Clinical trial NCT00362089: Fatty Acids During Pregnancy and Lactation and Body Fat Mass in Newborns
Official title: The Impact of the Nutritional Fatty Acids During Pregnancy and Lactation for Early Human Adipose Tissue Development
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight
Obesity
Keywords: n-3 fatty acids
n-6 fatty acids
long chain polyunsaturated fatty acids
pregnancy
lactation
breast feeding
breast milk
adipose tissue
newborn
fetal development
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: Else Kröner-Fresenius-Foundation; International Unilever-Foundation; Danone Research
name: EU funding by EARNEST consortium;German Ministry of Education and Research GF-GFGI01120708)
First posted: 2006-08-09
Enrollment: 208
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: amount of fat mass in the offspring
timeFrame: at birth, 6 weeks, 4 months, 1 year postpartum
Secondary outcomes:
measure: amount of fat mass in the offspring
timeFrame: at 1,5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum (follow-up)
measure: offspring body height
timeFrame: at birth, 6 weeks, 4 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum
measure: head circumference of newborns, infants and children
timeFrame: at birth, 6 weeks, 4 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum
measure: blood lipids of pregnant and lactating women
timeFrame: 15th wk gestation, 32nd wk gestation, 6 weeks pp, 4 months pp
measure: fatty acid profile of phospholipids and erythrocyte membrane lipids, fatty acid metabolites
timeFrame: 15th wk gestation, 32nd wk gestation, birth, 6 wks, 4 months, 1 year, 3 years postpartum
measure: daily intake of maternal fatty acids
timeFrame: 15 wks gestation, 32nd wks gestation, 6 wks pp
measure: offspring abdominal subcutaneous and preperitoneal fat
timeFrame: 6 weeks, 4 months , 1 year , 1.5 years , 2 years, 2.5 years, 3 years, 4 years, 5 years postpartum
measure: offspring fat mass, abdominal fat
timeFrame: 6 weeks, 4 months, 5 years postpartum
measure: maternal and offspring gene expression (mRNA, miRNA)
timeFrame: 15 wk gestation, 32nd wk gestation (maternal), birth, 3 years (offspring)
measure: maternal and offspring DNA analysis (SNPs, DNA methylation)
timeFrame: 15 wk gestation, 32nd wk gestation (maternal), birth, 3 years (offspring)
measure: epigenetic analyses (histone modification, DNA methylation)
timeFrame: birth
measure: cytokines, adipokines and hormone analysis
timeFrame: 15th wk gestation, 32nd wk gestation, 6 wks pp, 4 months pp (maternal), birth, 4 months, 1 year, 3 years postpartum (offspring)
measure: protein analysis, proteomics
timeFrame: 15th wk gestation, 32nd wk gestation (maternal), birth, 4 months, 1 year, 3 years postpartum (offspring)
measure: metabolomics, lipidomics
timeFrame: 15th wk gestation, 32nd wk gestation (maternal), birth, 4 months, 1 year, 3 years postpartum (offspring)
measure: breast milk oligosaccharides
timeFrame: 6 wks and 4 months postpartum
measure: offspring atopic eczema
timeFrame: 1.5 years - 5 years postpartum
measure: offspring allergic diseases (asthma, rhinitis)
timeFrame: 5 years postpartum
measure: developmental evaluation of children
timeFrame: 2 years - 5 years postpartum
measure: motor development of children
timeFrame: 4 years and 5 years postpartum
measure: physical activity of children
timeFrame: 2 years - 5 years postpartum
measure: dietary intake of children
timeFrame: 2 years - 5 years postpartum
measure: offspring body weight
timeFrame: at birth, 6 weeks, 4 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 4 years and 5 years postpartum
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Technische Universität München
Study officials:
affiliation: Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Technische Universität München
name: Hans Hauner, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Meyer DM, Brei C, Stecher L, Brunner S, Hauner H. Maternal insulin resistance, triglycerides and cord blood insulin are not determinants of offspring growth and adiposity up to 5 years: a follow-up study. Diabet Med. 2018 Oct;35(10):1399-1403. doi: 10.1111/dme.13765. Epub 2018 Aug 2.
citation: Meyer DM, Brei C, Stecher L, Much D, Brunner S, Hauner H. The relationship between breast milk leptin and adiponectin with child body composition from 3 to 5 years: a follow-up study. Pediatr Obes. 2017 Aug;12 Suppl 1:125-129. doi: 10.1111/ijpo.12192. Epub 2016 Nov 10.
citation: Brei C, Stecher L, Much D, Karla MT, Amann-Gassner U, Shen J, Ganter C, Karampinos DC, Brunner S, Hauner H. Reduction of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring body composition: follow-up results from a randomized controlled trial up to 5 y of age. Am J Clin Nutr. 2016 Jun;103(6):1472-81. doi: 10.3945/ajcn.115.128520. Epub 2016 Apr 6.
citation: Brei C, Much D, Heimberg E, Schulte V, Brunner S, Stecher L, Vollhardt C, Bauer JS, Amann-Gassner U, Hauner H. Sonographic assessment of abdominal fat distribution during the first year of infancy. Pediatr Res. 2015 Sep;78(3):342-50. doi: 10.1038/pr.2015.108. Epub 2015 Jun 8.
citation: Brunner S, Schmid D, Zang K, Much D, Knoeferl B, Kratzsch J, Amann-Gassner U, Bader BL, Hauner H. Breast milk leptin and adiponectin in relation to infant body composition up to 2 years. Pediatr Obes. 2015 Feb;10(1):67-73. doi: 10.1111/j.2047-6310.2014.222.x. Epub 2014 Apr 14.