Choline Supplementation on Fetal Growth in Gestational Diabetes Mellitus

NCT04302168 | Completed DMC

• 1 other identifier: 2019-07-06
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Gestational diabetes mellitus (GDM), characterized by maternal high blood sugar, affects up to 15% of pregnancies worldwide. GDM doubles the risk of fetal growth (i.e. macrosomia, large fetus,) which further predisposes the affected fetus to elevated risks of obesity, diabetes and cardiovascular disease later in life. The placenta mediates macrosomia by increasing fat and glucose transport to the fetus during GDM. Effective methods to normalize placental nutrient transport and prevent macrosomia are lacking. Choline is a semi-essential nutrient found in egg yolks, meat, fish and cruciferous vegetables. The demand for this nutrient increases substantially during pregnancy. Previous research demonstrated that maternal choline supplementation (MCS) normalized placental fat and glucose transport as well as fetal growth and fat mass in GDM mice. In this study, the investigators will recruit pregnant women with GDM and randomized them to receive a choline supplement (470mg/day, a dose with demonstrated safety), or a placebo for 8 weeks, starting after gestational week 28. The investigators will determine the effects of choline on fetal growth as well as the influence of choline on placental transport and epigenetic modifications in growth-related genes in the placenta and umbilical cord. Successful completion of this study will provide valuable insights into the use of choline supplement as a modifier of placental macronutrient homeostasis in GDM to improve fetal growth outcomes.

Conditions

Gestational Diabetes

Outcome Measures

Primary Outcomes (1)

• Birthweight

  Birthweight of neonate

  At time of birth

Secondary Outcomes (1)

• Gene expression of glucose transporters

  At time of birth

Study Arms (2)

Choline Supplement Group

ACTIVE COMPARATOR

Choline Supplement 470 mg twice daily for total of 8 weeks.

Dietary Supplement: Choline supplement

Placebo Group

PLACEBO COMPARATOR

Placebo pill twice daily for total of 8 weeks.

Dietary Supplement: Placebo

Interventions

Choline supplement DIETARY_SUPPLEMENT

Choline 470mg twice daily for 8 weeks.

Choline Supplement Group

Placebo DIETARY_SUPPLEMENT

Placebo pill twice daily for 8 weeks

Placebo Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• GDM pregnant women before gestational week 28.
• English or Spanish speaking, over 18 years of age
• singleton pregnancy
• intending to deliver their babies at Maimonides Medical Center

You may not qualify if:

• pre-existing hyperglycemia
• diabetes
• cardiovascular conditions and liver disease prior to pregnancy.

Sponsors & Collaborators

• Maimonides Medical Center: lead

Study Sites (1)

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Related Publications (58)

• Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care. 2007 Jul;30 Suppl 2:S141-6. doi: 10.2337/dc07-s206. No abstract available.

  PMID: 17596462 BACKGROUND

• Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003 Mar;111(3):e221-6. doi: 10.1542/peds.111.3.e221.

  PMID: 12612275 BACKGROUND

• Page KA, Romero A, Buchanan TA, Xiang AH. Gestational diabetes mellitus, maternal obesity, and adiposity in offspring. J Pediatr. 2014 Apr;164(4):807-10. doi: 10.1016/j.jpeds.2013.11.063. Epub 2013 Dec 31.

  PMID: 24388326 BACKGROUND

• Vohr BR, McGarvey ST, Tucker R. Effects of maternal gestational diabetes on offspring adiposity at 4-7 years of age. Diabetes Care. 1999 Aug;22(8):1284-91. doi: 10.2337/diacare.22.8.1284.

  PMID: 10480772 BACKGROUND

• Franks PW, Looker HC, Kobes S, Touger L, Tataranni PA, Hanson RL, Knowler WC. Gestational glucose tolerance and risk of type 2 diabetes in young Pima Indian offspring. Diabetes. 2006 Feb;55(2):460-5. doi: 10.2337/diabetes.55.02.06.db05-0823.

  PMID: 16443781 BACKGROUND

• Garcia-Vargas L, Addison SS, Nistala R, Kurukulasuriya D, Sowers JR. Gestational Diabetes and the Offspring: Implications in the Development of the Cardiorenal Metabolic Syndrome in Offspring. Cardiorenal Med. 2012 May;2(2):134-142. doi: 10.1159/000337734. Epub 2012 Apr 12.

  PMID: 22851962 BACKGROUND

• Lowe WL Jr, Karban J. Genetics, genomics and metabolomics: new insights into maternal metabolism during pregnancy. Diabet Med. 2014 Mar;31(3):254-62. doi: 10.1111/dme.12352.

