None listed
Conditions
Brief summary
Australian women receive 0.15-0.2 mg/d of folic acid from food containing fortified bread flour. In addition, >80% of Australian women take a multivitamin during pregnancy, with one of the most popular brands containing double the amount of folic acid recommended for pregnant women until 3 months gestation. (0.8 mg/d). There is no question that taking folic acid in early pregnancy is important to prevent neural tube defects. However, there is no proven benefit and potential harm from taking folic acid after neural tube closure at approximately 28 days post conception. We aim to determine if removing folic acid from prenatal supplements after 12 weeks of gestation results in lower blood concentrations of unmetabolised folic acid, a biomarker of excess folic acid, at 36 weeks’ gestation. We will also determine if removing folic acid from prenatal supplements after 12 weeks’ gestation allows women to maintain red blood cell folate concentrations >905 nmol/L at 36 weeks’ gestation.
Interventions
Participants will be randomised to receive either a prenatal micronutrient supplement containing 0.8 mg folic acid (Control) or an identical micronutrient supplement containing no folic acid (Intervention).
The composition of micronutrients within the intervention and control supplements are formulated to approximate the current leading brands of prenatal micronutrient supplements and both contain the following: calcium 250 mg, Iron 27 mg, thiamine 1.4 mg, riboflavin 1.4 mg, niacinamide 18 mg,
Participants will be randomised to receive either a prenatal micronutrient supplement containing 0.8 mg folic acid (Control) or an identical micronutrient supplement containing no folic acid (Intervention). The composition of micronutrients within the intervention and control supplements are formulated to approximate the current leading brands of prenatal micronutrient supplements and both contain the following: calcium 250 mg, Iron 27 mg, thiamine 1.4 mg, riboflavin 1.4 mg, niacinamide 18 mg, vitamin B-6 1.9 mg, vitamin B-12 2.6 mcg, pantothenic acid 6 mg, biotin 30 mg, vitamin C 85 mg, vitamin E 13.5 IU, magnesium 50 mg, zinc 7.5 mg, manganese 2.0 mg, iodine 0.22 mg, copper 1 mg, chromium 30 mcg, selenium 30 mcg, Vitamin D3 10 mcg, b-carotene 2500 IU. Intervention and control supplements will be in tablet form and are identical in size, shape, colour and packaging. They only differ in the removal of folic acid from the intervention supplement. Study supplements will be packaged and labelled in accordance with the Code of Good Manufacturing Practice (GMP) for Medicinal Products and Therapeutic Goods Administration (TGA) guidelines for clinical trial products, including; product identification number (Product ID), batch number, expiry date and include the statement “for clinical trial use only”. The intervention and control supplements will be manufactured and donated by Factors Group of Companies, Coquitlam, British Columbia, Canada. Participants will be supplied with supplements for the duration of their pregnancy. The initial supply will be dispensed following randomisation and enough supplements will be given to last until the 36 week clinic visit as well as additional supplements as a compliance measure. At the 36 week clinic visit, participants will then be issued with supplements to last the reminder of their pregnancy. The study supplements are ready to administer requiring no preparation. Participants will be instructed to take one supplement per day, orally from randomisation (>12 to <16 weeks gestation) until delivery. The Research Assistant will maintain regular contact with participating women by SMS/email or telephone (depending on participant preference) to monitor and encourage compliance. At each contact, women will be asked if they have missed any supplements in the last week and if so, how many have been missed. Women will be supplied with excess supplements and will be asked to return unused supplements at the 36 week clinic visit for a supplement count. The proportion of supplements returned will serve as an additional measure of adherence.
Sponsors
South Australian Health and Medical Research Institute (SAHMRI)
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
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for participation women must meet all of the following criteria; 1) a singleton pregnancy greater or equal to 12 weeks and less than 16 weeks gestation. 2) currently taking a folic acid containing supplement and planning to continue throughout pregnancy. 3) be able to give informed consent.
Exclusion criteria
Women will be ineligible for trial participation if they meet any the following criteria; 1) carrying a fetus with a confirmed or suspected fetal abnormality. 2) unwilling to cease current folic acid containing supplement/s 3) previous history of a NTD affected pregnancy 4) currently taking medication known to interfere with folate metabolism (i.e. anti-convulsant, anti-malaria medication or barbiturates). 5) Known haemolytic anaemia or haemoglobinopathy 6) Known malabsorption syndrome or MTHFR mutation 7) intolerance or allergy to prenatal vitamin and mineral supplements.
Outcome results
None listed