PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Aarhus
- Conditions
- Weight LossPregnancy RelatedOverweight and ObesityChild Nutrition SciencesBody Composition
- Interventions
- Behavioral: Weight loss intervention
- Registration Number
- NCT05798494
- Lead Sponsor
- Ulla Kampmann Opstrup
- 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 27-44.9 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 18-36), overweight or obese (BMI 27-44.9 kg/m\^2), between 18-38 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Weight loss intervention 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.
- Primary Outcome Measures
Name Time Method Neonatal fat mass Collected within the first week of birth (strived <48 hours) Offspring's neonatal fat mass (grams) assessed by air displacement plethysmography (Pea POD)
Difference in epigenetic changes in child 1 and 2 Assessed at birth 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
Name Time Method Adult reproduction - Time to pregnancy Registration of 2nd. pregnancy (up to tree years from birth of 1.st. child) 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
VO2-max adult - cardiorespiratory fitness Collected at study visit 3, 12 and 24 months pp after birth of 1st child The VO2-max test will be performed as an incremental exercise test on a bicycle ergometer.
Cardiac function offspring - TAPSE and RV fractional area change Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of TAPSE and RV fractional area change will be done.
Offspring blood sample - CD163 Collected 12 months after birth in both offsprings 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 - Hgb Collected 12 months after birth in both offsprings 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 - Triglyceride Collected 12 months after birth in both offsprings 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 LDL Collected 12 months after birth in both offsprings 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 - FGF-21 Collected 12 months after birth in both offsprings 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
Cord blood -Insulin Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Insulin
Cord blood -IGF-1 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGF-1
Cord blood -FGF21 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FGF21
Adult female blood sample - Prolactin Collected at GA34-GA36 in both pregnancies 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 Collected at GA34-GA36 in both pregnancies 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
Offspring blood sample - IGF-1 Collected 12 months after birth in both offsprings 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-1 Collected 12 months after birth in both offsprings 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
Adult Oral Glucose Tolerance Test (OGTT) during pregnancy (only female) Collected in GA28 of 1st and 2nd pregnancy (performed after risk score at gestational age~20 and ~28 or only ~28) OGTT performed during pregnancy according to the screening guidelines for GDM will be obtained from the mother's medical journal in both pregnancies.
Obstetric - pregnancy complications Collected at gestational age (GA) 34-36 and after birth of both offsprings 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.
Obstetrics - birth defects/abnormalities Collected at birth of both offsprings Birth defects/abnormalities
Offspring growth - small for gestational age Collected at birth of both offsprings Small for gestational age. Prevalence of offspring being small for gestational age (SGA).
Adult weight 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) Adult body weight is measured to the nearest 0.1 kg using a calibrated scale
Obstetrics outcome - length of gestational age Assessed at birth of both offsprings Length of gestational age
Fetal and offspring growth - femur length Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies, Femur length will be measured with ultrasound during pregnancy
Offspring blood pressure Collected 12 and 18 months after birth of both offsprings 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.
Adult medication use Collected at GA34-GA36 in 1st pregnancy, study visit 3, 12 and 24 months pp of 1st. child 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 glucose metabolism (OGTT) Performed at study visits 3, 12 and 24 months pp of 1st. child 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
Placenta - weight (gram) Collected at birth of both offsprings Placenta will be weighted after birth
Obstetric - delivery mode Collected at birth of both offsprings Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth).
Obstetric - obstetrics complications Collected at birth of both offsprings Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization).
Fetal and offspring growth - body weight 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 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 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 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 - crown circumference Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies Crown circumference will be measured with ultrasound during pregnancy
Offspring growth - weight for gestational age Collected at birth and 3, 12 and 18 months after birth of both offsprings Weight for gestational age. Measured as percent of normal weight related to gestational age.
Offspring growth Collected at birth and 3, 12 and 18 months after birth of offspring. 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 Collected within the first week of birth and 3 months post partum in both offsprings 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 heart rate Collected 12 and 18 months after birth of both offsprings 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 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 Self-reported body weight
Adult blood pressure 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 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.
Offspring medication use Birth, after 3, 12, and 18 months after birth of both offsprings 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.
Neonatal morbidities Collected at birth of both offsprings 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 - abdominal circumference 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 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 growth - fractional limb volume Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies, Fractional limb volume will be measured with ultrasound during pregnancy
Offspring growth - BMI z-score Collected at birth and 3, 12 and 18 months after birth of both offsprings Offspring body mass index (BMI) z-score (BMI adjusted for age and sex).
Offspring growth - large for gestational age Collected at birth of both offsprings Large for gestational age. Prevalence of infants being large for gestational age (LGA).
Offspring growth - self-reported height 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 Self-reported height
Obstetric - medication use Collected from initiation of labor until completed birth of both offsprings Medication use during labor
Obstetric - Neonatal unit admissions Collected at birth and until 12 months after birth of both offsprings Neonatal unit admissions
Offspring growth - apgar score Collected at birth of offspring of both offsprings Apgar score (0-10). The higher the score, the better health condition of the offspring)
Adult Height Collected in GA34-GA36 in index pregnancy Adult height will be measured to the nearest 0.5 cm using a wall-mounted stadiometer.
Adult BMI 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). Calculated as weight (kg)/height(m)\^2
Adult anthropometric 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) 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 body composition by DEXA scan Collected at study visits 3, 12 and 24 months pp. of 1st child 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 Collected at study visits 3, 12 and 24 months pp. of 1st child Bone mineral content (g) assessed by a Dual-energy X-ray absorptiometry-scan.
Adult resting metabolic rate Collected at study visit 3, 12, and 24 months pp after 1st child. 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.
