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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05798494
Recruitment Status : Recruiting
First Posted : April 4, 2023
Last Update Posted : January 18, 2024
Sponsor:
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
Information provided by (Responsible Party):
Ulla Kampmann Opstrup, Aarhus University Hospital

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.

Condition or disease Intervention/treatment Phase
Overweight and Obesity Weight Loss Pregnancy Related Child Nutrition Sciences Body Composition Behavioral: Weight loss intervention Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Prevention
Official Title: PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - Aarhus
Actual Study Start Date : June 1, 2023
Estimated Primary Completion Date : April 11, 2025
Estimated Study Completion Date : April 11, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Behavioral: Weight loss intervention
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.

No Intervention: Control
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.



Primary Outcome Measures :
  1. Neonatal fat mass [ Time Frame: Collected within the first week of birth (strived <48 hours) ]
    Offspring's neonatal fat mass (grams) assessed by air displacement plethysmography (Pea POD)

  2. Difference in epigenetic changes in child 1 and 2 [ Time Frame: 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 :
  1. Obstetrics outcome - length of gestational age [ Time Frame: Assessed at birth of both offsprings ]
    Length of gestational age

  2. Obstetric - medication use [ Time Frame: Collected from initiation of labor until completed birth of both offsprings ]
    Medication use during labor

  3. Obstetric - delivery mode [ Time Frame: Collected at birth of both offsprings ]
    Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth).

  4. Obstetric - pregnancy complications [ Time Frame: 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.

  5. Obstetric - Neonatal unit admissions [ Time Frame: Collected at birth and until 12 months after birth of both offsprings ]
    Neonatal unit admissions

  6. Obstetric - obstetrics complications [ Time Frame: 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).

  7. Obstetrics - birth defects/abnormalities [ Time Frame: Collected at birth of both offsprings ]
    Birth defects/abnormalities

  8. Neonatal morbidities [ Time Frame: 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.

  9. Fetal and offspring growth - body weight [ 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 ]
    Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale.

  10. Fetal and offspring growth - 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 ]
    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.

  11. Fetal and offspring growth - abdominal circumference [ 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 ]
    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

  12. Fetal and offspring growth - crown circumference [ Time Frame: Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies ]
    Crown circumference will be measured with ultrasound during pregnancy

  13. Fetal and offspring growth - femur length [ Time Frame: Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies, ]
    Femur length will be measured with ultrasound during pregnancy

  14. Fetal growth - fractional limb volume [ Time Frame: 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

  15. Offspring growth - BMI z-score [ Time Frame: 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).

  16. Offspring growth - weight for gestational age [ Time Frame: 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.

  17. Offspring growth - large for gestational age [ Time Frame: Collected at birth of both offsprings ]
    Large for gestational age. Prevalence of infants being large for gestational age (LGA).

  18. Offspring growth - small for gestational age [ Time Frame: Collected at birth of both offsprings ]
    Small for gestational age. Prevalence of offspring being small for gestational age (SGA).

  19. Offspring growth - apgar score [ Time Frame: Collected at birth of offspring of both offsprings ]
    Apgar score (0-10). The higher the score, the better health condition of the offspring)

  20. Offspring growth [ Time Frame: 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.

  21. Offspring growth - body composition by the POD system [ Time Frame: 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)

  22. Offspring blood pressure [ Time Frame: 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.

  23. Offspring heart rate [ Time Frame: 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.

  24. Offspring growth - 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 ]
    Self-reported body weight

  25. Offspring growth - 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 ]
    Self-reported height

  26. Adult weight [ 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) ]
    Adult body weight is measured to the nearest 0.1 kg using a calibrated scale

  27. Adult Height [ Time Frame: Collected in GA34-GA36 in index pregnancy ]
    Adult height will be measured to the nearest 0.5 cm using a wall-mounted stadiometer.

  28. Adult BMI [ 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). ]
    Calculated as weight (kg)/height(m)^2

  29. Adult anthropometric [ 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) ]
    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.