  PMID: 24528228 BACKGROUND

• Poston L, Bell R, Croker H, Flynn AC, Godfrey KM, Goff L, Hayes L, Khazaezadeh N, Nelson SM, Oteng-Ntim E, Pasupathy D, Patel N, Robson SC, Sandall J, Sanders TA, Sattar N, Seed PT, Wardle J, Whitworth MK, Briley AL; UPBEAT Trial Consortium. Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2015 Oct;3(10):767-77. doi: 10.1016/S2213-8587(15)00227-2. Epub 2015 Jul 9.

  PMID: 26165396 BACKGROUND

• Sagedal LR, Overby NC, Bere E, Torstveit MK, Lohne-Seiler H, Smastuen M, Hillesund ER, Henriksen T, Vistad I. Lifestyle intervention to limit gestational weight gain: the Norwegian Fit for Delivery randomised controlled trial. BJOG. 2017 Jan;124(1):97-109. doi: 10.1111/1471-0528.13862. Epub 2016 Jan 14.

  PMID: 26768233 BACKGROUND

• Han S, Crowther CA, Middleton P, Heatley E. Different types of dietary advice for women with gestational diabetes mellitus. Cochrane Database Syst Rev. 2013 Mar 28;(3):CD009275. doi: 10.1002/14651858.CD009275.pub2.

  PMID: 23543574 BACKGROUND

• Bain E, Crane M, Tieu J, Han S, Crowther CA, Middleton P. Diet and exercise interventions for preventing gestational diabetes mellitus. Cochrane Database Syst Rev. 2015 Apr 12;(4):CD010443. doi: 10.1002/14651858.CD010443.pub2.

  PMID: 25864059 BACKGROUND

• Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ. 2017 Feb 8;356:j1. doi: 10.1136/bmj.j1.

  PMID: 28179267 BACKGROUND

• Caudill MA. Pre- and postnatal health: evidence of increased choline needs. J Am Diet Assoc. 2010 Aug;110(8):1198-206. doi: 10.1016/j.jada.2010.05.009.

  PMID: 20656095 BACKGROUND

• Jiang X, West AA, Caudill MA. Maternal choline supplementation: a nutritional approach for improving offspring health? Trends Endocrinol Metab. 2014 May;25(5):263-73. doi: 10.1016/j.tem.2014.02.001. Epub 2014 Mar 26.

  PMID: 24680198 BACKGROUND

• Zeisel SH. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis. Clin Chem Lab Med. 2013 Mar 1;51(3):467-75. doi: 10.1515/cclm-2012-0518.

  PMID: 23072856 BACKGROUND

• Corbin KD, Zeisel SH. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol. 2012 Mar;28(2):159-65. doi: 10.1097/MOG.0b013e32834e7b4b.

  PMID: 22134222 BACKGROUND

• Geraghty AA, Lindsay KL, Alberdi G, McAuliffe FM, Gibney ER. Nutrition During Pregnancy Impacts Offspring's Epigenetic Status-Evidence from Human and Animal Studies. Nutr Metab Insights. 2016 Feb 16;8(Suppl 1):41-7. doi: 10.4137/NMI.S29527. eCollection 2015.

  PMID: 26917970 BACKGROUND

• Nam J, Greenwald E, Jack-Roberts C, Ajeeb TT, Malysheva OV, Caudill MA, Axen K, Saxena A, Semernina E, Nanobashvili K, Jiang X. Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity. J Nutr Biochem. 2017 Nov;49:80-88. doi: 10.1016/j.jnutbio.2017.08.004. Epub 2017 Aug 12.

  PMID: 28915389 BACKGROUND

• Jack-Roberts C, Joselit Y, Nanobashvili K, Bretter R, Malysheva OV, Caudill MA, Saxena A, Axen K, Gomaa A, Jiang X. Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity. Nutrients. 2017 Aug 18;9(8):899. doi: 10.3390/nu9080899.

  PMID: 28820499 BACKGROUND

• Dabelea D. The predisposition to obesity and diabetes in offspring of diabetic mothers. Diabetes Care. 2007 Jul;30 Suppl 2:S169-74. doi: 10.2337/dc07-s211. No abstract available.

  PMID: 17596467 BACKGROUND

• Ferrara A, Kahn HS, Quesenberry CP, Riley C, Hedderson MM. An increase in the incidence of gestational diabetes mellitus: Northern California, 1991-2000. Obstet Gynecol. 2004 Mar;103(3):526-33. doi: 10.1097/01.AOG.0000113623.18286.20.

  PMID: 14990417 BACKGROUND

• Chen Y, Quick WW, Yang W, Zhang Y, Baldwin A, Moran J, Moore V, Sahai N, Dall TM. Cost of gestational diabetes mellitus in the United States in 2007. Popul Health Manag. 2009 Jun;12(3):165-74. doi: 10.1089/pop.2009.12303.

