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

PRE-Pregnancy Weight Loss And the Reducing Effect on CHILDhood Overweight - a Randomized Controlled Study in Copenhagen

The study is a single site parallel randomized controlled study.

The study will be assessing the effect of approximately 10% weight loss intervention vs a control group among healthy females/couples where the prospective mother is overweight or obese (BMI 27-45 kg/m^2) and between 18-38 years. The investigators will recruit a total of 240 healthy females/couples who will be randomized 1:1 to either intervention or control, stratified according to maternal pre-pregnancy BMI.

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 investigators hypothesize that parental weight loss intervention, initiated before conception, will facilitate lower parental insulin resistance, inflammation, body weight and adiposity, incretin responses compared to usual care. For the offspring the investigators hypothesize that the intervention will reduce adverse pregnancy outcomes with a reduction in offspring neonatal adiposity, reduced risk of being born large for gestational age (LGA) and with lower BMI z-score at 18 months.

Study Overview

• Status: Recruiting
• Conditions: Weight Loss; Pregnancy Related; Overweight and Obesity
• Intervention / Treatment: Behavioral: Weight loss intervention

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Malene Nygaard, MSC; Phone Number: +45 35 32 02 66; Email: nygaard@nexs.ku.dk
• Study Contact Backup: Name: Faidon Magkos, PhD; Phone Number: +4535333671; Email: fma@nexs.ku.dk

Study Locations

• Denmark
  • DK
    • Frederiksberg, DK, Denmark, 1958
      • Recruiting
      • University of Copenhagen
      • Contact: Malene Nygaard, MSC; Phone Number: +4535320266; Email: nygaard@nexs.ku.dk
      • Contact: Faidon Magkos, PhD; Phone Number: +4535333671; Email: fma@nexs.ku.dk
      • Principal Investigator: Christian Mølgaard, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Maternal inclusion Criteria:

• Maternal pre-pregnancy BMI 27.0-44.9 kg/m^2
• Maternal age range 18-38 years
• Connected to Hvidovre Hospital as place of birth or willing to change from other Hospitals in Region H to Hvidovre Hospital
• Not pregnant or breastfeeding

Paternal Inclusion Criteria - full protocol (optional participation):

• Paternal pre-pregnancy BMI 18.5-44.9 kg/m^2
• Paternal age range 18-55 years
• Biological father

Parental Inclusion Criteria:

• Planning pregnancy within 1 year
• 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 (intrauterine insemination allowed)
• ≥4 consecutive spontaneous pregnancy loss (female)
• Having tried to conceive or prior time to pregnancy of more than 12 months
• 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
• Engagement in elite sports or similar strenuous exercise ≥5 h/week
• Blood donation or transfusion within the past month before baseline
• Blood donation during the study
• Inability or unwillingness to follow the study protocol and instructions given by the study personnel
• Pregnancy registered between baseline visit and 4 weeks after the baseline visit (urinary analysis with dipstick)

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
• Amenorrhea
• Severely reduced semen quality incl. azoospermia

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:

