Fish Oil and Folate Supplementation During Pregnancy

Study Overview
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Brief Summary
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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.

Official Title
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Dietary Supply of Docosahexaenoic Acid (DHA) and 5-methyl-tetrahydro-folate (MTHF) During the Second Half of Pregnancy and Early Infancy

Conditions
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Perinatal DHA and Folate Status, Neurological Development

Intervention / Treatment
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* Dietary Supplement: fish oil
* Dietary Supplement: folate
* Dietary Supplement: fish oil + folate
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 41 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fish oil<br>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<br>* 400 mg of DHA and 150 mg of eicosapentaenoic acid per day<br>|
| Experimental: folate<br>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<br>* 400 µg per day<br>|
| Experimental: fish oil + folate<br>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<br>* 500 mg DHA, 150 mg eicosapentaenoic acid, 400 µg MTHF per day<br>|
| Placebo Comparator: placebo<br>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<br>* only vitamins and minerals as recommended, but no fish oil or folate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage contribution of docosahexaenoic acid (DHA) to total phospholipid fatty acids in cord blood | 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 | labour | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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docosahexaenoic acid, folate, neurological development, allergies, long term consequences for the offspring, allergy risk