Source: COLORADO STATE UNIVERSITY submitted to
RELATIONSHIP BETWEEN INFANT GROWTH & NEUROCOGNITIVE DEVELOPMENT & MATERNAL DIETARY INTAKE OF OMEGA 3 DOCOSAHEXAENOIC ACID
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0211082
Grant No.
2007-35200-18315
Project No.
COL0-2007-02318
Proposal No.
2007-02318
Multistate No.
(N/A)
Program Code
31.0
Project Start Date
Aug 1, 2007
Project End Date
Jul 31, 2012
Grant Year
2007
Project Director
Harris, M.
Recipient Organization
COLORADO STATE UNIVERSITY
(N/A)
FORT COLLINS,CO 80523
Performing Department
FOOD SCIENCE & HUMAN NUTRITION
Non Technical Summary
This project will examine the effect of DHA supplementation during pregnancy on infant growth and cognitive development throughout the first two years of life.
Animal Health Component
(N/A)
Research Effort Categories
Basic
20%
Applied
80%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7025010101050%
7025010307050%
Goals / Objectives
The objectives of this study are to: 1) Determine the effect of supplementation with DHA during pregnancy on early neurocognitive development and infant growth. 2) Determine whether early neurocognitive effects of DHA intake during pregnancy and lactation persist through the first two years of life 3) Evaluate the effect of exclusive breastfeeding on neurocognitive development in infants whose mothers are supplemented with 300 mg DHA vs. controls. This will be accomplished by extending the duration and exclusivity of breastfeeding by the use of an in-home breastfeeding support program employing one-on-one support provided by well trained paraprofessional lactation counselors.
Project Methods
The study will examine the relationship between maternal n-3 DHA intake during pregnancy and lactation and infant neurocognitive development throughout the first two years of life. The method we will use is a 3-year random assignment double blind placebo controlled clinical trial in which 200 women with singleton pregnancies will complete a clinical trial to increase DHA intake by taking 300 mg DHA /day vs controls which will receive placebo (oil vehicle only) during the third trimester of pregnancy and throughout lactation. Capsules will be used to double blind the study at a level which approximates dietary intakes and bioavailability obtainable with increased consumption of fatty fish and/or DHA-enriched functional foods. Maternal blood will be obtained at 36 weeks of gestation to examine DHA levels as a measure of maternal DHA status. Enrichment of breast milk with DHA will be measured in a breast milk sample obtained at 2 and 4 months of lactation. Habituation and recognition memory will be measured using the Fagan Test of Infant Intelligence at 4 months and 12 months of age and look duration at 4 months. An additional measure of cognitive performance, the Bayley Mental Development Index will be performed at 6 months, 12 months and 24 months of age to examine neurocognitive development and to compare to the current literature examining the effect of breast milk vs formula with and without added DHA on infant cognitive development. Infant temperament, shown to be related to later behavioral problems, will be assessed using the Infant Characteristics Questionnaire at 6 months and 12 months of age. Previous studies on breastfed infants have been complicated by the lack of exclusive breastfeeding of adequate duration to draw conclusions about the effect of breastfeeding on infant outcomes. Therefore, we will employ the highly successful North Carolina In-Home Breastfeeding Support Program to extend duration and exclusivity of breastfeeding during the first year of life. By administering the In-Home Breastfeeding Support Program in conjunction with the research study, we are assuring that sufficient numbers of the infants followed by the study will be exclusively breastfeed for the first six months of life. Expected outcomes are that infants born to mothers with higher DHA intakes throughout pregnancy and lactation who were exclusively breastfed will have improved cognitive development which will persist throughout the first two years of life.

