Fish Oil and Folate Supplementation During Pregnancy (NUHEAL)

• ClinicalTrials.gov Identifier: NCT01180933
• Recruitment Status: Completed
• First Posted: August 12, 2010
• Last Update Posted: July 30, 2014
• Sponsor: Ludwig-Maximilians - University of Munich
• Collaborator: European Union
• Information provided by: Ludwig-Maximilians - University of Munich

Study Description

Brief Summary:

Pregnant women are randomised to supplementation with fish oil, methyl tetrahydro folic acid, both or a placebo during the second half of pregnancy. Biochemical measures are determined in maternal blood during pregnancy and in cord blood.

Non invasive follow up examinations of infants at ages 4, 5.5, 6.5, 7.5, 8, 9 and 9.5 years focus on long term effects of supplementation anthropometric development, neurological development and allergy risk.

Condition or disease	Intervention/treatment	Phase
Perinatal DHA and Folate Status; Neurological Development	Dietary Supplement: fish oil; Dietary Supplement: folate; Dietary Supplement: fish oil + folate; Dietary Supplement: placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 315 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dietary Supply of Docosahexaenoic Acid (DHA) and 5-methyl-tetrahydro-folate (MTHF) During the Second Half of Pregnancy and Early Infancy
• Study Start Date: November 2001
• Actual Primary Completion Date: August 2003
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: fish oil; the participating women receive a milk based supplement providing vitamins and mineral as recommended for pregnant women and 500 mg DHA and 150 eicosapentaenoic acid per day from gestational week 22 until delivery	Dietary Supplement: fish oil; 400 mg of DHA and 150 mg of eicosapentaenoic acid per day
Experimental: folate; the participating women receive a milk based supplement providing vitamins and mineral as recommended for pregnant women and 400 µg folate (methyltetrahydrofolate)per day from gestational week 22 until delivery	Dietary Supplement: folate; 400 µg per day
Experimental: fish oil + folate; the participating women receive a milk based supplement providing vitamins and mineral as recommended for pregnant women and 500 mg DHA, 150 mg eicosapentaenoic acid and 400 µg MTHF per day from gestational week 22 until delivery	Dietary Supplement: fish oil + folate; 500 mg DHA, 150 mg eicosapentaenoic acid, 400 µg MTHF per day
Placebo Comparator: placebo; the participating women receive a milk based supplement providing vitamins and mineral as recommended for pregnant women from gestational week 22 until delivery	Dietary Supplement: placebo; only vitamins and minerals as recommended, but no fish oil or folate

Outcome Measures

Primary Outcome Measures :

1. percentage contribution of docosahexaenoic acid (DHA) to total phospholipid fatty acids in cord blood [ Time Frame: labour ]
   the biochemical efficacy of supplementation during pregnancy is tested by measuring the DHA content of cord blood phospholipids, as direct supplementation (fish oil) or increased perfusion of the placenta (MTHF) could both influence this parameter

Secondary Outcome Measures :

1. neurological and cognitive development of the offspring [ Time Frame: age 4 years, 5.5 years, 6.5 years, 7.5 years, 8 years, 9 years, 9.5 years ]
   non invasive, age adequate, tests of neurological and cognitive function are performed at various ages of the offspring
2. weight development [ Time Frame: age 4 years, 5.5 years, 6.5 years, 8 years, 9.5 years ]
   body weight (including weight of fat and non fat mass by bioelectrical impedance at later ages) is determined
3. height [ Time Frame: age 4 years, 5.5 years, 6.5 years, 8 years, 9.5 years ]
   body height is measured at ages 4 years, 5.5 years, 6.5 years, 8 years, 9.5 years
4. life style and diet [ Time Frame: age 4 years, 5.5 years, 6.5 years, 7.5 years, 8 years, 9 years, 9.5 years ]
   information on medical history, life sytyle and dietary habits is collected via questionnaires and non invasivly collected of biological samples (urine, cheek cells)
5. electroencephalography (EEG) [ Time Frame: age 8 years and 9.5 years ]
   at age 8 years and 9.5 years an EEG is obtained while the children are performing defined tests

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 41 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• singleton pregnancy
• gestation <20 week at enrollment
• intention to deliver in one of the study centers
• body weight at time of enrollment from 50 kg to 92 kg

Exclusion Criteria:

• serious chronic illness (eg, diabetes, hepatitis)
• use fish oil supplements since the beginning of pregnancy
• use of folate or vitamin B-12 supplements after gestation week 16

Contacts and Locations

Locations

Germany

Dr. von Hauner Childrens Hospital, Ludwig-Maximilians-University

Munich, Germany, 80337

Hungary

University of Pecs

Pecs, Hungary, 7623

Spain

Department of Paediatrics, University of Granada

Granada, Spain, 18012

Sponsors and Collaborators

Ludwig-Maximilians - University of Munich

European Union

Investigators

• Study Director: Berthold Koletzko, Prof.; Dr. von Hauner Childrens Hospital, Ludwig-Maximilians-University Munich

More Information

Publications of Results:

Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H, Jiménez M, Gil A, Rivero M, Veszprémi B, Decsi T, Koletzko BV; Nutrition and Health Lifestyle (NUHEAL) Study Group. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr. 2007 May;85(5):1392-400.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Catena A, Muñoz-Machicao JA, Torres-Espínola FJ, Martínez-Zaldívar C, Diaz-Piedra C, Gil A, Haile G, Györei E, Molloy AM, Decsi T, Koletzko B, Campoy C. Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial. Am J Clin Nutr. 2016 Jan;103(1):115-27. doi: 10.3945/ajcn.115.109108. Epub 2015 Nov 11.

Campoy C, Escolano-Margarit MV, Ramos R, Parrilla-Roure M, Csábi G, Beyer J, Ramirez-Tortosa MC, Molloy AM, Decsi T, Koletzko BV. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. Am J Clin Nutr. 2011 Dec;94(6 Suppl):1880S-1888S. doi: 10.3945/ajcn.110.001107. Epub 2011 Aug 17.

Escolano-Margarit MV, Ramos R, Beyer J, Csábi G, Parrilla-Roure M, Cruz F, Perez-Garcia M, Hadders-Algra M, Gil A, Decsi T, Koletzko BV, Campoy C. Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. J Nutr. 2011 Jun;141(6):1216-23. doi: 10.3945/jn.110.129635. Epub 2011 Apr 27.

• Responsible Party: Prof. Dr. Berthold Koletzko, Ludwig-Maximilians University of Munich
• ClinicalTrials.gov Identifier: NCT01180933
• Other Study ID Numbers: 01111
• First Posted: August 12, 2010
• Last Update Posted: July 30, 2014
• Last Verified: June 2014

Keywords provided by Ludwig-Maximilians - University of Munich:

docosahexaenoic acid; folate; neurological development; allergies; long term consequences for the offspring; allergy risk

Additional relevant MeSH terms:

Folic Acid; Vitamin B Complex; Hematinics; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs