associated methylation change. Genome-wide DNA methylation changes in response to possible ALL-risk exposures (i.e. breast feeding, infection history, day care attendance, maternal smoking, alcohol, caffeine, folic acid, iron and radiation exposure) were investigated in a sub-population of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort using an epigenome-wide association study (EWAS) approach (n = 861-927), and compared to a list of ALL disease-associated methylation changes compiled from published data. Hypergeometric probability tests suggested that the number of directionally concordant gene methylation changes observed in ALL disease and in response to the following exposures; maternal radiation exposure (p = 0.001), alcohol intake (p = 0.006); sugary caffeinated drink intake during pregnancy (p = 0.045); and infant day care attendance (p = 0.003), were not due to chance. Data presented suggests that DNA methylation may be one mediating mechanism in the multiple hit pathway needed for ALL disease manifestation.

Early-life exposome and lung function in children in Europe: an analysis of data from the longitudinal, population-based HELIX cohort

Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children. In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures. In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions. Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease. European Community's Seventh Framework Programme (HELIX project).

Addressing the complexity of prenatal and postnatal environmental exposures affecting childhood lung function

Addressing the complexity of prenatal and postnatal environmental exposures affecting childhood lung function

Pre- and postnatal environmental boron exposure and infant growth: Results from a mother-child cohort in northern Argentina

BackgroundExperimental studies show developmental toxicity of boron and we recently found impaired weight and length in newborns of mothers exposed to boron through drinking water during pregnancy. ObjectivesTo evaluate potential impact of pre- and postnatal boron exposure on infant anthropometry. MethodsIn our mother-child cohort (n = 177) in Argentinean Andes, where drinking water concentrations of boron, lithium and arsenic have been found to vary considerably, we collected maternal blood and urine during and after pregnancy, placenta, breast milk, as well as infant urine and blood during the first 6 months of life. In all samples, boron and other potentially toxic elements were measured by ICP-MS. Infant weight (g), length (cm) and head circumference (cm) were measured at birth, 0–3 (n = 120) and/or 3–6 months (n = 120; 79 overlap) of age. ResultsBoron concentrations in breast milk (range: 46–786 µg/L) correlated strongly with those in maternal serum (range: 47–624 µg/L; rs = 0.94) 0–3 months post-partum. In multivariable-adjusted linear regression, urinary boron (log2-transformed; range 60–9200 µg/L) in the youngest infants, but not maternal serum boron during pregnancy, was inversely associated with body weight at both 0–3 months (B: −141, 95% CI: −240; −42, p = 0.006) and 3–6 months (B: −200, 95% CI: −377; −23, p = 0.027). Infant urinary boron was also inversely associated with head circumference at 0–3 months (B: −0.39, 95% CI: −0.74; −0.04, p = 0.028), as well as length (B: −0.57, 95% CI: −1.1; −0.03, p = 0.040) and head circumference (B: −0.30, 95% CI: −0.64; 0.04, p = 0.083) at 3–6 months. ConclusionsThe observed first evidence that elevated environmental boron exposure in early infancy may adversely affect growth supports previous findings of boron-related impaired fetal growth. More research is needed to verify the findings at older age and in other populations.