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PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Aarhus (PREPARE CHILD)

Primary Purpose

Overweight and Obesity, Weight Loss, Pregnancy Related

Status
Not yet recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Weight loss intervention
Sponsored by
Ulla Kampmann Opstrup
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Overweight and Obesity focused on measuring Overweight, Pregnancy, Weight loss, Diet, Reducing, Epigenetics, Healthy Lifestyle, DNA Methylation, Exercise, Offspring's neonatal fat mass, Pea Pod, Infant, Large for Gestational Age, Body Fat Distribution

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Maternal inclusion Criteria: Maternal pre-pregnancy BMI 27.0-44.9 kg/m^2 Maternal age range 18-35 years Connected to Aarhus University Hospital as place of birth Pregnant Paternal Inclusion Criteria: Paternal pre-pregnancy BMI 18.5-44.9 kg/m^2 Paternal age range 18-55 years Parental Inclusion Criteria: Couples (male and female) Planning pregnancy within 3 years Provided voluntary informed consent Danish or English speaking Intention to permit the planned offspring to participate in the follow-up study Able to store biological samples from the offspring at home in the freezer in a box given by the study personnel Parental Exclusion Criteria: Diabetes mellitus (Type 1 or 2) Previous or present eating disorder Allergy towards ingredients in the very low calorie diet products Severe heart, liver or kidney disease Conception by in vitro fertilization Any medical condition or concomitant medication as judged by the medical responsible Adherence to vegan diets or other diets interfering with the dietary guidelines in the study Participation in other clinical trial that can affect the results of the current study Engagement in elite sports or similar strenuous exercise ≥5 h/week at inclusion Blood donation or transfusion within the past month before screening Blood donation during the study Inability or unwillingness to follow the study protocol and instructions given by the study personnel A detailed description of the exclusion criteria is given below: Medical conditions as known by the participant: Diabetes mellitus (type 1 and 2) History or diagnosis of eating disorder (e.g. restrained eating, disinhibition, emotional eating) Any significant medical condition as assessed by the investigator (e.g. dysregulated thyroid disease or reproductive diseases) Any significant psychiatric disorder (i.e. schizophrenia, bipolar disease or depression) as assessed by the investigator Severe chronic heart, liver and kidney disease Polycystic ovary syndrome with irregular cycle Medication: Current use of medication or use within the previous three months with a potential to affect body weight or pregnancy as judged by the investigator (e.g. systemic corticoids) Personal/other: Severe food allergies, food intolerances or dislike expected to interfere with the study, including allergy towards ingredients in the VLCD products Engagement in elite sports or similar strenuous exercise ≥5 h/week Blood donation or transfusion within the past month before screening Planned blood donation for other purpose than this study during participation Alcohol abuse, as judged by the investigator, within the previous 12 months Drug abuse, as judged by the investigator, within the previous 12 months Psychological or behavioral problems which, in the judgement of the investigator, would lead to difficulty in complying with the study protocol Participation in other clinical trials within the past three months or intention to do so during the study, which are judged by the investigator to affect the present study Unable to consume the interventional product for religious reasons, swallowing disorders, other physiological reasons or any other reasons for not being able to follow the recommended diet Inability or unwillingness to give written informed consent or communicate with study personnel Inability or unwillingness to follow the study protocol and instructions given by the study personnel Illiteracy or inadequate understanding of Danish or English language. Any other condition that judged by the investigator may interfere with the adherence to the study protocol

Sites / Locations

  • Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention

Control

Arm Description

Intervention group will receive dietary counseling by a trained dietitian from 3 months post-partum of the 1st child until birth of the 2nd child. The mother will receive advice to provide a moderate caloric restriction (-500 to 1000 kcal/d) and attend physical activity sessions to attain a 10 % weight loss according to pre-pregnancy weight. If the father is also overweight or obese, he will receive the same advice.

The control group will receive standard care and will not receive any dietary advice prior to pregnancy. During pregnancy control subjects will receive dietary advice according to standard care which means no counselling from a dietitian unless there are special needs (e.g., gestational diabetes), then they will receive counseling from a dietitian in accordance with standard care.

Outcomes

Primary Outcome Measures

Neonatal fat mass
Offspring's neonatal fat mass (grams) assessed by air displacement plethysmography (Pea POD)
Difference in epigenetic changes in child 1 and 2
Cord blood from offspring will be collected at birth and stored at -80 °C until use. At the Department of Molecular Medicine AUH genomic DNA will be extracted from peripheral blood using standard methods e.g., QIAmp® Mini Kit (Qiagen, Germany). 1 μg of genomic DNA will be bisulfide converted using Illumina iScan (platform). The methylation level will be measured using Infinium MethylationEPIC DNA Analysis BeadChip (Array type) at Eurofins Genomics AS (Denmark) or similar methods. The stated required sample size (140 couples) is calculated based on the neonatal fat mass. As no other studies have performed methylation analysis using WGBS in similar cohorts, precise power calculations on epigenetic changes are impractical. However, since the EPICOM study found differentially methylated regions in only 20 cases and 20 controls using Illumina's 450K methylation assay, the power to elucidate epigenetic changes is considered sufficient in the planned study.