• Having tried to conceive or prior time to pregnancy of more than 12 months
• Weight changes ± 5% three months prior to inclusion
• 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 baseline
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Rapid moderate weight loss (approximately 10% of body weight at baseline over 8-10 weeks or BMI 23 kg/m^2 is achieved) by very low-calorie diet (VLCD), reintroduction (4 weeks), weight loss maintenance until pregnancy (up to 12 months), and a high protein, high fiber diet during pregnancy (n=120 females/couples).	Behavioral: Weight loss intervention; Subjects will receive very low-calorie diet for 8-10 weeks to introduce a rapid weight loss of approximately 10%. Once target weight is achieved, participants will be reintroduced to foods to introduce weight stability. The male will follow the maternal randomization, i.e. weight loss if BMI ≥25 until a BMI of 23 or a weight loss of approximately 10% is obtained. During weight loss maintenance, subjects will receive dietary counseling to follow a diet high in protein (corresponding to 22-25E%), high fiber and wholegrain while fulfilling the requirements for essential fatty acids, micronutrients and trace elements in accordance with Nordic Nutrition Recommendations (NNR) 2012. Throughout the study period participants will be encouraged to follow the official recommendations for physical activity as recommended by the Danish health authorities 2022.
No Intervention: Standard of care; The control group will not receive any dietary advice prior to pregnancy. During pregnancy control subjects will receive dietary advice similar to the intervention group, i.e. a high protein, high fiber diet (n=120 females/couples).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal fat mass	Offspring's neonatal fat mass (grams) assessed by air displacement plethysmography (Pea POD)	Assessed at birth (strived <24 hours, but allow <48 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obstetrics outcome - length of gestational age	Length of gestational age.	Assessed at birth of offspring.
Obstetric - medication use	Medication use during labor	Collected from initiation of labor until completed birth of offspring.
Obstetric - delivery mode	Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth).	Collected at birth of offspring.
Obstetric - pregnancy complications	Pregnancy complications e.g. miscarriage, abortion (induced and indication for abortion), hydramnios, gestational hypertension, preeclampsia, need for maternal corticosteroid treatment for fetal lung maturation, urinary tract infection).	Collected at registration of pregnancy, in gestational age (GA) 8, GA13, GA20, GA28, GA36 and GA39).
Obstetric - Neonatal unit admissions	Neonatal unit admissions.	Collected at birth and until 6 months after birth of offspring.
Obstetric - obstetrics complications	Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization).	Collected at birth of offspring
Obstetrics - birth defects/abnormalities	Birth defects/abnormalities	Collected at birth of offspring
Neonatal morbidities	Neonatal morbidity (e.g. major congenital malformations (ICD10 Q00-Q99 or requiring medical or surgical treatment), birth injury, respiratory distress, transient tachypnoea, neonatal hypoglycemia, systemic infections, admission to neonatal intensive care unit, number of admission days, hyperbilirubinemia), deaths.	Collected at birth of offspring
Fetal and offspring growth - body weight	Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale.	Collected in gestational age (GA)11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
Fetal and offspring growth - length	Fetal length will be measured with ultrasound during pregnancy and offspring length will be measured using using an infantometer as appropriate for measuring infant, baby and toddler length.	Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
Fetal and offspring growth - abdominal circumference	Abdominal circumference will be measured with ultrasound during pregnancy and offspring abdominal circumference will be measured three times to the nearest 0.1 cm using a stretch-resistant measuring tape	Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
Fetal and offspring growth - crown circumference	Crown circumference will be measured with ultrasound during pregnancy and offspring crown circumference will be measured three times to the nearest 0.1 cm using a stretch-resistant measuring tape	Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
Fetal and offspring growth - femur length	Femur length will be measured with ultrasound during pregnancy and offspring thigh will be measured three times to the nearest 0.1 cm using a stretch-resistant measuring tape.	Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6, 12 and 18 months after birth.
Fetal growth - fractional limb volume	Fractional limb volume will be measured with ultrasound during pregnancy.	Collected in gestational age 28.
Offspring growth - BMI z-score	Offspring body mass index (BMI) z-score (BMI adjusted for age and sex).	Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
Offspring growth - weight for gestational age	Weight for gestational age. Measured as percent of normal weight related to gestational age.	Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
Offspring growth - large for gestational age	Large for gestational age. Prevalence of infants being LGA.	Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
Offspring growth - small for gestational age	Small for gestational age. Prevalence of offspring being small for gestational age (SGA).	Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
Offspring growth - apgar score	Apgar score (0-10). The higher the score, the better health condition of the offspring)	Collected at birth of offspring
Offspring growth	Offspring circumference (upper arm and hip) and 5 points skinfold (bi- and triceps, subscapularis, belly and waist). 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	Collected at birth and 3, 6, 12 and 18 months after birth of offspring.
Offspring growth - body composition by the POD system	Offspring fat free mass (g) and fat mass (g) will be assessed by air displacement plethysmography using the POD system (either the Pea POD or the Bod POD system depending on the most appropriate for age)	Collected at birth (strived <24 hours, but allow <48 hours), 3, 6, 12 and 18 months after birth of offspring.
