This prospective observational cohort study aims to investigate the impact of the maternal and early-life exposome on neonatal and early childhood health outcomes in twin pregnancies followed at University Hospital of Montpellier (France). Grounded in the Developmental Origins of Health and Disease (DOHaD) framework, the study focuses on how environmental, biological, and lifestyle exposures during pregnancy and the first year of life influence fetal growth, neonatal health, and early development. A total of 120 women with monochorionic or dichorionic twin pregnancies and their 240 children will be included. Maternal exposome assessment includes air pollution exposure, lifestyle, diet, medical history, and biological measurements. Neonatal outcomes, including abnormal birth weight, will be evaluated at birth, and children will be followed until one year of age to assess growth, health events, and developmental outcomes. Biological samples collected at different times during the study will allow the assessment of chemical exposures and epigenetic markers. This study aims to generate original French twin pregnancy data and to improve understanding of environmental determinants of early-life health.
Introduction: Over the past two decades, growing epidemiological evidence in humans and experimental studies in animals have supported the concept of the Developmental Origins of Health and Disease (DOHaD), initially proposed by Barker. This hypothesis suggests that environmental and maternal conditions during critical periods of development-particularly the first 1,000 days of life, from conception to early childhood-can induce long-term effects on organogenesis, metabolic pathways, and physiological functions, ultimately influencing physical and mental health throughout life. In parallel, the concept of the exposome, introduced by Wild in 2005, aims to comprehensively characterize all environmental exposures (chemical, physical, biological, behavioral, and socioeconomic) encountered by an individual from conception onwards. Twin pregnancies represent a particularly valuable model for exposome research, as they allow the study of shared and differential exposures within the same intrauterine environment. Establishing a large French cohort of twin pregnancies is therefore essential to generate national data and to investigate the impact of environmental exposures on pregnancy outcomes, neonatal health, and early childhood development. Primary Aim: Assess the impact of maternal exposome during twin pregnancies followed at Montpellier University Hospital on the occurrence of abnormal neonatal birth weight (small for gestational age) at birth. Secondary Aims: * Evaluate the impact of maternal exposome on neonatal abnormalities at birth and on child health outcomes during the first year of life. * Assess the association between maternal exposome and the occurrence of obstetric complications. * Compare outcomes between twins from monochorionic (monozygotic) and dichorionic pregnancies (dizygotic, different-sex twins), focusing on: The impact of maternal exposome during pregnancy on child health outcomes. The impact of the child's own exposome on health outcomes during the first year of life. Methods: This is a prospective observational cohort study including women with twin pregnancies (monochorionic or dichorionic) of at least 25 weeks of gestation, followed and delivering at University Hospital of Montpellier (France). A total of 120 pregnant women and their 240 twin children will be enrolled. Maternal data will be collected during pregnancy through electronic questionnaires and medical records, including sociodemographic characteristics, medical and obstetric history, lifestyle, diet, and environmental exposures. Maternal exposome assessment includes long-term exposure to ambient air pollutants from two years before pregnancy and throughout gestation, as well as biological measurements such as urinary lead levels at 25 weeks of gestation. At delivery, biological samples will be collected from the mother, placenta, and umbilical cord (blood and tissue). Neonatal data will include anthropometric measurements and clinical outcomes at birth. The child exposome will be assessed through environmental exposure data during pregnancy and the first year of life, questionnaires on lifestyle and environment, and biological analyses including exposure to PFAS, heavy metals, and genomic/epigenetic markers from cord blood and tissue samples.