Secondary Outcome Measures

Obstetrics outcome - length of gestational age
Length of gestational age
Obstetric - medication use
Medication use during labor
Obstetric - delivery mode
Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth).
Obstetric - pregnancy complications
Pregnancy complications e.g. miscarriage, abortion (induced and indication for abortion), hydramnios, gestational hypertension, preeclampsia, need for maternal corticosteroid treatment for fetal lung maturation, urinary tract infection) will be collected from medical record.
Obstetric - Neonatal unit admissions
Neonatal unit admissions
Obstetric - obstetrics complications
Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization).
Obstetrics - birth defects/abnormalities
Birth defects/abnormalities
Neonatal morbidities
Neonatal morbidity (e.g. major congenital malformations (ICD10 Q00-Q99 or requiring medical or surgical treatment), birth injury, respiratory distress, transient tachypnoea, neonatal hypoglycemia, systemic infections, admission to neonatal intensive care unit, number of admission days, hyperbilirubinemia), deaths.
Fetal and offspring growth - body weight
Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale.
Fetal and offspring growth - length
Fetal length will be measured with ultrasound during pregnancy and offspring length will be measured using an infantometer as appropriate for measuring infant, baby and toddler length.
Fetal and offspring growth - abdominal circumference
Abdominal circumference will be measured with ultrasound during pregnancy and offspring abdominal circumference will be measured three times to the nearest 0.1 cm using a stretch-resistant measuring tape
Fetal and offspring growth - crown circumference
Crown circumference will be measured with ultrasound during pregnancy
Fetal and offspring growth - femur length
Femur length will be measured with ultrasound during pregnancy
Fetal growth - fractional limb volume
Fractional limb volume will be measured with ultrasound during pregnancy
Offspring growth - BMI z-score
Offspring body mass index (BMI) z-score (BMI adjusted for age and sex).
Offspring growth - weight for gestational age
Weight for gestational age. Measured as percent of normal weight related to gestational age.
Offspring growth - large for gestational age
Large for gestational age. Prevalence of infants being large for gestational age (LGA).
Offspring growth - small for gestational age
Small for gestational age. Prevalence of offspring being small for gestational age (SGA).
Offspring growth - apgar score
Apgar score (0-10). The higher the score, the better health condition of the offspring)
Offspring growth
Offspring circumference (thigh and upper arm) and skinfold (triceps, subscapularis and suprailiac). Circumferences will be measured to the nearest 0.1 cm using a stretch-resistant measuring tape and skinfolds are measured to the nearest 0.02 cm using a caliper to lightly pinch the skin and the underlying fat.
Offspring growth - body composition by the POD system
Offspring fat free mass (g) and fat mass (g) will be assessed by air displacement plethysmography using the POD system (Pea POD for 1-8kg)
Offspring blood pressure
Offspring blood pressure (diastolic and systolic blood pressure) will be measured three times after 10 minutes rest using an automated device placed on the arm and in direct contact with the skin.
Offspring heart rate
Offspring heart rate will be measured three times after 10 minutes rest using an automated device placed on the arm and in direct contact with the skin.
Offspring growth - self-reported body weight
Self-reported body weight
Offspring growth - self-reported height
Self-reported height
Adult weight
Adult body weight is measured to the nearest 0.1 kg using a calibrated scale
Adult Height
Adult height will be measured to the nearest 0.5 cm using a wall-mounted stadiometer.
Adult BMI
Calculated as weight (kg)/height(m)^2
Adult anthropometric
Waist- and hip circumference will be measured to the nearest 0.1 cm. During pregnancy and at birth the waist of the female will not be measured.
Adult blood pressure
Blood pressure (diastolic and systolic blood pressure) will be measured three times with two minutes apart in right arm after 15 minutes rest using a validated automatic device. The reading is recorded to the nearest 1 mmHg.
Adult heart rate
Heart rate will be measured three times with two minutes apart in right arm after 5-10 minutes rest using a validated automatic device. The reading is recorded to the nearest 1 beats/minute for heart rate
Adult resting metabolic rate
Resting metabolic rate (calories/24-h) will be measured by indirect calorimetry using a ventilated hood system. Participants will lie in the supine position and rest for at least 30 min before measurements commence. The measurement will last for 20 min.
Adult resting respiratory quotient + substrate
Resting respiratory quotient (RQ), will be measured by indirect calorimetry using a ventilated hood system. Participants will lie in the supine position and rest for at least 30 min before measurements commence. The measurement will last for 20 min. Lipid, glucose and protein oxidation will be estimated.
Adult medication use
Use of medication will be collected throughout the study and for each medication the start date, stop date or continuing, form and indication will be noted in appropriate form.
Offspring medication use
Use of medication will be collected throughout the study and for each medication the start date, stop date or continuing, form and indication will be noted in appropriate form.
Adult reproduction - Time to pregnancy
Duration of time to conception defined from selfreported time point they started to try get pregnant to registration of pregnancy. The time of conception will be calculated from the ultrasound scan in week 12
Adult glucose metabolism (OGTT)
3-h oral glucose tolerance test (OGTT) will be performed at with 75g of glucose dissolved in 250 ml of water and added 1 gram of paracetamol. Blood will collected for measurements of blood glucose, hormones (insulin, C-Peptide, glucagon), paracetamol, glucagon-like-peptide-1 (GLP-1), Glucose insulinotropic polypeptide (GIP) and metabolites (FFA). Blood samples will be drawn at time 0, 15, 30, 45, 60, 90, 120 and 180 min
Adult Oral Glucose Tolerance Test (OGTT) during pregnancy (only female)
OGTT performed during pregnancy according to the screening guidelines for GDM will be obtained from the mother's medical journal in both pregnancies.
Placenta - weight (gram)
Placenta will be weighted after birth
VO2-max adult - cardiorespiratory fitness
The VO2-max test will be performed as an incremental exercise test on a bicycle ergometer.
Cardiac function offspring - Left ventricular and right ventricular morphology
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Interventricular septal thickness diastole and valve- and chamber dimensions will be done.
Cardiac function offspring - left centricular ejection fraction
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of left ventricular ejection fraction will be done.
Cardiac function offspring - fractional shortening
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of fractional shortening will be done.
Cardiac function offspring - Systolic function, strain
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain will be done.
Cardiac function offspring - Systolic function, strain rate
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain rate will be done.
Cardiac function offspring - TAPSE and RV fractional area change
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of TAPSE and RV fractional area change will be done.
Cardiac function offspring - Diastolic function, left ventricular E/A-ratio
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of left ventricular E/A-ratio will be done.
Cardiac function offspring - Diastolic function, tissue velocities (E', A', S')
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of tissue velocities (E', A', S') will be done.
Cardiac function offspring - Diastolic function, strain
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain will be done.
Cardiac function offspring - Overall cardiac function
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Myocardial performance index (MPI) and cardiac torsion will be done.
Cardiac function offspring - Pulmonary artery acceleration time
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Pulmonary artery acceleration time will be done.
Cardiac function offspring - Pulmonary artery pressure
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Pulmonary artery pressure will be done.
Cardiac function offspring - Persistent ductus arteriosus (PDA)
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of PDA open or closed and PDA shunt will be done.
Cord blood - Telomore length
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Telomore length.
Cord blood - pH
Cord blood will be drawn immediately after birth. pH will be assessed.
Cord blood - Epigenetics
Epigenetics analyses from whole blood. Will be analysed for methylation changes. metabolomics and exosome.
Adult body composition by DEXA scan
Lean mass (g), fat mass (g), abdominal fat (g), visceral fat (g) assessed by a Dual-energy X-ray absorptiometry (DEXA) -scan .
Adult bone markers by DEXA scan - bone mineral content
Bone mineral content (g) assessed by a Dual-energy X-ray absorptiometry-scan.
Adult bone markers by DEXA scan - bone area
Bone area (cm^2) assessed by a Dual-energy X-ray absorptiometry-scan.
Adult bone markers by DEXA scan - bone mineral density
Bone mineral density (g/cm^2) assessed by a Dual-energy X-ray absorptiometry-scan.
Adult blood sample - glucose
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for glucose
Adult blood sample - CD163
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for CD163
Adult blood sample - HbA1c
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for markers of glucose metabolism HbA1c
Adult blood sample - Kreatinin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for kreatinin
Adult blood sample - eGFR
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for kreatinin and GFR will be estimated
Adult blood sample - C-reaktivt protein (CRP)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for CRP
Adult blood sample - Alanintransaminase (ALAT)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for ALAT
Adult blood sample - Gamma-GT (GGT)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for GGT
Adult blood sample - Basisk fosfatase (BASP)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for BASP
Adult blood sample - Bilirubin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Bilirubin
Adult blood sample - Ferritin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Ferritin
Adult blood sample - Hemoglobin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Hemoglobin
Adult blood sample - Leukocytter
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Leucocytter
Adult blood sample - platelets
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for platelets
Adult blood sample - Triglyceride
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for triglyceride
Adult blood sample - Cholesterol HDL
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Cholesterol HDL
Adult blood sample - Cholesterol LDL
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Cholesterol LDL
Adult blood sample - Total Cholesterol
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Total Cholesterol
Adult blood sample - vitamin B12
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for B12
Adult blood sample - vitamin D3
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for vitamin D3
Adult blood sample - c-peptide
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for c-peptide
Adult blood sample - Insulin-like Growth Factor-1 (IGF-1)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IGF-1
Adult blood sample - Insulin-like growth factor-binding protein-1 (IGFBP-1)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IGFBP-1
Adult blood sample - Insulin-like growth factor-binding protein-3 (IGFBP-3)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IGFBP-3
Adult blood sample - Fibroblast growth factor 21 (FGF-21)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for FGF-21
Adult blood sample - Leptin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Leptin
Adult blood sample - Adiponectin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Adiponectin
Adult blood sample - Ghrelin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Ghrelin
Adult blood sample - Growth Hormone (GH)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for GH
Adult blood sample - Free fatty Acids (FFA)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for FFA
Adult blood sample - Interleukin 6 (IL-6)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IL-6
Adult blood sample - Interleukin 6 (IL-10)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IL-10
Adult blood sample - Interleukin-1 alpha (IL-1 alpha)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IL-1 alpha
Adult blood sample - Interferon gamma (IFN-γ)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IFN-γ
Adult blood sample - Tumor Necrosis Factor alfa (TNF-α)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for TNF-α
Adult female blood sample - Humant choriogonadotropin (hCG)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for hCG
Adult female blood sample - Progesterone
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Progesterone
Adult female blood sample - Proinsulin C-peptide
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Proinsulin C-peptide
Adult female blood sample - sex hormone binding globulin (SHBG)
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for SHBG
Adult female blood sample - Prolactin
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Prolactin
Adult blood sample -Cortisol
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Cortisol
Adult female blood sample -Estradiol
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Estradiol
Offspring blood sample - glucose
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for glucose
Offspring blood sample - c-peptide
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for c-peptide
Offspring blood sample - insulin
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Insulin
Offspring blood sample - IGF-1
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for IGF-1
Offspring blood sample - IGFBP-3
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for IGFBP-3
Offspring blood sample - IGFBP-1
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for IGFBP-1
Offspring blood sample - CD163
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for CD163
Offspring blood sample - Ferritin
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Ferritin
Offspring blood sample - HgbA1c
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for HgbA1c
Offspring blood sample - Hgb
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Hgb
Offspring blood sample - CRP
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for CRP
Offspring blood sample - Triglyceride
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Triglyceride
Offspring blood sample - Cholesterol HDL
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Cholesterol HDL
Offspring blood sample - Cholesterol LDL
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Cholesterol LDL
Offspring blood sample - Total Cholesterol
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Total Cholesterol
Offspring blood sample - FGF-21
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for FGF-21
Offspring blood sample - Leptin
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Leptin
Offspring blood sample - Adiponectin
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Adiponectin
Offspring blood sample - FFA
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for FFA
Offspring blood sample - Growth Hormone (GH)
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for GH
Offspring blood sample - cTroponin I (cTnI)
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for cTnI
Offspring blood sample - BNP
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for BNP
Cord blood - c-peptide
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for C-peptide
Cord blood -Insulin
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Insulin
Cord blood -IGFBP-3
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-3
Cord blood -IGFBP-1
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-1
Cord blood -IGF-1
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGF-1
Cord blood -Ferritin
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Ferritin
Cord blood -cTnI
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for cTnI
Cord blood -BNP
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for BNP
Cord blood -CRP
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CRP
Cord blood -CD163
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CD163
Cord blood -FGF21
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FGF21
Cord blood -Leptin
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Leptin
Cord blood -Adiponectin
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Adiponectin
Cord blood -FFA
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FFA
Cord blood - Vitamin D3
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Vitamin D3
Cord blood - HbA1c
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for HbA1c
Cord blood - IL-6
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-6
Cord blood - IL-10
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-10
Cord blood - IL-1 alpha
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-1 alpha
Cord blood -TNF- alpha
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for-TNF- alpha
Cord blood -IFN- gamma
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IFN- gamma

