Cohort Profile: The French national cohort of children (ELFE): birth to 5 years
In various scientific domains, the early stages of development have been found critical to understanding individual health and social trajectories. The theory of the developmental origin of health and diseases (DOHAD) has stressed the plasticity of the developing organism in response to environmental cues and the role of some early developmental adaptations in programming later health.1 Life course epidemiology, initially developed by social scientists,2 offers a conceptual framework for the study of health and social trajectories. The framework integrates critical early life periods into the different pathways laid down by the familial, social and cultural environments and modulated by personal psychosocial and behavioural factors. Long-term longitudinal studies are the best tool to disentangle these factors that interact over time. In France, several regional birth cohorts of children were launched in the 1990s to study the effect of exposure to environmental contaminants3,4 or to a broader set of exposures,5 on children’s health. In the 2000s, two national projects were set up. The first study, led by the French Institute for Demographic Studies (Ined), was initiated in response to a series of recommendations from several national institutions and bodies that called for a French longitudinal study of children to better understand their life conditions, especially with respect to socioeconomic and health inequalities.6 For example, data were needed on the living conditions and developmental outcomes of children raised in single-parent families (in 2011, 10% of children under age 3 and 19% of children 3 to 6 years old were living with only one parent)7 or children with a migrant background (in 2011, 30% of children under age 18 lived with parents who were first- or second-generation immigrants).8 Regarding health inequalities, the increasing disparities in the prevalence of obesity in 5-year-old children by socioeconomic status was also a concern: although decreasing from 3.1% to 1.8% between 2000 and 2006 in private schools, it has remained higher and almost unchanged (5.6% to 5.1%) among children attending schools in socially disadvantaged areas.9 The second project was proposed by the French Institute for Public Health Surveillance (InVS) at the request of the Ministry of Health, as part of the first French National Environmental Health Plan. Despite growing evidence of the potentially deleterious effects of new emerging pollutants present at low doses and acting in synergy on developing organisms,10 there were no national data on the level of exposure of French pregnant women and children. For practical and financial reasons, the two projects were merged into a single, large national birth cohort, known as the ELFE cohort (Etude Longitudinale Française depuis l'Enfance/French Longitudinal Study since Childhood), with recruitment representative of live births in France. This merger offered a unique opportunity to set up a truly multidisciplinary project. Calls for proposals to select research priorities for the cohort were sent out to the French research community in 2005–06. More than 60 research teams responded. Researchers started to work in thematic groups to construct study protocol under the leadership of an overall coordinating team. The general objective of the cohort is to study determinants of child development, health and socialization from birth to adulthood. The priority research themes selected for ELFE were: aspects of children's environment that have undergone the most striking changes over recent decades including: modification of nutritional intake; reduction of physical activity; exposure to emerging exogenous pollutants; new communication technologies; weakening of the traditional family model (notably divorce and step-families); an increased proportion of working women; new patterns of care seeking, due to changes in medical practice and demography; the relationship of these changes to the development of cognitive, language and socio-affective skills, educational outcomes, social integration and common childhood diseases; the complex interactions between biological, behavioural and social factors. A study sample of 20 000 births (1/40 annual births) was chosen as feasible while still offering the statistical power required to address the main research questions. For an outcome prevalence of 10%, this sample size provides a power of 90% with an alpha risk of 5% to evidence relative risks from 1.12 to 1.77 when the frequency of exposure varies from 30% to 1%. For a less frequent outcome prevalence of 1%, corresponding relative risks would be from 1.41 to 4.1. A joint unit of the French National Institute of Health and Medical Research (Inserm) and Ined was created in 2010 to support the project. At the same time, a study of the short- and -long-term outcomes of very preterm births, the Epipage 2 study,11 was being planned and it was decided that ELFE, which would not include very preterm births, would provide a control group for the Epipage 2 study. The Ministries of the Environment, Health and Research provided initial funding for the ELFE cohort. The funding for the first 5 years of childhood follow-up was obtained from the national ‘Investment for the Future’ research funding programme for a joint project bringing together the ELFE and Epipage 2 cohorts. After a small-scale pilot cohort in 200712 and a national information campaign, the national cohort was launched in 2011. A total of 349 maternity units were randomly selected in