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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00362089
• Other study ID #: EKFZ001_CN
• Secondary ID: INFAT
• Status: Completed
• Phase: N/A
• First received: August 8, 2006
• Last updated: February 3, 2014
• Start date: June 2006
• Est. completion date: November 2010

Study information

• Verified date: February 2014
• Source: Technische Universität München
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

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

Locations

Country	Name	City	State
Germany	Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Technische Universität München	Munich

Sponsors (3)

Lead Sponsor	Collaborator
Technische Universität München	Else Kröner-Fresenius-Foundation; International Unilever-Foundation; Danone Research, EU funding by EARNEST consortium;German Ministry of Education and Research GF-GFGI01120708)

Country where clinical trial is conducted

Germany, 

References & Publications (6)

Brunner S, Schmid D, Hüttinger K, Much D, Brüderl 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. — View Citation

Brunner S, Schmid D, Hüttinger K, Much D, Heimberg E, Sedlmeier EM, Brüderl 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. — View 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 g — View 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. — View Citation

Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Brüderl 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. — View Citation

Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Brüderl 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	amount of fat mass in the offspring	skinfold thickness measurements	at birth, 6 weeks, 4 months, 1 year postpartum	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	blood lipids of pregnant and lactating women		15th wk gestation, 32nd wk gestation, 6 weeks pp, 4 months pp	No
Secondary	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	No
Secondary	daily intake of maternal fatty acids	7 day dietary records	15 wks gestation, 32nd wks gestation, 6 wks pp	No
Secondary	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	No
Secondary	offspring fat mass, abdominal fat	magnetic resonance imaging	6 weeks, 4 months, 5 years postpartum	No
Secondary	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)	No
Secondary	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)	No
Secondary	epigenetic analyses (histone modification, DNA methylation)	placenta, umbilical cord tissue, white blood cells	birth	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	breast milk oligosaccharides		6 wks and 4 months postpartum	No
Secondary	offspring atopic eczema	parent questionnaire	1.5 years - 5 years postpartum	No
Secondary	offspring allergic diseases (asthma, rhinitis)	parent questionnaire	5 years postpartum	No
Secondary	developmental evaluation of children	parent questionnaire (based on Minnesota Scales)	2 years - 5 years postpartum	No
Secondary	motor development of children		4 years and 5 years postpartum	No
Secondary	physical activity of children	parent questionnaire	2 years - 5 years postpartum	No
Secondary	dietary intake of children	3 day dietary record	2 years - 5 years postpartum	No
Secondary	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	No