Cohort Profile: Barcelona Life Study Cohort (BiSC)

Abstract

The Barcelona Life Study Cohort (BiSC) is an exposome cohort, aiming to comprehensively evaluate the socio-environmental and genetic determinants (i) of foetal and child health, growth, and development towards adult life and (ii) of maternal mental and physical health and wellbeing during pregnancy and afterwards, while shedding light on the underlying biological mechanisms. The enrolment of the BiSC participants was carried out between October 2018 and April 2021 at three tertiary university hospitals in Barcelona, Spain. Participants were recruited and had their first data collected at the end of the first trimester of pregnancy, with follow-ups in the second and third trimesters of pregnancy, delivery, and months 1, 2, 6, 8, 12 and 18 postnatally. Of 1080 pregnant women (mean (standard deviation) age: 34.1 (4.7) years) enrolled at baseline, 1032 (95.6%) were followed at delivery and out of 970 participants who remained in the cohort at the 18-month follow-up, 828 (76.7%) actively participated in this follow-up. BiSC has collected data on external, personal, and internal exposomes including demographic and socioeconomic characteristics, maternal and child lifestyle, and a large array of exposures and biomarkers together with a wide range of maternal and child mental and physical health and development outcomes. To collect these data, a wide array of sources/methods were applied including face-to-face interviews, online questionnaires, home visits, personal sensors/monitors, hospital records, clinical and physical examinations, imaging techniques including ultrasound and magnetic resonance imaging (MRI), and molecular measurements in a wide range of biological samples. BiSC welcomes external collaborations and provides a gated access to its data and biological samples. Information regarding the procedure for data requests can be found in the BiSC website (https://projectebisc.org/) or through [email protected]. Early life, including prenatal and early postnatal periods, is a window of vulnerability to the effects of socio-environmental factors.1 According to the Developmental Origins of Health and Diseases (DOHaD) concept, the impact of exposures during this period is not limited to pregnancy and childhood outcomes and can spill over into adulthood and the elderly.2,3 DOHaD postulates that exposures during early life could permanently alter the metabolism, physiology, and structure of the human body and such alteration can eventually promote health or, on the contrary, induce disease long after the environmental exposure has ceased.3 In parallel with recent advances in the understanding of DOHaD, there has been a growing interest in characterizing the ‘early-life exposome’. The ‘exposome’, defined as the totality of human environmental exposures from conception onwards,4 provides a framework to holistically evaluate the environmental determinants of health and disease to account for the complexity of exposure to interrelated environmental factors in real life. Birth cohorts have been instrumental in generating knowledge regarding different aspects of DOHaD and more recently in characterizing the early-life exposome.5,6 The advancements in tools and methods to characterise the exposome (e.g. personal sensors and monitors, novel biomarkers of exposure, high-resolution analytical chemistry methods to characterize omics in biological samples, etc) and also health outcomes (e.g. ultrasound techniques, neuroimaging methods, computerized tests, biomarkers of early health effects, etc) have provided an unprecedented opportunity to establish a new generation of exposome birth cohorts. Capitalizing on these advancements, the Barcelona Life Study Cohort (BiSC) aims to comprehensively evaluate the socio-environmental as well as genetic determinants (i) of foetal and child health, growth, and development towards adult life through a DOHaD perspective and (ii) of maternal mental and physical health and wellbeing during pregnancy and afterwards, while shedding light on the underlying mechanisms. BiSC was initially founded through merging two projects: (i) Prenatal Exposure to Urban AIR Pollution and Pre- and Postnatal Brain Development (AIR-NB), funded by a European Research Council (ERC)-Advanced Grant (grant no. 785994) and (ii) Traffic-related air pollution and birth weight: the roles of noise, placental function, green space, physical activity, and socioeconomic status (FRONTIER), funded by the Health Effects Institute (grant no. 4959-RFA17-1/18–1-5). The merger of the two projects occurred before setting up the BiSC and a common protocol based on requirements of the two projects were developed to establish the cohort. Afterwards, it has been further funded through other projects as listed in the Funding section below. BiSC pregnant women were recruited during their first routine hospital visit (weeks 11–14 of gestation) at three tertiary university hospitals in Barcelona, Spain, including Hospital Sant Joan de Déu, Hospital de la Santa Creu i Sant Pau, and Hospital Clínic de Barcelona, and their corresponding primary healthcare centres. Briefly, we distributed posters and flyers about the study in the aforementioned centres to inform potential participants about the study. At the time of the first routine hospital visit at the end of the first trimester, a trained nurse approached the pregnant women attending the visit, explained the study aims and objectives, the planned follow-ups, and expected tasks from the participants. If the pregnant woman agreed