ClinicalTrials.gov Identifier: NCT06509776

Early life determinants of skeletal maturation and endocrine health in young adults
 A nationwide birth cohort

EPIPEAK

Why study early life factors and young adult health?

In recent years it has become increasingly clear that intrauterine and early life exposures have consequences for adult health. Research has been challenging due to the scarcity of data on early life, other than birth weight records, for diseases that become manifest some decades into adult life. For the skeleton, it is unknown if the amount of bone laid down during the teenage years is pre-programmed as a chrono-switch or if peak bone mass (PBM) merely reflects mechano-sensing so that bone gain ends not due to a certain age being reached but due to the skeleton reaching a ‘sufficient’ mechanical competence to meet the demands. It is unclear, for example, if low bone mass due to anorexia or ill health in the teenage years can be recovered in the 3rd decade of life or if a chronostat mechanism prevents further gain. As a disease of late adulthood, osteoporosis research has focused little on bone health in young adulthood.

While epigenetic modifications could be transient, differences in DNA methylation in genes known to be associated with bone mass have been demonstrated between bone tissue from healthy postmenopausal women and women with osteoporosis suggesting persistence through adult life. Moreover, though the consequences of severe hormonal excess or deficits in infancy are well known to endocrinologists, not least for the thyroid axis, we have had few or no opportunities to study the effects of more subtle and/or transient differences on subsequent adult health. However, achieved dried blood spots (DBS) collected at birth may provide an opportunity to study such associations, and our group demonstrated the feasibility of using DBS measured vitamin D status at birth in relation to various childhood and adulthood health outcomes, including childhood fractures and epigenetic analyses in DBS are also feasible.

In summary, factors driving persistent hormonal changes, body size and bone mass in young adults are very poorly understood. Thus, to advance this research further, studies that make use of material collected at birth, and life course measures of bone density and growth, are needed. The present research proposal fills this gap, by including an in-depth examination of the influence of already prospectively collected early life indicators that may serve as determinants, and we propose to combine register data and archived biological material through establishing a new population-based cohort of 2,000 18-year-olds for assessment of hormonal status, lipids, bone turnover markers, bone mineral density, fat mass and lean body mass as outcomes.

What we aim to do:

The project addresses whether the following sets of potential determinants are associated with young adult hormonal status, lipids, bone turnover markers, bone mineral density (BMD), fat mass and lean body mass at age 18 years: a) maternal risk factors during preconception and pregnancy; b) risk factors at birth; c) neonatal epigenetic signature; d) childhood risk factors.

Study design and methods:

Population-based, nationwide, cross-sectional, clinical study (n=2,000) with already available early life exposure data including bio banked neonatal biological samples (Dried Blood Spots, DBS).
The Danish Civil registration system will be used to identify all 18-year-old individuals born in Denmark, i.e., live births from year 2006 and 2007.

The eligibility criteria are the following:

Inclusion criteria

• Individuals (n=2,000) born in Denmark in 2006 or 2007
• Are 18 years old and alive at the time of the clinical examination

Exclusion criteria

• Pregnancy or lactation
• No DBS samples available
• Lack of consent to use DBS samples or national health registries
• Emigration or disappearance

International collaborators

• MRC Lifecourse Epidemiology Centre, University of Southampton
  Professor Nick Harvey, Director
  Beth Curtis, associate professor

The study diagram displays an overview of the project aims and work packages: