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

Overview

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.

Full Title of Study: “The Impact of the Nutritional Fatty Acids During Pregnancy and Lactation for Early Human Adipose Tissue Development”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2010

Detailed Description

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.

Interventions

  • Dietary Supplement: Marinol D-40
    • Marinol D-40, three capsules per day, from 15th week of gestation until 4th month of lactation

Arms, Groups and Cohorts

  • Active Comparator: Marinol
    • Intervention group with Marinol D40 fish oil capsules
  • No Intervention: Nutrition counseling
    • Control group

Clinical Trial Outcome Measures

Primary Measures

  • amount of fat mass in the offspring
    • Time Frame: at birth, 6 weeks, 4 months, 1 year postpartum
    • skinfold thickness measurements

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 43 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Technical University of Munich
  • Collaborator
    • Else Kröner-Fresenius-Foundation; International Unilever-Foundation; Danone Research
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ulrike Amann-Gassner, PhD – Technical University of Munich
  • Overall Official(s)
    • Hans Hauner, Prof., Principal Investigator, Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Technische Universität München

References

Hauner H, Vollhardt C, Schneider KT, Zimmermann A, Schuster T, Amann-Gassner U. The impact of nutritional fatty acids during pregnancy and lactation on early human adipose tissue development. Rationale and design of the INFAT study. Ann Nutr Metab. 2009;54(2):97-103. doi: 10.1159/000209267. Epub 2009 Mar 19.

Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Bruderl M, Heimberg E, Bartke N, Boehm G, Bader BL, Amann-Gassner U, Hauner H. Effect of dietary intervention to reduce the n-6/n-3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age. Eur J Clin Nutr. 2013 Mar;67(3):282-8. doi: 10.1038/ejcn.2013.2. Epub 2013 Jan 23.

Brunner S, Schmid D, Huttinger K, Much D, Bruderl M, Sedlmeier EM, Kratzsch J, Amann-Gassnerl U, Bader BL, Hauner H. Effect of reducing the n-6/n-3 fatty acid ratio on the maternal and fetal leptin axis in relation to infant body composition. Obesity (Silver Spring). 2014 Jan;22(1):217-24. doi: 10.1002/oby.20481. Epub 2013 Sep 10.

Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Bruderl M, Heimberg E, Bartke N, Boehm G, Bader BL, Amann-Gassner U, Hauner H. Breast milk fatty acid profile in relation to infant growth and body composition: results from the INFAT study. Pediatr Res. 2013 Aug;74(2):230-7. doi: 10.1038/pr.2013.82. Epub 2013 May 28.

Brunner S, Schmid D, Huttinger K, Much D, Heimberg E, Sedlmeier EM, Bruderl M, Kratzsch J, Bader BL, Amann-Gassner U, Hauner H. Maternal insulin resistance, triglycerides and cord blood insulin in relation to post-natal weight trajectories and body composition in the offspring up to 2 years. Diabet Med. 2013 Dec;30(12):1500-7. doi: 10.1111/dme.12298. Epub 2013 Sep 11.

Citations Reporting on Results

Hauner H, Much D, Vollhardt C, Brunner S, Schmid D, Sedlmeier EM, Heimberg E, Schuster T, Zimmermann A, Schneider KT, Bader BL, Amann-Gassner U. Effect of reducing the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on infant adipose tissue growth within the first year of life: an open-label randomized controlled trial. Am J Clin Nutr. 2012 Feb;95(2):383-94. doi: 10.3945/ajcn.111.022590. Epub 2011 Dec 28.

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