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The FACT Biomarker Subgroup Analysis is a pilot study of mothers who participated in the Folic Acid Clinical Trial (FACT, NCT01355159). This subgroup analysis aims to determine the effect of high-dose folic acid supplementation in pregnancy on maternal folate status and subsequent impact on risk for pre-eclampsia.
The Folic Acid Clinical Trial (FACT) was developed to conclusively determine the effect of high dose folic acid supplementation in pregnancy on the prevention of preeclampsia (PE) in a randomized controlled trial (RCT) design.
The primary objective of the FACT Biomarker Subgroup Analysis is to determine the folate status and its impact on risk for PE in a subgroup of women participating in FACT. Our secondary objectives are to:
i) To determine serum vitamin B6 and B12 status, modifiers of folate metabolism, and their impact on risk for PE in women participating in the FACT
ii) To determine plasma homocysteine status, a folate-responsive biomarker for PE risk, and its relationship with risk for PE in women participating in the FACT
iii) To determine the modifying effect of single nucleotide polymorphisms (SNPs) in key folate metabolic enzymes (MTHFR, MTHFD1, MTR) on PE risk in women participating in the FACT
iv) To determine the effect of folic acid supplementation and folate status on biomarkers of PE (sFLT, sENG, PlGF) and their association with PE risk in women participating in the FACT
Folate biomarker analyses will provide key information to identify modifiers of the response to folic acid treatment and elucidate the mechanism(s) underlying the relationship between folic acid treatment and PE risk. Folate status will vary in response to folic acid treatment depending on a number of factors including compliance in taking the study supplement, folate intake from the diet (natural folate and folic acid used for enrichment), vitamin B12 status, and genetic polymorphisms in enzymes involved in folate metabolism that have been shown to effect placental development/function. As such, variation in the response to folic acid treatment may account for differences in observed PE risk.
Folic acid supplementation may also reduce homocysteine, its related endothelial dysfunction and consequently reduce PE risk. In addition, homocysteine metabolism is dependent on vitamins B12 and B6, the deficiency of which can result in hyperhomocysteinemia. Thus, homocysteine, B12 and B6 will each be evaluated.
Lastly, it will be useful to assess biomarkers of placental health and PE risk (sFlt-1, sEng, PlGF) that are found in maternal circulation and determine their association with folate intake and status.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FACT High-dose folic acid treatment group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy. |
| |
| FACT Placebo treatment group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 4.0mg Folic Acid received through participation in FACT (NCT01355159) | Other | Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid intervention are provided below: Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid |
| Measure | Description | Time Frame |
|---|---|---|
| Folate Status | The primary outcome measure is maternal folate status. Folate status will be determined by:
| From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation. |
| Measure | Description | Time Frame |
|---|---|---|
| Homocysteine Status | Maternal homocysteine concentrations will be determined. | From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation. |
| Status of Modifiers of Folate metabolism_vitamin B-12 |
Not provided
Individuals participating in FACT (NCT01355159) will be eligible to participate. FACT eligibility criteria are as follows:
INCLUSION criteria
Capability of subject to comprehend and comply with study requirements
≥ 18 years of age at time of consent
Subject is taking ≤1.1 mg of folic acid daily at the time of randomization
Live fetus (documented positive fetal heart prior to randomization)
Gestational age between 8+0 and 16+6 weeks of pregnancy (Gestational age (GA) of subjects will be calculated based on the first day of the last menstrual period (LMP) or ultrasound performed before 12+6. If early ultrasound and LMP dates differ by ≤ 7 days, base GA estimate on LMP date; if > 7 days, use early < 12+6 ultrasound)
Subject plans to give birth in a participating hospital site
Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):
EXCLUSION Criteria:
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The FACT Biomarker Subgroup Analysis is a pilot study that aims to determine the folate status and its impact on risk for pre-eclampsia in a subgroup of women participating in FACT (NCT01355159).
