Overweight and Obesity, Pregnancy Related, Weight Loss
Conditions
Brief summary
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 12 months.
Interventions
BEHAVIORALWeight 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.
Sponsors
Christian Mølgaard
Hvidovre University Hospital
Rigshospitalet, Denmark
University of Copenhagen
Centre for Childhood Health, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 38 Years
Healthy volunteers
Yes
Inclusion criteria
Maternal inclusion Criteria: * Maternal pre-pregnancy BMI 27.0-44.9 kg/m\^2 * Maternal age range 18-38 years * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal fat mass | Assessed at birth (strived <24 hours, but allow <48 hours) | Offspring's neonatal fat mass (grams) assessed by air displacement plethysmography (Pea POD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Obstetrics outcome - length of gestational age | Assessed at birth of offspring. | Length of gestational age. |
| Obstetric - medication use | Collected from initiation of labor until completed birth of offspring. | Medication use during labor |
| Obstetric - delivery mode | Collected at birth of offspring. | Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth). |
| Obstetric - pregnancy complications | Collected at registration of pregnancy, in gestational age (GA) 8, GA13, GA20, GA28, GA36 and GA39). | 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). |
| Obstetric - Neonatal unit admissions | Collected at birth and until 6 months after birth of offspring. | Neonatal unit admissions. |
| Obstetric - obstetrics complications | Collected at birth of offspring | Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization). |
| Obstetrics - birth defects/abnormalities | Collected at birth of offspring | Birth defects/abnormalities |
| Neonatal morbidities | Collected at birth of offspring | Neonatal morbidity (e.g. major congenital malformations (ICD10 Q00-Q99 or requiring medical or surgical treatment), birth injury, respiratory distress, transient tachypnoea, neonatal hypoglycemia, systemic infections, admission to neonatal intensive care unit, number of admission days, hyperbilirubinemia), deaths. |
| Fetal and offspring growth - body weight | Collected in gestational age (GA)11-13, GA19-21 and GA28, at birth and 3, 6 and 12 months after birth. | Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale. |
| Fetal and offspring growth - length | Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6 and 12 months after birth. | 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. |
| Fetal and offspring growth - abdominal circumference | Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6 and 12 months after birth. | Abdominal circumference will be measured with ultrasound during pregnancy and offspring abdominal circumference will be measured three times to the nearest 0.1 cm using a stretch-resistant measuring tape |
| Fetal and offspring growth - crown circumference | Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6 and 12 months after birth. | 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 |
| Fetal and offspring growth - femur length | Collected in gestational age (GA) 11-13, GA19-21 and GA28, at birth and 3, 6 and 12 months after birth. | 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. |
| Fetal growth - fractional limb volume | Collected in gestational age 28. | Fractional limb volume will be measured with ultrasound during pregnancy. |
| Offspring growth - BMI z-score | Collected at birth and 3, 6 and 12 months after birth of offspring. | Offspring body mass index (BMI) z-score (BMI adjusted for age and sex). |
| Offspring growth - weight for gestational age | Collected at birth and 3, 6 and 12 months after birth of offspring. | Weight for gestational age. Measured as percent of normal weight related to gestational age. |
| Offspring growth - large for gestational age | Collected at birth and 3, 6 and 12 months after birth of offspring. | Large for gestational age. Prevalence of infants being LGA. |
| Offspring growth - small for gestational age | Collected at birth and 3, 6 and 12 months after birth of offspring. | Small for gestational age. Prevalence of offspring being small for gestational age (SGA). |
| Offspring growth - apgar score | Collected at birth of offspring | Apgar score (0-10). The higher the score, the better health condition of the offspring) |
| Offspring growth | Collected at birth and 3, 6 and 12 months after birth of offspring. | 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 |
| Offspring growth - body composition by the POD system | Collected at birth (strived <24 hours, but allow <48 hours) and 3 months after birth of offspring. | 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) |
| Offspring blood pressure | Collected 12 months after birth of offspring | 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. |
| Offspring heart rate | Collected 12 months after birth of offspring | 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. |
| Offspring growth - self-reported body weight | 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. | Self-reported body weight |
| Offspring growth - self-reported height | 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. | Self-reported height |