to participate and met the inclusion criteria, she was enrolled into the cohort after providing written informed consent. In the same visit, women were also asked to pass the information and consent forms to their partners, so the partners could also be enrolled in the cohort. We included pregnant women between 18 and 45 years of age with singleton pregnancy from the general population who were living in the catchment area of the aforementioned three hospitals and were able to communicate in Spanish/Catalan. We excluded those women residing outside the catchment area, aged <18 years or >45 years, illiterate, with a multiparous pregnancy or having a foetus with known congenital anomalies. The enrolment of the BiSC participants started in October 2018 and ended in April 2021, with a total of 1080 pregnant women recruited. The sociodemographic characteristics of the participants are presented in Table 1. From a subsample (n = 79) of those eligible pregnant women who declined to participate in the BiSC, we asked permission to obtain their education level. As presented in Supplementary Table S1 (available as Supplementary data at IJE online), those who declined to participate had relatively lower education levels compared with those who agreed to participate. Similarly, the BiSC participants had a slightly higher educational level compared with the general population of women (20–44 years old) residing in Barcelona (2019)7 (Supplementary Table S1, available as Supplementary data at IJE online). Sociodemographic characteristics of Barcelona Life Study Cohort (BiSC) participants End of the first trimester of pregnancy. P-value for differences between participants and non-participants in the 18-month follow-up using the chi-squared test for the categorical variables and Welch’s t-test for the continuous variables. BiSC has already carried out the following pre- and postnatal follow-ups: (i) Trimester 1 (baseline visit) at median [interquartile range (IQR): 12.7 (0.7)] week of pregnancy, (ii) Trimester 2 at 20.6 (0.7) week of pregnancy, (iii) Trimester 3 at 31.7 (1.3) week of pregnancy, (iv) delivery, (v) Month 1 at median (IQR) 1 (0.2) months old, (vi) Month 2 at 2.3 (0.6) months old, (vii) Month 6 at 6.5 (0.8) months old, (viii) Month 8 at 8.7 (1) months old, (ix) Month 12 at 12.6 (0.9) months old and (x) Month 18 at 18.6 (1) months old. At the 18-month follow-up, there were 970 participants remaining in the cohort; of whom, 828 participated in the follow-up. The number of participants in each follow-up and the corresponding periods for each follow-up are presented in Figure 1 and Supplementary Figure S1 (available as Supplementary data at IJE online), respectively. Barcelona Life Study Cohort (BiSC) follow-ups and the number of participants in each follow-up up to the child age of 18 months BiSC has collected comprehensive data from pregnant women, their partners, and offspring as summarized in Table 2. During the pregnancy period, in addition to two hospital visits, one in the first (at the recruitment time around week 12 of gestation) and one in the third (around week 32 of gestation) trimester, we conducted 1-week personal and home environmental measurement campaigns that were carried out through home visits after the hospital visits in the first and third trimesters. During these home visits, the BiSC fieldworkers (i) implemented monitors/sensors to simultaneously measure air pollution (personal, home-indoor, and home-outdoor levels), noise (home-outdoor level), and temperature and humidity (home-indoor level), (ii) implemented personal physical activity and geolocation sensors and applied an interactive GIS platform to characterize participants’ time-activity patterns and commuting mode, (iii) generated a detailed record of the participants’ home characteristics and (iv) interviewed the participants to fill in some questionnaires (Table 3). Postnatally, families were contacted at 1, 2, 6, 8, 12 and 18 months for the follow-up of the mother (maternal mental health) and child. At all follow-ups (except for the 2-month follow-up where participants answered questionnaires via a phone call) families answered online questionnaires on maternal and child health and habits. Additionally, at the 6- and 18-month follow-ups families were invited to an in-person visit with our neuropsychologist. However, the visit at 6 months had to be cancelled due to the COVID-19 pandemic and a later postnatal follow-up at the age of 8 months was set up with the aim to assess the children’s neurodevelopment avoiding in-person visits. Description of data collected in prenatal and postnatal Barcelona Life Study Cohort (BiSC) follow-ups NO2, nitrogen dioxide; PM2.5, particulate matter with aerodynamic diameter <2.5 µm Description of collected data in Barcelona Life Study Cohort (BiSC) during the home visits Working at 4 L/min with a Personal Environmental Monitor (PEM) Model 200 Black, SKC Ltd, USA, collecting particles in 37 mm polytetrafluoroethylene–Teflon® filters. PM2.5, particulate matter with aerodynamic diameter <2.5 µm; NO2, nitrogen dioxide; GPS, global positioning system; QGIS, Quantum Geographic Information System. The description of the data collection for clinical history, maternal mental health and cognitive function as well as collected biological samples are presented in Table 2 and also Supplementary Material (available as Supplementary data at IJE online). In addition to the characterization of the social exposome at both household and neighbourhood levels, we assessed exposure to air pollution, noise, temperature, humidity, green