Women participating in FACT (NCT01355159) will be eligible to participate.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Moncton Hospital | Moncton | New Brunswick | E1C 6Z8 | Canada | ||
| Kingston General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30209050 | Background | Wen SW, White RR, Rybak N, Gaudet LM, Robson S, Hague W, Simms-Stewart D, Carroli G, Smith G, Fraser WD, Wells G, Davidge ST, Kingdom J, Coyle D, Fergusson D, Corsi DJ, Champagne J, Sabri E, Ramsay T, Mol BWJ, Oudijk MA, Walker MC; FACT Collaborating Group. Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial. BMJ. 2018 Sep 12;362:k3478. doi: 10.1136/bmj.k3478. | |
| 18166303 |
| Label | URL |
|---|---|
| High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention (FACT) ClinicalTrials.gov registration | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | FACT High-dose Folic Acid Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy. 4.0mg Folic Acid received through participation in FACT (NCT01355159): Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid intervention are provided below: Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid |
| FG001 | FACT Placebo Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy. Placebo received through participation in FACT: Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid placebo are provided below: Placebo x 4 tablets will be taken daily by oral administration. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | FACT High-dose Folic Acid Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy. 4.0mg Folic Acid received through participation in FACT (NCT01355159): Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid intervention are provided below: Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Folate Status | The primary outcome measure is maternal folate status. Folate status will be determined by:
| Posted | Median | Inter-Quartile Range | nmol/L | From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FACT High-dose Folic Acid Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy. 4.0mg Folic Acid received through participation in FACT (NCT01355159): Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid intervention are provided below: Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid |
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Selection bias and generalizability: convenience sample from a larger trial of individuals at high risk for preeclampsia
Small sample size
Lack of baseline folate measurements and the single time-point evaluation of folate status: prevents analysis of changes in folate status and 1-carbon metabolism over the course of pregnancy
Samples were non-fasting and information on the timing of sample collection relative to ingestion of the daily folic acid supplements was not collected
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alysha Harvey | Ottawa Hospital Research Institute | 613-737-8899 | 73838 | alyharvey@ohri.ca |
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| ID | Term |
|---|---|
| D011225 | Pre-Eclampsia |
| ID | Term |
|---|---|
| D046110 | Hypertension, Pregnancy-Induced |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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Peripheral Whole Blood, Plasma, Serum
|
| Placebo received through participation in FACT | Other | Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid placebo are provided below: Placebo x 4 tablets will be taken daily by oral administration. |
|
Status of modifiers of folate metabolism will be determined by Vitamin B6 and B12 concentrations |
| Taken at one time point between 24 and 26 completed weeks gestation. |
| Angiogenic Potential | Angiogenic potential will be determined from measurement of maternal circulating s-FLT-1, s-ENG-1 and placental growth factor concentrations. | From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation. |
| Status of Modifiers of Folate metabolism_MTHFR Genotype (C677T) | Status of modifiers of folate metabolism will be determined by frequency of single nucleotide polymorphisms (SNPs) in the key folate metabolic enzyme MTHFR | Taken at one time point between 24 and 26 completed weeks gestation. |
| Status of Modifiers of Folate metabolism_ Vitamin B6 (Pyridoxal 5-phosphate) | Status of modifiers of folate metabolism will be determined by Vitamin B6 and B12 concentrations | Taken at one time point between 24 and 26 completed weeks gestation. |
| Kingston |
| Ontario |
| K7L 2V7 |
| Canada |
| The Ottawa Hospital | Ottawa | Ontario | K1Y 4E9 | Canada |
| Health Canada | Ottawa | Ontario | Canada |