Offspring growth - body composition by DEXA scan	Offspring fat free mass (g) and fat mass (g) will be assessed by a Dual-energy X-ray absorptiometry-scan (DEXA).	Collected at 6, 12 and 18 months after birth of offspring.
Offspring growth - bone markers by DEXA scan	Offspring bone area (cm^2), bone mineral density (g/cm^2) and bone mineral content (g) will be assessed by a Dual-energy X-ray absorptiometry-scan (DEXA).	Collected at 6, 12 and 18 months after birth of offspring.
Offspring blood pressure	Offspring blood pressure (diastolic and systolic blood pressure) will be measured three times after 5-10 minutes rest using an automated device placed on the arm and in direct contact with the skin.	Collected 6, 12 and 18-months after birth of offspring
Offspring heart rate	Offspring heart rate will be measured three times after 5-10 minutes rest using an automated device placed on the arm and in direct contact with the skin.	Collected 6, 12 and 18-months after birth of offspring
Offspring growth - self-reported body weight	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 14 of age.
Offspring growth - self-reported height	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 14 of age.
Adult weight	Adult body weight is measured to the nearest 0.1 kg using a calibrated scale	The intervention: each visit(V) throughout the study (baseline to 18mo. after birth). The control: before pregnancy (baseline, V11 and V14), all visits during pregnancy, at birth, at V27≤6days after birth and 3,6,12 and 18mo. after birth
Adult self-reported body weight (control group)	The control group will be instructed to self-report their body weight in a fasting state (no food or drink besides a maximum of 500 mL of water from 10 pm the night before) by using their own personal weight scale at home after having emptied their bladder at time point 9 and approximately monthly from time point 9 until registration of pregnancy.	From baseline to registration of pregnancy (4, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 52 weeks after baseline)
Adult Height	Adult height will be measured to the nearest 0.5 cm using a wall-mounted stadiometer.	Collected at baseline (V0).
Adult BMI	Calculated ad weight (kg)/height(m)^2	Collected baseline, visit (V)1-19, registration of pregnancy, in gestational age (GA)8, GA13, GA20, GA28, GA36, GA39, when giving birth and at 3, 6, 12 and 18 months after birth.
Adult anthropometric	Waist- and hip circumference will be measured to the nearest 0.5 cm. During pregnancy and at birth the waist of the female will not be measured.	Collected prior to pregnancy (at baseline, visit(V)5, V6, V7, V8, V12, and V16 (V5-V16 only the intervention)), during pregnancy (at registration of pregnancy, in gestational age(GA)13 and GA36), and at 3, 6, 12, and 18 months after birth of offspring.
Adult body composition by DEXA scan	Lean mass (g), fat mass (g), abdominal fat (g), visceral fat (g) assessed by a Dual-energy X-ray absorptiometry-scan.	Collected at baseline (visit (V)0), at registration of pregnancy (only male) and after birth (≤6 days after birth of offspring). Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult bone markers by DEXA scan	Bone area (cm^2), bone mineral density (g/cm^2) and bone mineral content (g) assessed by a Dual-energy X-ray absorptiometry-scan.	Collected at baseline (visit (V)0), at registration of pregnancy (only male) and after birth (≤6 days after birth of offspring). Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult blood pressure	Blood pressure (diastolic and systolic blood pressure) will be measured three times with two minutes apart after 5-10 minutes rest using a validated automatic device.	Collected at baseline (visit (V)0) and in gestational age (GA)36. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult heart rate	Heart rate will be measured three times with two minutes apart after 5-10 minutes rest using a validated automatic device.	Collected at baseline (visit (V)0) and in gestational age (GA)36. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult resting metabolic rate	Resting metabolic rate (calories/24-h) and respiratory quotient will be measured by indirect calorimetry using a ventilated hood system. Participants will lie in the supine position and rest for at least 5 min before measurements commence. The measurement will be performed twice and last for 25 min with 5 min between measurements.	Collected at baseline visit (V)0. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult resting respiratory quotient	Resting respiratory quotient will be measured by indirect calorimetry using a ventilated hood system. Participants will lie in the supine position and rest for at least 5 min before measurements commence. The measurement will be performed twice and last for 25 min with 5 min between measurements.	Collected at baseline visit (V)0. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult medication use	Use of medication will be collected throughout the study.	Use of medication will be collected at all visits.
Offspring medication use	Use of medication will be collected throughout the study.	Birth, after 3, 6, 12, and 18 months after birth of offspring.
Adult reproduction - Time to pregnancy	Duration of time to conception defined from time point allowed to conceive to registration of pregnancy.	Registration of pregnancy
Adult reproduction - Success rate	Success rate of pregnancy defined as number of achieved pregnancies.	Registration of pregnancy
Reproduction (male) - Sperm motility	Sperm motility (%).	Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
Reproduction (male) - Sperm concentration	Concentration (in million sperm cells/ml).	Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
Reproduction (male) - Sperm morphology	Morphology (%).	Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
Reproduction (male) - Sperm acrosomal status	Acrosomal status (%).	Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
