NCT05681923

Brief Summary

Neurodevelopmental disorders such as attention deficit disorder with or without hyperactivity, autism spectrum disorder, language and social communication disorder, motor coordination disorder, learning disorder (dyslexia, dyscalculia, dysorthography), intellectual development disorder are frequent and long-lasting developmental difficulties that can be observed in children in various domains. They are often associated and have a significant impact on daily functioning at school and at home. The rate of people affected by neurodevelopmental disorders including autism spectrum disorder have increased significantly over the past 20 years. Improved screening only partly explains this evolution. A genetic predisposition plays an important role in the occurrence of these disorders, however, current scientific data suggest a multifactorial origin. Exposures such as those related to the use of pesticides, air pollution or the presence of endocrine disruptors in our diet could be involved in the genesis of neurodevelopmental disorders, particularly during intrauterine life, a period of great vulnerability. The current diagnostic pathways for autism rarely enable the early identification of babies at risk. Without early detection and timely targeted intervention, these children have a poor health outcome and do not reach their full potential. The general objective of the MARIANNE cohort is to constitute a French research infrastructure dedicated to research on the biological and environmental determinants of neurodevelopmental disorders including autism. This cohort is based on the follow-up of 1200 families with already a child affected by an autism spectrum disorder, which implies a high risk of neurodevelopmental disorders including autism spectrum disorder for the siblings, and of 500 families from the general population with no excess risk of neurodevelopmental disorders. The total number of subjects to be included (mother, father, unborn child and ASD sibling for the HR group) is thus 6300. The inclusion of these families will be at the beginning of a new pregnancy and the follow-up will be carried out from the second trimester of pregnancy until the children are 6 years old, the age at which the diagnosis of neurodevelopmental disorders is possible. Biological, clinical, social and environmental data will be collected at different stages of the follow-up and will be included into a large database.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6,300

participants targeted

Target at P75+ for all trials

Timeline
95mo left

Started Apr 2023

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress28%
Apr 2023Mar 2034

First Submitted

Initial submission to the registry

January 3, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

January 12, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

April 19, 2023

Completed
10.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2034

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2034

Last Updated

January 16, 2025

Status Verified

January 1, 2025

Enrollment Period

10.9 years

First QC Date

January 3, 2023

Last Update Submit

January 15, 2025

Conditions

Keywords

exposomechild developmentgenomerisk factorsprenatal cohort

Outcome Measures

Primary Outcomes (9)

  • Autism Spectrum Disorder diagnosis

    ASD diagnosis will be determined by the ADOS-2 (Autism Diagnostic Observation Schedule)

    between 60 and 66 months

  • Autism Spectrum Disorder diagnosis

    ASD diagnosis will be determined by the ADOS-2 (Autism Diagnostic Observation

    between 24 and 30 months

  • Developmental Intelligence Disorder diagnosis

    Measure of intelligence quotient by scales adapted to the child's age and level of development and developmental level: Weschler, or Mullen scales

    at 72 months

  • Developmental Coordination Disorder diagnosis

    Description: the diagnosis will be determined by the DCDQ-FE (Developmental Coordination Disorder Parent Questionnaire Coordination), a 15 items scale, which is the French-European version of the DCDQ-0, Developmental Coordination Disorder Parent Questionnaire Coordination to help identify Developmental Coordination Disorder in children aged 5 to 15 years. The items are grouped into three subdomains: 1) control during movement, 2) fine motor/writing, and 3) global coordination. Each item is rated on a 5-point scale, from 1 ("does not match my child at all") to 5 ("matches my child perfectly")."

    at 72 months

  • Attention Deficit Hyperactivity Disorder diagnosis

    The diagnosis will be determined by ADHD-RS, which is a parent questionnaire for the assessment of Attention Deficit Hyperactivity Disorder (ADHD). The items are rated on a 4-point scale (from 0= rarely or never, to 3= very often). A score greater than or equal to 28 is required to qualify as significant ADHD with this scale.

    at 72 months

  • Diagnosis of Language and Learning Disorder

    the diagnosis will be determined with the Parents' Evaluation of developmental status (PEDS: DM), which targets the concerns of parents of children aged 0 to 8 years in 8 domains (gross and fine motor skills and writing and mathematics; social/emotional; oral/written language and reading; adaptive behavior). This questionnaire has been validated in several countries and covers several domains, each with 6 to 8 questions and 3 answer choices. The results are evaluated as normal/delayed "Are you worried about your child's development? Yes/No" with details of the reasons, the age of onset and a question on the wish to have an interview with a psychologist or a child psychiatrist.

    at 72 months

  • Socioeconomic and lifestyle risk factors for neurodevelopmental disorders including autism spectrum disorder

    Parental self-questionnaire

    at inclusion

  • Maternal diet and medication use during pregnancy

    Parental self-questionnaire

    at inclusion

  • Environmental exposition

    Parental self-questionnaire. A biological collection is realized for the realization of future assays

    at inclusion

Study Arms (2)

