Prospective Twin Pregnancy Cohort at Montpellier University Hospital

Twin Pregnancy Cohort at Montpellier University Hospital for a Study of the Impact of the Exposome: Pilot Study

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.

Mother's inclusion Criteria:

• Patient of legal age (≥ 18 years)
• Patient pregnant with a twin pregnancy ≥ 25 weeks of gestation
• Pregnancy initially twin, triplet, or quadruplet, progressing to a twin pregnancy after spontaneous or medical embryo reduction, or after selective termination of pregnancy
• Delivery planned at Montpellier University Hospital

Twins' inclusion Criteria:

• Twins born in a twin pregnancy ≥ 25 weeks of gestation

Mother's exclusion Criteria:

• Pregnant woman with at least one fetus presenting with a chromosomal or genetic abnormality or a polymalformative syndrome, and for whom early postnatal death is anticipated.
• Planned travel preventing the study from being completed
• Failure to obtain informed and written consent from the patient for participation in the study and the collection of biological samples
• Patient unable to read and/or write French
• Patient unable to understand and/or speak French
• Patient not benefiting from a national health insurance scheme
• Person under legal protection, guardianship or curatorship
• Person participating in other interventional research study

Twins' exclusion Criteria:

• Mother's absence from or withdrawal from the study
• Birth in a facility other than Montpellier University Hospital
• One or two children under guardianship
• Lack of informed and written consent from legal representatives
• One of the two fetuses is expected to die
• Lack of informed and written consent from the prospective parent(s) for participation in the study and the collection of biological samples
• Parents unable to read and/or write French
• Parents not understanding and/or speaking French