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

Overview

The study is a single site parallel randomized controlled study. The study will be assessing the effect of a 10% pre-conceptional weight loss intervention vs a control group among healthy couples where the prospective mother is pregnant and overweight or obese (BMI 27-44.9 kg/m\^2). The couples in intervention group will receive dietitian counseling and participate in physical activity sessions to attain the 10% weight loss. The overall objective is to test whether a comprehensive pre-conceptional parental weight loss intervention effectively reduces the risk of offspring overweight, and adiposity and its complications compared to a control group.

Detailed description

The study is a single site parallel randomized controlled study. The study will be assessing the effect of a pre-conceptional weight loss intervention vs a control group among healthy couples where the prospective mother is pregnant (recruited at gestational age 18-36), overweight or obese (BMI 27-44.9 kg/m\^2), between 18-38 years and planning an additional pregnancy within the following 3 years.

The investigators will recruit a total of 140 healthy pregnant couples who will be randomized 1:1 to either intervention or control, stratified according to maternal pre-pregnancy BMI and previous or present diagnosis of gestational diabetes.

The couples in intervention group will receive dietary counseling by a dietitian from 3 months post-partum of the 1st child until birth of the 2nd child. The goal is to achieve a healthy lifestyle and a moderate weight loss of 10% according to pre-pregnancy weight during the first year. Hereafter, the couples will be guided in weight maintenance until pregnancy of the second child. During pregnancy the goal is to achieve a healthy weight gain. Couples in intervention group will also participate in physical activity sessions every 2nd week and advised to walk with moderate intensity at least 2-4 times a week for at least half an hour.

The overall objective is to test whether a comprehensive pre-conceptional parental weight loss intervention effectively reduces the risk of offspring overweight, and adiposity and its complications compared to a control group. The 1st baby born before intervention is started will be the "index child" and the metabolic and anthropometric parameters of the 1st child will be compared to parameters of the second child to assess the effect of the parent's healthy lifestyle between the two pregnancies.

The investigators hypothesize that parental weight loss intervention, initiated before conception, will facilitate lower parental insulin resistance, inflammation, body weight and adiposity, incretin responses and energy expenditure compared to usual care. For the offspring the investigators hypothesize that the intervention will reduce adverse pregnancy outcomes with a short-term reduction in the risk of being born large for gestational age with excessive fat mass and a long-term reduction in the risk of developing overweight or obesity as a consequence of both social (family approach) and biological (epigenetic modifications) pathways.

Interventions

• 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 t

Primary outcome measures

• Neonatal fat mass [Time frame: Collected within the first week of birth (strived <48 hours)]
• Difference in epigenetic changes in child 1 and 2 [Time frame: Assessed at birth]

Secondary outcome measures (12)

• Obstetrics outcome - length of gestational age [Time frame: Assessed at birth of both offsprings]
• Obstetric - medication use [Time frame: Collected from initiation of labor until completed birth of both offsprings]
• Obstetric - delivery mode [Time frame: Collected at birth of both offsprings]
• Obstetric - pregnancy complications [Time frame: Collected at gestational age (GA) 34-36 and after birth of both offsprings]
• Obstetric - Neonatal unit admissions [Time frame: Collected at birth and until 12 months after birth of both offsprings]
• Obstetric - obstetrics complications [Time frame: Collected at birth of both offsprings]
• Obstetrics - birth defects/abnormalities [Time frame: Collected at birth of both offsprings]
• Neonatal morbidities [Time frame: Collected at birth of both offsprings]
• 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 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 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]
• Fetal and offspring growth - crown circumference [Time frame: Collected from medical record during pregnancy, measured in GA34-GA36 via ultrasound in both pregnancies]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Denmark · 1 center

• Aarhus University Hospital — Aarhus

Publications

• Rasmussen L, Knorr S, Antoniussen CS, Bruun JM, Ovesen PG, Fuglsang J, Kampmann U. The Impact of Lifestyle, Diet and Physical Activity on Epigenetic Changes in the Offspring-A Systematic Review. Nutrients. 2021 Aug 17;13(8):2821. doi: 10.3390/nu13082821. PMID 34444981

Identifiers

NCT: NCT05798494 · Prepare Child AUH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