  30. Adult blood pressure [ 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 ]
    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.

  31. Adult 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 ]
    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

  32. Adult resting metabolic rate [ Time Frame: 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.

  33. Adult resting respiratory quotient + substrate [ Time Frame: 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.

  34. Adult medication use [ Time Frame: 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.

  35. Offspring medication use [ Time Frame: 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.

  36. Adult reproduction - Time to pregnancy [ Time Frame: 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

  37. Adult glucose metabolism (OGTT) [ Time Frame: 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

  38. Adult Oral Glucose Tolerance Test (OGTT) during pregnancy (only female) [ Time Frame: 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.

  39. Placenta - weight (gram) [ Time Frame: Collected at birth of both offsprings ]
    Placenta will be weighted after birth

  40. VO2-max adult - cardiorespiratory fitness [ Time Frame: 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.

  41. Cardiac function offspring - Left ventricular and right ventricular morphology [ Time Frame: 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.

  42. Cardiac function offspring - left centricular ejection fraction [ Time Frame: 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.

  43. Cardiac function offspring - fractional shortening [ Time Frame: 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.

  44. Cardiac function offspring - Systolic function, strain [ Time Frame: 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.

  45. Cardiac function offspring - Systolic function, strain rate [ Time Frame: 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.

  46. Cardiac function offspring - TAPSE and RV fractional area change [ Time Frame: 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.

  47. Cardiac function offspring - Diastolic function, left ventricular E/A-ratio [ Time Frame: 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.

  48. Cardiac function offspring - Diastolic function, tissue velocities (E', A', S') [ Time Frame: 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.

  49. Cardiac function offspring - Diastolic function, strain [ Time Frame: 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.

  50. Cardiac function offspring - Overall cardiac function [ Time Frame: 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.

  51. Cardiac function offspring - Pulmonary artery acceleration time [ Time Frame: 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.

  52. Cardiac function offspring - Pulmonary artery pressure [ Time Frame: 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.

  53. Cardiac function offspring - Persistent ductus arteriosus (PDA) [ Time Frame: 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.

  54. Cord blood - Telomore length [ Time Frame: Collected at birth of both offsprings ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Telomore length.

  55. Cord blood - pH [ Time Frame: Collected at birth ]
    Cord blood will be drawn immediately after birth. pH will be assessed.

  56. Cord blood - Epigenetics [ Time Frame: Collected at birth of both offsprings ]
    Epigenetics analyses from whole blood. Will be analysed for methylation changes. metabolomics and exosome.

  57. Adult body composition by DEXA scan [ Time Frame: 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 .

  58. Adult bone markers by DEXA scan - bone mineral content [ Time Frame: 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.

  59. Adult bone markers by DEXA scan - bone area [ Time Frame: 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.

  60. Adult bone markers by DEXA scan - bone mineral density [ Time Frame: 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.

  61. Adult blood sample - 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 ]
    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

  62. Adult blood sample - 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 ]
    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

  63. Adult blood sample - 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 ]
    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

  64. Adult blood sample - 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 ]
    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

  65. Adult blood sample - eGFR [ 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 ]
    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

  66. Adult blood sample - C-reaktivt protein (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 ]
    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

  67. Adult blood sample - Alanintransaminase (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 ]
    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

  68. Adult blood sample - Gamma-GT (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 ]
    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

  69. Adult blood sample - Basisk fosfatase (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 ]
    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

  70. Adult blood sample - 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 ]
    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

  71. Adult blood sample - 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 ]
    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

  72. Adult blood sample - 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 ]
    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

  73. Adult blood sample - Leukocytter [ 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 ]
    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

  74. Adult blood sample - 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 ]
    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

  75. Adult blood sample - 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 ]
    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

  76. Adult blood sample - 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 ]
    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

  77. Adult blood sample - 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 ]
    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

  78. Adult blood sample - 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 ]
    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

  79. Adult blood sample - vitamin 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 ]
    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

  80. Adult blood sample - 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 ]
    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

  81. Adult blood sample - 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 ]
    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

  82. Adult blood sample - Insulin-like Growth Factor-1 (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 ]
    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

  83. Adult blood sample - Insulin-like growth factor-binding protein-1 (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 ]
    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

  84. Adult blood sample - Insulin-like growth factor-binding protein-3 (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 ]
    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

  85. Adult blood sample - Fibroblast growth factor 21 (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 ]
    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

  86. Adult blood sample - 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 ]
    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

  87. Adult blood sample - 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 ]
    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

  88. Adult blood sample - 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 ]
    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

  89. Adult blood sample - Growth Hormone (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 ]
    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

  90. Adult blood sample - Free fatty Acids (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 ]
    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

  91. Adult blood sample - Interleukin 6 (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 ]
    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

  92. Adult blood sample - Interleukin 6 (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 ]
    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

  93. Adult blood sample - Interleukin-1 alpha (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 ]
    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

  94. Adult blood sample - Interferon gamma (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 ]
    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

  95. Adult blood sample - Tumor Necrosis Factor alfa (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 ]
    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

  96. Adult female blood sample - Humant choriogonadotropin (hCG) [ Time Frame: 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

  97. Adult female blood sample - Progesterone [ Time Frame: 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

  98. Adult female blood sample - Proinsulin C-peptide [ Time Frame: 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

  99. Adult female blood sample - sex hormone binding globulin (SHBG) [ Time Frame: 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