| Background |
| Wen SW, Chen XK, Rodger M, White RR, Yang Q, Smith GN, Sigal RJ, Perkins SL, Walker MC. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol. 2008 Jan;198(1):45.e1-7. doi: 10.1016/j.ajog.2007.06.067. |
| 3927946 | Background | Shane B, Stokstad EL. Vitamin B12-folate interrelationships. Annu Rev Nutr. 1985;5:115-41. doi: 10.1146/annurev.nu.05.070185.000555. |
| 19437229 | Background | Guven MA, Coskun A, Ertas IE, Aral M, Zencirci B, Oksuz H. Association of maternal serum CRP, IL-6, TNF-alpha, homocysteine, folic acid and vitamin B12 levels with the severity of preeclampsia and fetal birth weight. Hypertens Pregnancy. 2009 May;28(2):190-200. doi: 10.1080/10641950802601179. |
| 16232172 | Background | Lindblad B, Zaman S, Malik A, Martin H, Ekstrom AM, Amu S, Holmgren A, Norman M. Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses. Acta Obstet Gynecol Scand. 2005 Nov;84(11):1055-61. doi: 10.1111/j.0001-6349.2005.00876.x. |
| 7762494 | Background | Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest J Jr. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. Am J Cardiol. 1995 Jun 1;75(16):1107-11. doi: 10.1016/s0002-9149(99)80739-5. |
| 9855605 | Background | Powers RW, Evans RW, Majors AK, Ojimba JI, Ness RB, Crombleholme WR, Roberts JM. Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol. 1998 Dec;179(6 Pt 1):1605-11. doi: 10.1016/s0002-9378(98)70033-x. |
| 15298442 | Background | Stover PJ. Physiology of folate and vitamin B12 in health and disease. Nutr Rev. 2004 Jun;62(6 Pt 2):S3-12; discussion S13. doi: 10.1111/j.1753-4887.2004.tb00070.x. |
| 17436239 | Background | Hustad S, Midttun O, Schneede J, Vollset SE, Grotmol T, Ueland PM. The methylenetetrahydrofolate reductase 677C-->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet. 2007 May;80(5):846-55. doi: 10.1086/513520. Epub 2007 Mar 13. |
| 16552426 | Background | Parle-McDermott A, Kirke PN, Mills JL, Molloy AM, Cox C, O'Leary VB, Pangilinan F, Conley M, Cleary L, Brody LC, Scott JM. Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet. 2006 Jun;14(6):768-72. doi: 10.1038/sj.ejhg.5201603. |
| 15633187 | Background | Parle-McDermott A, Mills JL, Kirke PN, Cox C, Signore CC, Kirke S, Molloy AM, O'Leary VB, Pangilinan FJ, O'Herlihy C, Brody LC, Scott JM. MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae. Am J Med Genet A. 2005 Feb 1;132A(4):365-8. doi: 10.1002/ajmg.a.30354. |
| 16123074 | Background | Parle-McDermott A, Pangilinan F, Mills JL, Signore CC, Molloy AM, Cotter A, Conley M, Cox C, Kirke PN, Scott JM, Brody LC. A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod. 2005 Jul;11(7):477-80. doi: 10.1093/molehr/gah204. |
| 18771981 | Background | Furness DL, Fenech MF, Khong YT, Romero R, Dekker GA. One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency. Am J Obstet Gynecol. 2008 Sep;199(3):276.e1-8. doi: 10.1016/j.ajog.2008.06.020. |
| 15937596 | Background | Tam LE, McDonald SD, Wen SW, Smith GN, Windrim RC, Walker MC. A survey of preconceptional folic acid use in a group of Canadian women. J Obstet Gynaecol Can. 2005 Mar;27(3):232-6. doi: 10.1016/s1701-2163(16)30515-1. |
| 20739423 | Background | Shakur YA, Garriguet D, Corey P, O'Connor DL. Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians. Am J Clin Nutr. 2010 Oct;92(4):818-25. doi: 10.3945/ajcn.2010.29696. Epub 2010 Aug 25. |
| 10413330 | Background | Czeizel AE, Tomcsik M. Acute toxicity of folic acid in pregnant women. Teratology. 1999 Jul;60(1):3-4. doi: 10.1002/(SICI)1096-9926(199907)60:13.0.CO;2-4. No abstract available. |
| 7979565 | Background | Czeizel AE, Dudas I, Metneki J. Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report. Arch Gynecol Obstet. 1994;255(3):131-9. doi: 10.1007/BF02390940. |
| 7883469 | Background | Czeizel AE, Susanszky E. Diet intake and vitamin supplement use of Hungarian women during the preconceptional period. Int J Vitam Nutr Res. 1994;64(4):300-5. |
| 11665336 | Background | Ericson A, Kallen B, Aberg A. Use of multivitamins and folic acid in early pregnancy and multiple births in Sweden. Twin Res. 2001 Apr;4(2):63-6. doi: 10.1375/1369052012155. |
| 1489222 | Background | Kirke PN, Daly LE, Elwood JH. A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group. Arch Dis Child. 1992 Dec;67(12):1442-6. doi: 10.1136/adc.67.12.1442. |
| 20410093 | Background | Stevens VL, McCullough ML, Sun J, Gapstur SM. Folate and other one-carbon metabolism-related nutrients and risk of postmenopausal breast cancer in the Cancer Prevention Study II Nutrition Cohort. Am J Clin Nutr. 2010 Jun;91(6):1708-15. doi: 10.3945/ajcn.2009.28553. Epub 2010 Apr 21. |
