Prenatal exposure to NO2 and ultrasound measures of fetal growth in the Spanish INMA cohort

__Background:__ Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability. __Objective:__ The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study. Methods: Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis. __Results:__ A 10-μg/m3 increase in average exposure to NO2 during weeks 0-12 was associated with reduced growth at weeks 0-12 in AC (-2.1%; 95% CI: -3.7, -0.6) and EFW (-1.6%; 95% CI: -3.0, -0.3). The same exposure was inversely associated with reduced growth at weeks 20-34 in BPD (-2.6%; 95% CI: -3.9, -1.2), AC (-1.8%; 95% CI: -3.3, -0.2), and EFW (-2.1%; 95% CI: -3.7, -0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers. __Conclusi

Air pollution exposure during pregnancy and childhood autistic traits in four European population-based cohort studies : the ESCAPE project

Background: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. Objectives: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. Methods: Ours was a collaborative study of four European population-based birth/child cohorts— CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PMcoarse), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. Results: A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10‑μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score. Conclusions: Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies.NonePublishe

Exposure to natural environments during pregnancy and birth outcomes in 11 european birth cohorts

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas. © 2022Funding text 1: This project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No 733206; EUCAN-Connect grant agreement No 824989). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. For more information of each cohort individual funding, see Supplementary Material s, Information S2. ; Funding text 2: We would like to thanks to all the mothers, fathers, and children for their generous contribution as participants in the cohorts that are part of the LifeCycle project. For more information of each cohort individual acknowledgment, see Supplementary Materials, Information S1. This project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No 733206; EUCAN-Connect grant agreement No 824989). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. For more information of each cohort individual funding, see Supplementary Materials, Information S2. DAL has received support from Medtronic Ltd and Roche Diagnostics for research unrelated to this study. All the other authors declare that they have no competing interests

Spatial and temporal variability of personal environmental exposure to radio frequency electromagnetic fields in children in Europe

Exposure to radiofrequency electromagnetic fields (RF-EMF) has rapidly increased and little is known about exposure levels in children. This study describes personal RF-EMF environmental exposure levels from handheld devices and fixed site transmitters in European children, the determinants of this, and the day-to-day and year-to-year repeatability of these exposure levels.; Personal environmental RF-EMF exposure (μW/m; 2; , power flux density) was measured in 529 children (ages 8-18 years) in Denmark, the Netherlands, Slovenia, Switzerland, and Spain using personal portable exposure meters for a period of up to three days between 2014 and 2016, and repeated in a subsample of 28 children one year later. The meters captured 16 frequency bands every 4 s and incorporated a GPS. Activity diaries and questionnaires were used to collect children's location, use of handheld devices, and presence of indoor RF-EMF sources. Six general frequency bands were defined: total, digital enhanced cordless telecommunications (DECT), television and radio antennas (broadcast), mobile phones (uplink), mobile phone base stations (downlink), and Wireless Fidelity (WiFi). We used adjusted mixed effects models with region random effects to estimate associations of handheld device use habits and indoor RF-EMF sources with personal RF-EMF exposure. Day-to-day and year-to-year repeatability of personal RF-EMF exposure were calculated through intraclass correlations (ICC).; Median total personal RF-EMF exposure was 75.5 μW/m; 2; . Downlink was the largest contributor to total exposure (median: 27.2 μW/m; 2; ) followed by broadcast (9.9 μW/m; 2; ). Exposure from uplink (4.7 μW/m; 2; ) was lower. WiFi and DECT contributed very little to exposure levels. Exposure was higher during day (94.2 μW/m; 2; ) than night (23.0 μW/m; 2; ), and slightly higher during weekends than weekdays, although varying across regions. Median exposures were highest while children were outside (157.0 μW/m; 2; ) or traveling (171.3 μW/m; 2; ), and much lower at home (33.0 μW/m; 2; ) or in school (35.1 μW/m; 2; ). Children living in urban environments had higher exposure than children in rural environments. Older children and users of mobile phones had higher uplink exposure but not total exposure, compared to younger children and those that did not use mobile phones. Day-to-day repeatability was moderate to high for most of the general frequency bands (ICCs between 0.43 and 0.85), as well as for total, broadcast, and downlink for the year-to-year repeatability (ICCs between 0.49 and 0.80) in a small subsample.; The largest contributors to total personal environmental RF-EMF exposure were downlink and broadcast, and these exposures showed high repeatability. Urbanicity was the most important determinant of total exposure and mobile phone use was the most important determinant of uplink exposure. It is important to continue evaluating RF-EMF exposure in children as device use habits, exposure levels, and main contributing sources may change

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth

Genome-wide association study of placental weight in 65,405 newborns and 113,620 parents reveals distinct and shared genetic influences between placental and fetal growth

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

This is the final version. Available on open access from Nature Research via the DOI in this record. Data availability: Individual cohorts contributing to the meta-analysis should be contacted directly as each cohort has different data access policies. GWAS summary statistics from this study are available via the EGG website (https://egg-consortium.org/placental-weight-2023.html, https://www.ebi.ac.uk/gwas/), as well as the GWAS catalog (https://www.ebi.ac.uk/gwas/, accession numbers GCST90275189, GCST90275190, GCST90275191, GCST90275192, GCST90275193, GCST90275194, GCST90275195, GCST90275196, GCST90275197, GCST90275198, GCST90275199). Access to personal-level information from Gen3G (including methylation array data) is subject to controlled access according to participants’ consent concerning sharing of personal data. Request for conditions of access and for data access should be addressed to Center Hospitalier Universitaire de Sherbrooke institutional ethics committee: [email protected] availability: Analysis code is available from https://github.com/EarlyGrowthGenetics/placental_weight_codeA well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.Wellcome Trus

The association between passive and active tobacco smoke exposure and child weight status among Spanish children.

OBJECTIVE: To assess the impact of passive and active tobacco smoke exposure, both pre- and postnatally, on child body mass index (BMI) and overweight. METHODS: Pregnant women were enrolled into the Spanish INMA prospective birth cohort during 1997 to 2008. Tobacco smoke exposure was assessed by questionnaire and corroborated by pre- and postnatal cotinine measurements. Children were followed up until 4 years in newer subcohorts (N = 1866) and until 14 years in one older subcohort (N = 427). Child age- and sex-specific BMI Z-scores were calculated, and generalized estimating equations were used to model their relationship with repeated measures of tobacco smoke exposure. RESULTS: Associations between prenatal passive exposure to tobacco smoke (adjusted beta = 0.15, 95% CI: 0.05-0.25) and active maternal smoking (adjusted beta = 0.20, 95% CI: 0.08-0.33) and child zBMI up to 4 years were observed. Stronger associations were observed in the older subcohort between both prenatal and child passive smoke exposure and zBMI up to 14 years. CONCLUSIONS: Evidence for an effect of both passive and maternal active smoking on child postnatal growth has been provided. Although residual confounding cannot be completely ruled out, associations were robust to adjustment for a range of lifestyle factors