The chemical exposoMe of pregnAnt womeN with GestatiOnal diabetes mellitus

Project Information

MANGO

Grant agreement ID: 101067260

DOI

10.3030/101067260

Project terminated on 18 October 2024

EC signature date 14 June 2022

Start date 1 April 2023

End date 31 March 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 261 380,64

Coordinated by

UNIVERSITAT ROVIRA I VIRGILI
Spain

Periodic Reporting for period 1 - MANGO (The chemical exposoMe of pregnAnt womeN with GestatiOnal diabetes mellitus)

Reporting period: 2023-04-01 to 2025-03-31

Summary of the context and overall objectives of the project

The MANGO project is rooted in the understanding that environmental chemical exposures contribute significantly to chronic disease development, especially in vulnerable populations like pregnant women. In today’s world, individuals are exposed to a complex array of chemicals—both low concentrations of high-toxicity chemicals and high levels of those considered lower in toxicity. This layered exposure scenario has driven the European Commission to prioritize reducing hazardous chemical exposure, reflected in initiatives like the HBM4EU or PARC and SDG3 for Good Health and Well-being.

To address the intricate nature of these exposures, the concept of the exposome—defined as the totality of an individual’s environmental exposures from conception onwards—has emerged as a critical framework. The exposome encompasses the wide variety of chemical exposures and their potential interactions over time, offering a comprehensive approach to understand how these factors collectively influence health. MANGO applies this exposomic perspective to capture a broad, untargeted profile of chemical exposures specific to the maternal-fetal window, which is known to be particularly sensitive to environmental influences.

MANGO’s primary objective is to conduct an exposome-wide analysis to identify chemical exposures that may elevate the risk of Gestational Diabetes Mellitus (GDM). Leveraging biological samples from the “Diabetes and Pregnancy” (DaP) cohort at IISPV/Hospital Joan XXIII, this project utilizes advanced analytical chemistry tools and statistical models to chart the unique exposomic signatures associated with GDM. In doing so, MANGO aims to establish a robust evidence base for chemical exposure-related health policies and develop a targeted pilot program for exposure prevention during pregnancy. This program will offer actionable recommendations to reduce hazardous exposures, contributing both to maternal-fetal health and broader regulatory frameworks across Europe.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

T1.1 DaP Cohort: Participant Selection, Sample Distribution, and Database Creation
Activities: The initial tasks for MANGO focused on selecting participants from the DaP cohort, organizing the shipment of biological samples, and developing the MANGO database. Key variables such as socio-demographics, dietary and lifestyle factors, and clinical metrics were compiled for MANGO participants.
Achievements:
Milestone (MS1.1): Successful selection of participants and shipment of biological samples to Columbia University.
Deliverable (D1.1): Creation of the MANGO database containing socio-demographic, dietary, lifestyle, and clinical data.

T1.2 Sample Treatment and LC-HRMS Sample Analysis
Activities: MANGO’s analytical phase began with the treatment of biological samples and their analysis using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). This phase also included developing a smart screening suspect list for targeted chemicals in alignment with project goals.
Achievements:
Milestone (MS1.2): Definition of the smart screening suspect list of chemicals (bisphenols, phthalates, parabens, organophosphate flame retardants, tire additives, PFAS, food additives).
Milestone (MS1.3): Completion of sample analysis (maternal urine, maternal serum, umbilical cord serum and placenta).
Deliverable (D1.2): Comprehensive report on validated LC-HRMS analytical methods, ensuring the robustness and accuracy of analytical approaches for detecting relevant chemicals in biological samples.

T4.2 Teaching and Lectures
Activities: Conducted teaching sessions to share insights into the chemical exposome with colleagues and students. This included seminar/course for colleagues at the Department of Health Sciences at Columbia and preparations for additional educational engagements.
Achievements:
Milestone (MS4.1): Prepared and delivered an agenda for the course on the chemical exposome.
Deliverable (D4.2): Produced minutes for the course on the chemical exposome, detailing session content and participant feedback for project's success.
Milestone (MS4.4): Successfully assigned a PhD student.