and blue spaces, built environment, water pollution, ultraviolet radiation, artificial light at night, occupational exposures, micro- and nano-plastics and a wide range of chemical exposures, using a combination of personal and home monitoring, modelling approaches, geospatial analyses, remote sensing data, chemical analysis of biological samples and questionnaires. Furthermore, we collected objective (e.g. personal monitors) and subjective (e.g. questionnaire) data on maternal lifestyle including physical activity, sleep, diet, dietary biomarkers, active and passive smoking, alcohol consumption and illicit drug use as well as the child’s diet and sleep. The detailed description of the methods to characterize external exposome for the BiSC participants is presented in the Supplementary Material (available as Supplementary data at IJE online) (Page 5). As described in Supplementary Material (available as Supplementary data at IJE online) (Page 13), biomarkers of response to environmental exposures and health effects were measured in biological samples using targeted or untargeted techniques. Briefly, we have assessed thyroid hormones and anti-thyroid peroxidase antibodies in maternal plasma and iodine in maternal urine in the first trimester; steroid hormones in maternal urine and hair and placental angiogenic factors in maternal serum in the third trimester; a large number of endogenous metabolites in maternal serum in the first and third trimesters, cord blood, and placenta; placental DNA methylation, small non-coding RNAs, telomere length, and mitochondrial DNA content; brain related proteins in umbilical cord blood; and child’s gut microbiota composition and activity at 6 and 18 months of age. We have also obtained maternal and child genome-wide genetic data. In addition to biomarkers of health effects and maternal mental health status, we collected data, both pre and postnatally, on a wide range of physical health outcomes for mothers as well as the health and developmental outcomes of their children (Table 2). We applied a large array of tools including ultrasound and neuroimaging techniques, physical and clinical examinations, paraclinical tests, neuropsychological tests, questionnaires and hospital records to collect data on these health outcomes. Data on pregnancy complications were collected from hospital records and questionnaires. Furthermore, we characterized placental function based on Doppler ultrasound examination of fetoplacental haemodynamics in the second and third trimesters, as described in the Supplementary Material (available as Supplementary data at IJE online) (Page 17). Moreover, information on birth outcomes such as gestational age at delivery, type of delivery, birth weight, height, head circumference, sex of the child, and postpartum maternal and foetal complications were abstracted from hospital records. Detailed description of the methods applied to characterize the foetal and child growth and development is presented in Tables 2 and 4 and Supplementary Material (available as Supplementary data at IJE online). Briefly, we characterized foetal growth trajectories through transabdominal ultrasonographic measurements in the second and third trimesters. Foetal echocardiography was conducted in the third trimester to characterize foetal cardiovascular remodelling using different cardiac morphometric and functional parameters. At the same visit, we conducted transvaginal (or transabdominal when the foetus was in breech presentation) neurosonography to characterize structural development and maturation of the foetal brain. Additionally, we captured neonatal brain magnetic resonance imaging (MRI) including three dimensional (3D)-T1, Flair-T2, functional MRI (resting state) and diffusion tension intensity (DTI) in a subset of neonates at around one month of age. We also conducted an extensive neurodevelopmental evaluation of the BiSC children to evaluate different aspects of the early neurodevelopment as well as autism spectrum disorders (ASD) traits as detailed in Table 4. In addition, we collected information on respiratory infections and symptoms, anthropometric growth and sleeping patterns. Neurodevelopmental evaluation of Barcelona Life Study Cohort (BiSC) children Bayley III, Bayley Scales of Infant and Toddler Development; CBCL 1–1 ½, Child Behaviour Checklist; DP-3, Developmental Profile 3; IBQ-R, Infant Behaviour Questionnaire-Revised (Short form); M-Chat-R/F, Modified Checklist for Autism in Toddlers, Revised with Follow-Up; CDI-I, MacArthur-Bates Communicative Development Inventories. On 14 March 2020, Catalonia, alongside with the rest of Spain, started a strict home confinement due to the COVID-19 pandemic, essentially halting all nonessential works and severely limiting the freedom of movement of its residents. As part of these measures, hospitals across Catalonia halted all ongoing research activities apart from those that were dealing with COVID-19. in out during three in Barcelona ended on 18 During this period, all including clinical visits at the biological and environmental at participants’ were on the the recruitment and clinical and environmental were using inclusion and a of hospital and home visits as detailed in the Supplementary Material (available as Supplementary data at IJE online), The BiSC is ongoing with on environmental and genetic determinants of maternal and child health and development The be listed on the BiSC website The first study based on the BiSC data to characterize the human chemical exposome in maternal and samples of a