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BackgroundPrenatal urban environmental exposures have been associated with blood pressure in children. The dynamic of these associations across childhood and later ages is unknown.ObjectivesTo assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adulthood.MethodsRepeated measures of systolic (SBP) and diastolic blood pressure (DBP) were collected in up to 7,454 participants from a UK birth cohort. Prenatal urban exposures (n=42) covered measures of noise, air pollution, built environment, natural spaces, traffic, meteorology, and food environment. An exposome-wide association study approach was used. Linear spline mixed-effects models were used to model associations of each exposure with trajectories of blood pressure. Replication was sought in four independent European cohorts (N up to 9,261).ResultsIn discovery analyses, higher humidity was associated with a faster increase (mean yearly change in SBP for an interquartile range [IQR] increase in humidity: 0.29 mmHg/year, 95%CI 0.20; 0.39) and higher temperature with a slower increase (mean yearly change in SBP per IQR increase in temperature: -0.17 mmHg/year, 95%CI -0.28; -0.07) in SBP in childhood. Higher levels of humidity and air pollution were associated with faster increase in DBP in childhood and slower increase in adolescence. There was little evidence of an association of other exposures with change in SBP or DBP. Results for humidity and temperature, but not for air pollution, were replicated in other cohorts.ConclusionReplicated findings suggest that higher prenatal humidity and temperature could modulate blood pressure changes across childhood.

ImportanceLittle is known about long-term associations of early-life exposure to extreme temperatures with child health and lung function.ObjectivesTo investigate the association of prenatal and postnatal heat or cold exposure with newborn lung function and identify windows of susceptibility.Design, Setting, and ParticipantsThis 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.ExposuresMean, SD, minimum, and maximum temperatures at the mother-child’s residence, estimated using a state-of-the-art spatiotemporally resolved model.Main Outcomes and MeasuresOutcome 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.ResultsA 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.Conclusions and RelevanceIn 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.

Background Ambient temperature, particularly heat, is increasingly acknowledged as a trigger for preterm delivery but study designs have been limited and results mixed. We aimed to comprehensively evaluate the association between ambient temperature throughout pregnancy and preterm delivery. Methods We estimated daily temperature throughout pregnancy using a cutting-edge spatiotemporal model for 5347 live singleton births from three prospective cohorts in France, 2002–2018. We performed Cox regression (survival analysis) with distributed lags to evaluate time-varying associations with preterm birth simultaneously controlling for exposure during the first 26 weeks and last 30 days of pregnancy. We examined weekly mean, daytime, night-time and variability of temperature, and heatwaves accounting for adaptation to location and season. Results Preterm birth risk was higher following cold (5th vs 50th percentile of mean temperature) 7–9 weeks after conception [relative risk (RR): 1.3, 95% CI: 1.0–1.6 for 2°C vs 11.6°C] and 10–4 days before delivery (RR: 1.6, 95% CI: 1.1–2.1 for 1.2°C vs 12.1°C). Night-time heat (95th vs 50th percentile of minimum temperature; 15.7°C vs 7.4°C) increased risk when exposure occurred within 5 weeks of conception (RR: 2.0, 95% CI: 1.05–3.8) or 20–26 weeks after conception (RR: 2.9, 95% CI: 1.2–6.8). Overall and daytime heat (high mean and maximum temperature) showed consistent effects. We found no clear associations with temperature variability or heatwave indicators, suggesting they may be less relevant for preterm birth. Conclusions In a temperate climate, night-time heat and chronic and acute cold exposures were associated with increased risk of preterm birth. These results suggest night-time heat as a relevant indicator. In the context of rising temperatures and more frequent weather hazards, these results should inform public health policies to reduce the growing burden of preterm births.

We would like to thank all the families that participated in these studies for their generous contribution. Detailed acknowledgements and funding can be found in Sup plementary Material., Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41467-021-24558-y, Maternal smoking during pregnancy contributes to poor birth outcomes. Here the authors perform a meta-analysis of the associations between maternal smoking during pregnancy and placental DNA methylation and identify links between these and poor birth outcomes, which may better inform the mechanisms through which smoking impacts placental function and fetal growth. Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth., Canadian Institutes of Health Research (CIHR) MOP 115071, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Environmental Health Sciences (NIEHS) P30 ES019776 - R01 ES022223 - P01 ES022832, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of General Medical Sciences (NIGMS) P20 GM104416, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) R01 MH094609