Reproduction (male) - Sperm DNA fragmentation	DNA fragmentation (%)	Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult glucose metabolism (OGTT, only female)	2-h oral glucose tolerance test (OGTT) will be performed at gestational age~20 and ~28 or only ~28.	Collected at gestational age (GA)20 and 28 or only 28 (only female)
Adult glucose metabolism (CGM, only female)	A continuous glucose monitoring system will be attached to the designated area on the upper body as stated by the manufacture.	Collected at gestational age (GA)28+GA29
Adult glucose metabolism	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 fasting glucose, insulin, C-peptide and HbA1c	Collected at baseline (visit(V)0) and during pregnancy in gestational age (GA)36 (only female). Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult lipid profile	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 triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low-density lipoprotein VLDL and total cholesterol	Collected at baseline (visit(V)0) and during pregnancy in gestational age (GA)36 (only female). Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult inflammation markers	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 hsCRP, Tumor necrosis factor alpha (TNF-α) and interleukin (IL6).	Collected at baseline (visit(V)0) and during pregnancy in gestational age (GA)36 (only female). Additionally, at V8 (prior to pregnancy) for the intervention group.
Offspring glucose metabolism	Total amount of venous blood will be drawn at 6-, 12- and 18-months follow-up visit. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for glucose, insulin, C-peptide and HbA1c	Collected at 6, 12 and 18 months after birth
Offspring lipid profile	Total amount of venous blood will be drawn at 6-, 12- and 18-months follow-up visit. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for triglycerides, LDL, HDL, VLDL and total cholesterol.	Collected at 6, 12 and 18 months after birth
Offspring inflammation markers	Total amount of venous blood will be drawn at 6-, 12- and 18-months follow-up visit. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for hsCRP, TNF-α and IL6.	Collected at 6, 12 and 18 months after birth
Offspring growth factors and hormones	Total amount of venous blood will be drawn at 6-, 12- and 18-months follow-up visit. Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Insulin-like Growth Factor 1 (IGF-1) and growth hormone (GH).	Collected at 6, 12 and 18 months after birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cord blood - epigenetics	Cord blood will be drawn immediately after birth and analysed for epigenetic profile.	Collected at birth
Cord blood - pH	Cord blood will be drawn immediately after birth. pH will be assessed.	Collected at birth
Cord tissue	A sample of cord tissue will be collected immediately after birth and analysed for epigenetic profile.	Collected at birth
Placenta	Placenta weight (gram).	Collected at birth
Placenta - biopsies	Eight biopsies will be collected, four on the maternal site and four on the fetal side - one in each quadrant. The samples will be analyzed for protein expression patterns, placental markers, metabolomics, proteomics, markers of inflammation, immune markers and exosomes.	Collected at birth
Vaginal swab (female) - Microbiome	The females will be instructed how to perform the vaginal swab at the study site. Changes in microbiome will be assessed from vaginal swab samples.	Collected at baseline, at gestional age(GA) 13 and GA36. Additionally, the intervention group will collect a sample at visit (V)8 during the intervention period.
Vaginal swab (female) - pH	The females will be instructed how to perform the vaginal swab at the study site. Changes in pH will be assessed from vaginal swab samples.	Collected at baseline, at gestional age(GA) 13 and GA36. Additionally, the intervention group will collect a sample at visit (V)8 during the intervention period.
Offspring feces - Microbiom	Will be analysed for microbiome.	Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring feces - Short chain fatty acids	Will be analysed for short chain fatty acids.	Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring feces - Metabolomics	Will be analysed for metabolomics.	Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring feces - Proteomics	Will be analysed for proteomics.	Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring feces - pH	Will be assessed for pH.	Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring feces - Inflammation markers	Will be analysed for inflammation markers.	Collected at birth (the 4 th day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring feces - consistency and frequency	Whenever a fecal sample is collected stool consistency of the collected sample, and an estimate of stool frequency will be collected with a questionnaire.	Collected at birth (the 4 the day after birth or as soon as possible thereafter) and at 1, 3, 6, 12 and 18 months after birth.
Offspring urine	Parents will be instructed to collect offspring's urine samples. Offspring urine will be analyzed for metabolomics.	Collected at birth and at 1, 3, 6, 12 and 18 months of age.
Adult feces - Microbiome	Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for microbiome.	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult feces - Short chain fatty acids	Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for short chain fatty acids.	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult feces - Metabolomics	Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for metabolomics	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult feces - Proteomics	Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for proteomics.	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult feces - Inflammation markers	Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be analysed for inflammation markers.	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult feces - pH	Participants will collect a fecal spot sample at home maximum 24 hours before the planned visit. Will be assessed for pH.	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult feces - consistency and frequency	Whenever a fecal sample is collected stool consistency of the collected sample, and an estimate of stool frequency will be collected with a questionnaire.	