N-3 Fatty Acid Requirements for Human Development

To Compare Measures of Central Nervous System Maturity of Visual Acuity, Language, Mental and Motor Skill Development in Term Infants Following Maternal Supplementation Wit the n-3 Fatty Acid Docosahexaenoic Acid (DHA) During Gestation.

Polyunsaturated fatty acids known as n-3 fatty acids are essential dietary nutrients for humans, and are known to be important to reducing the risk of certain diseases, particularly those related to neural system, cardiovascular system and immune system. Among the different n-3 fatty acids, docosahexaenoic acid (DHA) is present in particularly high amounts in the brain and retina, and is accumulated in large amounts in these organs during the last trimester of fetal development and first few months after birth. The n-3 fatty acids are present in the diet as linolenic acid which is found in vegetable and seed oils, and as DHA which is only found in animal tissue fats, with fatty fish being the richest dietary source. Humans are able to convert linolenic acid to DHA, but the conversion is believed to be slow in human and possibly inadequate to support the needs for DHA for the developing brain. Information from our work and those of others has suggested that DHA is important during pregnancy, however specific evidence is lacking to show that the DHA status of pregnant women in low, or that improvement in the DHA status of Canadian women during pregnancy will have benefit to early infant an child development. There is no evidence that infants of vegans and vegetarians, or women who do not eat DHA are at risk for developmental delays. The purpose of this study is to investigate whether a dietary supplement of DHA during pregnancy has any effect on infant birth weight, or indices of infant growth, visual, mental and motor skill development.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Dietary supplement: omega 3 fatty acids; Dietary supplement: vegetable oil

Detailed Description

This is a randomized, blinded prospective study with 2 groups: placebo and group supplemented with DHA. Women are randomized at 16 weeks gestation without knowledge of their dietary fatty acid intake. Only healthy women expecting to deliver a single infant with no known or anticipated maternal or fetal complications are enrolled. Maternal venous blood is collected at 16 and 36 weeks of gestation and used to assess the maternal DHA status and effect of DHA supplementation. Dietary information is collected at 16 and 36 weeks of gestation to determine usual fatty acid intakes. Following delivery, fetal cord blood is collected to assess transfer of DHA from mother to fetus. Breast milk samples are collected from all breast feeding mothers at 1 and 2 months postpartum. The mother -infant pairs are followed for 18 months. Measures include visual acuity, language, motor and mental development, and growth and dietary intakes.

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's & Women's Health Centre of British Columbia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 12-16 weeks gestation
• Low risk pregnancy
• Expected to deliver single full term
• No maternal metabolic or infectious disease
• No known fetal complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; The dietary supplement is 400 mg/day of the omega 3 fatty acid docosahexaenoic acid . The docosahexaenoic acid is provided in triglycerides from Martek Biosciences, Maryland. The supplement is a blend of soybean and canola oil, blended to resemble the usual fat composition of the diet. Both the supplement and placebo provide a total of about 10 calories per day to the diet.	Dietary supplement: omega 3 fatty acids; The supplements are taken orally with a meal, each day. The amount of the omega 3 fatty acid docosahexaenoic acid is 400 mg/day; taken in two 500 mg capsules each providing 200 mg docosahexaenoic acid. The placebo is two 500 mg capsules soybean/canola oil. Both the supplement and placebo are a total of 1 gm/day (2x500 mg) and about 10 calories per day.
Other: 2; Dietary supplement is vegetable oil, the placebo.	Dietary supplement: vegetable oil; The supplement is a dietary supplement of vegetable oil as a placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome is measuring of infant CNS maturity to 18 months of age	Primary outcome is measuring of infant CNS maturity to 18 months of age	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of gestation and infant birth weight, infant growth (weight, length and head circumference) at 1,2 6,9,12,14,and 18 months Language development at 14 and 16 months	Length of gestation and infant birth weight, infant growth (weight, length and head circumference) at 1,2 6,9,12,14,and 18 months; Diet, blood an dbreast milk fatty acids	72 months

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Sheila M. Innis, Ph.D, University of British Columbia

Publications and helpful links

General Publications

• Mulder KA, King DJ, Innis SM. Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy. PLoS One. 2014 Jan 10;9(1):e83764. doi: 10.1371/journal.pone.0083764. eCollection 2014.
• Friesen RW, Innis SM. Linoleic acid is associated with lower long-chain n-6 and n-3 fatty acids in red blood cell lipids of Canadian pregnant women. Am J Clin Nutr. 2010 Jan;91(1):23-31. doi: 10.3945/ajcn.2009.28206. Epub 2009 Nov 18.
• Friesen RW, Innis SM. Dietary arachidonic acid to EPA and DHA balance is increased among Canadian pregnant women with low fish intake. J Nutr. 2009 Dec;139(12):2344-50. doi: 10.3945/jn.109.112565. Epub 2009 Oct 28.
• van Dijk CE, Innis SM. Growth-curve standards and the assessment of early excess weight gain in infancy. Pediatrics. 2009 Jan;123(1):102-8. doi: 10.1542/peds.2007-3382.

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: February 11, 2008
• First Submitted That Met QC Criteria: February 20, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Estimate): June 1, 2016
• Last Update Submitted That Met QC Criteria: May 30, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: n-3 supplementation during pregnancy; DHA and pregnancy, infant development; n-3 status and gestation; DHA and visual acuity and cognition during infancy
• Other Study ID Numbers: H03-70242; CW03-0084