Growing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by ...studying many exposures simultaneously.
This study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children.
Systolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously.
Decreases in systolic BP were observed with facility density (β change for an interquartile-range increase in exposure: −1.7 mm Hg 95% confidence interval (CI): −2.5 to −0.8 mm Hg), maternal concentrations of polychlorinated biphenyl 118 (−1.4 mm Hg 95% CI: −2.6 to −0.2 mm Hg) and child concentrations of dichlorodiphenyldichloroethylene (DDE: −1.6 mm Hg 95% CI: −2.4 to −0.7 mm Hg), hexachlorobenzene (−1.5 mm Hg 95% CI: −2.4 to −0.6 mm Hg), and mono−benzyl phthalate (−0.7 mm Hg 95% CI: −1.3 to −0.1 mm Hg), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg 95% CI: 0.2 to 2.9 mm Hg), high fish intake during pregnancy (2.0 mm Hg 95% CI: 0.4 to 3.5 mm Hg), maternal cotinine concentrations (1.2 mm Hg 95% CI: -0.3 to 2.8 mm Hg), and child perfluorooctanoate concentrations (0.9 mm Hg 95% CI: 0.1 to 1.6 mm Hg). Decreases in diastolic BP were observed with outdoor temperature at examination (−1.4 mm Hg 95% CI: −2.3 to −0.5 mm Hg) and child DDE concentrations (−1.1 mm Hg 95% CI: −1.9 to −0.3 mm Hg), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg 95% CI: 0.1 to 1.4 mm Hg), high fish intake during pregnancy (1.2 mm Hg 95% CI: −0.2 to 2.7 mm Hg), and child copper concentrations (0.9 mm Hg 95% CI: 0.3 to 1.6 mm Hg).
This study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children.
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PurposeEssential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was ...to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations.ParticipantsThe HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6–11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level).Findings to dateCohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6–11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder.Future plansHELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.
Phenols and phthalates may have immunomodulatory and proinflammatory effects and thereby adversely affect respiratory health.
We estimated the associations between gestational exposure to select ...phthalates and phenols and respiratory health in boys.
Among 587 pregnant women from the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l'Enfant) cohort who delivered a boy, 9 phenols and 11 phthalates metabolites were quantified in spot pregnancy urine samples. Respiratory outcomes were followed up by questionnaires until age 5, when forced expiratory volume in 1 s (FEV1) was measured by spirometry. Adjusted associations of urinary metabolites log-transformed concentrations with respiratory outcomes and FEV1 in percent predicted (FEV1%) were estimated by survival and linear regression models, respectively.
No phenol or phthalate metabolite exhibited clear deleterious associations simultaneously with several respiratory outcomes. Ethyl-paraben was associated with increased asthma rate hazard rate (HR)=1.10; 95% confidence interval (CI): 1.00, 1.21 and tended to be negatively associated with FEV1% (beta=-0.59; 95% CI: -1.24, 0.05); bisphenol A tended to be associated with increased rates of asthma diagnosis (HR=1.23; 95% CI: 0.97, 1.55) and bronchiolitis/bronchitis (HR=1.13; 95% CI: 0.99, 1.30). Isolated trends for deleterious associations were also observed between 2,5-dichlorophenol and wheezing, and between monocarboxynonyl phthalate, a metabolite of di-isodecyl phthalate (DIDP), and wheezing.
Ethyl-paraben, bisphenol A, 2,5-dichlorophenol, and DIDP tended to be associated with altered respiratory health, with ethyl-paraben and bisphenol A exhibiting some consistency across respiratory outcomes. The trends between bisphenol A pregnancy level and increased asthma and bronchiolitis/bronchitis rates in childhood were consistent with a previous cohort study. https://doi.org/10.1289/EHP1015.
Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract ...illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.
History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R
), frequency-dependence of resistance (R
), reactance at 7 Hz (X
), area of the reactance curve (AX), end-inspiratory and end-expiratory R (R
, R
) and X (X
, X
), and volume-dependence of resistance (ΔR = R
-R
) was estimated by linear regression adjusted on confounders.
Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher R
, R
, ΔR and R
and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R
and AX and lower X
and bronchitis with higher R
. No statistically significant association was observed for hospitalisation.
Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.