subset of BiSC The including personal and The levels of these with their levels in the the of using as a of the human exposure at the population level. study the between levels of and in the water and third trimester plasma samples of BiSC found a between levels in water and plasma samples. on recent and advancements, BiSC is a new generation exposome cohort with a of data on a wide range of socio-environmental and lifestyle factors as well as molecular and health and developmental outcomes. conducted around measurements of and home-outdoor air pollution levels, together with measurements of personal exposure to air pollution, BiSC has generated one of the of its in the when it to birth cohorts. The measurement of noise at with noise as well as data on noise and is of the BiSC, has been in other birth cohorts at this To our BiSC is the first birth cohort to measure temperature and humidity together with detailed data on (e.g. air and during pregnancy. BiSC has also characterized the time-activity patterns of participants using personal data have been with air pollution data using a and to not exposure in all commuting and also the of is a in the of exposure to air pollution pregnant to the chemical we have collected 12 obtained during and of in the first and third trimesters in total for each a detailed evaluation of exposure to In of health apart from the molecular BiSC has applied ultrasound techniques to collect data on foetal brain and cardiovascular with of placental function and foetal growth as well as brain MRI of neonates and a large of neuropsychological tests, other pre- and postnatal outcomes. of the BiSC is its healthcare exposure environmental and who the different aspects of this has generated a platform that can be by from different to BiSC also some and BiSC is one of the exposome cohorts with detailed personal measurements as described its is relatively could in a limited for some of the COVID-19 pandemic and its we could not home and hospital visits and collect biological samples from some of the BiSC and this generated data for those visits. We were also to some of the aspects of our data collection as described these the cohort during and after the pandemic could a opportunity to evaluate the of socio-environmental factors with the pandemic in with maternal and child health and is of the the visit and the 18-month follow-up, there was a to follow-up. To the we have carried out a number of activities such as providing families with of the and neurodevelopmental providing and about the in the BiSC and social for the BiSC children and for BiSC that the recruitment of the BiSC participants was conducted at the end of the first trimester of pregnancy, our data collection not the the part of the first trimester, could be a window of for some of our exposures and outcomes. However, we obtained during those periods and environmental exposures to participants for those BiSC was planned to also establish a cohort of partners, in addition to the cohorts of mothers and the of the partners in BiSC was with of partners in BiSC welcomes external collaborations and provides a gated access to its data. Data requests for or and biological requests be following the available on the BiSC BiSC evaluate the requests and in the of the of the for data a data and for access to biological samples, a be with the about the and the information for the are presented on the BiSC The BiSC Sant Joan de Clínic de de and Hospital Sant Joan de of Barcelona and de Sant Sant Joan de de i de Hospital de Sant and de Sant were obtained from the corresponding in all the and hospitals including Research of the de Research of the de Hospital de la Santa Creu i Sant de Barcelona and of the Sant Joan de to their enrolment into the cohort during their routine first trimester hospital visit, participants were informed by a BiSC or nurse about the study and their to the study at If the woman agreed to the consent including the permission to collect biological samples as well as were and a was to of of all children was also included in the consent and to the of study consent forms for genetic were also to the mothers and of the the consent forms were by the of the Supplementary data are available at IJE and the and obtained and the of the and the of the exposure methods for related exposome and defined the protocol for data and analysis of this the of biological samples and and data and and the and of the exposure and and implemented the environmental and and the data. the of the postnatal follow-ups of the defined the MRI protocol and the analysis of this and defined the ultrasound and implemented defined the neuropsychological to be implemented and and conducted the neuropsychological provided assessed on the neuropsychological to be implemented and the of the cohort; provided on data analysis and air pollution and the while the rest of and the all the of the and with its and all are in the analytical and of the was by the European Research Council the European research and and the Health Effects Institute an funded by the Environmental and and The of this not the of or its the and of the or and of the that of the can be found at from the funded by and from the de through the a funded by de de III, by European in from the European research and the and funded by the and the European has from de Clínic de Barcelona by Hospital Clínic de We to all the participants and their families for their We are also to all the and BiSC for their to this cohort. We to the of Joan de the from the hospitals in the study and the and

Topics & Concepts