metropolitan France and the children were recruited at birth from the 320 maternity units that agreed to participate. A stratified sampling strategy based on the size of each unit was adopted to allow for oversampling in larger units, thus reducing the cost of data collection (Figure 1). Recruitment took place during 25 selected days in 2011, grouped into four periods over the year; 12 of these days were selected to coincide with the French permanent demographic sample, a regular national survey of individuals born on specific days every year.13 Inclusion criteria were single or twin live births at ≥33 weeks of gestation, mother ≥18 years old, no plan to leave metropolitan France within 3 years and informed consent signed by the parents or the mother alone, with the father being informed of his right to deny consent for participation. Information and consent documents were provided in French, Arabic, Turkish and English, the most common languages of women giving birth in France. Randomly selected maternity units for the recruitment in the ELFE cohort (dots) and biological treatment and storage units (square). More than 96% of the mothers who satisfied the first two inclusion criteria (n = 37 494) were contacted by research assistants during their stay in the maternity unit and 51% (18 040) agreed to participate in the cohort. The women gave birth to 18 329 babies, including 289 pairs of twins. With ethics approval, some data on births to mothers who refused to take part were collected from birth certificates and stored anonymously. This collection made it possible to apply a weighting procedure to correct for non-representativeness. The weights take into account the sampling plan and refusals at both maternity unit and individual levels; details on the research section/data and questionnaire are available at [https://www.ELFE-france.fr/en/]. Variance calculations were adapted for the sampling frame.14 The raw and weighted frequencies for the main sociodemographic and health characteristics of the cohort are presented in Table 1, with national data for comparison if available. Main characteristics at birth of mothers and children included in the ELFE cohort and comparison with the national references (birth certificates or 2010 National Perinatal Surveya) SD, standard deviation; SE, standard error; BMI, body mass index. [http://www.europeristat.com/images/French%20National%20Perinatal%20Surveys%202003-2010-2.pdf]. Mothers or infants with available data at time of analysis (some included subjects have asked for withdrawal of their data). National reference when available, restricted to a population with the same eligibility criteria for the National Perinatal Survey but not for the birth certificates. Variables used for marginal calibration of weighted variables (in addition to region of residence). Main characteristics at birth of mothers and children included in the ELFE cohort and comparison with the national references (birth certificates or 2010 National Perinatal Surveya) SD, standard deviation; SE, standard error; BMI, body mass index. [http://www.europeristat.com/images/French%20National%20Perinatal%20Surveys%202003-2010-2.pdf]. Mothers or infants with available data at time of analysis (some included subjects have asked for withdrawal of their data). National reference when available, restricted to a population with the same eligibility criteria for the National Perinatal Survey but not for the birth certificates. Variables used for marginal calibration of weighted variables (in addition to region of residence). Ethical approvals for data collection in maternity units and for each data collection wave during follow-up were obtained from the national advisory committee on information processing in health research (CCTIRS: Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé), the national data protection authority (CNIL: Comission Nationale Informatique et Liberté) and, in case of invasive data collection such as biological sampling, the committee for protection of persons engaged in research (CPP: Comité de Protection des Personnes). The ELFE study was also approved by the national committee for statistical information (CNIS: Conseil National de l’Information Statistique). Follow-up was intensive in the infancy and pre-school periods (from 2011 to 2015), including telephone interviews of both parents at age 2 months and 1 and 2 years, and one parent (the mother or, if not available, the father) at age 3.5 years (Figure 2). Follow-up schedule. ELFE cohort: birth to 5 years. In addition to telephone interviews, information on infant feeding was collected every month from age 2 to 10 months via the internet or paper questionnaires. Parents were also given a questionnaire to be completed by the child’s physician at age 2 years. A home visit was organized at age 3.5 years. With the collaboration of 30 district maternal and child welfare services, the results of the medical examination performed at nursery school at age 3 to 4 years15 were collected for 3124 ELFE children and 6815 control children born on the same day. A nursery schoolteacher survey was performed when the children were 4 to 5 years old. It involved 5178 ELFE children and 10 877 control children with birthdays closest in time to those of the ELFE children. Participation rates for the 2-month, 1- and 2-year and 3.5-year main surveys are presented in Figure 3. Some participants did not complete the questionnaires in full, but the rate of non-completers has remained low and stable at around 4% at each wave. Withdrawals from the study consist of families who sent a