Study Type
OBSERVATIONAL
Enrollment
360
During pregnancy, the research team collects: \- 15 ml of urine from the expectant mother. Immediately after delivery, the research team collects: * 10 ml of peripheral blood from the mother * One or two 2 cm x 2 cm pieces of placenta, depending on the type of pregnancy * 12 ml of cord blood for each twin * A 5 cm fragment of cord tissue for each twin
The day after delivery, the reserch team collects: \- A meconium sample from each twin At 6 months and 1 year of age, the parents collect: \- A stool sample from each twin
Maternal extern exposome
Exposure to air pollutants (NO₂, PM₂.₅, O₃, VOCs) during the two years prior to and during pregnancy: these values will be derived from the Chimera model, and an area under the exposure curve will be calculated. The level of exposure will be calculated based on the mother's home addresses during the two years prior to inclusion, at the time of inclusion, and based on her work addresses during pregnancy if she worked for more than four months during pregnancy. These data will be assessed individually and incorporated into a statistical model. Data from the patient follow-up log, data from questionnaires: * Environment, general health, lifestyle, and diet. * Obstetric, medical, and surgical history, current pregnancy. These data will be assessed individually and incorporated into a statistical model.
Time frame: From two years before pregnancy until delivery
Maternal intern exposome
Amount of lead in urine at 25 weeks of gestation. Lead will be measured by Montpellier University Hospital in a urine sample taken during the sixth month of pregnancy (inclusion) using ICP-Ms. These data will be assessed individually and incorporated into a statistical model.
Time frame: From two years before pregnancy until delivery
Abnormal newborn weight
Growth retardation: Abnormal birth weight (in kg) for at least one of the two children (\< 3rd percentile according to the Olsen curve).
Time frame: At childbirth
Abnormalities in children
* Occurrence of one or more altered anthropometric characteristics (outside reference values) at birth: fetal macrosomia, abnormal height, abnormal head circumference. * Occurrence of one or more altered anthropometric characteristics (outside reference values) at D+15, 1, 3, 6, 8, 10 months and 1 year: abnormal weight (\<3rd or \>97th percentile, Olsen curve), abnormal height (\<5th or \>95th percentile), abnormal head circumference (\<5th or \>95th percentile). * Occurrence of a serious health problem at birth or during the first year of life. * Knowledge of occurrence of one or more of the following conditions during the first year: ENT, respiratory, gastroenterological, dermatological conditions, recognized atopy/allergies, early neurodevelopmental disorder. All these data will be assessed individually and incorporated into a statistical model.
Time frame: From childbirth to the twins' first birthday
Obstetric complications
Occurrence of at least one of the obstetric complications listed in the patient follow-up record.
Time frame: At childbirth
Comparison of the Twins
* Type of pregnancy from which the twins originate: monochorionic (monoamniotic or biamniotic) or dichorionic. * Sex of twins: 2 girls, or 2 boys, or 1 girl and 1 boy
Time frame: At childbirth
Children's extern exposome
Exposure to air pollutants (NO2, PM2.5, O3, VOCs) throughout pregnancy and during the first year of life: these values will be derived from the Chimera model, and an area under the exposure curve will be calculated. The level of exposure will be determined based on the mother's personal and professional addresses during pregnancy and the first year of the children's lives. These data will be assessed individually and incorporated into a statistical model. Data from the patient follow-up log, data from questionnaires: • Environment, lifestyle, diet, treatments received, games and care. These data will be assessed individually and incorporated into a statistical model.
Time frame: From childbirth to the twins' first birthday
Children's intern exposome
• Exposure to PFAS (per- and polyfluoroalkyl substances) substances can be measured using a piece of umbilical cord taken at birth. The measurement of PFAS in a piece of umbilical cord will be outsourced to a competent laboratory. The PFAS will be extracted from the tissue, then separated and finally quantified using a highly accurate analytical technique. These data will be assessed individually and incorporated into a statistical model. • Exposure to heavy metals can be measured using a sample of umbilical cord blood taken at birth. The measurement of heavy metals will be entrusted to a competent laboratory. The elements (lead, manganese, copper, zinc, mercury, cadmium, arsenic, selenium) present in the blood are measured by inductively coupled plasma mass spectrometry (ICP-MSMS) after being mineralised (internal method ESS\_ANA\_PT\_641). These data will be assessed individually and incorporated into a statistical model.
Time frame: From childbirth to the twins' first birthday
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