Full Information

First Posted
February 21, 2023
Last Updated
March 23, 2023
Sponsor
Ulla Kampmann Opstrup
Collaborators
Per Ovesen, Professor Dept. of Obsteterics, Aarhus University Hospital, Jens Meldgaard Bruun, Professor Steno Diabetes Center Aarhus, Aarhus University Hospital, Sine Knorr, PhD Steno Diabetes Center Aarhus, Aarhus University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05798494
Brief Title
PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Aarhus
Acronym
PREPARE CHILD
Official Title
PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Aarhus
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 11, 2023 (Anticipated)
Primary Completion Date
April 11, 2025 (Anticipated)
Study Completion Date
April 11, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ulla Kampmann Opstrup
Collaborators
Per Ovesen, Professor Dept. of Obsteterics, Aarhus University Hospital, Jens Meldgaard Bruun, Professor Steno Diabetes Center Aarhus, Aarhus University Hospital, Sine Knorr, PhD Steno Diabetes Center Aarhus, Aarhus University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study is a single site parallel randomized controlled study. The study will be assessing the effect of a 10% pre-conceptional weight loss intervention vs a control group among healthy couples where the prospective mother is pregnant and overweight or obese (BMI 28-45 kg/m^2). The couples in intervention group will receive dietitian counseling and participate in physical activity sessions to attain the 10% weight loss. The overall objective is to test whether a comprehensive pre-conceptional parental weight loss intervention effectively reduces the risk of offspring overweight, and adiposity and its complications compared to a control group.
Detailed Description
The study is a single site parallel randomized controlled study. The study will be assessing the effect of a pre-conceptional weight loss intervention vs a control group among healthy couples where the prospective mother is pregnant (recruited at gestational age 32-34), overweight or obese (BMI 28-45 kg/m^2), between 18-35 years and planning an additional pregnancy within the following 3 years. The investigators will recruit a total of 140 healthy pregnant couples who will be randomized 1:1 to either intervention or control, stratified according to maternal pre-pregnancy BMI and previous or present diagnosis of gestational diabetes. The couples in intervention group will receive dietary counseling by a dietitian from 3 months post-partum of the 1st child until birth of the 2nd child. The goal is to achieve a healthy lifestyle and a moderate weight loss of 10% according to pre-pregnancy weight during the first year. Hereafter, the couples will be guided in weight maintenance until pregnancy of the second child. During pregnancy the goal is to achieve a healthy weight gain. Couples in intervention group will also participate in physical activity sessions every 2nd week and advised to walk with moderate intensity at least 2-4 times a week for at least half an hour. The overall objective is to test whether a comprehensive pre-conceptional parental weight loss intervention effectively reduces the risk of offspring overweight, and adiposity and its complications compared to a control group. The 1st baby born before intervention is started will be the "index child" and the metabolic and anthropometric parameters of the 1st child will be compared to parameters of the second child to assess the effect of the parent's healthy lifestyle between the two pregnancies. The investigators hypothesize that parental weight loss intervention, initiated before conception, will facilitate lower parental insulin resistance, inflammation, body weight and adiposity, incretin responses and energy expenditure compared to usual care. For the offspring the investigators hypothesize that the intervention will reduce adverse pregnancy outcomes with a short-term reduction in the risk of being born large for gestational age with excessive fat mass and a long-term reduction in the risk of developing overweight or obesity as a consequence of both social (family approach) and biological (epigenetic modifications) pathways.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overweight and Obesity, Weight Loss, Pregnancy Related, Child Nutrition Sciences, Body Composition
Keywords
Overweight, Pregnancy, Weight loss, Diet, Reducing, Epigenetics, Healthy Lifestyle, DNA Methylation, Exercise, Offspring's neonatal fat mass, Pea Pod, Infant, Large for Gestational Age, Body Fat Distribution