  100. Adult female blood sample - Prolactin [ Time Frame: 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

  101. Adult blood sample -Cortisol [ Time Frame: 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

  102. Adult female blood sample -Estradiol [ Time Frame: 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

  103. Offspring blood sample - glucose [ Time Frame: 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

  104. Offspring blood sample - c-peptide [ Time Frame: 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

  105. Offspring blood sample - insulin [ Time Frame: 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

  106. Offspring blood sample - IGF-1 [ Time Frame: 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

  107. Offspring blood sample - IGFBP-3 [ Time Frame: 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

  108. Offspring blood sample - IGFBP-1 [ Time Frame: 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

  109. Offspring blood sample - CD163 [ Time Frame: 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

  110. Offspring blood sample - Ferritin [ Time Frame: 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

  111. Offspring blood sample - HgbA1c [ Time Frame: 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

  112. Offspring blood sample - Hgb [ Time Frame: 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

  113. Offspring blood sample - CRP [ Time Frame: 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

  114. Offspring blood sample - Triglyceride [ Time Frame: 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

  115. Offspring blood sample - Cholesterol HDL [ Time Frame: 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

  116. Offspring blood sample - Cholesterol LDL [ Time Frame: 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

  117. Offspring blood sample - Total Cholesterol [ Time Frame: 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

  118. Offspring blood sample - FGF-21 [ Time Frame: 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

  119. Offspring blood sample - Leptin [ Time Frame: 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

  120. Offspring blood sample - Adiponectin [ Time Frame: 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

  121. Offspring blood sample - FFA [ Time Frame: 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

  122. Offspring blood sample - Growth Hormone (GH) [ Time Frame: 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

  123. Offspring blood sample - cTroponin I (cTnI) [ Time Frame: 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

  124. Offspring blood sample - BNP [ Time Frame: 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

  125. Cord blood - c-peptide [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for C-peptide

  126. Cord blood -Insulin [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Insulin

  127. Cord blood -IGFBP-3 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-3

  128. Cord blood -IGFBP-1 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGFBP-1

  129. Cord blood -IGF-1 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IGF-1

  130. Cord blood -Ferritin [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Ferritin

  131. Cord blood -cTnI [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for cTnI

  132. Cord blood -BNP [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for BNP

  133. Cord blood -CRP [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CRP

  134. Cord blood -CD163 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for CD163

  135. Cord blood -FGF21 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FGF21

  136. Cord blood -Leptin [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Leptin

  137. Cord blood -Adiponectin [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Adiponectin

  138. Cord blood -FFA [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for FFA

  139. Cord blood - Vitamin D3 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for Vitamin D3

  140. Cord blood - HbA1c [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for HbA1c

  141. Cord blood - IL-6 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-6

  142. Cord blood - IL-10 [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-10

  143. Cord blood - IL-1 alpha [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IL-1 alpha

  144. Cord blood -TNF- alpha [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for-TNF- alpha

  145. Cord blood -IFN- gamma [ Time Frame: Collected at birth of both offspring ]
    Cord blood will be drawn immediately after birth and analysed. Blood will be analyzed for IFN- gamma


Other Outcome Measures:
  1. Offspring feces - Microbiome [ 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 ]
    Will be analysed for microbiome. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.

  2. Offspring feces - Short chain fatty acids [ 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 ]
    Will be analysed for short chain fatty acids. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.

  3. Offspring feces - Metabolomics [ 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 ]
    Will be analysed for metabolomics. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.

  4. Offspring feces - Proteomics [ 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 ]
    Will be analysed for proteomics. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.

  5. Offspring feces - pH [ 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 ]
    Will be assessed for pH. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.

  6. Offspring feces - Inflammation markers [ 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 ]
    Will be analysed for inflammation markers. Collected at birth by researcher and home by parents preferable <24 hours before the planned visit.

  7. Offspring feces - consistency [ 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 ]
    Whenever a fecal sample is collected stool consistency of the collected sample will be collected with a questionnaire.

  8. Offspring feces - frequency [ 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 ]
    Whenever a fecal sample is collected an estimate of stool frequency during the last week will be collected with a questionnaire.

  9. Offspring feces - gastrointestinal symptoms [ 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 ]
    Whenever a fecal sample is collected any gastrointestinal symptoms of the offspring during the last week will be collected with a questionnaire.

  10. Offspring urine [ Time Frame: Collected within the first week of birth and at 3 and 12 months follow up of each offspring ]
    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.

  11. Adult feces - Microbiome [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]

    Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit.

    Will be analysed for microbiome.


  12. Adult feces - 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 ]
    Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for short chain fatty acids.

  13. Adult feces - Metabolomics [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]

    Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit.

    Will be analysed for metabolomics


  14. Adult feces - Proteomics [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]

    Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit.

    Will be analysed for proteomics.


  15. Adult feces - Inflammation markers [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]

    Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit.

    Will be analysed for inflammation markers.


  16. Adult feces - pH [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]

    Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit.

    Will be assessed for pH.


  17. Adult feces - consistency [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]
    Whenever a fecal sample is collected stool consistency of the collected sample will be collected with a questionnaire.

  18. Adult feces - frequency [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]
    Whenever a fecal sample is collected an estimate of stool frequency during the last week will be collected with a questionnaire.

  19. Adult feces - gastrointestinal symptoms [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]
    Whenever a fecal sample is collected gastrointestinal symptoms during the last week will be collected with a questionnaire.

  20. Adult urine [ Time Frame: Collected at GA34-GA36 in each pregnancy and at study visit 3, 12 and 24 months pp of 1st child ]
    Participants will collect a urine spot sample at the study site. Adult urine will be analyzed for metabolomics.

  21. Offspring nutritional milestones [ Time Frame: Collected at 12 and 18 months after offspring birth ]
    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)

  22. Offspring development, WHO milestones [ Time Frame: Collected at 12 and 18 months after offspring birth ]
    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)

  23. Adult physical activity [ Time Frame: Collected at study visit 3, 12 and 24 months pp of 1st child ]
    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

  24. Adult physical activity - Physical Activity Questionnaire (IPAQ) [ 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 ]
    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.

  25. Adult background quistionnaire, ethnicity, [ Time Frame: Collected after screening in GA34-GA36 of 1st child ]
    All information will be collected electronic in RedCap.

