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NCT Number: NCT07408973

Prospective Twin Pregnancy Cohort at Montpellier University Hospital

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.

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Key information

Conditions

Pregnancy Female Urogenital Diseases and Pregnancy Complications Obstetric Labor Complications Pregnancy Complications Twin Urogenital Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Biological samples from the mother

Other

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

Biological samples from the twins

Other

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

Primary outcomes

  1. Maternal extern exposome

    Time frame: From two years before pregnancy until delivery

    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.

  2. Maternal intern exposome

    Time frame: From two years before pregnancy until delivery

    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.

  3. Abnormal newborn weight

    Time frame: At childbirth

    Growth retardation: Abnormal birth weight (in kg) for at least one of the two children (< 3rd percentile according to the Olsen curve).

Secondary outcomes

  1. Abnormalities in children

    Time frame: From childbirth to the twins' first birthday

    • 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.

  2. Obstetric complications

    Time frame: At childbirth

    Occurrence of at least one of the obstetric complications listed in the patient follow-up record.

  3. Comparison of the Twins

    Time frame: At childbirth

    • 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

  4. Children's extern exposome

    Time frame: From childbirth to the twins' first birthday

    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.

  5. Children's intern exposome

    Time frame: From childbirth to the twins' first birthday

    • 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.

Other outcomes

  1. Supplement to the mother's exposome

    Time frame: From inclusion to childbirth

    Epigenetics:

    Maternal epigenome, characterization of the genome in a blood sample taken at delivery. Epigenetic analyses will be outsourced to a competent laboratory. Methylation sequencing will be performed using the Xgen Methyl-Seq DNA kit (IDT DNA).

    These data will be assessed individually and incorporated into a statistical model.

    Nutrient and Contaminant Profiling:

    • Nutrients (carbohydrates, amino acids, vitamins, minerals, fatty acids) in maternal blood at delivery. Analyses outsourced to a competent lab using methods specific to each nutrient type.
    • Heavy metal exposure:
    • Chronic: lead in urine; acute: heavy metals in blood (see "8. Children's internal exposome").
    • Maternal-fetal transfer: heavy metals in placenta, analyzed by a competent lab, using a specific method.

    These data will be assessed individually and incorporated into a statistical model.

  2. Supplement to the children's exposome

    Time frame: From inclusion to the twins' first birthday

    • Epigenome : obtained from umbilical cord blood at birth ; analyses outsourced to a competent lab. Methylation sequencing with Xgen Methyl-Seq DNA kit (IDT DNA). Data assessed individually and integrated into a statistical model.
    • Maternal metabolites : assessed in urine collected at inclusion ; outsourced to a competent lab. Urinary metabolomics (untargeted or targeted small metabolites) via LC-MS/MS, GC-MS, or ¹H-NMR on spot or 24h urine, creatinine-normalized, to profile maternal metabolism and exposome. Data assessed individually and modeled statistically.
    • Twins' microbiome : meconium at birth and stool at 6 months and 1 year ; analyzed by specialized external lab via sequencing. Data assessed individually and modeled statistically.
    • IgA and IgE: quantified in milk during newborns' stay; analyses by Montpellier University Hospital. Data assessed individually and modeled statistically.

  3. PM and PMT substances

    Time frame: At inclusion, 6 month of pregnancy

    Chemical contaminants in the environment (Persistent and Mobile (PM) and Persistent Mobile and Toxic (PMT)) will be quantified from a 5 ml urine sample taken from pregnant women. The urine sample will be analyzed by Elena Gomez's team at UMR 5151 Hydrosciences in Montpellier.

Study contacts

Contact information is provided by the study sponsor or research team.

Davide CAIMMI, MD, PhD

CONTACT

[email protected]

+334 67 33 61 03

Florent FUCHS, MD, PhD

CONTACT

[email protected]

+334 67 33 09 80

Sponsors and collaborators

Lead sponsor

University Hospital, Montpellier

Other

Collaborators

  • Institut National de la Santé Et de la Recherche Médicale, France

Registry information

Official study title

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

Acronym: COGEM

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Feb 13, 2026
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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