Cardiac function offspring - Diastolic function, left ventricular E/A-ratio Collected at birth and at 12 months follow up visit after birth of each child 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') Collected at birth and at 12 months follow up visit after birth of each child 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 Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain will be done.
Cardiac function offspring - Pulmonary artery acceleration time Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Pulmonary artery acceleration time will be done.
Cord blood - pH Collected at birth Cord blood will be drawn immediately after birth. pH will be assessed.
Adult heart rate 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 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
Cardiac function offspring - Left ventricular and right ventricular morphology Collected at birth and at 12 months follow up visit after birth of each child 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 - Systolic function, strain Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain will be done.
Adult bone markers by DEXA scan - bone mineral density Collected at study visits 3, 12 and 24 months pp. of 1st child Bone mineral density (g/cm\^2) assessed by a Dual-energy X-ray absorptiometry-scan.
Adult blood sample - CD163 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 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 - eGFR 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 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 - Ferritin 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 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 - Triglyceride 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 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 - Total Cholesterol 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 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 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 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 resting respiratory quotient + substrate Collected at study visit 3, 12, and 24 months pp after 1st child. 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.
Cardiac function offspring - left centricular ejection fraction Collected at birth and at 12 months follow up visit after birth of each child 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 Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of fractional shortening will be done.
Cardiac function offspring - Systolic function, strain rate Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of strain rate will be done.
Cardiac function offspring - Persistent ductus arteriosus (PDA) Collected at birth and at 12 months follow up visit after birth of each child 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 Collected at birth of both offsprings Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Telomore length.
Adult blood sample - C-reaktivt protein (CRP) 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 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 - Bilirubin 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 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 - vitamin D3 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 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
Cardiac function offspring - Pulmonary artery pressure Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Pulmonary artery pressure will be done.
Cord blood - Epigenetics Collected at birth of both offsprings Epigenetics analyses from whole blood. Will be analysed for methylation changes. metabolomics and exosome.
Adult blood sample - Kreatinin 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 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 - Basisk fosfatase (BASP) 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 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 - platelets 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 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 - Cholesterol HDL 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 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 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 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 - Fibroblast growth factor 21 (FGF-21) 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 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
Cardiac function offspring - Overall cardiac function Collected at birth and at 12 months follow up visit after birth of each child ECG and echocardiography will be performed according to standard imaging protocol. Assessment of Myocardial performance index (MPI) and cardiac torsion will be done.
Adult bone markers by DEXA scan - bone area Collected at study visits 3, 12 and 24 months pp. of 1st child Bone area (cm\^2) assessed by a Dual-energy X-ray absorptiometry-scan.
Adult blood sample - HbA1c 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 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 - Alanintransaminase (ALAT) 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 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) 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 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 - c-peptide 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 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) 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 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 - glucose 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 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 - Hemoglobin 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 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 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 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 - Insulin-like growth factor-binding protein-3 (IGFBP-3) 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 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 - Ghrelin 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 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 - Interleukin 6 (IL-10) 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 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) 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 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 - Tumor Necrosis Factor alfa (TNF-α) 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 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 blood sample - Insulin-like growth factor-binding protein-1 (IGFBP-1) 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 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 - Leptin 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 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 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 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 - Free fatty Acids (FFA) 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 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) 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 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
Offspring blood sample - insulin Collected 12 months after birth in both offsprings 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 - IGFBP-3 Collected 12 months after birth in both offsprings 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
Cord blood -FFA Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FFA
Cord blood -CRP Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CRP
Adult blood sample - Growth Hormone (GH) 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 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 - Interferon gamma (IFN-γ) 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 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 female blood sample - Progesterone Collected at GA34-GA36 in both pregnancies 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 - sex hormone binding globulin (SHBG) Collected at GA34-GA36 in both pregnancies 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 -Estradiol Collected at GA34-GA36 in both pregnancies 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 Collected 12 months after birth in both offsprings 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 - cTroponin I (cTnI) Collected 12 months after birth in both offsprings 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
Cord blood - c-peptide Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for C-peptide
Cord blood -IGFBP-1 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-1
Cord blood -Ferritin Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Ferritin
Adult female blood sample - Humant choriogonadotropin (hCG) Collected at GA34-GA36 in both pregnancies 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
Offspring blood sample - c-peptide Collected 12 months after birth in both offsprings 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 - HgbA1c Collected 12 months after birth in both offsprings 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 - Adiponectin Collected 12 months after birth in both offsprings 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 Collected 12 months after birth in both offsprings 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) Collected 12 months after birth in both offsprings 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
Cord blood -IGFBP-3 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-3
Cord blood -cTnI Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for cTnI
Adult female blood sample - Proinsulin C-peptide Collected at GA34-GA36 in both pregnancies 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
Offspring blood sample - Ferritin Collected 12 months after birth in both offsprings 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 - CRP Collected 12 months after birth in both offsprings 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 - Cholesterol HDL Collected 12 months after birth in both offsprings 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 - Total Cholesterol Collected 12 months after birth in both offsprings 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 - Leptin Collected 12 months after birth in both offsprings 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 - BNP Collected 12 months after birth in both offsprings 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 -BNP Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for BNP
Cord blood -CD163 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CD163
Cord blood -Leptin Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Leptin
Cord blood - HbA1c Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for HbA1c
Cord blood - IL-10 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-10
Cord blood - IL-1 alpha Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-1 alpha
Cord blood -IFN- gamma Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IFN- gamma
Cord blood -Adiponectin Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Adiponectin
Cord blood - IL-6 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-6
Cord blood -TNF- alpha Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for-TNF- alpha
Cord blood - Vitamin D3 Collected at birth of both offspring Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Vitamin D3
Trial Locations
- Locations (1)
Aarhus University Hospital
🇩🇰Aarhus, Denmark