None listed
Conditions
Brief summary
Adequate folic acid intake is a widely accepted preconception behaviour to improve fetal health and viability. Recent research has highlighted that women in preconception and pregnancy do not meet the required level of folate to support pregnancy from their diet alone and therefore to support a viable pregnancy they do need to take a prenatal multivitamin containing folate (Ledowsky et al., 2022). Prenatal multivitamins predominantly contain the synthetic form of folate, folic acid and contain upwards of 800mcg in each dose (Bailey et al., 2019; Masih et al., 2015; Murphy et al., 2021). The amount of folic acid therefore may exceed the upper tolerable limit as set by the Institute of medicine. The purpose of this study is to evaluate the feasibility of a larger trial to test a new form of folate (5-methyltetrahydrofolate (5-MTHF)) to reduce the incidence of miscarriage in those couples that have experienced recurrent miscarriage. The hypothesis is that unlike folic acid, 5-MTHF does not build up, does not mask a Vitamin B12 deficiency and can be better utilised by the body to support a healthy pregnancy, thereby reducing the risk of miscarriage.
Interventions
5-methyltetrahydrofolate (5-MTHF) based prenatal multivitamin (intervention - Arm 1)
Dose: 5-MTHF 2,500mcg per day
5-methyltetrahydrofolate (5-MTHF) is the biologically active form of folate. It does not build up like folic acid and can be utilised without being converted to the form required to support DNA integrity.
Participants will be required to take one dose (3 capsules) of their allocated prenatal multivitamin per day. They will also be provided to avoid folic acid fortified foods.
They w
5-methyltetrahydrofolate (5-MTHF) based prenatal multivitamin (intervention - Arm 1) Dose: 5-MTHF 2,500mcg per day 5-methyltetrahydrofolate (5-MTHF) is the biologically active form of folate. It does not build up like folic acid and can be utilised without being converted to the form required to support DNA integrity. Participants will be required to take one dose (3 capsules) of their allocated prenatal multivitamin per day. They will also be provided to avoid folic acid fortified foods. They will be asked to receive regular blood testing including: Methylenetetrahydrofolate reductase (MTHFR) polymorphism, Vitamin B12, methylmalonic acid (MMA), red cell folate, serum folate, homocysteine. The initial baseline blood test will be completed immediately upon recruitment ie: first 2 weeks, another blood test will be taken following 2 reproductive cycles. Participants who fall pregnant will receive a blood test each trimester of pregnancy for the duration of the trial. Provider - the PhD candidate is a naturopath with 12 years experience and therefore within her scope of practice to dispense the prenatal multivitamins. Delivery - Intervention will be sent every 3 months via mail with internet based meetings every 6 weeks Participants will be recruited Australia wide There will be a rolling recruitment period from January 16, 2023 to March 30, 2023. Participants recruited into the study will immediately commence on the prenatal multivitamin and continue until the trial period is completed, December 30, 2023. Participants will be therefore be participating in the trial for a minimum of 9 months, maximum 12 months, depending on their recruitment date. An internet based meeting will be conducted with the PhD Candidate who is a naturopath, every 6 weeks for approximately 30 minutes per participant. The purpose of this meeting will be to document and understand: 1. How the participant experiencing any tolerability issues with their intervention. 2. Does the participant need any support around folic acid avoidance diet 3. Are there any adherance issues - If more than 20% of supplement doses are missed then the participant will be ask to explain why they are unable to meet the requirements of the trial and if they are unable to improve fidelity they will be eliminated from the trial. 4. Have there been any adverse events 5. Is the participant experiencing any distress due to the protocols 6. Reproductive status ie: any hormonal issues, pregnancies to report
Sponsors
University of Technology Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
20 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
1. Women aged 20-49 years of age with two or more pregnancy losses before 22 weeks and their reproductive partners 2. Ability to speak and understand English sufficiently to comprehend the purpose and risks of the study and to provide consent 3. Ability to attend a pathology centre for specimen collection 4. Ability to not take concomitant medications, vitamins, food containing folic acid
Exclusion criteria
1. Pregnant or lactating women 2. Couples who are currently undergoing assisted reproductive technologies 3. Men and women taking folate antagonist medication (phenytoin, valproic acid, valproate sodium, carbamazepine, methotrexate, trimethoprim hydrochloride, trimethoprim sulphate, trimethoprim, aminopterin sodium, phenobarbital, phenobarbital sodium, primidone, divalproex) 4. Individuals with a known sensitivity to any ingredients in the products 5. History or presence of psychiatric disorders (including depression and severe anxiety), autoimmune disease, and cancer 6. History of gynaecological and/or genetic problems– antiphospholipid syndrome, blocked fallopian tubes, Pelvic inflammatory disease, Primary ovarian insufficiency, endometriosis, Uterine fibroids, Factor V Leiden
Outcome results
None listed