  26. Adult background quistionnaire, education [ Time Frame: Collected after screening in GA34-GA36 of 1st child ]
    All information will be collected electronic in RedCap.

  27. Adult background quistionnaire, parity [ Time Frame: Collected after screening in GA34-GA36 of 1st child ]
    All information will be collected electronic in RedCap.

  28. Adult background quistionnaire, pre-pregnancy weight [ Time Frame: Collected after screening in GA34-GA36 of 1st child ]
    Pre-pregnancy weight, ethnicity, education and parity. All information will be collected electronic in RedCap.

  29. Adult background quistionnaire, demographic information [ Time Frame: Collected after screening in GA34-GA36 of 1st child ]
    All information will be collected electronic in RedCap.

  30. Adult wellbeing - Depression, Major depression questionnaire (ICD-10) [ 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 ]

    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.


  31. Adult wellbeing - Quality of life, Short form-36 (SF-36) [ 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 ]
    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.

  32. Adult wellbeing - Stress, Perceived Stress Scale [ 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 ]
    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

  33. Adult sleep [ 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 ]
    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.

  34. Adult dietary intake, 24-h recall [ 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 ]
    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).

  35. Adult dietary intake, FFQ [ 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 ]
    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.

  36. Offspring dietary intake [ Time Frame: Collected within the first week of birth and 3, 12 and 18 months after birth off each offspring ]
    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.

  37. Breast milk - nutrients biomarkers [ Time Frame: Collected within the first week of birth and 3 months pp after each birth ]
    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.

  38. Breast milk - Hormonal and inflammatory markers [ Time Frame: Collected within the first week of birth and 3 months pp after each birth ]
    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

  39. Breast milk - Metabolomics [ Time Frame: Collected within the first week of birth and 3 months pp after each birth ]
    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

  40. Breast milk - Proteomics [ Time Frame: Collected within the first week of birth and 3 months pp after each birth ]
    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.

  41. Breast milk - Short chain fatty acids and related metabolites [ Time Frame: Collected within the first week of birth and 3 months pp after each birth ]
    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

  42. Adult participation - dietitian guidance [ Time Frame: Every 1-2 month from 3 months pp of 1st child to birth of 2nd child ]
    It will be recorded how many times of individual and group dietitian guidance the participant attends

  43. Adult participation - physical session and power walk [ Time Frame: Every 2nd week from 3 months pp of 1st child to birth of 2nd child ]
    It will be recorded how many times the participant participates in physical activity sessions and how much the person have power walked



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 38 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Maternal inclusion Criteria:

  • Maternal pre-pregnancy BMI 27.0-44.9 kg/m^2
  • Maternal age range 18-38 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05798494


Contacts
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Contact: Ulla K Opstrup, MD, PhD +4522370857 ullaopst@rm.dk
Contact: Louise Rasmussen, MSc +4528731648 louisesuder@clin.au.dk

Locations
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Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8200
Contact: Ulla K Opstrup         
Principal Investigator: Ulla K Opstrup, MD, PhD         
Sponsors and Collaborators
Ulla Kampmann Opstrup
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
Investigators
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Principal Investigator: Ulla K Opstrup, Assoc Aarhus University Hospital
Publications:
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Responsible Party: Ulla Kampmann Opstrup, Associate professor, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT05798494    
Other Study ID Numbers: Prepare Child AUH
First Posted: April 4, 2023    Key Record Dates
Last Update Posted: January 18, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ulla Kampmann Opstrup, Aarhus University Hospital:
DNA Methylation
Overweight
Pregnancy
Weight loss
Diet, Reducing
Epigenetics
Healthy Lifestyle
Exercise
Offspring's neonatal fat mass
Pea Pod
Infant, Large for Gestational Age
Body Fat Distribution
Additional relevant MeSH terms:
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Overweight
Pediatric Obesity
Body Weight
Weight Loss
Overnutrition
Nutrition Disorders
Body Weight Changes
Obesity