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| 18984888 | Background | Zhang SM, Cook NR, Albert CM, Gaziano JM, Buring JE, Manson JE. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA. 2008 Nov 5;300(17):2012-21. doi: 10.1001/jama.2008.555. |
| 12618502 | Background | Zhang SM, Willett WC, Selhub J, Hunter DJ, Giovannucci EL, Holmes MD, Colditz GA, Hankinson SE. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst. 2003 Mar 5;95(5):373-80. doi: 10.1093/jnci/95.5.373. |
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| 20820900 | Background | Kim DH, Smith-Warner SA, Spiegelman D, Yaun SS, Colditz GA, Freudenheim JL, Giovannucci E, Goldbohm RA, Graham S, Harnack L, Jacobs EJ, Leitzmann M, Mannisto S, Miller AB, Potter JD, Rohan TE, Schatzkin A, Speizer FE, Stevens VL, Stolzenberg-Solomon R, Terry P, Toniolo P, Weijenberg MP, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hunter DJ. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control. 2010 Nov;21(11):1919-30. doi: 10.1007/s10552-010-9620-8. Epub 2010 Sep 5. |
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| 18053387 | Background | Wilson RD; GENETICS COMMITTEE; MOTHERISK. RETIRED: Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can. 2007 Dec;29(12):1003-1013. doi: 10.1016/S1701-2163(16)32685-8. English, French. |
| BG001 | FACT Placebo Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy. Placebo received through participation in FACT: Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid placebo are provided below: Placebo x 4 tablets will be taken daily by oral administration. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | FACT Placebo Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy. Placebo received through participation in FACT: Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid placebo are provided below: Placebo x 4 tablets will be taken daily by oral administration. |
|
|
| Secondary | Homocysteine Status | Maternal homocysteine concentrations will be determined. | Two participants in the High-dose Folic Acid Treatment Group and one participant in the Placebo Treatment Group had missing data for this outcome. | Posted | Median | Inter-Quartile Range | nmol/L | From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation. |
|
|
|
| Secondary | Status of Modifiers of Folate metabolism_vitamin B-12 | Status of modifiers of folate metabolism will be determined by Vitamin B6 and B12 concentrations | For Vitamin B-12 measurement, sample data are not available for one participant in the high-dose folic acid treatment group, and one participant in the placebo treatment group. Missing data are due to insufficient sample volume or compromised sample quality. | Posted | Median | Inter-Quartile Range | pmol/L | Taken at one time point between 24 and 26 completed weeks gestation. |
|
|
|
| Secondary | Angiogenic Potential | Angiogenic potential will be determined from measurement of maternal circulating s-FLT-1, s-ENG-1 and placental growth factor concentrations. | Posted | Median | Inter-Quartile Range | pg/mL | From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation. |
|
|
|
| Secondary | Status of Modifiers of Folate metabolism_MTHFR Genotype (C677T) | Status of modifiers of folate metabolism will be determined by frequency of single nucleotide polymorphisms (SNPs) in the key folate metabolic enzyme MTHFR | The baseline distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT are describe in each row. | Posted | Count of Participants | Participants | Taken at one time point between 24 and 26 completed weeks gestation. |
|
|
|
| Secondary | Status of Modifiers of Folate metabolism_ Vitamin B6 (Pyridoxal 5-phosphate) | Status of modifiers of folate metabolism will be determined by Vitamin B6 and B12 concentrations | For Vitamin B-6 (pyridoxal 5-phosphate), sample data are not available for one participant in the high-dose folic acid treatment group. Missing data are due to insufficient sample volume or compromised sample quality. | Posted | Median | Inter-Quartile Range | nmol/L | Taken at one time point between 24 and 26 completed weeks gestation. |
|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | FACT Placebo Treatment Group | Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy. Placebo received through participation in FACT: Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid placebo are provided below: Placebo x 4 tablets will be taken daily by oral administration. | 0 | 31 | 0 | 31 |
Not provided
Not provided
| soluble endoglin (sEng-1) |
|
| TT |
|