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
140 couples will be recruited and randomized to either intervention og control. Participants includes the mother, father and 1st and 2nd child, therefore the total number of participants will be 560.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
Intervention group will receive dietary counseling by a trained dietitian from 3 months post-partum of the 1st child until birth of the 2nd child. The mother will receive advice to provide a moderate caloric restriction (-500 to 1000 kcal/d) and attend physical activity sessions to attain a 10 % weight loss according to pre-pregnancy weight. If the father is also overweight or obese, he will receive the same advice.
Arm Title
Control
Arm Type
No Intervention
Arm Description
The control group will receive standard care and will not receive any dietary advice prior to pregnancy. During pregnancy control subjects will receive dietary advice according to standard care which means no counselling from a dietitian unless there are special needs (e.g., gestational diabetes), then they will receive counseling from a dietitian in accordance with standard care.
Intervention Type
Behavioral
Intervention Name(s)
Weight loss intervention
Intervention Description
Subjects will receive dietary counseling by a dietitian from 3 months post-partum of the 1st child until birth of the 2nd child. The mother (and father if overweight, BMI ≥25 kg/m^2) will receive advice to provide a moderate caloric restriction (-500 to 1000 kcal/d) and power walk 2-4 times a week for a half an hour and attend physical activity sessions every 2nd week to attain a minimum weight loss of approximately 0,5-1,0 kg/week. The weight loss will last until a 10% weight loss (according to pre-pregnancy weight) has been achieved or until 1-year post-partum. If the subject has not achieved a weight loss of 10%, she or he will receive Very low-calorie diet (VLCD) until target weight loss is reached, though no longer than 8 weeks. After weight loss subjects will receive counseling to maintain weight loss and healthy weight gain during pregnancy until birth of the 2nd child.
Primary Outcome Measure Information:
Title
Neonatal fat mass
Description
Offspring's neonatal fat mass (grams) assessed by air displacement plethysmography (Pea POD)
Time Frame
Collected within the first week of birth (strived <48 hours)
Title
Difference in epigenetic changes in child 1 and 2
Description
Cord blood from offspring will be collected at birth and stored at -80 °C until use. At the Department of Molecular Medicine AUH genomic DNA will be extracted from peripheral blood using standard methods e.g., QIAmp® Mini Kit (Qiagen, Germany). 1 μg of genomic DNA will be bisulfide converted using Illumina iScan (platform). The methylation level will be measured using Infinium MethylationEPIC DNA Analysis BeadChip (Array type) at Eurofins Genomics AS (Denmark) or similar methods. The stated required sample size (140 couples) is calculated based on the neonatal fat mass. As no other studies have performed methylation analysis using WGBS in similar cohorts, precise power calculations on epigenetic changes are impractical. However, since the EPICOM study found differentially methylated regions in only 20 cases and 20 controls using Illumina's 450K methylation assay, the power to elucidate epigenetic changes is considered sufficient in the planned study.
Time Frame
Assessed at birth
Secondary Outcome Measure Information:
Title
Obstetrics outcome - length of gestational age
Description
Length of gestational age
Time Frame
Assessed at birth of both offsprings
Title
Obstetric - medication use
Description
Medication use during labor
Time Frame
Collected from initiation of labor until completed birth of both offsprings
Title
Obstetric - delivery mode
Description
Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth).
Time Frame
Collected at birth of both offsprings
Title
Obstetric - pregnancy complications
Description
Pregnancy complications e.g. miscarriage, abortion (induced and indication for abortion), hydramnios, gestational hypertension, preeclampsia, need for maternal corticosteroid treatment for fetal lung maturation, urinary tract infection) will be collected from medical record.
Time Frame
Collected at gestational age (GA) 34-36 and after birth of both offsprings
Title
Obstetric - Neonatal unit admissions
Description
Neonatal unit admissions
Time Frame
Collected at birth and until 12 months after birth of both offsprings
Title
Obstetric - obstetrics complications
Description
Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization).
Time Frame
Collected at birth of both offsprings
Title
Obstetrics - birth defects/abnormalities
Description
Birth defects/abnormalities
Time Frame
Collected at birth of both offsprings
Title
Neonatal morbidities
Description
Neonatal morbidity (e.g. major congenital malformations (ICD10 Q00-Q99 or requiring medical or surgical treatment), birth injury, respiratory distress, transient tachypnoea, neonatal hypoglycemia, systemic infections, admission to neonatal intensive care unit, number of admission days, hyperbilirubinemia), deaths.
Time Frame
Collected at birth of both offsprings
Title
Fetal and offspring growth - body weight
Description
Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale.
Time Frame
Collected from medical record during pregnancy, measured in gestational age (GA) GA34-GA36 via ultrasound in both pregnancies, at birth and 3, 12 and 18 months after birth of both offsprings
Title
Fetal and offspring growth - length
Description
Fetal length will be measured with ultrasound during pregnancy and offspring length will be measured using an infantometer as appropriate for measuring infant, baby and toddler length.
Time Frame
Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies, and measured at birth and 3, 12 and 18 months after birth of both offsprings
Title
Fetal and offspring growth - abdominal circumference
Description
Abdominal circumference will be measured with ultrasound during pregnancy and offspring abdominal circumference will be measured three times to the nearest 0.1 cm using a stretch-resistant measuring tape
Time Frame
Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies, and measured at birth and 3, 12 and 18 months after birth of both offsprings
Title
Fetal and offspring growth - crown circumference
Description
Crown circumference will be measured with ultrasound during pregnancy
Time Frame
Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies
Title
Fetal and offspring growth - femur length
Description
Femur length will be measured with ultrasound during pregnancy
Time Frame
Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies,
Title
Fetal growth - fractional limb volume
Description
Fractional limb volume will be measured with ultrasound during pregnancy
Time Frame
Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies,
Title
Offspring growth - BMI z-score
Description
Offspring body mass index (BMI) z-score (BMI adjusted for age and sex).
Time Frame
Collected at birth and 3, 12 and 18 months after birth of both offsprings
Title
Offspring growth - weight for gestational age
Description
Weight for gestational age. Measured as percent of normal weight related to gestational age.
Time Frame
Collected at birth and 3, 12 and 18 months after birth of both offsprings
Title
Offspring growth - large for gestational age
Description
Large for gestational age. Prevalence of infants being large for gestational age (LGA).
Time Frame
Collected at birth of both offsprings
Title
Offspring growth - small for gestational age
Description
Small for gestational age. Prevalence of offspring being small for gestational age (SGA).
Time Frame
Collected at birth of both offsprings
Title
Offspring growth - apgar score
Description
Apgar score (0-10). The higher the score, the better health condition of the offspring)
Time Frame
Collected at birth of offspring of both offsprings
Title
Offspring growth
Description
Offspring circumference (thigh and upper arm) and skinfold (triceps, subscapularis and suprailiac). Circumferences will be measured to the nearest 0.1 cm using a stretch-resistant measuring tape and skinfolds are measured to the nearest 0.02 cm using a caliper to lightly pinch the skin and the underlying fat.
Time Frame
Collected at birth and 3, 12 and 18 months after birth of offspring.
Title
Offspring growth - body composition by the POD system
Description
Offspring fat free mass (g) and fat mass (g) will be assessed by air displacement plethysmography using the POD system (Pea POD for 1-8kg)
Time Frame
Collected within the first week of birth and 3 months post partum in both offsprings
Title
Offspring blood pressure
Description
Offspring blood pressure (diastolic and systolic blood pressure) will be measured three times after 10 minutes rest using an automated device placed on the arm and in direct contact with the skin.
Time Frame
Collected 12 and 18 months after birth of both offsprings
Title
Offspring heart rate
Description
Offspring heart rate will be measured three times after 10 minutes rest using an automated device placed on the arm and in direct contact with the skin.
Time Frame
Collected 12 and 18 months after birth of both offsprings
Title
Offspring growth - self-reported body weight
Description
Self-reported body weight
Time Frame
18 months after birth the study staff will make an annual follow-up phone call to the parents to collect information about the offspring's self-reported body weight until the offspring is 18 of age
Title
Offspring growth - self-reported height
Description
Self-reported height
Time Frame
18 months after birth the study staff will make an annual follow-up phone call to the parents to collect information about the offspring's self-reported body weight until the offspring is 18 of age
Title
Adult weight
Description
Adult body weight is measured to the nearest 0.1 kg using a calibrated scale
Time Frame
Intervention: each visit throughout study (GA34-36 of 1st child to 18mo. after birth of 2nd child). Control: In GA34-36 in both pregnancies, at study visits (3, 12 and 24mo. pp) and follow up visits (3, 12 and 18 months pp of 2nd child)
Title
Adult Height
Description
Adult height will be measured to the nearest 0.5 cm using a wall-mounted stadiometer.
Time Frame
Collected in GA34-GA36 in index pregnancy
Title
Adult BMI
Description
Calculated as weight (kg)/height(m)^2
Time Frame
Collected in GA34-36 in 1st pregnancy, study visits 3, 12 and 24mo. pp after 1st child, GA34-36 in 2nd pregnancy and at follow up vist (3, 12 and 18mo. pp of 2nd child).
Title
Adult anthropometric
Description
Waist- and hip circumference will be measured to the nearest 0.1 cm. During pregnancy and at birth the waist of the female will not be measured.
Time Frame