written request to end their participation, those who could not be contacted during any of the three previous waves or those who ever gave an oral request for withdrawal and could not be contacted thereafter. Families who moved out of metropolitan France were not eligible for telephone interviews but received a short paper version of the questionnaire. Participation in the main surveys during the first 5 years of follow-up. ELFE cohort. Compared with mothers of children who were eligible for follow-up, mothers who have withdrawn from the study by the end of the 3.5-year survey (n = 2092) were more likely to be <25 years old at the child’s birth (18% vs 11%), not to have a university degree (38% vs 54%), be unemployed or housewives (21% vs 13%), to have been born outside France (17% vs 13%) or to be single mothers (8% vs 5%) (all p < 0.0001). However, the two groups did not differ in parity, maternal health before or during pregnancy, mode of delivery or mean birthweight. Table 2 summarizes the main types of information collected at inclusion and each follow-up. For more details, English translated questionnaires are available at the study website: [https://www.ELFE-france.fr/en/the-research/access-to-data-and-questionnaires] Dataa collected in the ELFE study (2011–16) The table specifies whether information was collected through health records or physician (), self-administered () or web () questionnaires, face-to-face interview or test by survey technician (), telephone interview (), environmental, biological sampling (x). Questions asked to: M mother, F father, F(M) father or mother if father is not participating, MorF mother or father if mother not available, C child, T teacher. Some data have been collected only on Table feeding data for the months collected by or Dataa collected in the ELFE study (2011–16) The table specifies whether information was collected through health records or physician (), self-administered () or web () questionnaires, face-to-face interview or test by survey technician (), telephone interview (), environmental, biological sampling (x). Questions asked to: M mother, F father, F(M) father or mother if father is not participating, MorF mother or father if mother not available, C child, T teacher. Some data have been collected only on Table feeding data for the months collected by or Table 3 the standard used in in the questionnaires or, to the of interviews to less than 60 with a of A frequency from the questionnaire used in the on the in the 3 months of was completed in 2011 in the maternity unit by mothers in questionnaires included in the telephone interviews, ELFE study et et et et et Public Health M et C et et et des et et et et et de questionnaires included in the telephone interviews, ELFE study et et et et et Public Health M et C et et et des et et et et et de At a of maternity units for their of and their to biological treatment and storage units made available by the French Figure were to biological (n = agreed to participate. The biological included maternal and at in the maternity unit for and at and from the and from mothers during the initial stay in the maternity unit ELFE study ELFE study were randomly in maternity to the of were provided in 2011 to a of mothers to be in the during the first 2 to the in of the analysis Participation rate in specific data collection in ELFE study as of families with criteria who were proposed to participate at the = with at one biological by the of an days before home visit for the families who agreed to participate of those Participation rate in specific data collection in ELFE study as of families with criteria who were proposed to participate at the = with at one biological by the of an days before home visit for the families who agreed to participate of those In with children 3.5 years, of the families still eligible for follow-up and contacted for a telephone interview (n = were recruited for a home For children born before 2011, eligible families were selected by stratified sampling with a for families that provided biological at and a to the inclusion weights for the cohort in to families with a of participation. However, of recruitment than families with an ELFE child born 2011 were eligible for home The main objective of the home visit was to the child’s this of development is to by by the parents The test of the was chosen for this it is a used in national The test the child’s to and test and to It be by research assistants and is on in developed to provide and for the of children with be before age 4 years in a test of was also to to the of the In three were performed to of and asked the child to a with both The children were also asked to a on a of The were the and to the child’s level of A of the child’s physical and was obtained by of an for families when one of a total of was available at days before the planned home In performed biological sampling and from in families from biological from the mother or child been collected at In families for which both maternal and at inclusion were available, obtained of from the home (from the and the of the the child most The was to a of children with available for environmental exposure at different life stages In when most children were in 2 of nursery school years questionnaires to be completed by the children’s were sent to parents who provided a school address at the 3.5-year telephone In schools were informed by and a to was sent to the schools and was used to ELFE children as as three children in the same who were born closest in time to the ELFE child, as a control The their understanding of and as