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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-A02160-47 | Other Identifier | ID-RCB |
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| Name | Class |
|---|---|
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Women pregnant with twins |
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| Twins newborns |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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:
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| 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. | 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). | At childbirth |
| Measure | Description | Time Frame |
|---|---|---|
| Abnormalities in children |
All these data will be assessed individually and incorporated into a statistical model. |
| Measure | Description | Time Frame |
|---|---|---|
| Supplement to the mother's exposome | 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:
These data will be assessed individually and incorporated into a statistical model. |
Mother's inclusion Criteria:
Twins' inclusion Criteria:
Mother's exclusion Criteria:
Twins' exclusion Criteria:
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Any dichorionic or monochorionic twin pregnancy of more than 25 weeks' gestation, monitored at the University Hospital of Montpellier.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Florent FUCHS, MD, PhD | Contact | +334 67 33 09 80 | f-fuchs@chu-montpellier.fr | |
| Davide CAIMMI, MD, PhD | Contact | +334 67 33 61 03 | dp-caimmi@chu-montpellier.fr |
| Name | Affiliation | Role |
|---|---|---|
| Florent FUCHS, MD, PhD | University Hopistal of Montpellier | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11179140 | Background | Robinson R. The fetal origins of adult disease. BMJ. 2001 Feb 17;322(7283):375-6. doi: 10.1136/bmj.322.7283.375. No abstract available. | |
| 21772139 | Background | Kozyrskyj AL, Bahreinian S, Azad MB. Early life exposures: impact on asthma and allergic disease. Curr Opin Allergy Clin Immunol. 2011 Oct;11(5):400-6. doi: 10.1097/ACI.0b013e328349b166. |
| Label | URL |
|---|---|
| French perinatal survey 2021 | View source |
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NC
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| ID | Term |
|---|---|
| D007744 | Obstetric Labor Complications |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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White blood cells derived from maternal blood. Whole blood from the umbilical cord of each twin.
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| 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 |
|
| 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. | At childbirth |
| Comparison of the Twins |
| 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. | 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. | From childbirth to the twins' first birthday |
| From inclusion to childbirth |
| Supplement to the children's exposome |
| From inclusion to the twins' first birthday |
| PM and PMT substances | 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. | At inclusion, 6 month of pregnancy |
| 16103423 | Background | Wild CP. Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1847-50. doi: 10.1158/1055-9965.EPI-05-0456. No abstract available. |
| 34097167 | Background | Gordon H, Blad W, Trier Moller F, Orchard T, Steel A, Trevelyan G, Ng S, Harbord M. UK IBD Twin Registry: Concordance and Environmental Risk Factors of Twins with IBD. Dig Dis Sci. 2022 Jun;67(6):2444-2450. doi: 10.1007/s10620-021-07080-5. Epub 2021 Jun 7. |
| 22302586 | Background | Southwest Thames Obstetric Research Collaborative (STORK). Prospective risk of late stillbirth in monochorionic twins: a regional cohort study. Ultrasound Obstet Gynecol. 2012 May;39(5):500-4. doi: 10.1002/uog.11110. Epub 2012 Mar 7. |
| 15188793 | Background | Garne E, Andersen HJ. The impact of multiple pregnancies and malformations on perinatal mortality. J Perinat Med. 2004;32(3):215-9. doi: 10.1515/JPM.2004.040. |
| 24412490 | Background | Bricker L. Optimal antenatal care for twin and triplet pregnancy: the evidence base. Best Pract Res Clin Obstet Gynaecol. 2014 Feb;28(2):305-17. doi: 10.1016/j.bpobgyn.2013.12.006. Epub 2013 Dec 17. |
| 10586523 | Background | Campbell DM, MacGillivray I. Preeclampsia in twin pregnancies: incidence and outcome. Hypertens Pregnancy. 1999;18(3):197-207. doi: 10.3109/10641959909016193. |
| 10521752 | Background | Schwartz DB, Daoud Y, Zazula P, Goyert G, Bronsteen R, Wright D, Copes J. Gestational diabetes mellitus: metabolic and blood glucose parameters in singleton versus twin pregnancies. Am J Obstet Gynecol. 1999 Oct;181(4):912-4. doi: 10.1016/s0002-9378(99)70324-8. |
| 33678251 | Background | Tang HHF, Teo SM, Sly PD, Holt PG, Inouye M. The intersect of genetics, environment, and microbiota in asthma-perspectives and challenges. J Allergy Clin Immunol. 2021 Mar;147(3):781-793. doi: 10.1016/j.jaci.2020.08.026. |
| 36615802 | Background | Delvert R, Ghozal M, Adel-Patient K, Kadawathagedara M, Heude B, Charles MA, Annesi-Maesano I, Tafflet M, Leynaert B, Varraso R, de Lauzon-Guillain B, Bedard A. Maternal Diet Quality during Pregnancy and Allergic and Respiratory Multimorbidity Clusters in Children from the EDEN Mother-Child Cohort. Nutrients. 2022 Dec 28;15(1):146. doi: 10.3390/nu15010146. |
| 34503987 | Background | Mensink-Bout SM, van Meel ER, de Jongste JC, Annesi-Maesano I, Aubert AM, Bernard JY, Chen LW, Cooper C, Crozier SR, Hanke W, Harvey NC, Hebert JR, Heude B, Jerzynska J, Kelleher CC, Mehegan J, McAuliffe FM, Phillips CM, Polanska K, Relton CL, Shivappa N, Suderman M, Jaddoe VWV, Duijts L. Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children. Eur Respir J. 2022 Apr 21;59(4):2101315. doi: 10.1183/13993003.01315-2021. Print 2022 Apr. |
| 36771248 | Background | Collado-Soler R, Alferez-Pastor M, Torres FL, Trigueros R, Aguilar-Parra JM, Navarro N. A Systematic Review of Healthy Nutrition Intervention Programs in Kindergarten and Primary Education. Nutrients. 2023 Jan 20;15(3):541. doi: 10.3390/nu15030541. |
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