In humans, studies based on Developmental Origins of Health and Disease (DOHaD) concept and targeting short half-lived chemicals, including many endocrine disruptors, generally assessed exposures ...from spot biospecimens. Effects of early-life exposure to atmospheric pollutants were reported, based on outdoor air pollution levels. For both exposure families, exposure misclassification is expected from these designs: for non-persistent chemicals, because a spot biospecimen is unlikely to capture exposure over windows longer than a few days; for air pollutants, because indoor levels are ignored. We developed a couple-child cohort relying on deep phenotyping and extended personal exposure assessment aiming to better characterize the effects of components of the exposome, including air pollutants and non-persistent endocrine disruptors, on child health and development. Pregnant women were included in SEPAGES couple-child cohort (Grenoble area) from 2014 to 2017. Maternal and children exposure to air pollutants was repeatedly assessed by personal monitors. DNA, RNA, serum, plasma, placenta, cord blood, meconium, child and mother stools, living cells, milk, hair and repeated urine samples were collected. A total of 484 pregnant women were recruited, with excellent compliance to the repeated urine sampling protocol (median, 43 urine samples per woman during pregnancy). The main health outcomes are child respiratory health using early objective measures, growth and neurodevelopment. Compared to former studies, the accuracy of assessment of non-persistent exposures is expected to be strongly improved in this new type of birth cohort tailored for the exposome concept, with deep phenotyping and extended exposure characterization. By targeting weaknesses in exposure assessment of the current approaches of cohorts on effects of early life environmental exposures with strong temporal variations, and relying on a rich biobank to provide insight on the underlying biological pathways whereby exposures affect health, this design is expected to provide deeper understanding of the interplay between the Exposome and child development and health.
To evaluate the associations between the evolution of household use of cleaning products with the asthma symptom score and its evolution over 8 years.
Our study is based on 509 women participating in ...the last two surveys of the Epidemiological study on the Genetics and Environment of Asthma (EGEA) study (EGEA2: 2003-2007 (44 years, 19% current smokers) and EGEA3: 2011-2013). We assessed an asthma symptom score and the use of household cleaning products through standardised questionnaires. We studied longitudinal associations of the evolution of weekly use of irritant or spayed cleaning products with (1) the asthma symptom score at EGEA3 and a stable symptom score between EGEA2-EGEA3 (negative binomial models) and (2) the incidence/evolution of asthma symptoms between EGEA2-EGEA3 (logistic/polytomous logistic regressions). Models accounted for familial dependence and were adjusted for age, smoking status, body mass index and occupational exposure to asthmagens.
Persistent and increased (40% and 16%, respectively) weekly use of irritants or sprays were associated with a higher risk of asthma symptoms at EGEA3 (Mean Score Ratio (MSR)=1.51 (95% CI 1.06 to 2.14) and 1.33 (95% CI 0.85 to 2.08), respectively). A decreased use (19%) was associated with a lower risk of symptoms at EGEA3, compared with a persistent use (MSR=0.59 (95% CI 0.39 to 0.88)). We also observed an association between an increased use of sprays and the incidence of asthma symptoms (OR=2.30 (95% CI 1.08 to 4.91)), compared with no weekly use of irritants/sprays.
This longitudinal study, with repeated assessment of exposure and respiratory health, supports the hypothesis that a persistent or increased weekly use of sprayed cleaning products over time may have an adverse effect on the evolution of asthma symptoms.
Little is known about long-term associations of early-life exposure to extreme temperatures with child health and lung function.
To investigate the association of prenatal and postnatal heat or cold ...exposure with newborn lung function and identify windows of susceptibility.
This population-based cohort study (SEPAGES) recruited pregnant women in France between July 8, 2014, and July 24, 2017. Data on temperature exposure, lung function, and covariates were available from 343 mother-child dyads. Data analysis was performed from January 1, 2021, to December 31, 2021.
Mean, SD, minimum, and maximum temperatures at the mother-child's residence, estimated using a state-of-the-art spatiotemporally resolved model.
Outcome measures were tidal breathing analysis and nitrogen multiple-breath washout test measured at 2 months of age. Adjusted associations between both long-term (35 gestational weeks and first 4 weeks after delivery) and short-term (7 days before lung function test) exposure to ambient temperature and newborn lung function were analyzed using distributed lag nonlinear models.
A total of 343 mother-child pairs were included in the analyses (median IQR maternal age at conception, 32 30.0-35.2 years; 183 53% male newborns). A total of 246 mothers and/or fathers (72%) held at least a master's degree. Among the 160 female newborns (47%), long-term heat exposure (95th vs 50th percentile of mean temperature) was associated with decreased functional residual capacity (-39.7 mL; 95% CI, -68.6 to -10.7 mL for 24 °C vs 12 °C at gestational weeks 20-35 and weeks 0-4 after delivery) and increased respiratory rate (28.0/min; 95% CI, 4.2-51.9/min for 24 °C vs 12 °C at gestational weeks 14-35 and weeks 0-1 after delivery). Long-term cold exposure (5th vs 50th percentile of mean temperature) was associated with lower functional residual capacity (-21.9 mL; 95% CI, -42.4 to -1.3 mL for 1 °C vs 12 °C at gestational weeks 15-29), lower tidal volume (-23.8 mL; 95% CI, -43.1 to -4.4 mL for 1 °C vs 12 °C at gestational weeks 14-35 and weeks 0-4 after delivery), and increased respiratory rate (45.5/min; 95% CI, 10.1-81.0/min for 1 °C vs 12 °C at gestational weeks 6-35 and weeks 0-1 after delivery) in female newborns as well. No consistent association was observed for male newborns or short-term exposure to cold or heat.