| Adult weight | The intervention: each visit(V) throughout the study (baseline to 12mo. after birth). The control: before pregnancy (baseline, V11 and V14), all visits during pregnancy, at birth, at V27≤6days after birth and 3, 6 and 12 mo. after birth | Adult body weight is measured to the nearest 0.1 kg using a calibrated scale |
| Adult self-reported body weight (control group) | From baseline to registration of pregnancy (4, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 52 weeks after baseline) | 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. |
| Adult Height | Collected at baseline (V0). | Adult height will be measured to the nearest 0.5 cm using a wall-mounted stadiometer. |
| Adult BMI | 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 and 12 months after birth. | Calculated ad weight (kg)/height(m)\^2 |
| Adult anthropometric | 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 and 12 months after birth of offspring. | 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. |
| Adult body composition by DEXA 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. | Lean mass (g), fat mass (g), abdominal fat (g), visceral fat (g) assessed by a Dual-energy X-ray absorptiometry-scan. |
| Adult bone markers by DEXA 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. | Bone area (cm\^2), bone mineral density (g/cm\^2) and bone mineral content (g) assessed by a Dual-energy X-ray absorptiometry-scan. |
| Adult blood pressure | Collected at baseline (visit (V)0) and in gestational age (GA)36. Additionally, at V8 (prior to pregnancy) for the intervention group. | 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. |
| Adult heart rate | Collected at baseline (visit (V)0) and in gestational age (GA)36. Additionally, at V8 (prior to pregnancy) for the intervention group. | Heart rate will be measured three times with two minutes apart after 5-10 minutes rest using a validated automatic device. |
| Adult resting metabolic rate | Collected at baseline visit (V)0. Additionally, at V8 (prior to pregnancy) for the intervention group. | 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. |
| Adult resting respiratory quotient | Collected at baseline visit (V)0. Additionally, at V8 (prior to pregnancy) for the intervention group. | 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. |
| Adult medication use | Use of medication will be collected at all visits. | Use of medication will be collected throughout the study. |
| Offspring medication use | Birth, after 3, 6 and 12 months after birth of offspring. | Use of medication will be collected throughout the study. |
| Adult reproduction - Time to pregnancy | Registration of pregnancy | Duration of time to conception defined from time point allowed to conceive to registration of pregnancy. |
| Adult reproduction - Success rate | Registration of pregnancy | Success rate of pregnancy defined as number of achieved pregnancies. |
| Reproduction (male) - Sperm motility | Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group. | Sperm motility (%). |
| Reproduction (male) - Sperm concentration | Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group. | Concentration (in million sperm cells/ml). |
| Reproduction (male) - Sperm morphology | Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group. | Morphology (%). |
| Reproduction (male) - Sperm acrosomal status | Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group. | Acrosomal status (%). |
| Reproduction (male) - Sperm DNA fragmentation | Collected baseline and at visit (V) 11. Additionally, at V8 (prior to pregnancy) for the intervention group. | DNA fragmentation (%) |
| Adult glucose metabolism (OGTT, only female) | Collected at gestational age (GA)20 and 28 or only 28 (only female) | 2-h oral glucose tolerance test (OGTT) will be performed at gestational age\~20 and \~28 or only \~28. |
| Adult glucose metabolism (CGM, only female) | Collected at gestational age (GA)28+GA29 | A continuous glucose monitoring system will be attached to the designated area on the upper body as stated by the manufacture. |
| Adult glucose metabolism | 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. | 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 |
| Adult lipid profile | 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. | 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 |
| Adult inflammation markers | 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. | 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). |
| Offspring glucose metabolism | Collected at 12 months after birth | Total amount of venous blood will be drawn at 12-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 |
| Offspring lipid profile | Collected at 12 months after birth | Total amount of venous blood will be drawn at 12-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. |
| Offspring inflammation markers | Collected at 12 months after birth | Total amount of venous blood will be drawn at 12-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. |
| Offspring growth factors and hormones | Collected at 12 months after birth | Total amount of venous blood will be drawn at 12-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). |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORChristian Mølgaard, MD
University of Copenhagen
Outcome results
None listed