  PMID: 19534581 BACKGROUND

• Kolu P, Raitanen J, Rissanen P, Luoto R. Health care costs associated with gestational diabetes mellitus among high-risk women--results from a randomised trial. BMC Pregnancy Childbirth. 2012 Jul 24;12:71. doi: 10.1186/1471-2393-12-71.

  PMID: 22827919 BACKGROUND

• American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.

  PMID: 24357209 BACKGROUND

• Deputy NP, Sharma AJ, Kim SY, Hinkle SN. Prevalence and characteristics associated with gestational weight gain adequacy. Obstet Gynecol. 2015 Apr;125(4):773-781. doi: 10.1097/AOG.0000000000000739.

  PMID: 25751216 BACKGROUND

• Langer O. Management of gestational diabetes: pharmacologic treatment options and glycemic control. Endocrinol Metab Clin North Am. 2006 Mar;35(1):53-78, vi. doi: 10.1016/j.ecl.2005.09.007. No abstract available.

  PMID: 16310642 BACKGROUND

• Rosario FJ, Powell TL, Jansson T. Activation of placental insulin and mTOR signaling in a mouse model of maternal obesity associated with fetal overgrowth. Am J Physiol Regul Integr Comp Physiol. 2016 Jan 1;310(1):R87-93. doi: 10.1152/ajpregu.00356.2015. Epub 2015 Oct 21.

  PMID: 26491103 BACKGROUND

• Jones HN, Woollett LA, Barbour N, Prasad PD, Powell TL, Jansson T. High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice. FASEB J. 2009 Jan;23(1):271-8. doi: 10.1096/fj.08-116889. Epub 2008 Sep 30.

  PMID: 18827021 BACKGROUND

• Brett KE, Ferraro ZM, Yockell-Lelievre J, Gruslin A, Adamo KB. Maternal-fetal nutrient transport in pregnancy pathologies: the role of the placenta. Int J Mol Sci. 2014 Sep 12;15(9):16153-85. doi: 10.3390/ijms150916153.

  PMID: 25222554 BACKGROUND

• Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol. 2006 Oct;195(4):1100-3. doi: 10.1016/j.ajog.2006.06.014. Epub 2006 Jul 26.

  PMID: 16875645 BACKGROUND

• Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, Navder K, Yu A, Dorsey K, Gallagher D. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol. 2011 Sep;205(3):211.e1-7. doi: 10.1016/j.ajog.2011.04.004. Epub 2011 Apr 14.

  PMID: 21621185 BACKGROUND

• Qiao L, Guo Z, Bosco C, Guidotti S, Wang Y, Wang M, Parast M, Schaack J, Hay WW Jr, Moore TR, Shao J. Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice. Diabetes. 2015 Sep;64(9):3111-20. doi: 10.2337/db14-1627. Epub 2015 May 6.

  PMID: 25948680 BACKGROUND

• Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, Beiser A. Choline, an essential nutrient for humans. FASEB J. 1991 Apr;5(7):2093-8.

  PMID: 2010061 BACKGROUND

• Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2011 Jan;8(1):35-44. doi: 10.1038/nrgastro.2010.191. Epub 2010 Nov 30.

  PMID: 21119613 BACKGROUND

• Fischer LM, da Costa KA, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9. doi: 10.3945/ajcn.2010.30064. Epub 2010 Sep 22.

  PMID: 20861172 BACKGROUND

• Raubenheimer PJ, Nyirenda MJ, Walker BR. A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet. Diabetes. 2006 Jul;55(7):2015-20. doi: 10.2337/db06-0097.

  PMID: 16804070 BACKGROUND

• Fujiki K, Kano F, Shiota K, Murata M. Expression of the peroxisome proliferator activated receptor gamma gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol. 2009 Jul 10;7:38. doi: 10.1186/1741-7007-7-38.

  PMID: 19589179 BACKGROUND

• Cai D, Jia Y, Lu J, Yuan M, Sui S, Song H, Zhao R. Maternal dietary betaine supplementation modifies hepatic expression of cholesterol metabolic genes via epigenetic mechanisms in newborn piglets. Br J Nutr. 2014 Nov 14;112(9):1459-68. doi: 10.1017/S0007114514002402. Epub 2014 Sep 12.

  PMID: 25216241 BACKGROUND

• Dimasuay KG, Boeuf P, Powell TL, Jansson T. Placental Responses to Changes in the Maternal Environment Determine Fetal Growth. Front Physiol. 2016 Jan 29;7:12. doi: 10.3389/fphys.2016.00012. eCollection 2016.

  PMID: 26858656 BACKGROUND

• Kavitha JV, Rosario FJ, Nijland MJ, McDonald TJ, Wu G, Kanai Y, Powell TL, Nathanielsz PW, Jansson T. Down-regulation of placental mTOR, insulin/IGF-I signaling, and nutrient transporters in response to maternal nutrient restriction in the baboon. FASEB J. 2014 Mar;28(3):1294-305. doi: 10.1096/fj.13-242271. Epub 2013 Dec 13.

