Changes in fetal DNA modification associated with maternal blood sugar during pregnancy

ISRCTN	ISRCTN13534922
DOI	https://doi.org/10.1186/ISRCTN13534922
Secondary identifying numbers	1.0

Submission date: 06/09/2017
Registration date: 13/09/2017
Last edited: 13/09/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims:
Infants born to mothers with pregnancy diabetes have increased risk of type 2 diabetes later in life. The aim of this study is to examine the extent to which maternal metabolism and habits during pregnancy are related to modifications of genetic material from the fetus during pregnancy. Fetal gene information is collected from the woman's blood during pregnancy using standard blood collection.

Who can participate?:
Scandinavian women aged 25-35 years in early pregnancy. In total, 30 women will be recruited before pregnancy week 12+6. Of these participants, 50% will have a high risk of pregnancy-diabetes while 50% are expected to have a normal pregnancy.

What does the study involve?
This study involves three study visits during pregnancy (all including blood collection from the woman), passive bio-sample collection at delivery (e.g. from the placenta), and one study visit two months after delivery (blood collection from mother and infant). In addition to clinical visits, participating women are followed with continuous monitoring of blood-sugar and physical activity, and report their own weight.

What are the possible benefits and risks of participating?:
There are no direct medical benefits of participating in the study. However, the closer monitoring of blood-sugar in pregnancy could potentially lead to earlier detection of pregnancy-diabetes. The main risk of participating should be potential skin-reactions from devices monitoring blood-sugar and physical activity. Standard blood collection through venipuncture is also associated with a small risk of infection.

Where is the study run from?:
Skåne University Hospital in Lund/Malmö (Sweden)

When is study starting and how long is it expected to run for?:
September 2017 to 2019

Who is the main contact?:
Miss Angela Estampador
angela.estampador@med.lu.se

Contact information

Ms Angela Estampador
Public

Genetic and Molecular Epidemiology Unit
Lund University Diabetes Centre
Clinical Research Centre
Box 503 32
Malmö
202 13
Sweden

Prof Paul Franks
Scientific

Genetic and Molecular Epidemiology Unit
Lund University Diabetes Centre
Clinical Research Centre
Box 503 32
Malmö
202 13
Sweden

Study information

Study design	Observational cohort study
Primary study design	Observational
Secondary study design	Cohort study
Study setting(s)	Hospital
Study type	Other
Participant information sheet	No participant information sheet available
Scientific title	The Diabetogenic Perturbations of the Fetal Methylome Project
Study acronym	DIAPRIME
Study objectives	We hypothesize that intrauterine exposure to maternal blood glucose during gestation will correlate with differences in patterns of fetal methylation; fetal methylation patterns will vary by timing and degree of intrauterine exposure to maternal glucose.
Ethics approval(s)	Regional Ethical Review Board in Lund, Sweden, 01/09/2016, ref: 2016/489 with amendment 2016/1098
Health condition(s) or problem(s) studied	Maternal-fetal effects of metabolism in pregnancy
Intervention	Participants attend study visits at three time points in pregnancy (approximately at 12, 26, and 34 gestational weeks) during which maternal blood, questionnaire data on lifestyle, and anthropometry are collected. Participants are also monitored between study visits with self-reported weight, continuous glucose monitoring and physical activity (wrist accelerometry) from recruitment in early pregnancy to delivery. At delivery, bio-sampling is performed (e.g. placental material and cord blood) and at approximately two months postpartum, additional maternal and infant data is collected, including blood sampling.
Intervention type	Other
Primary outcome measure	Changes in fetal/placental DNA methylation at three time points in pregnancy are measured using cell-free fetal DNA isolated from maternal blood and next generation sequencing at approximately 12, 26, and 34 gestational weeks.
Secondary outcome measures	1. Maternal physical activity as measured by wrist accelerometer from early pregnancy to delivery 2. Maternal blood-glucose as measured by a continuous glucose monitor and OGTT from early pregnancy to delivery 3. Maternal weight gain and body composition (daily weighing using a medical scale and/or clinically measured using the Styku 3D body scanning system) throughout pregnancy and postpartum
Overall study start date	01/01/2016
Completion date	15/09/2019

Eligibility

Participant type(s)	Mixed
Age group	Adult
Sex	Female
Target number of participants	30
Key inclusion criteria	In total, we will recruit around 30 pregnant women: 1. Aged 25-35 before gestational week 12+6 Half of the recruited women (50%) will have a high risk of gestational diabetes mellitus: 1. Family history of diabetes 2. Prior pregnancy affected by diabetes 3. Current obesity Half of the recruited women (50%) are expected to have a normal pregnancy not complicated by gestational diabetes mellitus (controls). If a control woman develops gestational diabetes, she will be invited to continue to take part in the study and be monitored as per standard of care; we will then seek to recruit an additional woman to the control arm to ensure an adequate number of participants in the study.
Key exclusion criteria	1. Not of Scandinavian origin 2. Use of assisted reproductive technology 3. History of three or more first trimester miscarriages 4. Tobacco use (smoking/snus) in the previous three months 5. Diagnosed PCOS 6. History of gastric bypass surgery 7. Type 1 diabetes 8. Non-Swedish speaker 9. Planned termination of pregnancy or planning to give up infant for adoption
Date of first enrolment	20/09/2017
Date of final enrolment	15/09/2018

Locations

Countries of recruitment

Sweden

Study participating centre

Skåne University Hospital

Lund/Malmö
222 41
Sweden

Sponsor information

Lund University
University/education

Box 117
Lund
221 00
Sweden

Website	www.lu.se

Skåne University Hospital
Hospital/treatment centre

Getingevägen 4
Lund
222 41
Sweden

Lund University
Not defined

Website	http://www.lunduniversity.lu.se/
"ROR"	https://ror.org/012a77v79

Funders

Funder type

Charity

The European Foundation for the Study of Diabetes

No information available

The Swedish Heart-Lung Foundation

No information available

Novo Nordisk Foundation

No information available

Results and Publications

Intention to publish date	01/09/2020
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Planned publication in relevant peer-reviewed scientific journal.
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date.