Collected at baseline (visit(V)0), during pregnancy (gestational age (GA)36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult urine	Participants will collect a urine spot sample at the study site. Adult urine will be analyzed for metabolomics.	Collected at baseline (visitV)0), during pregnancy (GA36, only female) and 12 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult dietary intake	24-h dietary recall performed by trained personnel.	Collected at baseline (visit(V)0), during pregnancy (GA13 and GA36) and 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Offspring dietary intake	At birth (< 48 hours after birth) and at 3 months after offspring birth of offspring we will collect information on offspring dietary intake including breast feeding, use of formula and type as well as use of antibiotics. The offspring's dietary intake will be registered (either as 24-h dietary recall performed by trained personnel or by electronic software) at each follow-up visit (6, 12 and 18 months).	Collected at birth, after 3, 6, 12 and 18 months after offspring birth.
Semen epigenetics marks	Epigenetic profile based on array-measurements. Analysed for methylation changes.	Collected at baseline (visit(V)0) and at V11. Additionally, at V8 (prior to pregnancy) for the intervention group.
Cognitive development of offspring	Offspring cognitive development will be assessed by a Habituation and Free Play Test.	Collected at 6, 12 and 18 months after birth.
Offspring development	Diet, physical activity and sleep will be assessed by validated questionnaires.	3, 6, 12 and 18 months after offspring birth.
Offspring language development	Offspring language development will be assessed by validated questionnaires.	Collected 12 and 18 months after offspring birth.
Epigenetics	Epigenetics analyses from whole blood. Will be analysed for methylation changes.	Collected at baseline (visit(V)0) and at V8 (only intervention group) and in gestational age (GA)36 - only female). Collected at birth for offspring.
Adult physical activity	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.	Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 (only females during pregnancy). Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult physical activity	Physical activity will be assessed by the International Physical Activity Questionnaire (IPAQ).	Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult background	Demographic information.	Collected prior baseline V0
Adult wellbeing - Depression	Depression will be assessed by Major depression questionnaire (ICD-10).	Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult wellbeing - Quality of life	Quality of life will be assessed by the validated tool, Short form-36 (SF-36).	Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult wellbeing - Stress	Stress will be assessed by validated tool, Perceived Stress Scale.	Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult sleep	Sleep will be assessed by the validated tool, Pittsburgh sleep quality index questionnaire (PSQI).	Collected at baseline (visit(V)0), at gestational age (GA)13 and GA36 and 3, 6, 12 and 18 months after birth of offspring. Additionally, at V8 (prior to pregnancy) for the intervention group.
Adult sexual score	Sexual score assessed by questionnaire.	Collected at baseline (visit(V)0). Additionally, at V8 (prior to pregnancy) for the intervention group.
Adults liver steatosis and stiffness by Liver ultrasound elastography (FibroScan)	Measured by Liver ultrasound elastography (FibroScan)	Collected at baseline (Visit(v)0), prior to pregnancy for the intervention group (v8), week 52 in the pre-pregnancy period if pregnancy is not achieved (v19), at gestational age (GA)20 (v23), and 3 months after birth of offspring (v28).
Offspring liver steatosis and stiffness by Liver ultrasound elastography (FibroScan)	Measured by Liver ultrasound elastography (FibroScan)	Measured at 3 and 18 months after offspring birth.
Breast milk from mother - establishment of lactation	Non-fasting breast milk. Mothers will empty one full breast at each time point with an electric pump. Breast milk will be analysed for sodium:potasium ratio	Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
Breast milk from mother - establishment of lactation - inflammatory markers	Non-fasting breast milk. Mothers will empty one full breast at each time point with an electric pump. Breast milk will be analysed for inflammatory markers	Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
Breast milk from mother - establishment of lactation - immune markers	Non-fasting breast milk. Mothers will empty one full breast at each time point with an electric pump. Breast milk will be analysed for immune markers	Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
Breast milk from mother - establishment of lactation - growth factors	Non-fasting breast milk. Mothers will empty one full breast at each time point with an electric pump. Breast milk will be analysed for growth factors	Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
Breast milk from mother - establishment of lactation - appetite regulation hormones	Non-fasting breast milk. Mothers will empty one full breast at each time point with an electric pump. Breast milk will be analysed for appetite regulation hormones	Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)
Breast milk from mother - establishment of lactation - microbiome	Non-fasting breast milk. Mothers will empty one full breast at each time point with an electric pump. Breast milk will be analysed for microbiome	Collected at visit 27 (6 days after birth), visit 28 (3 months after birth), visit 29 (6 months after birth)

Collaborators and Investigators

• Sponsor: Christian Mølgaard
• Collaborators: University of Copenhagen; Dept. of Obstetrics and Gynecology, Hvidovre Hospital, Denmark; Department of Growth and Reproduction Rigshospitalet, Denmark; Center for Healthy Childhood, Denmark
• Investigators: Principal Investigator: Christian Mølgaard, MD, University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: November 11, 2022
• First Posted (Actual): November 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight Changes; Obesity; Pediatric Obesity; Weight Loss; Overweight; Body Weight
• Other Study ID Numbers: L101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No