The purpose of this study is to determine whether choline supplementation influences the availability of docosahexaenoic acid throughout pregnancy.
Metabolic synergy exists between choline, phospholipid, and polyunsaturated fatty acid metabolism. Previous evidence from our laboratory has shown that higher dietary choline intakes increase the amount of docosahexaenoic acid (DHA) incorporated into phosphatidylcholine (PC), as measured by PC-DHA concentrations in circulating erythrocytes. PC-DHA results from the production of PC through the phosphatidyl N-ethanolamine methyltransferase (PEMT) pathway and is critical for exporting fat from the liver to peripheral tissues. We are expanding this work to pregnant women, for whom DHA intake is critical to support the developing infant's growth, by undertaking a double blind, randomized controlled trial of choline supplementation (500mg) throughout the 2nd and 3rd trimesters of pregnancy. All women will consume 200mg of docosahexaenoic acid (DHA), a prenatal vitamin, and 25-50mg of deuterated choline (choline d9) daily throughout the duration of the trial. The use of a stable isotope will allow for modeling of choline dynamics throughout the 2nd and 3rd trimester of pregnancy, and calculate the activity of PEMT in pregnant women. Consenting participants will provide a baseline blood draw, followed by 2 additional blood draws throughout their pregnancies, and maternal/cord blood at birth, in addition to the placenta. This trial will test the hypothesis that choline supplementation increases the amount of PC-DHA in the blood of pregnant women and increase its supply to the developing fetus.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
40
Choline chloride is a water soluble choline salt that will be provided in a juice solution to participants to be consumed daily. The intervention will increase dietary choline intake by 500mg/day.
Human Metabolic Research Unit, Cornell University
Ithaca, New York, United States
RECRUITINGDHA-Containing Phosphatidylcholine Species in Circulating Erythrocytes
Phosphatidylcholine species contain 2 fatty acid tails; phosphatidylcholines containing DHA at either the sn-1 or sn-2 positions are found circulating in erythrocytes and serve as a long term marker of DHA status. Erythrocyte PC-DHA is partially supplied by albumin bound lysophosphatidylcholine enriched with DHA, a product of the phosphatidylethanolamine methyltransferase pathway in the liver, which has been shown to be sensitive to dietary choline intakes in non-pregnant women.
Time frame: Gestational Weeks 12-16 through Gestational Weeks 38-41
Circulating labeled and unlabeled choline metabolites in maternal plasma
The concentrations and isotopic enrichments of choline and its metabolites (betaine, dimethylglycine,sarcosine, total phosphatidylcholine) will be determined in the maternal, placental and fetal compartments by Liquid Chromatography Tandem Mass Spectrometry
Time frame: Gestational Weeks 12-16 through Gestational Weeks 38-41
The impact of dietary choline on total DHA concentrations in the maternal, fetal and placental compartments
The total concentrations of docosahexaenoic acid (DHA; % total fatty acids as determined by Gas Chromatography-Flame Ionization Detector) will be measured in the maternal blood throughout this study. Additionally, at term, placenta and cord blood will be collected and analyzed for total DHA measurements.
Time frame: Gestational Weeks 12-16 through Gestational Weeks 38-41
The Association of Maternal Choline Supplementation with Infant Visual Recognition Memory Novelty Score
The composite novelty score (proportion of looking to the novel image) is obtained from a series of 9 visual paired comparison tests. The novelty score is a measure of visual recognition memory for infants and has been shown to predict cognitive outcomes in childhood.
Time frame: 5, 7, 10, and 13 months of age
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The Association of Maternal Choline Supplementation with Infant Visual Attention Orienting Speed Score
Visual attention orienting speed is measured by the latency to initiate a stimulus-guided fixation shift to a peripheral visual target (mean of up to 20 target presentations). The orienting score was found to be sensitive to maternal choline supplementation in infants of this age and has shown acceptable test-retest reliability and prediction of attention, memory, and intelligence quotient outcomes in childhood.
Time frame: 5, 7, 10, and 13 months of age
The Association of Maternal Choline Supplementation with Infant Sustained Focused Attention Score
Sustained focused attention is measured during a 5-minute period in which infants are engaged in solitary play with a complex toy. The score is the average duration of infant engagement in a state of focused attention on the toy. Infants who sustain focused attention for longer durations have been found to have fewer attentional problems as children.
Time frame: 5, 7, 10, and 13 months of age
The Association of Maternal Choline Supplementation with Infant Recall Memory Score
Recall memory is measured with a deferred imitation protocol. The infant watches an adult perform a novel sequence of actions on a set of objects to produce an interesting result. After a distraction-filled 15-minute delay the infant is given the objects and encouraged to engage in the modeled actions. The score is the number of target actions reproduced (average of 3 problems). Infants who achieve greater recall memory scores perform better on tests of memory during childhood.
Time frame: 13 months of age