Intervention: each visit throughout study (GA34-36 of 1st child to 18mo. after birth of 2nd child). Control: In GA34-36 in both pregnancies, at study visits (3, 12 and 24mo. pp) and follow up visits (3, 12 and 18 months pp of 2nd child)
Title
Adult blood pressure
Description
Blood pressure (diastolic and systolic blood pressure) will be measured three times with two minutes apart in right arm after 15 minutes rest using a validated automatic device. The reading is recorded to the nearest 1 mmHg.
Time Frame
Collected at GA34-36 in 1st pregnancy, study visits 3, 12 and 24 months pp. of 1st child, GA34-36 in 2nd pregnancy and 3 months pp after 2nd child
Title
Adult heart rate
Description
Heart rate will be measured three times with two minutes apart in right arm after 5-10 minutes rest using a validated automatic device. The reading is recorded to the nearest 1 beats/minute for heart rate
Time Frame
Collected at GA34-36 in 1st pregnancy, study visits 3, 12 and 24 months pp. of 1st child, GA34-36 in 2nd pregnancy and 3 months pp after 2nd child
Title
Adult resting metabolic rate
Description
Resting metabolic rate (calories/24-h) will be measured by indirect calorimetry using a ventilated hood system. Participants will lie in the supine position and rest for at least 30 min before measurements commence. The measurement will last for 20 min.
Time Frame
Collected at study visit 3, 12, and 24 months pp after 1st child.
Title
Adult resting respiratory quotient + substrate
Description
Resting respiratory quotient (RQ), will be measured by indirect calorimetry using a ventilated hood system. Participants will lie in the supine position and rest for at least 30 min before measurements commence. The measurement will last for 20 min. Lipid, glucose and protein oxidation will be estimated.
Time Frame
Collected at study visit 3, 12, and 24 months pp after 1st child.
Title
Adult medication use
Description
Use of medication will be collected throughout the study and for each medication the start date, stop date or continuing, form and indication will be noted in appropriate form.
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st. child
Title
Offspring medication use
Description
Use of medication will be collected throughout the study and for each medication the start date, stop date or continuing, form and indication will be noted in appropriate form.
Time Frame
Birth, after 3, 12, and 18 months after birth of both offsprings
Title
Adult reproduction - Time to pregnancy
Description
Duration of time to conception defined from selfreported time point they started to try get pregnant to registration of pregnancy. The time of conception will be calculated from the ultrasound scan in week 12
Time Frame
Registration of 2nd. pregnancy (up to tree years from birth of 1.st. child)
Title
Adult glucose metabolism (OGTT)
Description
3-h oral glucose tolerance test (OGTT) will be performed at with 75g of glucose dissolved in 250 ml of water and added 1 gram of paracetamol. Blood will collected for measurements of blood glucose, hormones (insulin, C-Peptide, glucagon), paracetamol, glucagon-like-peptide-1 (GLP-1), Glucose insulinotropic polypeptide (GIP) and metabolites (FFA). Blood samples will be drawn at time 0, 15, 30, 45, 60, 90, 120 and 180 min
Time Frame
Performed at study visits 3, 12 and 24 months pp of 1st. child
Title
Adult Oral Glucose Tolerance Test (OGTT) during pregnancy (only female)
Description
OGTT performed during pregnancy according to the screening guidelines for GDM will be obtained from the mother's medical journal in both pregnancies.
Time Frame
Collected in GA28 of 1st and 2nd pregnancy (performed after risk score at gestational age~20 and ~28 or only ~28)
Title
Placenta - weight (gram)
Description
Placenta will be weighted after birth
Time Frame
Collected at birth of both offsprings
Title
VO2-max adult - cardiorespiratory fitness
Description
The VO2-max test will be performed as an incremental exercise test on a bicycle ergometer.
Time Frame
Collected at study visit 3, 12 and 24 months pp after birth of 1st child
Title
Cardiac function offspring - Left ventricular and right ventricular morphology
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Interventricular septal thickness diastole and valve- and chamber dimensions will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - left centricular ejection fraction
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of left ventricular ejection fraction will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - fractional shortening
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of fractional shortening will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Systolic function, strain
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Systolic function, strain rate
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain rate will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - TAPSE and RV fractional area change
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of TAPSE and RV fractional area change will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Diastolic function, left ventricular E/A-ratio
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of left ventricular E/A-ratio will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Diastolic function, tissue velocities (E', A', S')
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of tissue velocities (E', A', S') will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Diastolic function, strain
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Overall cardiac function
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Myocardial performance index (MPI) and cardiac torsion will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Pulmonary artery acceleration time
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Pulmonary artery acceleration time will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Pulmonary artery pressure
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Pulmonary artery pressure will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cardiac function offspring - Persistent ductus arteriosus (PDA)
Description
ECG and echocardiography will be performed according to standard imaging protocol. Assessment of PDA open or closed and PDA shunt will be done.
Time Frame
Collected at birth and at 12 months follow up visit after birth of each child
Title
Cord blood - Telomore length
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Telomore length.
Time Frame
Collected at birth of both offsprings
Title
Cord blood - pH
Description
Cord blood will be drawn immediately after birth. pH will be assessed.
Time Frame
Collected at birth
Title
Cord blood - Epigenetics
Description
Epigenetics analyses from whole blood. Will be analysed for methylation changes. metabolomics and exosome.
Time Frame
Collected at birth of both offsprings
Title
Adult body composition by DEXA scan
Description
Lean mass (g), fat mass (g), abdominal fat (g), visceral fat (g) assessed by a Dual-energy X-ray absorptiometry (DEXA) -scan .
Time Frame
Collected at study visits 3, 12 and 24 months pp. of 1st child
Title
Adult bone markers by DEXA scan - bone mineral content
Description
Bone mineral content (g) assessed by a Dual-energy X-ray absorptiometry-scan.
Time Frame
Collected at study visits 3, 12 and 24 months pp. of 1st child
Title
Adult bone markers by DEXA scan - bone area
Description
Bone area (cm^2) assessed by a Dual-energy X-ray absorptiometry-scan.
Time Frame
Collected at study visits 3, 12 and 24 months pp. of 1st child
Title
Adult bone markers by DEXA scan - bone mineral density
Description
Bone mineral density (g/cm^2) assessed by a Dual-energy X-ray absorptiometry-scan.
Time Frame
Collected at study visits 3, 12 and 24 months pp. of 1st child
Title
Adult blood sample - glucose
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for glucose
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - CD163
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for CD163
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - HbA1c
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for markers of glucose metabolism HbA1c
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Kreatinin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for kreatinin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - eGFR
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for kreatinin and GFR will be estimated
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - C-reaktivt protein (CRP)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for CRP
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Alanintransaminase (ALAT)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for ALAT
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Gamma-GT (GGT)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for GGT
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Basisk fosfatase (BASP)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for BASP
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Bilirubin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Bilirubin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Ferritin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Ferritin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Hemoglobin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Hemoglobin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Leukocytter
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Leucocytter
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - platelets
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for platelets
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Triglyceride
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for triglyceride
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Cholesterol HDL
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Cholesterol HDL
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Cholesterol LDL
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Cholesterol LDL
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Total Cholesterol
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Total Cholesterol
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - vitamin B12
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for B12
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - vitamin D3
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for vitamin D3
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - c-peptide
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for c-peptide
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Insulin-like Growth Factor-1 (IGF-1)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IGF-1
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Insulin-like growth factor-binding protein-1 (IGFBP-1)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IGFBP-1
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Insulin-like growth factor-binding protein-3 (IGFBP-3)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IGFBP-3