Progress 08/01/07 to 07/31/12

Outputs
OUTPUTS: Conducted preliminary study to examine DHA intake in Larimer County population in the private practice vs WIC participants. Completd enrollment, DHA supplementation and testing on 110 pregnant and breastfeeding women. Developed highly successful omega-3 DHA supplement breastfeeding peer coaching program named the Omega Smart Baby Project to promote exclusive breastfeeding for the first 6 months of life. Testing competed incudced, dietary analysis of DHA intake during pregnancy and at 2 and 4 months of breastfeeding, RBC, plasma phospholipid and breastmilk fatty acid profiles, infant birthweitght, birth length and increments in weight and length at 2, 4 months and 1 year. Bayleys Scales of infant development and mismatch electronegativiey measuremens of cognitive development at 4 months and 1 year of age, Maternal IQ, Home environment and infant temperament scales. PARTICIPANTS: Mary Harris, PhD,RD Susan Baker, EdD Deanna Davalos,PhD Adam Chicco, PhD Stacy Miller, MS, PhD candidate Christopher Mulligan, MS, PhD candidate Jamie Williams, MS Carlyn Barnard, MS, RD TARGET AUDIENCES: pregnant and breastfeeding women and infants. PROJECT MODIFICATIONS: No major changes since last report.

Impacts
The code has only been broken this month and anaylsies are in progress. Preliminary breastfeeding statistics show the peer breastfeeding support program to be highly successful. To date, the Omega Smart Baby Project has exceeded all national goals for breastfeeding initiation and retention (6,7,8). The data compared to the maternal child health goalsare shown below: Objective 2020 Target Omega Smart Baby Project Initiated Breasfeeding 81.9% 100% Breastfeeding at 6 mo 60.6% 84% Brastfeeding at 1 yr 34.1% 59% BF exclusively thru 3m 46.2% 75% BF exclusively thru 6m 25.5% 37% Baseline intake: WIC population intake of DHA 238.9 mg/day + 27.9 (95% CI 183.7, 294.0) vs private practice 295.4 mg/day + 22.5(258.1, 332.8) p =0.058 DHA intake excluding DHA from prenatal supplements (mg/day)WIC 207.6 + 26.7 (154.8, 260.4) Private practice 262.0 + 20.7(227.7, 296.3) p = .054. Statistcal analysis of all other data is currently being conducted.

Publications

  • No publications reported this period


Progress 08/01/10 to 07/31/11

Outputs
OUTPUTS: OUTPUTS: This study is on a one-year extension of a three year randomized double blind placebo controlled trial. The study examines the relationship between maternal n-3 DHA intake during pregnancy and lactation and infant growth and neurocognitive development throughout the first two years of life. A peer breastfeeding coach model has been used successfully to assist mother's to breastfeed for the first six months of life. All subjects have been recruited and are being followed for the first 12 months of life. The model resulted in a very low drop out rate and to date only 11 mothers have been lost to follow up or discontinued breastfeeding early. Maternal dietary intakes of n-3 DHA have been obtained using a validated FFQ instrument and have been previosly reported. Cognitive development in infants,measured using the Bayley's IV Scales of Infant Development and a sensitive neurophysiologic measure which is associated with development of higher order cognition, mismatch negativity (MMN), are ongoing. DHA is being extracted for measurement of genetic variation in the desaturase gene cluster (a series of enzymes involved in essential fatty acid metabolism whic may represent the ability to convert plant based 18C omega-3 fatty acids to DHA and affect he ability to transfer maternal DHA stores to bresastmilk. To the best of our knowledge, this is the first dose response study of DHA during pregnancy and lactation on cognitive development and the first to characterize response on the basis of genetic variants in the FADSI FADS2 gene cluster. PARTICIPANTS: Mary Harris,PhD,RD (Dept of Food Science and Human Nutrition) Susan Baker, EdD(Dept of Food Science and Human Nutrition) Deanna Davalos, PhD (Dept of Psychology) Kathryn McGirr, MS(Dept of Food Science and Human Nutrition) Reserch Assistants: Stacy Miller, Phd candidate(Dept of Food Science and Human Nutrition) Christopher Mulligan,PhD candidate(Dept of Food Science and Human Nutrition) Alana Campbell, PHD candidate(Dept of Psychology) TARGET AUDIENCES: The target audience is pregnant and breastfeeding women. PROJECT MODIFICATIONS: No major changes.

Impacts
All study subjects have been recruited and are currently being followed. The results of the study will be available once all data are collected and the double blind code is broken. It is expected that the data will show dose response to DHA intake on infant cognitive development and growth. It is also expected that the dose required for improved infant cognitive development in response to omega-3 intake and breastmilk DHA content will be modulated by maternal genetic variation in the fatty acid desaturease complex.