In this cohort study, long-term heat and cold exposure from the second trimester until 4 weeks after birth was associated with newborn lung volumes, especially among female newborns.
Poly- and perfluoroalkyl substances (PFAS) are used in a wide range of products. Experimental studies suggested impaired lung development and pro-inflammatory response following exposure to some ...PFAS. We aimed to assess the associations between prenatal exposure to PFAS and children respiratory health.
The study is based on 433 mother-child pairs. 26 PFAS were measured in maternal serum collected during pregnancy. Lung function parameters were measured at 2 months using tidal breathing flow-volume loops and multiple-breath nitrogen washout and at 36 months using oscillometry. Incidence of respiratory health diseases (asthma, wheeze, bronchitis, bronchiolitis) in the first 36 months of life was assessed by repeated questionnaires. A cluster-based analysis was applied to identify prenatal PFAS exposure patterns. Adjusted linear and logistic regressions were performed to assess the associations between PFAS exposure patterns as well as individual PFAS, and each respiratory health parameter.
We excluded 13 PFAS due to low quantification (<5%). Relying on the 13 remaining PFAS, we identified three exposure clusters, characterized by low (N = 163), medium (N = 236) and high (N = 51) pregnancy PFAS concentrations. Compared to children belonging to the low exposure group, children in the moderate exposure group had higher reactance at 7 Hz (X7) and lower frequency dependence of resistance between 7 Hz and 19 Hz (R7-19) at 36 months, suggesting better lung function. No association of any exposure metric was detected with respiratory diseases in the first 3 years of life.
Our study relying on both mixture and uni-pollutant analyses, does not provide evidence for a deleterious effect of prenatal PFAS exposure on respiratory health at an early age.
•We measured 13 per- and polyfluoroalkyl substances in maternal serum.•A cluster-based analysis was applied to identify prenatal PFAS exposure patterns.•The moderate exposure group tended to have improved lung function at 36 months.•No association was detected with respiratory diseases in the first 3 years of life.•Overall, our study does not show a deleterious respiratory health effect of PFAS.
While strong evidence supports adverse effects of pre-natal air pollution on child's lung function, previous studies rarely considered fine particulate matter (PM2.5) or the potential role of ...offspring sex and no study examined the effects of pre-natal PM2.5 on the lung function of the newborn.
We examined overall and sex-specific associations of personal pre-natal exposure to PM2.5 and nitrogen (NO2) with newborn lung function measurements.
This study relied on 391 mother-child pairs from the French SEPAGES cohort. PM2.5 and NO2 exposure was estimated by the average concentration of pollutants measured by sensors carried by the pregnant women during repeated periods of one week. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple breath washout (N2MBW) test, performed at 7 weeks. Associations between pre-natal exposure to air pollutants and lung function indicators were estimated by linear regression models adjusted for potential confounders, and then stratified by sex.
Mean exposure to NO2 and PM2.5 during pregnancy was 20.2 μg/m3 and 14.3 μg/m3, respectively. A 10 μg/m3 increase in PM2.5 maternal personal exposure during pregnancy was associated with an adjusted 2.5 ml (2.3%) decrease in the functional residual capacity of the newborn (p-value = 0.11). In females, functional residual capacity was decreased by 5.2 ml (5.0%) (p = 0.02) and tidal volume by 1.6 ml (p = 0.08) for each 10 μg/m3 increase in PM2.5. No association was found between maternal NO2 exposure and newborns lung function.
Personal pre-natal PM2.5 exposure was associated with lower lung volumes in female newborns, but not in males. Our results provide evidence that pulmonary effects of air pollution exposure can be initiated in utero. These findings have long term implications for respiratory health and may provide insights into the underlying mechanisms of PM2.5 effects.
•Personal exposure measurements to PM2.5 and NO2 are conducted repeatedly during pregnancy.•Early measurements of child lung function are performed at 2 months of age.•Personal prenatal PM2.5 exposure, but not NO2, is associated with lower lung volumes in female newborns, but not in males.•Pulmonary effects of air pollution exposure can be initiated in utero.
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