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Fibroblast growth factor 21 (FGF-21)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for FGF-21
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Leptin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Leptin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Adiponectin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Adiponectin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Ghrelin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Ghrelin
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Growth Hormone (GH)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for GH
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Free fatty Acids (FFA)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for FFA
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Interleukin 6 (IL-6)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IL-6
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Interleukin 6 (IL-10)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IL-10
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Interleukin-1 alpha (IL-1 alpha)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IL-1 alpha
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Interferon gamma (IFN-γ)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for IFN-γ
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult blood sample - Tumor Necrosis Factor alfa (TNF-α)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for TNF-α
Time Frame
Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st child, at GA34 in 2nd pregnancy and at follow visit 3 months pp after 2nd child
Title
Adult female blood sample - Humant choriogonadotropin (hCG)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for hCG
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Adult female blood sample - Progesterone
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Progesterone
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Adult female blood sample - Proinsulin C-peptide
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Proinsulin C-peptide
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Adult female blood sample - sex hormone binding globulin (SHBG)
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for SHBG
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Adult female blood sample - Prolactin
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Prolactin
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Adult blood sample -Cortisol
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will be analysed for Cortisol
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Adult female blood sample -Estradiol
Description
All blood samples will be collected by venous puncture in the antecubital vein after an overnight fast from at least 10 pm the night before. Samples will only be collected from the female participant during pregnancy and be analysed for Estradiol
Time Frame
Collected at GA34-GA36 in both pregnancies
Title
Offspring blood sample - glucose
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for glucose
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - c-peptide
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for c-peptide
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - insulin
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Insulin
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - IGF-1
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for IGF-1
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - IGFBP-3
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for IGFBP-3
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - IGFBP-1
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for IGFBP-1
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - CD163
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for CD163
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Ferritin
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Ferritin
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - HgbA1c
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for HgbA1c
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Hgb
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Hgb
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - CRP
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for CRP
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Triglyceride
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Triglyceride
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Cholesterol HDL
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Cholesterol HDL
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Cholesterol LDL
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Cholesterol LDL
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Total Cholesterol
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Total Cholesterol
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - FGF-21
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for FGF-21
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Leptin
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Leptin
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Adiponectin
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Adiponectin
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - FFA
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for FFA
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - Growth Hormone (GH)
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for GH
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - cTroponin I (cTnI)
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for cTnI
Time Frame
Collected 12 months after birth in both offsprings
Title
Offspring blood sample - BNP
Description
A non-fasting venous blood will be drawn. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for BNP
Time Frame
Collected 12 months after birth in both offsprings
Title
Cord blood - c-peptide
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for C-peptide
Time Frame
Collected at birth of both offspring
Title
Cord blood -Insulin
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Insulin
Time Frame
Collected at birth of both offspring
Title
Cord blood -IGFBP-3
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-3
Time Frame
Collected at birth of both offspring
Title
Cord blood -IGFBP-1
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-1
Time Frame
Collected at birth of both offspring
Title
Cord blood -IGF-1
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGF-1
Time Frame
Collected at birth of both offspring
Title
Cord blood -Ferritin
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Ferritin
Time Frame
Collected at birth of both offspring
Title
Cord blood -cTnI
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for cTnI
Time Frame
Collected at birth of both offspring
Title
Cord blood -BNP
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for BNP
Time Frame
Collected at birth of both offspring
Title
Cord blood -CRP
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CRP
Time Frame
Collected at birth of both offspring
Title
Cord blood -CD163
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CD163
Time Frame
Collected at birth of both offspring
Title
Cord blood -FGF21
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FGF21
Time Frame
Collected at birth of both offspring
Title
Cord blood -Leptin
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Leptin
Time Frame
Collected at birth of both offspring
Title
Cord blood -Adiponectin
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Adiponectin
Time Frame
Collected at birth of both offspring
Title
Cord blood -FFA
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FFA
Time Frame
Collected at birth of both offspring
Title
Cord blood - Vitamin D3
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Vitamin D3
Time Frame
Collected at birth of both offspring
Title
Cord blood - HbA1c
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for HbA1c
Time Frame
Collected at birth of both offspring
Title
Cord blood - IL-6
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-6
Time Frame
Collected at birth of both offspring
Title
Cord blood - IL-10
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-10
Time Frame
Collected at birth of both offspring
Title
Cord blood - IL-1 alpha
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-1 alpha
Time Frame
Collected at birth of both offspring
Title
Cord blood -TNF- alpha
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for-TNF- alpha
Time Frame
Collected at birth of both offspring
Title
Cord blood -IFN- gamma
Description
Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IFN- gamma
Time Frame
Collected at birth of both offspring
Other Pre-specified Outcome Measures:
Title
Offspring feces - Microbiome
Description
Will be analysed for microbiome. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - Short chain fatty acids
Description
Will be analysed for short chain fatty acids. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - Metabolomics
Description
Will be analysed for metabolomics. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - Proteomics
Description
Will be analysed for proteomics. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - pH
Description
Will be assessed for pH. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - Inflammation markers
Description
Will be analysed for inflammation markers. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - consistency
Description
Whenever a fecal sample is collected stool consistency of the collected sample will be collected with a questionnaire.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - frequency
Description
Whenever a fecal sample is collected an estimate of stool frequency during the last week will be collected with a questionnaire.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring feces - gastrointestinal symptoms
Description
Whenever a fecal sample is collected any gastrointestinal symptoms of the offspring during the last week will be collected with a questionnaire.
Time Frame
Collected within the first week after birth (but should avoid to collect the first fecal excretion after birth (meconium)), at study visit 3 and 12 months after birth of each offspring
Title
Offspring urine
Description
Parents will be instructed to collect offspring's urine samples. A piece of bio-plastic will be placed in the diaper together with cotton balls to ensure that a sufficient amount of urine is absorbed into the cotton balls. Offspring urine will be analyzed for metabolomics.
Time Frame
Collected within the first week of birth and at 3 and 12 months follow up of each offspring
Title
Adult feces - Microbiome
Description
Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for microbiome.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - Short chain fatty acids
Description
Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for short chain fatty acids.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - Metabolomics
Description
Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for metabolomics
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - Proteomics
Description
Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for proteomics.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - Inflammation markers
Description
Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for inflammation markers.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - pH
Description
Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be assessed for pH.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - consistency
Description
Whenever a fecal sample is collected stool consistency of the collected sample will be collected with a questionnaire.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - frequency
Description
Whenever a fecal sample is collected an estimate of stool frequency during the last week will be collected with a questionnaire.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult feces - gastrointestinal symptoms
Description
Whenever a fecal sample is collected gastrointestinal symptoms during the last week will be collected with a questionnaire.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Adult urine
Description
Participants will collect a urine spot sample at the study site. Adult urine will be analyzed for metabolomics.
Time Frame
Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child
Title
Offspring nutritional milestones
Description
Parents will be instructed to register the age of the offspring when it reaches the World Health Organization (WHO) nutritional milestones (age when the offspring was introduced to specific food items)
Time Frame
Collected at 12 and 18 months after offspring birth
Title
Offspring development, WHO milestones
Description
Parents will be instructed to register the age of the offspring when it reaches the World Health Organization (WHO) developmental milestones (age when the offspring can sit, stands in crawl-position, stands with support, stand alone, walk with support, walk alone)
Time Frame
Collected at 12 and 18 months after offspring birth
Title
Adult physical activity
Description
Physical activity and sleep will be assessed by an accelerometer and the females and males will wear the accelerometer for 7 days and 8 nights. The participants will be asked to keep a physical activity and sleep log for when they wake up and when they try to sleep
Time Frame
Collected at study visit 3, 12 and 24 months pp of 1st child
Title
Adult physical activity - Physical Activity Questionnaire (IPAQ)
Description
Physical activity will be assessed by the International Physical Activity Questionnaire (IPAQ), in which time spent on strenuous and moderate activity and walks will be collected. The answers will be collected electronic via RedCap.
Time Frame
Collected at GA34-GA36 in each pregnancy, study visit at 3, 12 and 24 months pp of 1st child and 3 months pp visit after 2nd child
Title
Adult background quistionnaire, ethnicity,
Description
All information will be collected electronic in RedCap.
Time Frame
Collected after screening in GA34-GA36 of 1st child
Title
Adult background quistionnaire, education
Description
All information will be collected electronic in RedCap.
Time Frame
Collected after screening in GA34-GA36 of 1st child
Title
Adult background quistionnaire, parity
Description
All information will be collected electronic in RedCap.
Time Frame
Collected after screening in GA34-GA36 of 1st child
Title
Adult background quistionnaire, pre-pregnancy weight
Description
Pre-pregnancy weight, ethnicity, education and parity. All information will be collected electronic in RedCap.
Time Frame
Collected after screening in GA34-GA36 of 1st child
Title
Adult background quistionnaire, demographic information
Description
All information will be collected electronic in RedCap.
Time Frame
Collected after screening in GA34-GA36 of 1st child
Title
Adult wellbeing - Depression, Major depression questionnaire (ICD-10)
Description
Depression will be assessed by Major depression questionnaire (ICD-10). Mild depression: A score of 4 or 5 in two of the first three items. Plus a score of at least 3 on two or three of the last seven items. Moderate depression: A score of 4 or 5 in two or three of the first three items. Plus a score of at least 3 on four of the last seven items. Severe depression: A score of 4 or 5 in all of the first three items. Plus a score of at least 3 on five or more of the last seven items. Major depression: The number of items is reduced to nine, as Item 4 is part of Item 5. Include whichever of the two items has the highest score (item 4 or 5). A score on at least five items is required, to be scored as follows: the score on the first three items must be at least 4, and on the other items at least 3. Either Item 1 or 2 must have a score of 4 or 5.
Time Frame
Collected at GA34-GA36 in each pregnancy, study visit at 3, 12 and 24 months pp of 1st child and 3 months pp visit after 2nd child
Title
Adult wellbeing - Quality of life, Short form-36 (SF-36)
Description
Quality of life will be assessed by the validated tool, Short form-36 (SF-36). The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame
Collected at GA34-GA36 in each pregnancy, study visit at 3, 12 and 24 months pp of 1st child and 3 months pp visit after 2nd child
Title
Adult wellbeing - Stress, Perceived Stress Scale
Description
Stress will be assessed by validated tool, Perceived Stress Scale.Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. Scores ranging from 0-13 would be considered low stress. Scores ranging from 14-26 would be considered moderate stress. Scores ranging from 27-40 would be considered high perceived stress
Time Frame
Collected at GA34-GA36 in each pregnancy, study visit at 3, 12 and 24 months pp of 1st child and 3 months pp visit after 2nd child
Title
Adult sleep
Description
Sleep will be assessed by the validated tool, Pittsburgh sleep quality index questionnaire (PSQI). In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.
Time Frame
Collected at GA34-GA36 in each pregnancy, study visit at 3, 12 and 24 months pp of 1st child and 3 months pp visit after 2nd child
Title
Adult dietary intake, 24-h recall
Description
A 24 hour dietary recall is performed by a trained dietitian. Dietary recall will be registered and intake calculated using the food data program 'VITAKOST' (www.vitakost.dk).
Time Frame
Collected at GA34-GA36 in each pregnancy, at visit 3, 12 and 24 months pp of the 1st child and 3 months visit after 2nd child. Further collected at 6, 18, 30 and 36 months pp and in GA12 and GA20 of 2nd pregnancy in intervention group
Title
Adult dietary intake, FFQ
Description
Couples will be asked to perform an electronic Food Frequency Questionnaire (FFQ). Information on frequence intake of various food groups during the last month will be collected.
Time Frame
Collected at GA34-GA36 in each pregnancy, at study visit 3, 12 and 24 months pp of the 1st child and 3 month follow up vist after 2nd child
Title
Offspring dietary intake
Description
We will collect information on offspring dietary intake including breast feeding, use of formula and type as well as use of antibiotics. The intake frequency of different foods will be collected throughout a children questionnaire.
Time Frame
Collected within the first week of birth and 3, 12 and 18 months after birth off each offspring
Title
Breast milk - nutrients biomarkers
Description
Participants will collect breast milk within the first week following birth, at 1 and 3 months pp after each birth. Participants will receive written instructions in milk collection at home. First drops will not be collected, hereafter manually expressed milk will be obtained in a sterile container. Obtained around midday and minimum two hours after last breastfeeding. Breast milk will be analyzed for nutrients biomarkers.
Time Frame
Collected within the first week of birth and 3 months pp after each birth
Title
Breast milk - Hormonal and inflammatory markers
Description
Participants will collect breast milk within the first week following birth, at 1 and 3 months pp after each birth. Participants will receive written instructions in milk collection at home. First drops will not be collected, hereafter manually expressed milk will be obtained in a sterile container. Obtained around midday and minimum two hours after last breastfeeding. Breast milk will be analyzed for hormonal and inflammatory markers
Time Frame
Collected within the first week of birth and 3 months pp after each birth
Title
Breast milk - Metabolomics
Description
Participants will collect breast milk within the first week following birth, at 1 and 3 months pp after each birth. Participants will receive written instructions in milk collection at home. First drops will not be collected, hereafter manually expressed milk will be obtained in a sterile container. Obtained around midday and minimum two hours after last breastfeeding. Breast milk will be analyzed for metabolomics
Time Frame
Collected within the first week of birth and 3 months pp after each birth
Title
Breast milk - Proteomics
Description
Participants will collect breast milk within the first week following birth, at 1 and 3 months pp after each birth. Participants will receive written instructions in milk collection at home. First drops will not be collected, hereafter manually expressed milk will be obtained in a sterile container. Obtained around midday and minimum two hours after last breastfeeding. Breast milk will be analyzed for proteomics.
Time Frame
Collected within the first week of birth and 3 months pp after each birth
Title
Breast milk - Short chain fatty acids and related metabolites
Description
Participants will collect breast milk within the first week following birth, at 1 and 3 months pp after each birth. Participants will receive written instructions in milk collection at home. First drops will not be collected, hereafter manually expressed milk will be obtained in a sterile container. Obtained around midday and minimum two hours after last breastfeeding. Breast milk will be analyzed for short chain fatty acids and related metabolites
Time Frame
Collected within the first week of birth and 3 months pp after each birth
Title
Adult participation - dietitian guidance
Description
It will be recorded how many times of individual and group dietitian guidance the participant attends
Time Frame
Every 1-2 month from 3 months pp of 1st child to birth of 2nd child
Title
Adult participation - physical session and power walk
Description
It will be recorded how many times the participant participates in physical activity sessions and how much the person have power walked
Time Frame
Every 2nd week from 3 months pp of 1st child to birth of 2nd child

