NCT05733065

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

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: University Hospital, Ghent · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Detailed description

Rationale: The developmental origins of health and disease (DoHaD) hypothesis, states that antenatal and early life exposure to a suboptimal environment can predispose for adverse health outcomes in adult life, such as cardiometabolic disease. Modification of the epigenome, and more specifically the methylome, seems a plausible mechanism for this. It has been shown that a suboptimal early environment, such as famine during the periconception period, can perturb DNA methylation signatures of the offspring. Furthermore, the preimplantation period is likely to represent a critical window for the establishment of optimal DNA methylation as epigenetic reprogramming takes place during this time. The precise influence of environmental factors during this time is incompletely understood; human studies of the preimplantation period are complicated by an inaccessibility of samples and the high variability of the environment induced by maternal factors. Here, the study of monozygotic twins can be employed. Although monozygotic twins are genetically identical, they can differ phenotypically, for example in birth weight. Phenotype and methylome differences attributable to genetic and maternal differences can be ruled out, meaning that intra-pair differences must be a result of variation in their prentatal environment. Furthermore, the moment of splitting defines the point from which twins can experience environmental differences. 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. Study design: prospective twin cohort - using a subset of twins from the East Flanders Prospective Twin Study (EFPTS). Main study parameters/endpoints: Placenta (birth) and saliva (adulthood) DNA methylation. Questionnaire-based adult anthropometric measurements and cardiometabolic disease risk data. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no risk or benefit to participants associated with participation in this study as DNA methylation analyses cannot be used to identify disease (susceptibility). Placental tissue samples were already collected at birth and stored in a biobank. Further samples for DNA methylation analysis will be collected non-invasively by saliva sample. There is a minor time burden associated with participation in questionnaire-based data collection at the adult time point, however this is not expected to be excessive.

Conditions

• Twin Placenta

Interventions

Type	Name	Description
OTHER	saliva sample	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.
OTHER	questionnaire	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.

Timeline

• Start date: 2021-01-26
• Primary completion: 2025-02-01
• Completion: 2025-12-31
• First posted: 2023-02-17
• Last updated: 2024-02-29

Locations

1 site across 1 country: Belgium