Clinical trial NCT01127022: Effect of Maternal Choline Intake on Choline Status and Health Biomarkers During Pregnancy and Lactation
Official title: Effect of Maternal Choline Intake on Maternal/Fetal Biomarkers of Choline Status
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy
Lactation
Keywords: Pregnancy
Lactation
Choline
Cognition
Biomarkers
Lead sponsor: Cornell University
Sponsor class: OTHER
Collaborators: name: American Egg Board
name: National Cattlemen's Beef Association
name: USDA Beltsville Human Nutrition Research Center
First posted: 2010-05-20
Enrollment: 82
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to investigate the effect of varied maternal choline intake on maternal/fetal biomarkers of choline status, genomic expression and metabolomic profiling.

Detailed description: Choline is a micronutrient used for the structural integrity of cell membranes, lipid transport/metabolism, methylation reactions and cholinergic neurotransmission. Prenatal and early postnatal choline exposure plays a critical role in brain development and cognition based on animal data. Although it is recognized that choline use is particularly high during pregnancy and lactation, the level of choline intake needed to optimize maternal and fetal health outcomes is unknown. The primary objective of this study was to investigate the metabolic and genomic effects of two doses of choline intake, 450 mg/d (the adequate intake level for pregnant women) and 900 mg/d in pregnant, lactating, and nonpregnant control women. A secondary objective was to examine the effect of extra maternal choline intake on the child's cognitive performance (i.e, learning, memory and attention). To accomplish these objectives, pregnant women (wk 27 gestation), nonpregnant control women, and lactating women consumed controlled choline intakes of 480 or 930 mg/d for 10 to 12 weeks. The basal diet provided 380 mg/d; supplemental choline chloride, 100 or 550 mg/d, was used to achieve the target intake levels. During the last half of the study, a small portion (\~ 20%) of the total choline intake was derived from deuterium labeled choline, a stable isotope. Blood, urine and/or breast milk were collected at baseline and at select timepoints throughout the study duration. For pregnant women, a maternal blood sample was obtained at the time of delivery along with a cord blood sample and the placental tissue. Genomic and metabolomic profiling were performed on the collected biological samples along with specific measurements of choline status. Non-invasive tests assessing cognitive function were performed on the children of the pregnant and lactating study participants. This controlled feeding study has also been extended to investigate dose-response relationships for other micronutrients including folate, vitamin B12, vitamin D, and biotin.

Eligibility criteria: Inclusion Criteria:

* Pregnant (wk 27 gestation) or lactating (postnatal day 30) or nonpregnant
* Healthy
* Non-smoker

Exclusion Criteria:

* Liver or kidney problems
* Alcohol or illegal drug misuse/abuse

Primary outcomes:
measure: Maternal biomarkers of choline status
timeFrame: 10-12 Weeks
Secondary outcomes:
measure: Genomic expression as function of maternal choline intake
timeFrame: 10-12 Weeks
measure: Cognitive performance in children of study participants
timeFrame: 12 months
measure: Metabolomic profiling as a function of maternal choline intake
timeFrame: 10-12 Weeks
measure: Biomarkers for additional micronutrients
timeFrame: 10-12 Weeks
Other outcomes:
Locations:
city: Ithaca
country: United States
facility: Human Metabolic Research Unit, Cornell University
state: New York
Study officials:
affiliation: Cornell University
name: Marie A Caudill, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Stabler SP, Allen RH, Caudill MA. Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans. Am J Clin Nutr. 2012 May;95(5):1060-71. doi: 10.3945/ajcn.111.022772. Epub 2012 Mar 14.
citation: Jiang X, Bar HY, Yan J, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen FM, Wells MT, Caudill MA. Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women. PLoS One. 2012;7(11):e46736. doi: 10.1371/journal.pone.0046736. Epub 2012 Nov 2.
citation: Jiang X, Yan J, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Caudill MA. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 2012 Aug;26(8):3563-74. doi: 10.1096/fj.12-207894. Epub 2012 May 1.
citation: West AA, Yan J, Perry CA, Jiang X, Malysheva OV, Caudill MA. Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women. Am J Clin Nutr. 2012 Oct;96(4):789-800. doi: 10.3945/ajcn.112.037523. Epub 2012 Aug 29.
citation: Jiang X, Bar HY, Yan J, Jones S, Brannon PM, West AA, Perry CA, Ganti A, Pressman E, Devapatla S, Vermeylen F, Wells MT, Caudill MA. A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1). FASEB J. 2013 Mar;27(3):1245-53. doi: 10.1096/fj.12-221648. Epub 2012 Nov 29.
citation: West AA, Yan J, Jiang X, Perry CA, Innis SM, Caudill MA. Choline intake influences phosphatidylcholine DHA enrichment in nonpregnant women but not in pregnant women in the third trimester. Am J Clin Nutr. 2013 Apr;97(4):718-27. doi: 10.3945/ajcn.112.050211. Epub 2013 Feb 27.
citation: Bahnfleth CL, Strupp BJ, Caudill MA, Canfield RL. Prenatal choline supplementation improves child sustained attention: A 7-year follow-up of a randomized controlled feeding trial. FASEB J. 2022 Jan;36(1):e22054. doi: 10.1096/fj.202101217R.
citation: Klatt KC, McDougall MQ, Malysheva OV, Brenna JT, Roberson MS, Caudill MA. Reproductive state and choline intake influence enrichment of plasma lysophosphatidylcholine-DHA: a post hoc analysis of a controlled feeding trial. Br J Nutr. 2019 Dec 14;122(11):1221-1229. doi: 10.1017/S0007114519002009.
citation: Park H, Brannon PM, West AA, Yan J, Jiang X, Perry CA, Malysheva OV, Mehta S, Caudill MA. Vitamin D Metabolism Varies among Women in Different Reproductive States Consuming the Same Intakes of Vitamin D and Related Nutrients. J Nutr. 2016 Aug;146(8):1537-45. doi: 10.3945/jn.116.229971. Epub 2016 Jun 22.
citation: Davenport C, Yan J, Taesuwan S, Shields K, West AA, Jiang X, Perry CA, Malysheva OV, Stabler SP, Allen RH, Caudill MA. Choline intakes exceeding recommendations during human lactation improve breast milk choline content by increasing PEMT pathway metabolites. J Nutr Biochem. 2015 Sep;26(9):903-11. doi: 10.1016/j.jnutbio.2015.03.004. Epub 2015 Apr 15.
citation: Bae S, West AA, Yan J, Jiang X, Perry CA, Malysheva O, Stabler SP, Allen RH, Caudill MA. Vitamin B-12 Status Differs among Pregnant, Lactating, and Control Women with Equivalent Nutrient Intakes. J Nutr. 2015 Jul;145(7):1507-14. doi: 10.3945/jn.115.210757. Epub 2015 May 20.
citation: Perry CA, West AA, Gayle A, Lucas LK, Yan J, Jiang X, Malysheva O, Caudill MA. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet. J Nutr. 2014 Dec;144(12):1977-84. doi: 10.3945/jn.114.194472. Epub 2014 Aug 13.
citation: Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Brenna JT, Stabler SP, Allen RH, Gregory JF 3rd, Caudill MA. Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women. Am J Clin Nutr. 2013 Dec;98(6):1459-67. doi: 10.3945/ajcn.113.066092. Epub 2013 Oct 16.