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Maternal inclusion Criteria: Maternal pre-pregnancy BMI 27.0-44.9 kg/m^2 Maternal age range 18-35 years Connected to Aarhus University Hospital as place of birth Pregnant Paternal Inclusion Criteria: Paternal pre-pregnancy BMI 18.5-44.9 kg/m^2 Paternal age range 18-55 years Parental Inclusion Criteria: Couples (male and female) Planning pregnancy within 3 years Provided voluntary informed consent Danish or English speaking Intention to permit the planned offspring to participate in the follow-up study Able to store biological samples from the offspring at home in the freezer in a box given by the study personnel Parental Exclusion Criteria: Diabetes mellitus (Type 1 or 2) Previous or present eating disorder Allergy towards ingredients in the very low calorie diet products Severe heart, liver or kidney disease Conception by in vitro fertilization Any medical condition or concomitant medication as judged by the medical responsible Adherence to vegan diets or other diets interfering with the dietary guidelines in the study Participation in other clinical trial that can affect the results of the current study Engagement in elite sports or similar strenuous exercise ≥5 h/week at inclusion Blood donation or transfusion within the past month before screening Blood donation during the study Inability or unwillingness to follow the study protocol and instructions given by the study personnel A detailed description of the exclusion criteria is given below: Medical conditions as known by the participant: Diabetes mellitus (type 1 and 2) History or diagnosis of eating disorder (e.g. restrained eating, disinhibition, emotional eating) Any significant medical condition as assessed by the investigator (e.g. dysregulated thyroid disease or reproductive diseases) Any significant psychiatric disorder (i.e. schizophrenia, bipolar disease or depression) as assessed by the investigator Severe chronic heart, liver and kidney disease Polycystic ovary syndrome with irregular cycle Medication: Current use of medication or use within the previous three months with a potential to affect body weight or pregnancy as judged by the investigator (e.g. systemic corticoids) Personal/other: Severe food allergies, food intolerances or dislike expected to interfere with the study, including allergy towards ingredients in the VLCD products Engagement in elite sports or similar strenuous exercise ≥5 h/week Blood donation or transfusion within the past month before screening Planned blood donation for other purpose than this study during participation Alcohol abuse, as judged by the investigator, within the previous 12 months Drug abuse, as judged by the investigator, within the previous 12 months Psychological or behavioral problems which, in the judgement of the investigator, would lead to difficulty in complying with the study protocol Participation in other clinical trials within the past three months or intention to do so during the study, which are judged by the investigator to affect the present study Unable to consume the interventional product for religious reasons, swallowing disorders, other physiological reasons or any other reasons for not being able to follow the recommended diet Inability or unwillingness to give written informed consent or communicate with study personnel Inability or unwillingness to follow the study protocol and instructions given by the study personnel Illiteracy or inadequate understanding of Danish or English language. Any other condition that judged by the investigator may interfere with the adherence to the study protocol
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ulla K Opstrup, MD, PhD
Phone
+4522370857
Email
ullaopst@rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Louise Rasmussen, MSc
Phone
+4528731648
Email
louisesuder@clin.au.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulla K Opstrup, Assoc
Organizational Affiliation
Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34444981
Citation
Rasmussen L, Knorr S, Antoniussen CS, Bruun JM, Ovesen PG, Fuglsang J, Kampmann U. The Impact of Lifestyle, Diet and Physical Activity on Epigenetic Changes in the Offspring-A Systematic Review. Nutrients. 2021 Aug 17;13(8):2821. doi: 10.3390/nu13082821.
Results Reference
background

Learn more about this trial

PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Aarhus

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