as processing and The were to the children to by to on a A short test was to test the of the children’s Table 5 and rates for specific data collection in the are used to the environment by home with data in sociodemographic or environmental to the French National Health was in This for information on care and the mother during and the child since Some selected results of the first based on ELFE data are A complete of be found at Some of the collected at birth have been used by the French National Public Health as part of the first national The obtained data available at are included in the ELFE and are available to The results presented thus have the exposure of French pregnant women to a group of as with pregnant women in the This is with a in the French general of environmental The collected in the ELFE infants during their first 2 months of life was for the of specific to 10 one different were and a In the of and or and the of were with the The of this research project be to with children’s health and ELFE an of pregnant women during only a with a health and 10% used a during The of a health was among women of with an educational who were born outside France and who the to health care during ELFE also provided new data on French in the the the birth of a new child in families with two or three months the child’s if both parents were of mothers with a the to take leave since has been available to both parents and from 1 to 3 their maternity only of mothers in In these of the took their leave their social for the In when only one parent was the of with took the leave of those with not a a more of child care between and mothers as with previous French and between social ELFE is the first French national birth cohort, and as such provide information on children born in the for national and for For this in addition to the initial of to consent to in the cohort, weights are for each wave to account for However, individuals in very are in the ELFE cohort, and by weighting is not when based on a of selected ELFE is not a tool for these specific this not out the study of social social are over the of the as in the first from the with national health for which of the cohort provide health information for participants and also for those to follow-up. In both the medical and surveys performed in schools have collected data on children not included in the ELFE cohort but born on the same days as ELFE children in of and for some ELFE is also a of for children of the same age with specific such as children born in the study,11 or children of parents in the ELFE is a recent cohort, and care has been to data and for developing research such as the of environmental or of communication on child development and the role of the on risk of or the health and social of first- and second-generation in the French be the of and personal from birth to educational with information on outcomes at nursery school in a of children. ELFE is a multidisciplinary project. More than are working in the ELFE thematic groups the of and different of physical and environmental are by research data collection and each is the ELFE by and variables from specific that be used by with the support of a of The of a multidisciplinary is the needed to on the data to be on the part of the of the questionnaires for are made to the families informed of the study and results and to for their by offering to the children. the which be due in part to the study a for the ELFE families are over France over time, in some as the and present a example, for that would to In ELFE is the first French national birth cohort. It provide information on the development, health and socialization of children born in France in 2011 and to the research to better understand their a multidisciplinary cohort, it has to be and the to and However, the of data from the environmental and social for the of within each and information be found via the ELFE [https://www.ELFE-france.fr/en/]. The ELFE has an an for the research teams each of new Study questionnaires and the data be found also be via the data for by the ELFE proposals with the ELFE that be from the ELFE is the first French national birth cohort. objective is to study determinants of the development, health and socialization of children from birth to through a multidisciplinary A total of 18 329 children were recruited at birth in a sample of maternity units in metropolitan France during 25 selected days of 2011 over the Follow-up in the first 5 years of telephone interviews of both parents of the child at age 2 months and 1 and 2 years, and of one parent at age 3.5 a home visit at age 3.5 questionnaires to the child’s physician at age 2 years, the child’s nursery school at age 3 to 4 years, and the child’s nursery schoolteacher at age 4 years. Participation rates at the age 2-month, 1- and 2-year and 3.5-year interviews were and of contacted The main of data collected concern: sociodemographic family and life child development and child school and care and and childhood environmental The ELFE has an an each of new The study questionnaires and data be found [https://www.ELFE-france.fr/en/]. This work was by National Research for the programme French National Institute for Research in Public Health Ministry of and Ministry of Ministry of French for Public Ministry of and National are to: the of the ELFE the project would have and of the and for their and of the unit for support de and the who to the projects as of the ELFE thematic groups and their the research assistants and and the ELFE families who have their in and given up their time to the study. of