  PMID: 24334703 BACKGROUND

• Rosario FJ, Kanai Y, Powell TL, Jansson T. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth. Obesity (Silver Spring). 2015 Aug;23(8):1663-70. doi: 10.1002/oby.21165.

  PMID: 26193061 BACKGROUND

• Nanobashvili K, Jack-Roberts C, Bretter R, Jones N, Axen K, Saxena A, Blain K, Jiang X. Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts. Nutrients. 2018 Oct 15;10(10):1507. doi: 10.3390/nu10101507.

  PMID: 30326592 BACKGROUND

• Dhasarathy A, Roemmich JN, Claycombe KJ. Influence of maternal obesity, diet and exercise on epigenetic regulation of adipocytes. Mol Aspects Med. 2017 Apr;54:37-49. doi: 10.1016/j.mam.2016.10.003. Epub 2016 Nov 4. No abstract available.

  PMID: 27825817 BACKGROUND

• Heerwagen MJ, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R711-22. doi: 10.1152/ajpregu.00310.2010. Epub 2010 Jul 14.

  PMID: 20631295 BACKGROUND

• Kovacheva VP, Mellott TJ, Davison JM, Wagner N, Lopez-Coviella I, Schnitzler AC, Blusztajn JK. Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression. J Biol Chem. 2007 Oct 26;282(43):31777-88. doi: 10.1074/jbc.M705539200. Epub 2007 Aug 27.

  PMID: 17724018 BACKGROUND

• 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.

  PMID: 22549509 BACKGROUND

• Wallace TC, Fulgoni VL. Usual Choline Intakes Are Associated with Egg and Protein Food Consumption in the United States. Nutrients. 2017 Aug 5;9(8):839. doi: 10.3390/nu9080839.

  PMID: 28783055 BACKGROUND

• Harnack L, Stevens M, Van Heel N, Schakel S, Dwyer JT, Himes J. A computer-based approach for assessing dietary supplement use in conjunction with dietary recalls. J Food Compost Anal. 2008 Feb;21(Suppliment 1):S78-S82. doi: 10.1016/j.jfca.2007.05.004.

  PMID: 19190705 BACKGROUND

• Arab L, Tseng CH, Ang A, Jardack P. Validity of a multipass, web-based, 24-hour self-administered recall for assessment of total energy intake in blacks and whites. Am J Epidemiol. 2011 Dec 1;174(11):1256-65. doi: 10.1093/aje/kwr224. Epub 2011 Oct 20.

  PMID: 22021561 BACKGROUND

• Timperio A, Salmon J, Crawford D. Validity and reliability of a physical activity recall instrument among overweight and non-overweight men and women. J Sci Med Sport. 2003 Dec;6(4):477-91. doi: 10.1016/s1440-2440(03)80273-6.

  PMID: 14723397 BACKGROUND

• Garrison A. Screening, diagnosis, and management of gestational diabetes mellitus. Am Fam Physician. 2015 Apr 1;91(7):460-7.

  PMID: 25884746 BACKGROUND

• American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S137-S143. doi: 10.2337/dc18-S013.

  PMID: 29222384 BACKGROUND

• Wirfalt AK, Jeffery RW, Elmer PJ. Comparison of food frequency questionnaires: the reduced Block and Willett questionnaires differ in ranking on nutrient intakes. Am J Epidemiol. 1998 Dec 15;148(12):1148-56. doi: 10.1093/oxfordjournals.aje.a009599.

  PMID: 9867258 BACKGROUND

• Feskanich D, Sielaff BH, Chong K, Buzzard IM. Computerized collection and analysis of dietary intake information. Comput Methods Programs Biomed. 1989 Sep;30(1):47-57. doi: 10.1016/0169-2607(89)90122-3.

  PMID: 2582746 BACKGROUND

• Cho E, Holmes MD, Hankinson SE, Willett WC. Choline and betaine intake and risk of breast cancer among post-menopausal women. Br J Cancer. 2010 Feb 2;102(3):489-94. doi: 10.1038/sj.bjc.6605510. Epub 2010 Jan 5.

  PMID: 20051955 BACKGROUND

• 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.

  PMID: 24132975 BACKGROUND

• Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

  PMID: 21475195 BACKGROUND

• Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, Sutter JL, Caudill MA. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201600324. Epub 2016 Aug 3.

  PMID: 27377678 BACKGROUND

MeSH Terms

Conditions

Diabetes, Gestational

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: April 1, 2020
• Primary Completion: August 30, 2024
• Study Completion: October 31, 2024
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)