TwinLIFE: The Twin Longitudinal Investigation of FEtal Discordance

Abstract

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.

Twisting the theory on the origin of human umbilical cord coiling featuring monozygotic twins

“…Ethical statement hUCs from monozygotic (MZ) more specifically monochorionic twin pairs were collected at the Department of Obstetrics at the Leiden University Medical Center in the Netherlands with the ethical approval of the institutional medical ethical committee (P18.184). Written informed consent for the collection was obtained from all parents in the framework of the TwinLIFE study (International Clinical Trials Registry Platform ID NL7538) (68).…”

Mesenchymal stromal cells as a tool to unravel the developmental origins of disease

“…Hence, their scope and sample size were limited, and newborns were not followed to investigate long-term health outcomes. To fully exploit the advantages of MSCs and increase the mechanistic understanding linking an intrauterine environment to health outcomes later in life, prospective cohorts investigating the changes in hUC-MSCs in relation to the intrauterine environment and postnatal outcomes are needed [51,66].…”

India’s Opportunities and Challenges in Establishing a Twin Registry: An Unexplored Human Resource for the World’s Second-Most Populous Nation

“…Worldwide, established twin registries are doing a remarkable job in curating and cataloging precious samples from twins along with their detailed family histories (Craig et al, 2020). Different twin registries encompass a diverse age spectrum, with some recruiting before or at birth, for example the Peri/Postnatal Epigenetic Twins Study (PETS; Loke et al, 2013) and the Twin Longitudinal Investigation of FEtal Discordance (TwinLIFE; Groene et al, 2019). PETS is a longitudinal cohort of 250 pairs of Australian twins and their mothers who were recruited midway through They are genetically identical, sharing the same blood groups and sex.…”