Publications

  • No publications reported this period


Progress 08/01/09 to 07/31/10

Outputs
OUTPUTS: This study is in its second year of a three year randomized double blind placebo controlled trial. The study examines the relationship between maternal n-3 DHA intake during pregnancy and lactation and infant growth and neurocognitive development throughout the first two years of life. A number of changes have been made in the protocol since project recruiting began. Random assignment, complicated by contamination of the subject pool by the increasingly common use of DHA or fish oil containing prenatal vitamin supplements (ranging from 200 mg - 300 mg/day) has been addressed by development of a dose response model to increase DHA intake by taking the additional 300 mg DHA as highly purified fish oil/day or serve as controls who will receive placebo (oil vehicle only) during the third trimester of pregnancy and throughout the first three months of lactation. Breastfeeding coaches are employed to encourage exclusive breastfeeding . Coaches are trained using a modification of the North Carolina Breastfeeding Support model adapted to this population and including the most recent breastfeeding recommendations. Maternal dietary intakes of n-3 DHA obtained using a validated FFQ instrument show baseline intakes in this group are: 0.3110 + 0.0306 total DHA/day from food and supplements of which 0.1182 + 0.0.160 g/day was from foods and 0.1583 + 0.0191 g/day was from supplements. Cognitive development in infants is measured using the Bayley's IIII Scales of Infant Development and a sensitive neurophysiologic measure which is associated with development of higher order cognition, mismatch negativity (MMN) are ongoing. An important modification to this study includes a method to predict those women with increased needs for DHA based genetic variation in the desaturase gene cluster involved in essential fatty acid metabolism. To the best of our knowledge, this is the first dose response study of DHA during pregnancy and lactation on cognitive development and the first to characterize response on the basis of genetic variants in the FADSI FADS2 gene cluster. PARTICIPANTS: Harris, Mary A Baker, Susan Davalos, Deanna Campbell, Alana Mulligan, Christopher Miller, Stacy TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: A number of changes have been made in the protocol since project recruiting began. Random assignment, complicated by contamination of the subject pool by the increasingly common use of DHA or fish oil containing prenatal vitamin supplements (ranging from 200 mg - 300 mg/day) has been addressed by development of a dose response model to increase DHA intake by taking the additional 300 mg DHA as highly purified fish oil/day or serve as controls who will receive placebo (oil vehicle only) during the third trimester of pregnancy and throughout the first three months of lactation. Another important modification to this study includes a method to predict those women with increased needs for DHA based genetic variation in the desaturase gene cluster involved in essential fatty acid metabolism.

Impacts
The fatty acid, omega (n)-3 DHA, is an essential nutrient to promote healthy pregnancy outcomes and optimal infant cognitive development. Most women do not get enough n-3 DHA during pregnancy and lactation to meet their infant's optimal needs. The exact amount of DHA to promote optimal cognitive development is not known. This study will help to determine the optimal maternal intake of omega-3 DHA during critical stages of her infant's growth and neurocognitive development. The study may also help to identify individuals with increased needs for omega-3 DHA based upon genetic variations in the ability to convert plant based omega-3s to DHA.

Publications

  • Preliminary Report: Harris, M Baker, S and Davalos, D. Relationship between infant growth and neurocognitive development and maternal dietary intake of omega-3 (n-3) Docosahexaenoic Acid (DHA) IFT Abstracts, July 20, 2010 # 295-53.


