Fatty Acids During Pregnancy and Lactation and Body Fat Mass in Newborns

Study Overview
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Brief Summary
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Pregnant and lactating women receive n-3 fatty acids starting from week 15 of gestation until 4 months post-partum (pp) in comparison to a control group, who only gets information about adequately healthy nutrition during pregnancy and lactation. The amount of fat in newborns is measured through skinfold thickness, ultrasound, and magnetic resonance imaging (MRI). It is hypothesised that a reduction in arachidonic acid intake and an increase of n-3 LC PUFAs (long chain polyunsaturated fatty acids) via supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) could lead to less expansive fat tissue development in the first year of life.

Detailed Description
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The prevalence of overweight and obese children and adolescents dramatically increased during the last two decades. In Germany every 5th school child is overweight and 4 - 8% of all children are obese. Recent studies suggest that fatty acids in maternal nutrition may have an impact on the fat tissue development during the fetal period. Animal studies showed that a reduction in the arachidonic acid intake, a higher intake of n-3 LC PUFAs (i.e. DHA and EPA) and a resulting lower n-6/n-3 fatty acid ratio in food will cause less expansive fat tissue development in the first year of life. In vitro studies and personal observations in animal studies also showed that n-6 fatty acids (i.e. arachidonic acid) stimulate the differentiation of preadipocytes to adipocytes whereas n-3 fatty acids (i.e. DHA and EPA) have the contrary effect. The impact of the maternal fatty acid pattern on the early fat tissue development can only be clarified in an intervention study. Therefore it is planned to recruit 204 pregnant women in the 14th week of gestation. They will be randomly assigned to the intervention or control group. The intervention group will receive n-3 LC-PUFAs (DHA and EPA) as fish oil capsules from the 15th week of gestation until 4 months pp, the control group will get nutrition counselling according to the recommendations of the German Society for Nutrition during the same time period. Blood samples of the pregnant and lactating women, umbilical cord blood, placental tissue and blood of the newborns will be collected for fatty acid analysis. Body fat mass in newborns will be determined from delivery until 4 months pp via skinfold measurement, ultrasound, and MRI. The hypothesis is that newborns in the group of the supplemented mothers will have less expansive fat tissue development than children from mothers in the control group. This would be an innovative primary preventive approach in a period of increasing prevalence of overweight and obese children and adolescents.

Official Title
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The Impact of the Nutritional Fatty Acids During Pregnancy and Lactation for Early Human Adipose Tissue Development

Conditions
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Overweight, Obesity

Intervention / Treatment
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* Dietary Supplement: Marinol D-40


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age <= 15th week of gestation Age: 18-43 years Written informed consent Body mass index (BMI) before pregnancy between 18 and 30 km/m2 Exclusion Criteria: High risk pregnancy Hypertonus Chronic diseases (i.e. diabetes mellitus) Psychiatric diseases Former supplementation with LC-PUFA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Marinol<br>Intervention group with Marinol D40 fish oil capsules | Dietary Supplement: Marinol D-40<br>* Marinol D-40, three capsules per day, from 15th week of gestation until 4th month of lactation<br>|
| No Intervention: Nutrition counseling<br>Control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| amount of fat mass in the offspring | skinfold thickness measurements | at birth, 6 weeks, 4 months, 1 year postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| amount of fat mass in the offspring | skinfold thickness measurements | at 1,5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum (follow-up) | 
| offspring body height |  | at birth, 6 weeks, 4 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum | 
| head circumference of newborns, infants and children |  | at birth, 6 weeks, 4 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum | 
| blood lipids of pregnant and lactating women |  | 15th wk gestation, 32nd wk gestation, 6 weeks pp, 4 months pp | 
| fatty acid profile of phospholipids and erythrocyte membrane lipids, fatty acid metabolites | maternal and offspring blood cells and plasma, placenta, umbilical cord tissue, blood cells and plasma, breast milk | 15th wk gestation, 32nd wk gestation, birth, 6 wks, 4 months, 1 year, 3 years postpartum | 
| daily intake of maternal fatty acids | 7 day dietary records | 15 wks gestation, 32nd wks gestation, 6 wks pp | 
| offspring abdominal subcutaneous and preperitoneal fat | Ultrasonography | 6 weeks, 4 months , 1 year , 1.5 years , 2 years, 2.5 years, 3 years, 4 years, 5 years postpartum | 
| offspring fat mass, abdominal fat | magnetic resonance imaging | 6 weeks, 4 months, 5 years postpartum | 
| maternal and offspring gene expression (mRNA, miRNA) | placenta, umbilical cord tissue, white blood cells, blood plasma | 15 wk gestation, 32nd wk gestation (maternal), birth, 3 years (offspring) | 
| maternal and offspring DNA analysis (SNPs, DNA methylation) | placenta, umbilical cord tissue, white blood cells | 15 wk gestation, 32nd wk gestation (maternal), birth, 3 years (offspring) | 
| epigenetic analyses (histone modification, DNA methylation) | placenta, umbilical cord tissue, white blood cells | birth | 
| cytokines, adipokines and hormone analysis | maternal and offspring blood cells and plasma, placenta, umbilical cord blood cells and plasma, breast milk | 15th wk gestation, 32nd wk gestation, 6 wks pp, 4 months pp (maternal), birth, 4 months, 1 year, 3 years postpartum (offspring) | 
| protein analysis, proteomics | maternal and offspring blood cells and plasma, placenta, umbilical cord blood cells and plasma | 15th wk gestation, 32nd wk gestation (maternal), birth, 4 months, 1 year, 3 years postpartum (offspring) | 
| metabolomics, lipidomics | maternal and offspring blood cells and plasma, placenta, umbilical cord blood cells and plasma | 15th wk gestation, 32nd wk gestation (maternal), birth, 4 months, 1 year, 3 years postpartum (offspring) | 
| breast milk oligosaccharides |  | 6 wks and 4 months postpartum | 
| offspring atopic eczema | parent questionnaire | 1.5 years - 5 years postpartum | 
| offspring allergic diseases (asthma, rhinitis) | parent questionnaire | 5 years postpartum | 
| developmental evaluation of children | parent questionnaire (based on Minnesota Scales) | 2 years - 5 years postpartum | 
| motor development of children |  | 4 years and 5 years postpartum | 
| physical activity of children | parent questionnaire | 2 years - 5 years postpartum | 
| dietary intake of children | 3 day dietary record | 2 years - 5 years postpartum | 
| offspring body weight |  | at birth, 6 weeks, 4 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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newborn, n-3 fatty acids, n-6 fatty acids, long chain polyunsaturated fatty acids, pregnancy, lactation, breast feeding, breast milk, adipose tissue, fetal development