A Study of the Placental Methylome of Dichorionic and Monochorionic Monozygotic Twin Pairs to Establish a Timeline of Epigenetic Programming

NCT05733065 | Active Not Recruiting

• 1 other identifier: BC-08264
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The timing of the moment of splitting is variable amongst twins and can be inferred from chorionicity, allowing a time-line of early environmental influences to be established. Monozygotic twins can remain discordant for growth and health outcomes throughout life, implying the prenatal establishment of a regulatory program with effects that persist into adulthood. Objective: To investigate the effect of the moment of splitting (chorionicity) on the placental and saliva (in adulthood) methylome and cardiometabolic disease risk in monozygotic twin pairs. Birth weight discordance will be used as an indicator of prenatal environmental heterogeneity between the twins.

Conditions

Twin Placenta

Outcome Measures

Primary Outcomes (2)

• To identify differences in DNA methylation in placental biopsy.

  Placental DNA extraction will be carried out using a commercially available kit such as QIAamp DNA Mini Kit. We will first identify differences in placental DNA methylation that are associated with time-of splitting, i.e. chorionicity, to identify epigenome alterations that are attributable to the preimplantation period. Thereafter, birth weight discordance (weight of the heaver twin minus weight of the lighter twin, divided by weight of the heavier twin, multiplied by 100) will be used as a measure of antenatal environmental differences between the twins to identify loci of differential methylation that relate to environmental differences experienced in early gestation.

  1 year after saliva sample collection

• To identify differences in DNA methylation in saliva sample.

  Adult twins will be asked to send saliva samples. DNA will be extracted from the saliva using a commercially available kit. The adult methylome, deduced from saliva, will be interrogated to determine whether the methylation signatures associated with differences in the early embryonic environment persist into adulthood.

  1 year after saliva sample collection

Secondary Outcomes (1)

• To identify epigenetic alterations, present at birth that persist into adulthood, and predict growth/cardiometabolic disease risk parameters.

  1 year after saliva sample collection

Study Arms (1)

Monozygotic Twin

OTHER

we will include natural conceived twin pairs born before 2002, with known birth weight, sex and gestational age, and where both twins were live born without congenital abnormality. Twins born after pregnancies complicated by conditions such as TTTS will be excluded. MZ twins pairs will be ranked according to intra-pair birth weight difference. Next, we intend to include the 120 most discordant monozygotic twin pairs, stratified by chorionicity (1:1 ratio) and in the case of DC by fusion of the placentas (1:1 ratio). Only pairs where both twins consent to inclusion in the study will be included.

Other: saliva sample; Other: questionnaire

Interventions

saliva sample OTHER

Adult twins will be asked to send saliva samples in a reply envelope to Maastricht University, department of Genetics and Cell Biology, where they will be frozen and stored before analysis. DNA will be extracted from the saliva using a commercially available kit according to the manufacturer's instructions.

Monozygotic Twin

questionnaire OTHER

Along with saliva samples, adult twins, will be asked to complete a questionnaire about their health. Study subjects will be asked to self-report height and weight. Additionally, questions will focus on cardiometabolic risk, including questions about smoking, physical activities, medical diagnoses, current medications, family history of cardiometabolic disease, and for female twins an obstetric and gynaecological history, including number of pregnancies and pregnancy complications (such as gestational diabetes and pre-eclampsia). The questionnaire will take the form of a self-completed, web-based questionnaire which will be hosted by the Qualtrics platform (Qualtrics.com). This platform is supported by the University of Maastricht due to its security and privacy measures.

Monozygotic Twin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• natural conceived twin pairs born before 2002,
• with known birth weight, sex and gestational age,
• where both twins were live born without congenital abnormality

You may not qualify if:

• Twins born after pregnancies complicated by conditions such as TTTS will be excluded.

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Maastricht University Medical Center: collaborator

Study Sites (1)

Ghent University hospital

Ghent, 9000, Belgium

Location

MeSH Terms

Interventions

Surveys and Questionnaires

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 17, 2023
• Study Start: January 26, 2021
• Primary Completion: February 1, 2025
• Study Completion: December 31, 2025
• Last Updated: February 29, 2024

Record last verified: 2024-02

Locations

BE (1)