Progress 08/01/08 to 07/31/09

Outputs
OUTPUTS: There is currently a great deal of interest in the effects of DHA supplementation during pregnancy and in the neonatal period on infant growth and cognitive development. The vast majority of infant studies to date have involved outcome evaluations after postnatal infant DHA supplementation and little is known about the beneficial effects of prenatal exposure. This study is a randomized double blind case control trial which will assess post-natal growth and cognitive development in infants whose mothers were supplemented with an additional 300 mg DHA per day (given as a highly purified fish oil) and controls (no additional DHA) during the second half of pregnancy through the first three months of breastfeeding. Exclusive breastfeeding will be promoted by the use of a breastfeeding support program which utilizes peer breastfeeding coaches. Baseline levels of DHA in prenatal vitamins will be quantified (range from 0 to 300 mg/day) to provide a dose response measure. Additionally, three genetic polymorphisms in the FADS2 gene, the gene which codes for delta-6 dehydrogenase, the rate limiting step in DHA synthesis) will be used to predict responsiveness to DHA supplementation at high and low levels. PARTICIPANTS: Mary Harris, PhD,RD, BC-ADM and Susan Baker, EdD (Department of Food Science and Human Nutrition, Colorado State University)and Deanna Davalos (Department of Psychology, Colorado State University) are the PI's for the study. Research Assistants Christopher Mulligan, Stacy Miller, Carlynn Barnard (Department of Food Science and Human Nutrition), Alana Campbell and Elizabeth Burnette (Department of Psychology) participated in the project. One undergradute student, Sarah Deubler (Hughes Science Scholar), recieved training and participated in the study. Industry partner, NuMega Ingredients supplied the high purity fish oil and placebo for the study. TARGET AUDIENCES: Pregnant and breastfeeding mothers and their babies are the target population for this intervention study. PROJECT MODIFICATIONS: Measurement of three genetic polymorphisms in the FADS2 gene, the gene which codes for delta-6 dehydrogenase, the rate limiting step in DHA synthesis) has been added to predict responsiveness to DHA supplementation at high and low levels. Bayleys Scales of Infant Development (which is a less sensitive measure of the domains of learning impacted by DHA) have been replaced with objective and sensitive electrophysiological tests of cognitive development throughout the first year of life. This will be the first report of the impact of DHA on cognitive development using this approach. Algal source DHA has been replaced with high purity fish oil form NuMega Ingredients to take advantage of a more natural source and provide supplement in one capsule instead of six, for improved adherence to treatment.

Impacts
DHA intake in pregnant women is low in the United States. Increasing maternal intake during pregnancy may have a significant impact upon post-natal growth and development in term and preterm infants. A mother's ability to synthesize adequate amounts of DHA as determined by her FADS2 genetic polymorphism is expected to help quantify the need for DHA during pregnancy and breastfeeding to support optimal growth and cognitive development.

Publications

  • No publications reported this period


Progress 08/01/07 to 07/31/08

Outputs
OUTPUTS: This study examines the relationship between maternal n-3 DHA intake during pregnancy and lactation and infant growth and neurocognitive development throughout the first two years of life. The study is a random assignment double blind placebo controlled clinical trial. A final "n" of 200 women with singleton pregnancies are being recruited to either 1) increase DHA intake by taking an additional 300 mg DHA /day or 2) serve as controls who will receive placebo (oil vehicle only) during the third trimester of pregnancy and throughout the first six months of lactation. To address the issue that DHA is commonly provided in prenatal vitamin formula in doses ranging from 200 - 300 mg/day, a dose response model has been developed. Data from our previous study (Allen, KGD et al) showed improved maternal benefits of algal DHA supplements at 600 mg/day vs 300 mg/day or controls. To the best of our knowledge, no dose response study has been published on infant cognitive benefits. PARTICIPANTS: Susan Baker, EdD. Dept Food Science and Human Nutrition, Colorado State University Deanna Davalos, Phd Dept of Psychology, Colorado State University Christopher Mullins, MS, graduate assistant, Dept of Food Science and Human Nutrition, Colorado State University TARGET AUDIENCES: The target audience for this reseaerch is pregnant and lactating women. PROJECT MODIFICATIONS: The study has been modified by developing novel method for dealing with contamination of the subject pool by the increasingly common use of DHA or fish oil containing prenatal vitamin supplements (ranging from 200 mg - 300 mg/day). To address this issue, a dose response model has been developed in which additional DHA is provided utilizing the original randomized double blind placebo controlled design. Additionally, the study will measure genetic modification of the gene which codes delta-6 desaturase, the rate controlling enzyme in long chain polyunsaturated fatty acid synthesis.

Impacts
The expected outcome is that women who are supplemented with higher levels of DHA will give birth to infants with improved cognitive development, as measured by age appropriate tests of IQ and psychomotor development. In addition, the study will attempt to develop a method to identify women with increased needs for DHA based genetic alterations in the delta-6 desaturase enzyme.

Publications

  • No publications reported this period