We developed a nation-wide exposure model to NO2, PM10 and PM2.5 at a fine spatial and temporal resolution for France in order to study air pollutants exposure during pregnancy for the French Longitudinal Study of Children (ELFE). The exposure to air pollutants was estimated daily for years 2010 and 2011 by combining three simulation models at the national and regional scale (CHIMERE) and at the local urban scale (ADMS-Urban or SIRANE). The spatial resolution was 4 km for the national scale model, 3–4 km for regional models and from 10 to 200 m for urban-scale models. We developed a confidence index (from 0 to 10) based on the target plot to identify the best model to estimate exposure for a given address, year and pollutant. Air pollution exposure during pregnancy was then estimated using each modeling scale for the 17,427 women participating in the ELFE cohort. We described the exposure of the women during different time windows of pregnancy using each of the three models and using the most suitable model as estimated by the confidence index. The exposure estimates obtained from the three models were quite similar and highly correlated (spearman correlation between 0.64 and 0.96), especially for the national and regional models. For NO2 and PM10 predicted by the urban models, the minimum values were lower and the maximum values and the variability were higher, compared to the regional and national models. The averaged confidence indexes were comprised between 5.6 and 8 depending on the pollutant, year and exposure model considered. The best confidence index was observed for urban modeling (10) and the lowest for the regional modeling (0). In average during pregnancy, using the most suitable model, women were exposed to 21 μg/m3 for NO2, 16 μg/m3 for PM2.5 and 24 μg/m3 for PM10. To our knowledge, this is the first study combining three modeling tools available at different scales to estimate NO2, PM10 and PM2.5 concentrations at a fine spatial and temporal resolution over a large geographical area. The confidence index provides guidance in the choice of the exposure model. These exposure estimates will be used to investigate potential effects of air pollutants on the pregnant woman health and on health of the fetus and development of the child.

Background: Studies have reported associations between maternal exposure to atmospheric pollution and lower birth weight. However, the evidence is not consistent and uncertainties remain. We used advanced statistical approaches to robustly estimate the association of atmospheric pollutant exposure during specific pregnancy time windows with term birth weight (TBW) in a nationwide study. Methods: Among 13,334 women from the French Longitudinal Study of Children (ELFE) cohort, exposures to PM2.5, PM10 (particles &lt, 2.5 µm and &lt, 10 µm) and NO2 (nitrogen dioxide) were estimated using a fine spatio-temporal exposure model. We used inverse probability scores and doubly robust methods in generalized additive models accounting for spatial autocorrelation to study the association of such exposures with TBW. Results: First trimester exposures were associated with an increased TBW. Second trimester exposures were associated with a decreased TBW by 17.1 g (95% CI, −26.8, −7.3) and by 18.0 g (−26.6, −9.4) for each 5 µg/m3 increase in PM2.5 and PM10, respectively, and by 15.9 g (−27.6, −4.2) for each 10 µg/m3 increase in NO2. Third trimester exposures (truncated at 37 gestational weeks) were associated with a decreased TBW by 48.1 g (−58.1, −38.0) for PM2.5, 38.1 g (−46.7, −29.6) for PM10 and 14.7 g (−25.3, −4.0) for NO2. Effects of pollutants on TBW were larger in rural areas. Conclusions: Our results support an adverse effect of air pollutant exposure on TBW. We highlighted a larger effect of air pollutants on TBW among women living in rural areas compared to women living in urban areas.

International audience; Background: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures.Objective: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach.Methods: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV1) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation

ObjectiveExposure to cigarette smoking during pregnancy has been robustly associated with cord blood DNA methylation. However, little is known about such effects on the placenta; in particular, whether cigarette smoking before pregnancy could also induce epigenetic alterations in the placenta of former smokers is unknown.Design and resultsPlacental DNA methylation levels were measured in 568 women and compared among non-smokers and women either smoking during their pregnancy or who had ceased smoking before pregnancy. An Epigenome Wide Association Study identified 344 Differentially Methylated Regions (DMRs) significantly associated with maternal smoking status. Among these 344 DMRs, 262 showed “reversible” alterations of DNA methylation, only present in the placenta of current smokers, whereas 44 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. This observation was further supported by a significant demethylation of LINE-1 sequences in the placentas of both current (−0.43 (−0.83 to −0.02)) and former smokers (−0.55 (−1.02 to −0.08)) compared to nonsmokers. A comparative analysis of the epigenome landscape based on the ENCODE placenta data demonstrated an enrichment of all 344 DMRs in enhancers histone marks. Additionally, smoking-associated DMRs were found near and/or overlapping with 13 imprinting gene clusters encompassing 18 imprinted genes.ConclusionsDNA methylation patterns alterations were found in 344 genomic regions in the placenta of women smoking during their pregnancy, including 44 DMRs and LINE-1 elements, where methylation changes persisted in former smokers, supporting the hypothesis of an “epigenetic memory” of exposure to cigarette smoking before pregnancy. Enhancers regions, including imprinting control regions were also particularly affected by placenta methylation changes associated to smoking, suggesting a biological basis for the sensitivity of these regions to tobacco exposure and mechanisms by which fetal development could be impacted.