T5.1 Public Scientific Engagement
Activities: Participated in and organized scientific outreach activities, including chairing sessions and being invited to give a keynote lectures. I participated to the International Day of Women and Girls in Science event organized by 100tifiques giving a lecture to a 11-12 years old students. A session was chaired at SETAC (Seville, Spain), and a keynote lecture was presented at the Exposomics Symposium (Barcelona, Spain), fulfilling dissemination objectives.
Achievements:
Milestone (MS5.1): Set agendas for scientific talks.
Deliverables (D5.4 D5.5 D5.6): Released press communications (local, national and international level) and provided regular project updates on institutional websites (the Tecnatox website).

T6.1 Mentor Engagement and Reference Group Meetings
Activities: Conducted regular meetings with mentors (basically Columbia, due to the status of the project) to ensure project alignment and discuss progress within the MANGO framework.
Achievements:
Milestone (MS6.1): Completed scheduled reference group meetings, maintaining consistent collaboration and mentorship.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The MANGO project has achieved several pioneering results, advancing the understanding of chemical exposure during pregnancy and its role in the development of Gestational Diabetes Mellitus (GDM). MANGO’s application of an exposome-wide approach to GDM risk is particularly innovative, as previous studies have been limited in scope, often focusing on single chemical families without considering the broader spectrum of environmental exposures. This project is one of the first to adopt a comprehensive exposomics perspective, using high-resolution mass spectrometry (HRMS) and untargeted chemical screening to characterize a wide range of environmental exposures in pregnant women.

1. Key Results and Innovations (to date):
1.1. Development of a Smart Screening Suspect List: By identifying a suspect list of chemicals particularly relevant to pregnancy, MANGO enhances the precision of HRMS-based assessments, enabling a focused yet expansive capture of relevant exposures. This list, grounded in novel, non-targeted screening methods, goes beyond conventional approaches by identifying previously unexamined chemicals of potential concern.
1.2. Comprehensive Report on Validated LC-HRMS Analytical Methods: This report marks a crucial advancement by validating LC-HRMS methods tailored for untargeted screening in maternal biological samples. By establishing a reliable methodology, MANGO sets a standard for precise and reproducible chemical exposure assessments, paving the way for future exposomics studies to adopt these advanced protocols and improving the robustness of findings across studies.
1.3. Data-Rich MANGO Cohort Database: Integrating detailed socio-demographic, lifestyle, and clinical data alongside chemical exposure profiles allows MANGO to control for confounding variables in a nuanced way, setting a new standard for exposome-wide association studies. This dataset will serve as a valuable reference for researchers and policymakers alike in examining chemical exposures’ complex interactions with health outcomes in pregnancy. Note: by now, the database includes socio-demographic, lifestyle, and clinical data, as according to the project's chronogram, chemical levels are still being processed.

2. Potential Impacts (over the project):
2.1. Public Health and Policy: MANGO’s findings have the potential to inform health policies aimed at reducing chemical exposure during pregnancy. This research supports European Union (EU) goals for protecting maternal and fetal health and aligns with broader regulatory frameworks under HBM4EU and SDG3.
2.2. Scientific Advancements: The project establishes a replicable model for exposome-wide association studies, pushing the boundaries of chemical exposure science by addressing exposure to complex mixtures rather than isolated chemicals. This innovation has far-reaching implications for epidemiological studies of other chronic diseases, potentially broadening exposomics applications.

3. To maximize the long-term impact of these results, further support will be essential in several areas:
3.1. Further Research and Validation: Extending the current cohort with longitudinal studies to track exposure impacts beyond pregnancy and early childhood would solidify MANGO’s findings and expand its implications.
3.2. IPR Support and Internationalization: Protecting the innovative screening methods and prevention protocols developed under MANGO and promoting international collaborations can facilitate wider adoption and refinement of these tools.
3.3. Standardization and Regulatory Frameworks: Harmonizing exposure assessment standards and advocating for their inclusion in regulatory guidelines could support the translation of MANGO’s findings into actionable policy.

Overall, MANGO’s work provides a robust model for future exposomics research, offering critical insights into the prevention of GDM and setting new standards in maternal health research.