High-Risk Cohort

High family risk cohort for recurrence of autism and other developmental disorders in siblings (have at least one child with a confirmed diagnosis of autism) Specific to the High Risk cohort: Clinical observations of the unborn child will be performed at 3 months, 6 months, 12 months, between 24 and 30 months, 36 months, and 72 months by psychologists or child psychiatrists in the participating hospitals. They will allow to evaluate the child's behaviors in the areas of communication and social interaction. A video recording of the baby at 3 months of age will allow the analysis of the General Movements Assessment. If genetic consultation is provided to the family as part of the routine care, the results will be collected and additional blood samples may be taken

Other: QuestionnairesOther: Biospecimen collectionOther: Neurodevelopmental assessment visitOther: DNA collection

Low Risk Cohort

Low family risk cohort for recurrence of autism and occurrence of other developmental disorders in siblings. The risk is comparable to the risk observed in the general population (do not have a child with autism, nor with other developmental disorders). Clinical observations of the unborn child will be performed at 72 months by psychologists or child psychiatrists in the participating hospitals, so that children in the "Low family risk" group benefit from the same evaluations as children in the "High family risk" group..

Other: QuestionnairesOther: Biospecimen collectionOther: Neurodevelopmental assessment visit

Interventions

Parents will be asked to complete online self-questionnaires. These questionnaires will provide essential information on medical data, child development, lifestyle habits, nutritional habits, environmental exposures, and family social characteristics.

High-Risk CohortLow Risk Cohort

urine, hair, nails, baby tooth, stool, blood, umbilical cord blood, placenta

High-Risk CohortLow Risk Cohort

High-Risk Cohort : Clinical observations of the unborn child will be performed at 3 months, 6 months, 12 months, between 24 and 30 months, 36 months, and 72 months by psychologists or child psychiatrists in the participating hospitals. They will allow to evaluate the child's behaviors in the areas of communication and social interaction. A video recording of the baby at 3 months of age will allow the analysis of the General Movements Assessment. Low-Risk Cohort : linical observations of the unborn child will be performed at 72 months by psychologists or child psychiatrists in the participating hospitals.

High-Risk CohortLow Risk Cohort

If genetic consultation is provided to the family as part of the routine care, the results will be collected and additional blood samples may be taken.

High-Risk Cohort

Eligibility Criteria

Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Low risk cohort is a community based sample. High risk cohort is a community based sample as well as an active list of patients followed in specialized department in the management of children with neurodevelopmental disorders. The persons involved in the study are the pregnant woman, her partner (if he is the biological father of the unborn child and lives with the mother), the newborn child, and the older sibling with autism.

You may qualify if:

  • Mother:
  • Be pregnant (single or multiple pregnancy), at least 16 weeks of amenorrhea,
  • Have at least one biological child of 24 months or older,
  • At least 18 years of age
  • Father:
  • Be the biological father of the unborn child,
  • At least 18 years of age
  • Unborn Child:
  • \- Have a woman study participant as mother.
  • Autistic sibling: refers to the biological child(ren) of the mother and/or father participating in the study and being the parent(s) of the unborn child
  • Be at least 24 months old and less than 18 years old,
  • Have a confirmed diagnosis of Autism Spectrum Disorder based on medical records. If in doubt, the SRS-2 (Social Responsiveness Scale for Adults) and PEDS-DM (Parents' Evaluation of developmental status) questionnaires will be completed. Only children with positive scores on one of these questionnaires will be included after validation of the diagnosis by an expert committee,
  • In case of several children with Autism Spectrum Disorder based in the siblings, only the last born will be included.
  • Remarks:
  • Autism Spectrum Disorder siblings resulting from a medically assisted procreation are eligible provided that part of the genetic heritage is common to that of the mother or father of the unborn child participating in the study.
  • +1 more criteria

You may not qualify if:

  • Father and mother:
  • Unable to understand French or the study questionnaires
  • Participant on protective measures (guardianship or curatorship) or deprived of liberty by judicial or administrative decision, or subject to a legal protection measure
  • Not affiliated to a social security system
  • Refusal to participate. In the case of consent given for the born and unborn child, the consent must be given by the person(s) with parental authority.
  • Live at a distance from the recruitment center incompatible with follow-up.
  • Mother and/or father of unborn child:
  • \- Have a biological child with a diagnosis of Autism Spectrum Disorder or other neuro developmental disorder

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU Montpellier

Montpellier, 34 090, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

urine, hair, nails, baby tooth, stool, blood, umbilical cord blood, placenta

MeSH Terms

Conditions

Autism Spectrum DisorderNeurodevelopmental Disorders

Interventions

Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Child Development Disorders, PervasiveMental Disorders

Intervention Hierarchy (Ancestors)

Data CollectionEpidemiologic MethodsInvestigative TechniquesHealth Care Evaluation MechanismsQuality of Health CareHealth Care Quality, Access, and EvaluationPublic HealthEnvironment and Public Health

Central Study Contacts

Marie Christine Picot, MD PhD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 3, 2023

First Posted

January 12, 2023

Study Start

April 19, 2023

Primary Completion (Estimated)

March 1, 2034

Study Completion (Estimated)

March 1, 2034

Last Updated

January 16, 2025

Record last verified: 2025-01

Locations