An Optimized Programming of Healthy Children (APPROACH)

Study Overview
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Brief Summary
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The Nutrition Research Unit at Copenhagen University Hospital Herlev will during the fall 2013 initiate a randomized and controlled intervention study engaging 390 obese pregnant women. The overall aim of APPROACH is to investigate how an optimal diet during pregnancy influences the programming of the offspring. The children will after birth be included in a prospective cohort according to maternal randomization and examined six times from delivery until the age of nine years.

Detailed Description
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Overweight and excessive gestational weight gain (GWG) is associated with increased risk of high birth weight; furthermore there is increased risk of the child developing overweight, diabetes and other metabolic diseases in childhood or adulthood. The effect of reducing gestational weight gain while supplying optimized amount and sources of nutrients is not well investigated. Increased knowledge to the possibility and efficacy of preventing overweight and related diseases is necessary. Modification of protein source and increase in ratio of protein in relation to amount of carbohydrate and reduction of glycaemic index (GI) has in observational studies individually been linked to improved fetal body composition, metabolism and weight control later in life, and less weight gain and weight retention for the mother. The overall aim of APPROACH is to investigate how an optimal diet during pregnancy influences the programming of the offspring. This study will increase the knowledge of the effect of a specific nutrient composition and weight retention during pregnancy on growth and development during the foetal stage and until nine years off age, risk markers later metabolic diseases, especially diabetes and metabolic syndrome. APPROACH will be a dietary intervention investigating differences in responds to a high-protein, especially marine and dairy protein and low-GI diet versus a diet according to the Nordic Nutritional Recommendations. All visits and assessment will be performed by trained staff at Copenhagen University Hospital Herlev. Subjects will be women with expected delivery at Department of Gynaecology and Obstetrics and all examinations of gestational development and foetal growth will take place her; assessment of the children will be performed at the Department of Paediatrics. A total of 390 obese (body mass index (BMI) ≥ 30 kg/m2) pregnant women will be randomized to intervention or control and engage in the program from late first trimester or early second trimester to birth. After birth the children will be included in a prospective cohort according to maternal randomization and examined six times from delivery until the age of nine years. APPROACH will increase the knowledge of the effect of a nutrient composition with high protein for carbohydrate ratio and weight retention during pregnancy on growth and development during the foetal stage and until nine years off age, risk markers later metabolic diseases, especially diabetes and metabolic syndrome. Plasma lipids, markers of metabolic diseases, epigenetics and vitamin D status will be assessed at baseline and several times during pregnancy; and in both intervention and control group these data will increase the knowledge of the effect of supplementing with marine oils and vitamin D in pregnant women. Results from the intervention will be communicated to the general population and published in peer-relieved journals.

Official Title
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An Optimized Programming of Healthy Children (APPROACH) - The Most Favourable Dietary Protein:Carbohydrate Ratio During Pregnancy in the Context of New Nordic Diet

Conditions
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Pregnancy, Obesity, Gestational Age and Weight Conditions, Maternal Care for Excessive Fetal Growth, Metabolic Disorders

Intervention / Treatment
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* Other: High-Protein/Low-GI Diet
* Other: Low-protein/High-GI Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birth planed at Copenhagen University Hospital Herlev Pre-pregnancy BMI 28-45 Age 18-42 years Speak and understand oral and written Danish Singleton pregnancy Exclusion Criteria: Multiple pregnancy History of spontaneous abortions or gestational diabetes or preeclampsia or spontaneous preterm birth Dairy product intolerant or allergic > 10 kg weight change during the past year Abuse of alcohol or drugs (>14 units of alcohol per week) Critical or chronic disease: diabetes, kidney disease, medically treated heart diseases or arthritis, sarcoidosis, tuberculosis, cancer, liver disease, inflammatory gastrointestinal or lung disease, known active metabolic disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-protein/Low-GI Diet<br>High-protein (25-28 E%), especially marine- and dairy-protein (8-10 E%) and low-GI (GI<55) ad libitum Diet in accordance with the principles of palatability and sustainability of the New Nordic Diet. | Other: High-Protein/Low-GI Diet<br> <br> |
| Active Comparator: Low-protein/High-GI Diet<br>Ad libitum diet based on the Danish National Guidelines (NNR) (protein 10-20 E%; no information on restricting glycaemic load (GI   60)) and in accordance with the principles of palatability and sustainability of the New Nordic Diet. | Other: Low-protein/High-GI Diet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational weight gain | Changes in bodyweight, body composition (Magnetic Resonance Imaging) and measurements of body fat by means of skinfold thickness and mid-upper arm circumference. | Gestational week 14, 15, 17, 21, 25, 28, 36, 39 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth and development of fetus and child | Fetus: Nuchal Translucency Scan (once gw 11+3 - 14+0) and ultrasound scan (gw 28, 32, 36); child: Height, weight, body composition (Bioimpedance (month 6,18)and Dual-energy X-ray absorptiometry, DXA (month 0, 36, year 5, 9)), skin fold thickness and mid-upper arm circumference, IGF-1. | Gestational week 11+2, 14+0, 28, 32, 36 and month 0, 6, 18, 36 and year 5, 9 | 
| Fetal programming of obesity and metabolic disorders | Fasting blod samples (month 0 from umbilical cord), not at 6 months; dietary intake, physical activity, growth and development | Month 0, 6,18, 36 and year 5, 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gestational weight gain, Obese women, Fetal programming, Metabolic disorders, Development of obesity, Development og overweight, Complications during pregnancy and birth